Liver Disease

Autoimmune hepatitis that recurs following a liver transplant can impair both graft survival and overall survival, results of a large international study showed.

Among 736 patients with autoimmune hepatitis who underwent liver transplant and were followed for up to 20 years, those who had recurrent AIH had a more than 10-fold higher risk for graft failure and a more than twofold higher risk of death, compared with patients who did not have recurrences, reported Aldo J. Montano-Loza, MD, MSc, PhD, from the University of Alberta, Edmonton.

“Recurrent disease impacts graft and overall survival, highlighting the need for improved management strategies,” he said in an oral abstract presentation during the International Liver Congress sponsored by the European Association for the Study of the Liver.

AIH is characterized by the presence of high IgG levels, autoantibodies, and histologic evidence of interface hepatitis. Most patients with AIH respond to immunosuppressive therapy, but some have progression to end-stage liver disease; for these patients, a liver transplant can be lifesaving, with 1-year survival of approximately 90%, and 5-year survival of about 70%, he said.

AIH frequently recurs after transplant, and although previous studies have suggested that recurrent disease does not adversely affect either graft survival or long-term survival, those studies had limited patient numbers and inadequate follow-up, Dr. Montano-Loza said.

He cited two recent studies, one from UNOS, the United Network for Organ Sharing, and the other from ELTR, the European Liver Transplant Registry, that showed that overall survival after liver transplant was worse for patients with AIH, compared with those who underwent transplant for other autoimmune liver diseases.
 

Multicenter retrospective study

To get a better picture of long-term posttransplant outcomes in patients with AIH, investigators in 33 centers in North and South America, Europe, and Asia conducted a retrospective cohort study. Their goal was to establish the frequency of recurrent AIH, identify clinical factors and biomarkers for higher risk of recurrence, and evaluate the association between recurrent AIH and both patient and graft survival.

They accomplished this by performing chart reviews, including data on demographics, IgG levels before transplant, and Model for End-Stage Liver Disease scores.

They also collected data on serum liver function tests within the first year after transplant, posttransplant infections, rejection episodes, and immunosuppressive regimens, as well as variables such as donor age and sex, sex mismatch between donor and recipients, calendar year of transplant, and transplant volume for AIH at each center.

Of the 736 patients, 563 (76%) were female. The mean age at AIH diagnosis was 34 years, and the mean age at transplant was 42 years. About one-fifth of patients (21%) had concomitant autoimmune diseases.

Posttransplant immunosuppression regimens included the usual suspects: tacrolimus in 78% of patients, cyclosporine in 11%, prednisone in 76%, mycophenolate mofetil in 55%, and azathioprine in 10%.

In all, 147 of the 736 patients had a diagnosis of recurrent AIH. The investigators found that the cumulative probability of recurrent AIH was 49% after 20 years of follow-up.
 

Risk factors identified

In multivariate analysis controlling for age, concomitant disease, immunosuppressive regimens, organ-sex mismatch, acute rejection, liver function tests, bilirubin, and IgG, factors significantly associated with AIH recurrence included age 42 or younger at the time of transplant (hazard ratio, 3.15; P = .02), use of mycophenolate mofetil after transplant (HR, 3.06; P = .005), donor/recipient sex mismatch (HR, 2.57; P = .003), and high IgG levels pretransplant (HR, 1.04; P = .004).

Among 529 patients who had a liver biopsy after transplant, factors that remained as significant predictors of AIH recurrence were posttransplant mycophenolate mofetil (HR, 2.75; P = .003), donor/recipient sex mismatch (HR, 2.03; P = .02), and pretransplant IgG levels (HR, 1.04 per each g/L; P = .001).

An analysis of features associated with graft survival showed that recurrent AIH was associated with significantly increased risk for graft failure (HR, 10.79; P < .001). Patients with high bilirubin levels 1 year after transplantation were also at higher risk for failure (HR, 1.004 per micromol/L; P < .001).

Factors significantly associated with survival were recurrence of AIH (HR for death, 2.53; P = .001), elevated ALT at 12 months after transplant (HR, 1.002; P = .004), and elevated bilirubin at 12 months (HR, 1.003 per micromol/L; P < .001).

The investigators acknowledged that the study was limited by the retrospective design and by the fact that the diagnosis of recurrent AIH may have differed between centers that performed liver biopsy according to protocol and those that performed them only when clinically indicated, which may have resulted in differences in time to diagnosis.
 

Possible explanations for risk factors

In the question-and-answer session following his presentation, comoderator moderator Philip N. Newsome, PhD, from University Hospitals Birmingham (England), asked: “In terms of age, is that a reflection of worse disease, or is it adherence, or is it a combination, and should we be managing those patients more aggressively with immunosuppression?”

“We consider age is more a reflection of an aggressive disease,” Dr. Montano-Loza said. “Basically, in the univariate analysis we found that patients with a diagnosis at a younger age and even a transplant at a younger age were definitely associated with a higher risk of recurrence, so we think this is more related to an aggressive [disease] behavior in younger patient that translates into worse clinical outcomes.”

He added that patients younger than 40 who require transplants should be closely monitored for recurrence.

“Actually, we could make the argument that maybe these patients will benefit from protocol biopsies,” he said.

He noted that 15% of patients had significant fibrosis at the time of recurrent AIH diagnosis, and that the recurrences were not detected by laboratory monitoring alone.

Asked by an audience member why mycophenolate mofetil was associated with increased risk for recurrence, Dr. Montano-Loza replied that the retrospective nature of the data precludes the possibility of a definitive answer, but he noted that, for patients with other autoimmune liver diseases, the type of immunosuppression used has an impact on recurrence rates.

“For example, cyclosporine has a protective effect for patients transplanted for primary biliary cholangitis,” he said.

He said it may also be possible that there is a rebound effect leading to recurrence when patients are taken off mycophenolate or switched to another agent.

The study was supported by grants to individual researchers. Dr. Montano-Loza and Dr. Newsome reported having no relevant conflicts of interest.

Autoimmune hepatitis that recurs following a liver transplant can impair both graft survival and overall survival, results of a large international study showed.

Among 736 patients with autoimmune hepatitis who underwent liver transplant and were followed for up to 20 years, those who had recurrent AIH had a more than 10-fold higher risk for graft failure and a more than twofold higher risk of death, compared with patients who did not have recurrences, reported Aldo J. Montano-Loza, MD, MSc, PhD, from the University of Alberta, Edmonton.

“Recurrent disease impacts graft and overall survival, highlighting the need for improved management strategies,” he said in an oral abstract presentation during the International Liver Congress sponsored by the European Association for the Study of the Liver.

AIH is characterized by the presence of high IgG levels, autoantibodies, and histologic evidence of interface hepatitis. Most patients with AIH respond to immunosuppressive therapy, but some have progression to end-stage liver disease; for these patients, a liver transplant can be lifesaving, with 1-year survival of approximately 90%, and 5-year survival of about 70%, he said.

AIH frequently recurs after transplant, and although previous studies have suggested that recurrent disease does not adversely affect either graft survival or long-term survival, those studies had limited patient numbers and inadequate follow-up, Dr. Montano-Loza said.

He cited two recent studies, one from UNOS, the United Network for Organ Sharing, and the other from ELTR, the European Liver Transplant Registry, that showed that overall survival after liver transplant was worse for patients with AIH, compared with those who underwent transplant for other autoimmune liver diseases.
 

Multicenter retrospective study

To get a better picture of long-term posttransplant outcomes in patients with AIH, investigators in 33 centers in North and South America, Europe, and Asia conducted a retrospective cohort study. Their goal was to establish the frequency of recurrent AIH, identify clinical factors and biomarkers for higher risk of recurrence, and evaluate the association between recurrent AIH and both patient and graft survival.

They accomplished this by performing chart reviews, including data on demographics, IgG levels before transplant, and Model for End-Stage Liver Disease scores.

They also collected data on serum liver function tests within the first year after transplant, posttransplant infections, rejection episodes, and immunosuppressive regimens, as well as variables such as donor age and sex, sex mismatch between donor and recipients, calendar year of transplant, and transplant volume for AIH at each center.

Of the 736 patients, 563 (76%) were female. The mean age at AIH diagnosis was 34 years, and the mean age at transplant was 42 years. About one-fifth of patients (21%) had concomitant autoimmune diseases.

Posttransplant immunosuppression regimens included the usual suspects: tacrolimus in 78% of patients, cyclosporine in 11%, prednisone in 76%, mycophenolate mofetil in 55%, and azathioprine in 10%.

In all, 147 of the 736 patients had a diagnosis of recurrent AIH. The investigators found that the cumulative probability of recurrent AIH was 49% after 20 years of follow-up.
 

Risk factors identified

In multivariate analysis controlling for age, concomitant disease, immunosuppressive regimens, organ-sex mismatch, acute rejection, liver function tests, bilirubin, and IgG, factors significantly associated with AIH recurrence included age 42 or younger at the time of transplant (hazard ratio, 3.15; P = .02), use of mycophenolate mofetil after transplant (HR, 3.06; P = .005), donor/recipient sex mismatch (HR, 2.57; P = .003), and high IgG levels pretransplant (HR, 1.04; P = .004).

Among 529 patients who had a liver biopsy after transplant, factors that remained as significant predictors of AIH recurrence were posttransplant mycophenolate mofetil (HR, 2.75; P = .003), donor/recipient sex mismatch (HR, 2.03; P = .02), and pretransplant IgG levels (HR, 1.04 per each g/L; P = .001).

An analysis of features associated with graft survival showed that recurrent AIH was associated with significantly increased risk for graft failure (HR, 10.79; P < .001). Patients with high bilirubin levels 1 year after transplantation were also at higher risk for failure (HR, 1.004 per micromol/L; P < .001).

Factors significantly associated with survival were recurrence of AIH (HR for death, 2.53; P = .001), elevated ALT at 12 months after transplant (HR, 1.002; P = .004), and elevated bilirubin at 12 months (HR, 1.003 per micromol/L; P < .001).

The investigators acknowledged that the study was limited by the retrospective design and by the fact that the diagnosis of recurrent AIH may have differed between centers that performed liver biopsy according to protocol and those that performed them only when clinically indicated, which may have resulted in differences in time to diagnosis.
 

Possible explanations for risk factors

In the question-and-answer session following his presentation, comoderator moderator Philip N. Newsome, PhD, from University Hospitals Birmingham (England), asked: “In terms of age, is that a reflection of worse disease, or is it adherence, or is it a combination, and should we be managing those patients more aggressively with immunosuppression?”

“We consider age is more a reflection of an aggressive disease,” Dr. Montano-Loza said. “Basically, in the univariate analysis we found that patients with a diagnosis at a younger age and even a transplant at a younger age were definitely associated with a higher risk of recurrence, so we think this is more related to an aggressive [disease] behavior in younger patient that translates into worse clinical outcomes.”

He added that patients younger than 40 who require transplants should be closely monitored for recurrence.

“Actually, we could make the argument that maybe these patients will benefit from protocol biopsies,” he said.

He noted that 15% of patients had significant fibrosis at the time of recurrent AIH diagnosis, and that the recurrences were not detected by laboratory monitoring alone.

Asked by an audience member why mycophenolate mofetil was associated with increased risk for recurrence, Dr. Montano-Loza replied that the retrospective nature of the data precludes the possibility of a definitive answer, but he noted that, for patients with other autoimmune liver diseases, the type of immunosuppression used has an impact on recurrence rates.

“For example, cyclosporine has a protective effect for patients transplanted for primary biliary cholangitis,” he said.

He said it may also be possible that there is a rebound effect leading to recurrence when patients are taken off mycophenolate or switched to another agent.

The study was supported by grants to individual researchers. Dr. Montano-Loza and Dr. Newsome reported having no relevant conflicts of interest.

Autoimmune hepatitis that recurs following a liver transplant can impair both graft survival and overall survival, results of a large international study showed.

Among 736 patients with autoimmune hepatitis who underwent liver transplant and were followed for up to 20 years, those who had recurrent AIH had a more than 10-fold higher risk for graft failure and a more than twofold higher risk of death, compared with patients who did not have recurrences, reported Aldo J. Montano-Loza, MD, MSc, PhD, from the University of Alberta, Edmonton.

“Recurrent disease impacts graft and overall survival, highlighting the need for improved management strategies,” he said in an oral abstract presentation during the International Liver Congress sponsored by the European Association for the Study of the Liver.

AIH is characterized by the presence of high IgG levels, autoantibodies, and histologic evidence of interface hepatitis. Most patients with AIH respond to immunosuppressive therapy, but some have progression to end-stage liver disease; for these patients, a liver transplant can be lifesaving, with 1-year survival of approximately 90%, and 5-year survival of about 70%, he said.

AIH frequently recurs after transplant, and although previous studies have suggested that recurrent disease does not adversely affect either graft survival or long-term survival, those studies had limited patient numbers and inadequate follow-up, Dr. Montano-Loza said.

He cited two recent studies, one from UNOS, the United Network for Organ Sharing, and the other from ELTR, the European Liver Transplant Registry, that showed that overall survival after liver transplant was worse for patients with AIH, compared with those who underwent transplant for other autoimmune liver diseases.
 

Multicenter retrospective study

To get a better picture of long-term posttransplant outcomes in patients with AIH, investigators in 33 centers in North and South America, Europe, and Asia conducted a retrospective cohort study. Their goal was to establish the frequency of recurrent AIH, identify clinical factors and biomarkers for higher risk of recurrence, and evaluate the association between recurrent AIH and both patient and graft survival.

They accomplished this by performing chart reviews, including data on demographics, IgG levels before transplant, and Model for End-Stage Liver Disease scores.

They also collected data on serum liver function tests within the first year after transplant, posttransplant infections, rejection episodes, and immunosuppressive regimens, as well as variables such as donor age and sex, sex mismatch between donor and recipients, calendar year of transplant, and transplant volume for AIH at each center.

Of the 736 patients, 563 (76%) were female. The mean age at AIH diagnosis was 34 years, and the mean age at transplant was 42 years. About one-fifth of patients (21%) had concomitant autoimmune diseases.

Posttransplant immunosuppression regimens included the usual suspects: tacrolimus in 78% of patients, cyclosporine in 11%, prednisone in 76%, mycophenolate mofetil in 55%, and azathioprine in 10%.

In all, 147 of the 736 patients had a diagnosis of recurrent AIH. The investigators found that the cumulative probability of recurrent AIH was 49% after 20 years of follow-up.
 

Risk factors identified

In multivariate analysis controlling for age, concomitant disease, immunosuppressive regimens, organ-sex mismatch, acute rejection, liver function tests, bilirubin, and IgG, factors significantly associated with AIH recurrence included age 42 or younger at the time of transplant (hazard ratio, 3.15; P = .02), use of mycophenolate mofetil after transplant (HR, 3.06; P = .005), donor/recipient sex mismatch (HR, 2.57; P = .003), and high IgG levels pretransplant (HR, 1.04; P = .004).

Among 529 patients who had a liver biopsy after transplant, factors that remained as significant predictors of AIH recurrence were posttransplant mycophenolate mofetil (HR, 2.75; P = .003), donor/recipient sex mismatch (HR, 2.03; P = .02), and pretransplant IgG levels (HR, 1.04 per each g/L; P = .001).

An analysis of features associated with graft survival showed that recurrent AIH was associated with significantly increased risk for graft failure (HR, 10.79; P < .001). Patients with high bilirubin levels 1 year after transplantation were also at higher risk for failure (HR, 1.004 per micromol/L; P < .001).

Factors significantly associated with survival were recurrence of AIH (HR for death, 2.53; P = .001), elevated ALT at 12 months after transplant (HR, 1.002; P = .004), and elevated bilirubin at 12 months (HR, 1.003 per micromol/L; P < .001).

The investigators acknowledged that the study was limited by the retrospective design and by the fact that the diagnosis of recurrent AIH may have differed between centers that performed liver biopsy according to protocol and those that performed them only when clinically indicated, which may have resulted in differences in time to diagnosis.
 

Possible explanations for risk factors

In the question-and-answer session following his presentation, comoderator moderator Philip N. Newsome, PhD, from University Hospitals Birmingham (England), asked: “In terms of age, is that a reflection of worse disease, or is it adherence, or is it a combination, and should we be managing those patients more aggressively with immunosuppression?”

“We consider age is more a reflection of an aggressive disease,” Dr. Montano-Loza said. “Basically, in the univariate analysis we found that patients with a diagnosis at a younger age and even a transplant at a younger age were definitely associated with a higher risk of recurrence, so we think this is more related to an aggressive [disease] behavior in younger patient that translates into worse clinical outcomes.”

He added that patients younger than 40 who require transplants should be closely monitored for recurrence.

“Actually, we could make the argument that maybe these patients will benefit from protocol biopsies,” he said.

He noted that 15% of patients had significant fibrosis at the time of recurrent AIH diagnosis, and that the recurrences were not detected by laboratory monitoring alone.

Asked by an audience member why mycophenolate mofetil was associated with increased risk for recurrence, Dr. Montano-Loza replied that the retrospective nature of the data precludes the possibility of a definitive answer, but he noted that, for patients with other autoimmune liver diseases, the type of immunosuppression used has an impact on recurrence rates.

“For example, cyclosporine has a protective effect for patients transplanted for primary biliary cholangitis,” he said.

He said it may also be possible that there is a rebound effect leading to recurrence when patients are taken off mycophenolate or switched to another agent.

The study was supported by grants to individual researchers. Dr. Montano-Loza and Dr. Newsome reported having no relevant conflicts of interest.

Intermittent calorie restriction offers only modest advantages over a low-carbohydrate, high-fat (LCHF) diet for treating nonalcoholic fatty liver disease (NAFLD), researchers say.

The intermittent diet offers more benefit for liver stiffness and LDL cholesterol, and might be easier to maintain, said Magnus Holmer, MD, head of the hepatology unit at the Karolinska Institute in Stockholm.

But the intermittent diet also has drawbacks and the differences between the two were slight, he said in an interview.

“They were more or less identically effective in reducing liver steatosis in NAFLD and also reducing body weight,” he said. “And from this, we can say that the composition of macronutrients such as fat or sugar seems to be less important than how many calories you eat.”

Dr. Holmer and colleagues presented their findings at the meeting sponsored by the European Association for the Study of the Liver and published them in JHEP Reports

While previous studies have shown that dieting can effectively treat NAFLD, researchers have debated whether popular LCHF diets might cause more harm than good.

At the same time, intermittent-calorie restriction diets have also been gaining in popularity, particularly the 5:2 diet in which participants eat normally for 5 days a week and restrict their calories the other 2 days.
 

How do the two diets compare?

To see if one was more effective than the other, the researchers recruited 74 people with NAFLD. They diagnosed the patients either by radiologic assessment or a combination of controlled attenuation parameter (CAP) greater than 280 dB/m and obesity, or a CAP greater than 280 dB/m, elevated ALT, and overweight. Sixteen of the patients were being treated with statins.

The researchers randomly assigned 25 people to an LCHF diet, 25 to a 5:2 diet, and 24 to standard care. The groups were similar in diet, age, body mass index, liver stiffness, and most other criteria at baseline, although there were more women in the standard-care group.

At the start of the study, the participants in the standard-care group consulted with a hepatologist who advised them to avoid sweets and saturated fats, eat three meals a day, and avoid large portions.

The researchers asked women in the 5:2 diet to eat up to 500 kcal/day each of 2 days per week and up to 2,000 kcal/day each of the other 5 days. They asked men in the group to eat up to 600 kcal/day each of 2 days per week and up to 2,400 kcal/day the other 5 days.

They provided all the 5:2 participants with recipes that followed the Nordic Nutrition Recommendations, an adaptation of the Mediterranean diet that emphasizes foods traditional in Nordic countries, particularly grains such as whole-grain rye, oats, and barley; fruits such as apples, pears, berries, and plums; root vegetables, cabbages, onions, peas, beans, fish, boiled potatoes, and dairy products; and the use of rapeseed (canola) oil. The calories provided in the recipes were composed of 45%-60% carbohydrates, 25% fat, and 10%-20% protein.

The researchers asked women in the LCHF diet to eat an average of 1,600 kcal/day and men to eat an average of 1,900 kcal/day. All the participants used recipes based on meat, fish, eggs, low-carbohydrate vegetables, and dairy fat. Participants avoided sugar, bread, pasta, rice, pies, potatoes, and fruit. The calories in the recipes were composed of 5%-10% carbohydrates, 50%-80% fat, and 15%-40% protein.

All the participants reported what they ate over the previous 3 days, both at the start of the study and after 12 weeks. Participants in the 5:2 and LCHF groups also received follow-up calls to report their past 24 hours of eating at 2, 4, 8, and 12 weeks, and also at week 6, when they visited a dietitian.

In addition, the researchers measured the participants’ linoleic acid and alpha-linolenic acid intake to verify that the participants’ diets were different among the groups.

After 12 weeks, all three groups lost a significant amount of liver fat, but the LCHF and 5:2 groups lost more than the standard care group. Liver stiffness decreased significantly in the 5:2 and standard care groups, but not in the LCHF group.

The differences in steatosis change between the standard care and LCHF groups was statistically significant (P = .001), as it was between the standard care and 5:2 groups (P = .029). The differences between the LCHF and 5:2 groups were not statistically significant for weight or steatosis, but they were statistically significant for liver stiffness.

In addition, the 5:2 group significantly reduced total and LDL cholesterol, while the standard care group did not. In the LCHF group, levels of LDL cholesterol, HDL cholesterol, and total cholesterol all increased.

The long-term implications of the cholesterol findings are unclear, Dr. Holmer said. He hopes to follow up on these patients after 18-24 months. But the initial cholesterol findings are perhaps enough to constitute a red flag for anyone with a history of cardiovascular disease.
 

Diet adherence

Only one person dropped out of the 5:2 group, compared with five in the LCHF group and four in the standard-care group. More people in the LCHF group reported adverse events, such as gastrointestinal upset.

“With LCHF, it’s a drastic change for most people,” Dr. Holmer said. “Many patients are a bit shocked when they realize how much fat they are supposed to eat for breakfast, for lunch, and for dinner. They might eat bacon and eggs for breakfast every day.” The diet could be challenging for people who want to reduce their consumption of meat for environmental reasons.

The 5:2 group offers the advantage that people can choose what they want to eat as long as they adhere to the calorie restrictions, he pointed out. Still, he cautioned that the diet would not work well for people with insulin-dependent diabetes because of the difficulty of adjusting insulin levels on fasting days. He also recommended against this diet for people with cirrhosis because they need to eat frequent meals.
 

LCHF and 5:2 diets can work

But for most people the good news is that a variety of diets will work to treat NAFLD, Dr. Holmer said.

“I begin with saying to my patients that this can be completely cured, as long as you’re able to lose weight,” he said. “Then the next question is, how are they going to go ahead with that task? And if they’re already interested in some sort of specific diet, then I can, based on these findings, encourage that.”

Stephen Harrison, MD, a visiting professor of hepatology at Radcliffe Department of Medicine, University of Oxford, England, said that longer-term results will be important. For example, it will be interesting to see if the diets had effects on ballooning or inflammation.

Another limitation of the study is that it is relatively small in size, he said. He pointed out that people with NAFLD should increase their physical activity as well as eating less.

Still, Dr. Harrison greeted the findings enthusiastically, saying: “This is an important study.”

It’s useful to compare two popular diets head to head, and it’s also encouraging to get confirmation that either one can work, he added.

The study was supported by grants from the Stockholm County Council, the Dietary Science Foundation (Kostfonden), the Skandia Research Foundation, and the Åke Wiberg Foundation. Dr. Holmer has disclosed no relevant financial relationships. Harrison is a consultant to Madrigal Pharmaceuticals.

A version of this article first appeared on Medscape.com.

Intermittent calorie restriction offers only modest advantages over a low-carbohydrate, high-fat (LCHF) diet for treating nonalcoholic fatty liver disease (NAFLD), researchers say.

The intermittent diet offers more benefit for liver stiffness and LDL cholesterol, and might be easier to maintain, said Magnus Holmer, MD, head of the hepatology unit at the Karolinska Institute in Stockholm.

But the intermittent diet also has drawbacks and the differences between the two were slight, he said in an interview.

“They were more or less identically effective in reducing liver steatosis in NAFLD and also reducing body weight,” he said. “And from this, we can say that the composition of macronutrients such as fat or sugar seems to be less important than how many calories you eat.”

Dr. Holmer and colleagues presented their findings at the meeting sponsored by the European Association for the Study of the Liver and published them in JHEP Reports

While previous studies have shown that dieting can effectively treat NAFLD, researchers have debated whether popular LCHF diets might cause more harm than good.

At the same time, intermittent-calorie restriction diets have also been gaining in popularity, particularly the 5:2 diet in which participants eat normally for 5 days a week and restrict their calories the other 2 days.
 

How do the two diets compare?

To see if one was more effective than the other, the researchers recruited 74 people with NAFLD. They diagnosed the patients either by radiologic assessment or a combination of controlled attenuation parameter (CAP) greater than 280 dB/m and obesity, or a CAP greater than 280 dB/m, elevated ALT, and overweight. Sixteen of the patients were being treated with statins.

The researchers randomly assigned 25 people to an LCHF diet, 25 to a 5:2 diet, and 24 to standard care. The groups were similar in diet, age, body mass index, liver stiffness, and most other criteria at baseline, although there were more women in the standard-care group.

At the start of the study, the participants in the standard-care group consulted with a hepatologist who advised them to avoid sweets and saturated fats, eat three meals a day, and avoid large portions.

The researchers asked women in the 5:2 diet to eat up to 500 kcal/day each of 2 days per week and up to 2,000 kcal/day each of the other 5 days. They asked men in the group to eat up to 600 kcal/day each of 2 days per week and up to 2,400 kcal/day the other 5 days.

They provided all the 5:2 participants with recipes that followed the Nordic Nutrition Recommendations, an adaptation of the Mediterranean diet that emphasizes foods traditional in Nordic countries, particularly grains such as whole-grain rye, oats, and barley; fruits such as apples, pears, berries, and plums; root vegetables, cabbages, onions, peas, beans, fish, boiled potatoes, and dairy products; and the use of rapeseed (canola) oil. The calories provided in the recipes were composed of 45%-60% carbohydrates, 25% fat, and 10%-20% protein.

The researchers asked women in the LCHF diet to eat an average of 1,600 kcal/day and men to eat an average of 1,900 kcal/day. All the participants used recipes based on meat, fish, eggs, low-carbohydrate vegetables, and dairy fat. Participants avoided sugar, bread, pasta, rice, pies, potatoes, and fruit. The calories in the recipes were composed of 5%-10% carbohydrates, 50%-80% fat, and 15%-40% protein.

All the participants reported what they ate over the previous 3 days, both at the start of the study and after 12 weeks. Participants in the 5:2 and LCHF groups also received follow-up calls to report their past 24 hours of eating at 2, 4, 8, and 12 weeks, and also at week 6, when they visited a dietitian.

In addition, the researchers measured the participants’ linoleic acid and alpha-linolenic acid intake to verify that the participants’ diets were different among the groups.

After 12 weeks, all three groups lost a significant amount of liver fat, but the LCHF and 5:2 groups lost more than the standard care group. Liver stiffness decreased significantly in the 5:2 and standard care groups, but not in the LCHF group.

The differences in steatosis change between the standard care and LCHF groups was statistically significant (P = .001), as it was between the standard care and 5:2 groups (P = .029). The differences between the LCHF and 5:2 groups were not statistically significant for weight or steatosis, but they were statistically significant for liver stiffness.

In addition, the 5:2 group significantly reduced total and LDL cholesterol, while the standard care group did not. In the LCHF group, levels of LDL cholesterol, HDL cholesterol, and total cholesterol all increased.

The long-term implications of the cholesterol findings are unclear, Dr. Holmer said. He hopes to follow up on these patients after 18-24 months. But the initial cholesterol findings are perhaps enough to constitute a red flag for anyone with a history of cardiovascular disease.
 

Diet adherence

Only one person dropped out of the 5:2 group, compared with five in the LCHF group and four in the standard-care group. More people in the LCHF group reported adverse events, such as gastrointestinal upset.

“With LCHF, it’s a drastic change for most people,” Dr. Holmer said. “Many patients are a bit shocked when they realize how much fat they are supposed to eat for breakfast, for lunch, and for dinner. They might eat bacon and eggs for breakfast every day.” The diet could be challenging for people who want to reduce their consumption of meat for environmental reasons.

The 5:2 group offers the advantage that people can choose what they want to eat as long as they adhere to the calorie restrictions, he pointed out. Still, he cautioned that the diet would not work well for people with insulin-dependent diabetes because of the difficulty of adjusting insulin levels on fasting days. He also recommended against this diet for people with cirrhosis because they need to eat frequent meals.
 

LCHF and 5:2 diets can work

But for most people the good news is that a variety of diets will work to treat NAFLD, Dr. Holmer said.

“I begin with saying to my patients that this can be completely cured, as long as you’re able to lose weight,” he said. “Then the next question is, how are they going to go ahead with that task? And if they’re already interested in some sort of specific diet, then I can, based on these findings, encourage that.”

Stephen Harrison, MD, a visiting professor of hepatology at Radcliffe Department of Medicine, University of Oxford, England, said that longer-term results will be important. For example, it will be interesting to see if the diets had effects on ballooning or inflammation.

Another limitation of the study is that it is relatively small in size, he said. He pointed out that people with NAFLD should increase their physical activity as well as eating less.

Still, Dr. Harrison greeted the findings enthusiastically, saying: “This is an important study.”

It’s useful to compare two popular diets head to head, and it’s also encouraging to get confirmation that either one can work, he added.

The study was supported by grants from the Stockholm County Council, the Dietary Science Foundation (Kostfonden), the Skandia Research Foundation, and the Åke Wiberg Foundation. Dr. Holmer has disclosed no relevant financial relationships. Harrison is a consultant to Madrigal Pharmaceuticals.

A version of this article first appeared on Medscape.com.

Intermittent calorie restriction offers only modest advantages over a low-carbohydrate, high-fat (LCHF) diet for treating nonalcoholic fatty liver disease (NAFLD), researchers say.

The intermittent diet offers more benefit for liver stiffness and LDL cholesterol, and might be easier to maintain, said Magnus Holmer, MD, head of the hepatology unit at the Karolinska Institute in Stockholm.

But the intermittent diet also has drawbacks and the differences between the two were slight, he said in an interview.

“They were more or less identically effective in reducing liver steatosis in NAFLD and also reducing body weight,” he said. “And from this, we can say that the composition of macronutrients such as fat or sugar seems to be less important than how many calories you eat.”

Dr. Holmer and colleagues presented their findings at the meeting sponsored by the European Association for the Study of the Liver and published them in JHEP Reports

While previous studies have shown that dieting can effectively treat NAFLD, researchers have debated whether popular LCHF diets might cause more harm than good.

At the same time, intermittent-calorie restriction diets have also been gaining in popularity, particularly the 5:2 diet in which participants eat normally for 5 days a week and restrict their calories the other 2 days.
 

How do the two diets compare?

To see if one was more effective than the other, the researchers recruited 74 people with NAFLD. They diagnosed the patients either by radiologic assessment or a combination of controlled attenuation parameter (CAP) greater than 280 dB/m and obesity, or a CAP greater than 280 dB/m, elevated ALT, and overweight. Sixteen of the patients were being treated with statins.

The researchers randomly assigned 25 people to an LCHF diet, 25 to a 5:2 diet, and 24 to standard care. The groups were similar in diet, age, body mass index, liver stiffness, and most other criteria at baseline, although there were more women in the standard-care group.

At the start of the study, the participants in the standard-care group consulted with a hepatologist who advised them to avoid sweets and saturated fats, eat three meals a day, and avoid large portions.

The researchers asked women in the 5:2 diet to eat up to 500 kcal/day each of 2 days per week and up to 2,000 kcal/day each of the other 5 days. They asked men in the group to eat up to 600 kcal/day each of 2 days per week and up to 2,400 kcal/day the other 5 days.

They provided all the 5:2 participants with recipes that followed the Nordic Nutrition Recommendations, an adaptation of the Mediterranean diet that emphasizes foods traditional in Nordic countries, particularly grains such as whole-grain rye, oats, and barley; fruits such as apples, pears, berries, and plums; root vegetables, cabbages, onions, peas, beans, fish, boiled potatoes, and dairy products; and the use of rapeseed (canola) oil. The calories provided in the recipes were composed of 45%-60% carbohydrates, 25% fat, and 10%-20% protein.

The researchers asked women in the LCHF diet to eat an average of 1,600 kcal/day and men to eat an average of 1,900 kcal/day. All the participants used recipes based on meat, fish, eggs, low-carbohydrate vegetables, and dairy fat. Participants avoided sugar, bread, pasta, rice, pies, potatoes, and fruit. The calories in the recipes were composed of 5%-10% carbohydrates, 50%-80% fat, and 15%-40% protein.

All the participants reported what they ate over the previous 3 days, both at the start of the study and after 12 weeks. Participants in the 5:2 and LCHF groups also received follow-up calls to report their past 24 hours of eating at 2, 4, 8, and 12 weeks, and also at week 6, when they visited a dietitian.

In addition, the researchers measured the participants’ linoleic acid and alpha-linolenic acid intake to verify that the participants’ diets were different among the groups.

After 12 weeks, all three groups lost a significant amount of liver fat, but the LCHF and 5:2 groups lost more than the standard care group. Liver stiffness decreased significantly in the 5:2 and standard care groups, but not in the LCHF group.

The differences in steatosis change between the standard care and LCHF groups was statistically significant (P = .001), as it was between the standard care and 5:2 groups (P = .029). The differences between the LCHF and 5:2 groups were not statistically significant for weight or steatosis, but they were statistically significant for liver stiffness.

In addition, the 5:2 group significantly reduced total and LDL cholesterol, while the standard care group did not. In the LCHF group, levels of LDL cholesterol, HDL cholesterol, and total cholesterol all increased.

The long-term implications of the cholesterol findings are unclear, Dr. Holmer said. He hopes to follow up on these patients after 18-24 months. But the initial cholesterol findings are perhaps enough to constitute a red flag for anyone with a history of cardiovascular disease.
 

Diet adherence

Only one person dropped out of the 5:2 group, compared with five in the LCHF group and four in the standard-care group. More people in the LCHF group reported adverse events, such as gastrointestinal upset.

“With LCHF, it’s a drastic change for most people,” Dr. Holmer said. “Many patients are a bit shocked when they realize how much fat they are supposed to eat for breakfast, for lunch, and for dinner. They might eat bacon and eggs for breakfast every day.” The diet could be challenging for people who want to reduce their consumption of meat for environmental reasons.

The 5:2 group offers the advantage that people can choose what they want to eat as long as they adhere to the calorie restrictions, he pointed out. Still, he cautioned that the diet would not work well for people with insulin-dependent diabetes because of the difficulty of adjusting insulin levels on fasting days. He also recommended against this diet for people with cirrhosis because they need to eat frequent meals.
 

LCHF and 5:2 diets can work

But for most people the good news is that a variety of diets will work to treat NAFLD, Dr. Holmer said.

“I begin with saying to my patients that this can be completely cured, as long as you’re able to lose weight,” he said. “Then the next question is, how are they going to go ahead with that task? And if they’re already interested in some sort of specific diet, then I can, based on these findings, encourage that.”

Stephen Harrison, MD, a visiting professor of hepatology at Radcliffe Department of Medicine, University of Oxford, England, said that longer-term results will be important. For example, it will be interesting to see if the diets had effects on ballooning or inflammation.

Another limitation of the study is that it is relatively small in size, he said. He pointed out that people with NAFLD should increase their physical activity as well as eating less.

Still, Dr. Harrison greeted the findings enthusiastically, saying: “This is an important study.”

It’s useful to compare two popular diets head to head, and it’s also encouraging to get confirmation that either one can work, he added.

The study was supported by grants from the Stockholm County Council, the Dietary Science Foundation (Kostfonden), the Skandia Research Foundation, and the Åke Wiberg Foundation. Dr. Holmer has disclosed no relevant financial relationships. Harrison is a consultant to Madrigal Pharmaceuticals.

A version of this article first appeared on Medscape.com.

Patients who have received liver transplants or have advanced liver fibrosis may not get adequate protection against COVID-19 from two doses of the Pfizer vaccine, researchers say.

Physicians should test these patients and consider administering a third vaccine dose for those with low levels of antibodies to the SARS-CoV-2 virus, said Rifaat Safadi, MD, director of the Liver Unit in the Institute of Gastroenterology and Liver Diseases at Hadassah Hebrew University Medical Center, Jerusalem.

“If they are not responding, if the serology is going down to zero over the next year, you should revaccinate them or boost them,” Dr. Safadi said in an interview.

The suggestion contradicts the U.S. Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of vaccination against the virus and has not approved a three-dose regimen or booster of any SARS-CoV-2 vaccine.

But Dr. Safadi said he is more convinced by the data, which he presented at the meeting sponsored by the European Association for the Study of the Liver, than by the FDA’s recommendation.

“I’m not sure how scientific this recommendation is,” he said.

Several SARS-CoV-2 vaccines have proven highly effective in clinical trials and real-world studies. But some vaccinated people have sickened and even died from breakthrough infections, despite receiving Pfizer’s and Moderna’s mRNA vaccines, which have produced the most impressive results.

Few researchers have explored whether patients with weakened immune systems achieve the same level of protection as the general population. Fibrosis impairs the immune function of the liver, and people with transplants take immunosuppressant drugs to prevent rejection of the transplant.
 

New data on vaccine efficacy in the immunocompromised

To address this knowledge gap, Dr. Safadi and his colleagues measured antibodies (immunoglobulins) to the spike protein in the virus (S IgG) in vaccinated people who had liver transplants and in other vaccinated people whose liver fibrosis they had assessed with blood tests and biopsies.

About 32 of 90 people who received liver transplants at Hadassah University Medical Center and had received the Pfizer vaccine had an anti–S IgG less than 19 AU/mL, the researchers’ cutoff for a “good” antibody response to the vaccine.

Five other vaccinated people with liver transplants were diagnosed with COVID-19 after receiving the vaccine, one after the first dose and four after the second dose. Altogether, this added up to a 41.1% failure rate of the vaccine, Dr. Safadi said.

To determine the effectiveness of the vaccine in a larger population, Dr. Safadi and colleagues measured the S IgG levels in 719 employees of Hadassah University Medical Center who had received their second doses of the vaccine at least 7 days before (72% had received it 14 days before).

Of these, 708 (98.5%) had titers greater than 19 AU/mL.

Another eight (1.1%) had titers less than 12 AU/mL, which the researchers defined as a negative response. All eight had suppressed immune systems: two had kidney transplants, one had rheumatoid arthritis, two had lymphoma, two had metabolic syndrome, and one had both multiple sclerosis and metabolic syndrome.

The remaining three (0.4%) had S IgG titers from 12 to 19 AU/mL. Of this group, one person each had hemodialysis and cardiovascular disease, rheumatoid arthritis, cryoglobulinemia, and metabolic syndrome.

Of those patients with S IgG titers greater than 19 AU/mL, Fibrosis-4 (Fib-4) scores were available for 501 (the Fib-4 score is a measure of liver fibrosis based on levels of aspartate aminotransferase and alanine aminotransferase, platelet counts, and age). Those with higher Fib-4 scores had lower mean S IgG levels. Of those with Fib-4 scores less than 1.3, 68.0% had S IgG titers greater than 200 AU/mL, and of those with Fib-4 scores greater than 2, 44.2% had S IgG titers greater than 200 AU/mL. The difference was statistically significant (P = .002).

The researchers found a similar correlation when they measured liver health by biopsy for 140 vaccinated people with nonalcoholic fatty liver disease (NAFLD). They found that lower NAFLD activity scores corresponded to higher S IgG titers. Using FibroScan, they also found a trend toward lower S IgG titers with higher fibrosis kilopascals.

In addition, Dr. Safadi and colleagues noted that older age and male sex correlated with lower S IgG titers.
 

Differing opinions on value of antibody titers, third doses

The virus is likely to remain a threat for a year or more to come, and antibody tests may give some indication of who is likely to have the longest-lasting protection, Dr. Safadi said.

“I believe that stronger responders will maintain longer, while the weaker responders will maintain shorter and maybe will need a third shot at some time,” he added.

Pauline Vetter, MD, an infectious disease specialist at Geneva University Hospitals, questioned whether antibody titers can be used to estimate an individual’s level of resistance to the virus. There is some evidence that higher titers correlate with better protection, but it’s not clear to what degree, she said.

“There’s no definitive cutoff,” Dr. Vetter said in an interview. “I can’t say if you have more than a titer of 5, then you’re protected or you’re more protected – or if you have less, then you’re not protected.”

Testing to see whether a person has any S IgG antibodies at all following a vaccination might be worthwhile, she said. She noted that people who know that they did not have an antibody response may be more careful.

Dr. Vetter concluded that not enough is yet known to recommend a third dose or booster for people whose immunity is suppressed.

“There might be a benefit in these populations. But the question is, when and in which situations?” she said.

Dr. Vetter and Dr. Safadi have disclosed no relevant financial relationships.

Patients who have received liver transplants or have advanced liver fibrosis may not get adequate protection against COVID-19 from two doses of the Pfizer vaccine, researchers say.

Physicians should test these patients and consider administering a third vaccine dose for those with low levels of antibodies to the SARS-CoV-2 virus, said Rifaat Safadi, MD, director of the Liver Unit in the Institute of Gastroenterology and Liver Diseases at Hadassah Hebrew University Medical Center, Jerusalem.

“If they are not responding, if the serology is going down to zero over the next year, you should revaccinate them or boost them,” Dr. Safadi said in an interview.

The suggestion contradicts the U.S. Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of vaccination against the virus and has not approved a three-dose regimen or booster of any SARS-CoV-2 vaccine.

But Dr. Safadi said he is more convinced by the data, which he presented at the meeting sponsored by the European Association for the Study of the Liver, than by the FDA’s recommendation.

“I’m not sure how scientific this recommendation is,” he said.

Several SARS-CoV-2 vaccines have proven highly effective in clinical trials and real-world studies. But some vaccinated people have sickened and even died from breakthrough infections, despite receiving Pfizer’s and Moderna’s mRNA vaccines, which have produced the most impressive results.

Few researchers have explored whether patients with weakened immune systems achieve the same level of protection as the general population. Fibrosis impairs the immune function of the liver, and people with transplants take immunosuppressant drugs to prevent rejection of the transplant.
 

New data on vaccine efficacy in the immunocompromised

To address this knowledge gap, Dr. Safadi and his colleagues measured antibodies (immunoglobulins) to the spike protein in the virus (S IgG) in vaccinated people who had liver transplants and in other vaccinated people whose liver fibrosis they had assessed with blood tests and biopsies.

About 32 of 90 people who received liver transplants at Hadassah University Medical Center and had received the Pfizer vaccine had an anti–S IgG less than 19 AU/mL, the researchers’ cutoff for a “good” antibody response to the vaccine.

Five other vaccinated people with liver transplants were diagnosed with COVID-19 after receiving the vaccine, one after the first dose and four after the second dose. Altogether, this added up to a 41.1% failure rate of the vaccine, Dr. Safadi said.

To determine the effectiveness of the vaccine in a larger population, Dr. Safadi and colleagues measured the S IgG levels in 719 employees of Hadassah University Medical Center who had received their second doses of the vaccine at least 7 days before (72% had received it 14 days before).

Of these, 708 (98.5%) had titers greater than 19 AU/mL.

Another eight (1.1%) had titers less than 12 AU/mL, which the researchers defined as a negative response. All eight had suppressed immune systems: two had kidney transplants, one had rheumatoid arthritis, two had lymphoma, two had metabolic syndrome, and one had both multiple sclerosis and metabolic syndrome.

The remaining three (0.4%) had S IgG titers from 12 to 19 AU/mL. Of this group, one person each had hemodialysis and cardiovascular disease, rheumatoid arthritis, cryoglobulinemia, and metabolic syndrome.

Of those patients with S IgG titers greater than 19 AU/mL, Fibrosis-4 (Fib-4) scores were available for 501 (the Fib-4 score is a measure of liver fibrosis based on levels of aspartate aminotransferase and alanine aminotransferase, platelet counts, and age). Those with higher Fib-4 scores had lower mean S IgG levels. Of those with Fib-4 scores less than 1.3, 68.0% had S IgG titers greater than 200 AU/mL, and of those with Fib-4 scores greater than 2, 44.2% had S IgG titers greater than 200 AU/mL. The difference was statistically significant (P = .002).

The researchers found a similar correlation when they measured liver health by biopsy for 140 vaccinated people with nonalcoholic fatty liver disease (NAFLD). They found that lower NAFLD activity scores corresponded to higher S IgG titers. Using FibroScan, they also found a trend toward lower S IgG titers with higher fibrosis kilopascals.

In addition, Dr. Safadi and colleagues noted that older age and male sex correlated with lower S IgG titers.
 

Differing opinions on value of antibody titers, third doses

The virus is likely to remain a threat for a year or more to come, and antibody tests may give some indication of who is likely to have the longest-lasting protection, Dr. Safadi said.

“I believe that stronger responders will maintain longer, while the weaker responders will maintain shorter and maybe will need a third shot at some time,” he added.

Pauline Vetter, MD, an infectious disease specialist at Geneva University Hospitals, questioned whether antibody titers can be used to estimate an individual’s level of resistance to the virus. There is some evidence that higher titers correlate with better protection, but it’s not clear to what degree, she said.

“There’s no definitive cutoff,” Dr. Vetter said in an interview. “I can’t say if you have more than a titer of 5, then you’re protected or you’re more protected – or if you have less, then you’re not protected.”

Testing to see whether a person has any S IgG antibodies at all following a vaccination might be worthwhile, she said. She noted that people who know that they did not have an antibody response may be more careful.

Dr. Vetter concluded that not enough is yet known to recommend a third dose or booster for people whose immunity is suppressed.

“There might be a benefit in these populations. But the question is, when and in which situations?” she said.

Dr. Vetter and Dr. Safadi have disclosed no relevant financial relationships.

Patients who have received liver transplants or have advanced liver fibrosis may not get adequate protection against COVID-19 from two doses of the Pfizer vaccine, researchers say.

Physicians should test these patients and consider administering a third vaccine dose for those with low levels of antibodies to the SARS-CoV-2 virus, said Rifaat Safadi, MD, director of the Liver Unit in the Institute of Gastroenterology and Liver Diseases at Hadassah Hebrew University Medical Center, Jerusalem.

“If they are not responding, if the serology is going down to zero over the next year, you should revaccinate them or boost them,” Dr. Safadi said in an interview.

The suggestion contradicts the U.S. Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of vaccination against the virus and has not approved a three-dose regimen or booster of any SARS-CoV-2 vaccine.

But Dr. Safadi said he is more convinced by the data, which he presented at the meeting sponsored by the European Association for the Study of the Liver, than by the FDA’s recommendation.

“I’m not sure how scientific this recommendation is,” he said.

Several SARS-CoV-2 vaccines have proven highly effective in clinical trials and real-world studies. But some vaccinated people have sickened and even died from breakthrough infections, despite receiving Pfizer’s and Moderna’s mRNA vaccines, which have produced the most impressive results.

Few researchers have explored whether patients with weakened immune systems achieve the same level of protection as the general population. Fibrosis impairs the immune function of the liver, and people with transplants take immunosuppressant drugs to prevent rejection of the transplant.
 

New data on vaccine efficacy in the immunocompromised

To address this knowledge gap, Dr. Safadi and his colleagues measured antibodies (immunoglobulins) to the spike protein in the virus (S IgG) in vaccinated people who had liver transplants and in other vaccinated people whose liver fibrosis they had assessed with blood tests and biopsies.

About 32 of 90 people who received liver transplants at Hadassah University Medical Center and had received the Pfizer vaccine had an anti–S IgG less than 19 AU/mL, the researchers’ cutoff for a “good” antibody response to the vaccine.

Five other vaccinated people with liver transplants were diagnosed with COVID-19 after receiving the vaccine, one after the first dose and four after the second dose. Altogether, this added up to a 41.1% failure rate of the vaccine, Dr. Safadi said.

To determine the effectiveness of the vaccine in a larger population, Dr. Safadi and colleagues measured the S IgG levels in 719 employees of Hadassah University Medical Center who had received their second doses of the vaccine at least 7 days before (72% had received it 14 days before).

Of these, 708 (98.5%) had titers greater than 19 AU/mL.

Another eight (1.1%) had titers less than 12 AU/mL, which the researchers defined as a negative response. All eight had suppressed immune systems: two had kidney transplants, one had rheumatoid arthritis, two had lymphoma, two had metabolic syndrome, and one had both multiple sclerosis and metabolic syndrome.

The remaining three (0.4%) had S IgG titers from 12 to 19 AU/mL. Of this group, one person each had hemodialysis and cardiovascular disease, rheumatoid arthritis, cryoglobulinemia, and metabolic syndrome.

Of those patients with S IgG titers greater than 19 AU/mL, Fibrosis-4 (Fib-4) scores were available for 501 (the Fib-4 score is a measure of liver fibrosis based on levels of aspartate aminotransferase and alanine aminotransferase, platelet counts, and age). Those with higher Fib-4 scores had lower mean S IgG levels. Of those with Fib-4 scores less than 1.3, 68.0% had S IgG titers greater than 200 AU/mL, and of those with Fib-4 scores greater than 2, 44.2% had S IgG titers greater than 200 AU/mL. The difference was statistically significant (P = .002).

The researchers found a similar correlation when they measured liver health by biopsy for 140 vaccinated people with nonalcoholic fatty liver disease (NAFLD). They found that lower NAFLD activity scores corresponded to higher S IgG titers. Using FibroScan, they also found a trend toward lower S IgG titers with higher fibrosis kilopascals.

In addition, Dr. Safadi and colleagues noted that older age and male sex correlated with lower S IgG titers.
 

Differing opinions on value of antibody titers, third doses

The virus is likely to remain a threat for a year or more to come, and antibody tests may give some indication of who is likely to have the longest-lasting protection, Dr. Safadi said.

“I believe that stronger responders will maintain longer, while the weaker responders will maintain shorter and maybe will need a third shot at some time,” he added.

Pauline Vetter, MD, an infectious disease specialist at Geneva University Hospitals, questioned whether antibody titers can be used to estimate an individual’s level of resistance to the virus. There is some evidence that higher titers correlate with better protection, but it’s not clear to what degree, she said.

“There’s no definitive cutoff,” Dr. Vetter said in an interview. “I can’t say if you have more than a titer of 5, then you’re protected or you’re more protected – or if you have less, then you’re not protected.”

Testing to see whether a person has any S IgG antibodies at all following a vaccination might be worthwhile, she said. She noted that people who know that they did not have an antibody response may be more careful.

Dr. Vetter concluded that not enough is yet known to recommend a third dose or booster for people whose immunity is suppressed.

“There might be a benefit in these populations. But the question is, when and in which situations?” she said.

Dr. Vetter and Dr. Safadi have disclosed no relevant financial relationships.

Patients with cirrhosis treated at hospitals with the highest safety-net burden, defined by their proportion of Medicaid or uninsured patients, had a 5% higher mortality rate than patients who were treated at hospitals with the lowest burden, according to a study of over 300,000 patients.

The study, which was published in the Journal of Clinical Gastroenterology, analyzed inpatient data from the National Inpatient Sample (NIS) database focusing on a 4-year time span between 2012 and 2016. The hospitals were categorized by safety-net burden, which was defined as having either a high, medium, or low number of uninsured patients or patients with Medicaid.

This is the first-known study to evaluate the impact of a hospital’s safety-net burden on hospitalization outcomes in cirrhosis patients, wrote authors Robert J. Wong, MD, MS, of Stanford (Calif.) University and Grishma Hirode, MAS, of the University of Toronto. Previous studies have shown that safety-net hospitals, especially those with a high safety-net burden, have poorer patient outcomes. These hospitals also serve a patient population that is at high risk for chronic liver disease and cirrhosis.

The new analysis included 322,944 individual hospitalizations of patients with cirrhosis. Of these, 57.8% were male, 63.7% were White, 9.9% were Black, and 15.6% were Hispanic. In terms of safety-net burden, 107,446 hospitalizations were at high-burden hospitals, 103,508 were at medium-burden hospitals, and 111,990 hospitalizations were at low-burden hospitals.

Overall, cirrhosis-related hospitalizations in hospitals with the highest burden were found to have significantly greater odds of in-hospital mortality than the lowest tertile hospitals (odds ratio, 1.05, P = .044). The patients were also younger (mean age, 56.7 years vs. 59.8 years in low-burden hospitals). They also had a higher proportion of male patients, minority patients, Hispanic patients, and patients with Medicaid or no insurance.

The odds of hospitalization in the highest tertile hospitals were found to be significantly higher, compared with the middle and lowest tertiles for Blacks and Hispanics, compared with Whites (OR 1.26 and OR 1.63, respectively). Black patients (OR, 1.26; 95%CI, 1.17-1.35; P < .001) and Hispanic patients (OR, 1.63; 95% CI, 1.50-1.78; P< .001) were more likely to be admitted for care at high-burden hospitals (26% to 54%). In-hospital mortality rates among all hospitalizations were 5.95% and the rate did not significantly differ by hospital burden status.

“Despite adjusting for safety-net burden, our study continued to demonstrate ethnic disparities in in-hospital mortality among cirrhosis-related hospitalizations,” the researchers wrote. Overall, the odds of in-hospital mortality were 27% higher in Black patients as compared with White patients.

However, significantly lower mortality was observed in Hispanic patients as compared with White patients (4.9% vs. 6.0%, P < .001), but why this occurred was not entirely clear. “Hispanic patients may be more likely to have NASH [nonalcoholic steatohepatitis]-related cirrhosis, which generally has a slower disease progression, compared with [hepatitis C virus] or alcoholic cirrhosis. As such, it is likely that NASH-cirrhosis Hispanic patients had less severe disease at presentation,” the researchers wrote.
 

Study design has limitations, but shows concerning trends

The study findings were limited by several factors including the inability to show causality based on the observational study design and cross-sectional nature of the database, the researchers said. The NIS database records individual hospitalizations, not individual patient data which means that it may include repeat hospitalizations from the same patient. In addition, the study was limited by a lack of data on outpatient cirrhosis outcomes and non–liver-related comorbidities.

However, the finding that ethnic minorities with cirrhosis were significantly more likely to be hospitalized in high safety-net hospitals than White patients is concerning, and more research is needed, they said.

“These observations highlight that, while disparities in resources and health care delivery inherent to safety-net health systems may partly explain and provide opportunities to improve cirrhosis hospitalization care, they alone do not explain all of the ethnic disparities in cirrhosis outcomes observed,” they concluded.

The current study was important to conduct at this time because rates of cirrhosis are on the rise, Michael Volk, MD, of Loma Linda (Calif.) University Health, said in an interview. “Millions of patients receive care in safety-net hospitals across the country.”

Dr. Volk said that he was not surprised by the overall outcomes. “Unfortunately, I expected that patient outcomes would be worse at safety-net hospitals than wealthier hospitals. However, I was surprised that Blacks had higher in-hospital mortality than Whites, even after adjusting for the hospital.”

Dr. Volk echoed the study’s stated limitation of the lack of data to address disparities.

“Additional research is needed to determine whether the higher in-hospital mortality among Blacks is related to biological differences such as differential rates of disease progression, or social differences such as access to outpatient care,” he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Volk had no relevant financial conflicts to disclose.

Patients with cirrhosis treated at hospitals with the highest safety-net burden, defined by their proportion of Medicaid or uninsured patients, had a 5% higher mortality rate than patients who were treated at hospitals with the lowest burden, according to a study of over 300,000 patients.

The study, which was published in the Journal of Clinical Gastroenterology, analyzed inpatient data from the National Inpatient Sample (NIS) database focusing on a 4-year time span between 2012 and 2016. The hospitals were categorized by safety-net burden, which was defined as having either a high, medium, or low number of uninsured patients or patients with Medicaid.

This is the first-known study to evaluate the impact of a hospital’s safety-net burden on hospitalization outcomes in cirrhosis patients, wrote authors Robert J. Wong, MD, MS, of Stanford (Calif.) University and Grishma Hirode, MAS, of the University of Toronto. Previous studies have shown that safety-net hospitals, especially those with a high safety-net burden, have poorer patient outcomes. These hospitals also serve a patient population that is at high risk for chronic liver disease and cirrhosis.

The new analysis included 322,944 individual hospitalizations of patients with cirrhosis. Of these, 57.8% were male, 63.7% were White, 9.9% were Black, and 15.6% were Hispanic. In terms of safety-net burden, 107,446 hospitalizations were at high-burden hospitals, 103,508 were at medium-burden hospitals, and 111,990 hospitalizations were at low-burden hospitals.

Overall, cirrhosis-related hospitalizations in hospitals with the highest burden were found to have significantly greater odds of in-hospital mortality than the lowest tertile hospitals (odds ratio, 1.05, P = .044). The patients were also younger (mean age, 56.7 years vs. 59.8 years in low-burden hospitals). They also had a higher proportion of male patients, minority patients, Hispanic patients, and patients with Medicaid or no insurance.

The odds of hospitalization in the highest tertile hospitals were found to be significantly higher, compared with the middle and lowest tertiles for Blacks and Hispanics, compared with Whites (OR 1.26 and OR 1.63, respectively). Black patients (OR, 1.26; 95%CI, 1.17-1.35; P < .001) and Hispanic patients (OR, 1.63; 95% CI, 1.50-1.78; P< .001) were more likely to be admitted for care at high-burden hospitals (26% to 54%). In-hospital mortality rates among all hospitalizations were 5.95% and the rate did not significantly differ by hospital burden status.

“Despite adjusting for safety-net burden, our study continued to demonstrate ethnic disparities in in-hospital mortality among cirrhosis-related hospitalizations,” the researchers wrote. Overall, the odds of in-hospital mortality were 27% higher in Black patients as compared with White patients.

However, significantly lower mortality was observed in Hispanic patients as compared with White patients (4.9% vs. 6.0%, P < .001), but why this occurred was not entirely clear. “Hispanic patients may be more likely to have NASH [nonalcoholic steatohepatitis]-related cirrhosis, which generally has a slower disease progression, compared with [hepatitis C virus] or alcoholic cirrhosis. As such, it is likely that NASH-cirrhosis Hispanic patients had less severe disease at presentation,” the researchers wrote.
 

Study design has limitations, but shows concerning trends

The study findings were limited by several factors including the inability to show causality based on the observational study design and cross-sectional nature of the database, the researchers said. The NIS database records individual hospitalizations, not individual patient data which means that it may include repeat hospitalizations from the same patient. In addition, the study was limited by a lack of data on outpatient cirrhosis outcomes and non–liver-related comorbidities.

However, the finding that ethnic minorities with cirrhosis were significantly more likely to be hospitalized in high safety-net hospitals than White patients is concerning, and more research is needed, they said.

“These observations highlight that, while disparities in resources and health care delivery inherent to safety-net health systems may partly explain and provide opportunities to improve cirrhosis hospitalization care, they alone do not explain all of the ethnic disparities in cirrhosis outcomes observed,” they concluded.

The current study was important to conduct at this time because rates of cirrhosis are on the rise, Michael Volk, MD, of Loma Linda (Calif.) University Health, said in an interview. “Millions of patients receive care in safety-net hospitals across the country.”

Dr. Volk said that he was not surprised by the overall outcomes. “Unfortunately, I expected that patient outcomes would be worse at safety-net hospitals than wealthier hospitals. However, I was surprised that Blacks had higher in-hospital mortality than Whites, even after adjusting for the hospital.”

Dr. Volk echoed the study’s stated limitation of the lack of data to address disparities.

“Additional research is needed to determine whether the higher in-hospital mortality among Blacks is related to biological differences such as differential rates of disease progression, or social differences such as access to outpatient care,” he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Volk had no relevant financial conflicts to disclose.

Patients with cirrhosis treated at hospitals with the highest safety-net burden, defined by their proportion of Medicaid or uninsured patients, had a 5% higher mortality rate than patients who were treated at hospitals with the lowest burden, according to a study of over 300,000 patients.

The study, which was published in the Journal of Clinical Gastroenterology, analyzed inpatient data from the National Inpatient Sample (NIS) database focusing on a 4-year time span between 2012 and 2016. The hospitals were categorized by safety-net burden, which was defined as having either a high, medium, or low number of uninsured patients or patients with Medicaid.

This is the first-known study to evaluate the impact of a hospital’s safety-net burden on hospitalization outcomes in cirrhosis patients, wrote authors Robert J. Wong, MD, MS, of Stanford (Calif.) University and Grishma Hirode, MAS, of the University of Toronto. Previous studies have shown that safety-net hospitals, especially those with a high safety-net burden, have poorer patient outcomes. These hospitals also serve a patient population that is at high risk for chronic liver disease and cirrhosis.

The new analysis included 322,944 individual hospitalizations of patients with cirrhosis. Of these, 57.8% were male, 63.7% were White, 9.9% were Black, and 15.6% were Hispanic. In terms of safety-net burden, 107,446 hospitalizations were at high-burden hospitals, 103,508 were at medium-burden hospitals, and 111,990 hospitalizations were at low-burden hospitals.

Overall, cirrhosis-related hospitalizations in hospitals with the highest burden were found to have significantly greater odds of in-hospital mortality than the lowest tertile hospitals (odds ratio, 1.05, P = .044). The patients were also younger (mean age, 56.7 years vs. 59.8 years in low-burden hospitals). They also had a higher proportion of male patients, minority patients, Hispanic patients, and patients with Medicaid or no insurance.

The odds of hospitalization in the highest tertile hospitals were found to be significantly higher, compared with the middle and lowest tertiles for Blacks and Hispanics, compared with Whites (OR 1.26 and OR 1.63, respectively). Black patients (OR, 1.26; 95%CI, 1.17-1.35; P < .001) and Hispanic patients (OR, 1.63; 95% CI, 1.50-1.78; P< .001) were more likely to be admitted for care at high-burden hospitals (26% to 54%). In-hospital mortality rates among all hospitalizations were 5.95% and the rate did not significantly differ by hospital burden status.

“Despite adjusting for safety-net burden, our study continued to demonstrate ethnic disparities in in-hospital mortality among cirrhosis-related hospitalizations,” the researchers wrote. Overall, the odds of in-hospital mortality were 27% higher in Black patients as compared with White patients.

However, significantly lower mortality was observed in Hispanic patients as compared with White patients (4.9% vs. 6.0%, P < .001), but why this occurred was not entirely clear. “Hispanic patients may be more likely to have NASH [nonalcoholic steatohepatitis]-related cirrhosis, which generally has a slower disease progression, compared with [hepatitis C virus] or alcoholic cirrhosis. As such, it is likely that NASH-cirrhosis Hispanic patients had less severe disease at presentation,” the researchers wrote.
 

Study design has limitations, but shows concerning trends

The study findings were limited by several factors including the inability to show causality based on the observational study design and cross-sectional nature of the database, the researchers said. The NIS database records individual hospitalizations, not individual patient data which means that it may include repeat hospitalizations from the same patient. In addition, the study was limited by a lack of data on outpatient cirrhosis outcomes and non–liver-related comorbidities.

However, the finding that ethnic minorities with cirrhosis were significantly more likely to be hospitalized in high safety-net hospitals than White patients is concerning, and more research is needed, they said.

“These observations highlight that, while disparities in resources and health care delivery inherent to safety-net health systems may partly explain and provide opportunities to improve cirrhosis hospitalization care, they alone do not explain all of the ethnic disparities in cirrhosis outcomes observed,” they concluded.

The current study was important to conduct at this time because rates of cirrhosis are on the rise, Michael Volk, MD, of Loma Linda (Calif.) University Health, said in an interview. “Millions of patients receive care in safety-net hospitals across the country.”

Dr. Volk said that he was not surprised by the overall outcomes. “Unfortunately, I expected that patient outcomes would be worse at safety-net hospitals than wealthier hospitals. However, I was surprised that Blacks had higher in-hospital mortality than Whites, even after adjusting for the hospital.”

Dr. Volk echoed the study’s stated limitation of the lack of data to address disparities.

“Additional research is needed to determine whether the higher in-hospital mortality among Blacks is related to biological differences such as differential rates of disease progression, or social differences such as access to outpatient care,” he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Volk had no relevant financial conflicts to disclose.

New guidelines from the American College of Gastroenterology on idiosyncratic drug-induced liver injury (DILI) emphasize that idiosyncratic DILI is increasingly driven by the burgeoning popularity of herbal and dietary supplements, as well as tyrosine kinase inhibitors and immune checkpoint inhibitors used to treat cancer.

Sebastian Kaulitzki/Science Photo Library

The guidelines, which represent an update from 2014, are published in The American Journal of Gastroenterology.

DILI is commonly seen by gastroenterologists and hepatologists, but it is challenging to diagnose because there are many potential causes, and no objective diagnostic tests. Its incidence in the general population is low, but it must be considered when facing unexplained liver injury. Its potential presence should also be considered when prescribing gastrointestinal medications like azathioprine, anti–tumor necrosis factor agents, and sulfonamides.

DILI can be characterized as intrinsic or idiosyncratic. Intrinsic DILI is somewhat predictable, based on human or animal studies that have revealed the potential for liver toxicity at higher doses. The best-known example is acetaminophen. Idiosyncratic DILI is rarer and shows up in individuals with a preexisting susceptibility. Clinical signs of idiosyncratic DILI are more diverse than intrinsic DILI. The ACG guideline focuses on idiosyncratic DILI, since guidelines are already available for intrinsic DILI.

Idiosyncratic DILI diagnosis can have a wide range of presentations, including asymptomatic liver biochemistry, jaundice, liver failure, and chronic hepatitis. Diagnosis is made by eliminating other potential causes.

In the presence of hepatocellular jaundice, mortality can reach 10%. DILI patients who develop progressive jaundice, regardless of concomitant coagulopathy, should be sent to a tertiary center and may be a candidate for liver transplantation.

Corticosteroids may be considered when there is uncertainty if a liver injury is from DILI or autoimmune hepatitis, but this remains controversial because some studies have shown benefit, while others have not, according to Bubu Banini, MD, PhD, assistant professor of medicine and research director of the metabolic health and weight management program at Yale University, New Haven, Conn. “Large-scale randomized controlled trials are needed for further elucidation of the role of steroids in DILI. For now, the guideline recommends consideration of steroid therapy, particularly in patients with features of autoimmune hepatitis,” she added.

An important factor driving DILI is the increasing popularity of herbal supplements, as well as increased use of some cancer therapies. “With the advent of immune checkpoint inhibitors as effective therapies for a variety of malignancies, physicians need to be aware of the potential side effects of these agents and the possibility of immune checkpoint inhibitor–related drug induced liver injury,” Dr. Banini said. The updated ACG guideline summarizes current FDA-approved immune checkpoint inhibitors and their potential to cause DILI. The drugs can also lead to reactivation of hepatitis B infection. Studies have shown liver enzyme elevation occurs in about 30% of patients treated with immune checkpoint inhibitors.

The guidelines recommend assessing DILI patients for hepatitis B and C, and treating patients prior to, or in combination with, immune checkpoint inhibitors or other chemotherapy drugs. The recommendations are in line with preliminary data from the ICI field, according to Dr. Banini.

Dr. Banini also noted there has been an increase in the use of herbal and dietary supplements in the United States over the past decade, and these now account for about one-fifth of DILI cases. The guidelines recommend that severe cholestatic disease from these agents should be managed similarly to cases caused by prescription drugs, and patients should be considered for liver transplant if necessary.

A web-based 6-month mortality calculator for suspected DILI is available. It uses Model for End-Stage Liver Disease, Charlson comorbidity Index, and serum albumin data. Those variables predict mortality in liver disease, and an independent analysis showed they predict 6-month mortality in DILI.

DILI is difficult to diagnose, but physicians should keep it in mind when faced with a case of liver enzyme abnormality, where other possibilities have been excluded. “With over a thousand medications potentially causing DILI, physicians should be familiar with LiverTox as a very useful and practical resource. The DILI mortality calculator can serve as a clinical tool to predict 6-month mortality in patients with suspected DILI,” Dr. Banini said.

Some authors disclosed relationships with several pharmaceutical companies. Dr. Banini reports having nothing to disclose.

New guidelines from the American College of Gastroenterology on idiosyncratic drug-induced liver injury (DILI) emphasize that idiosyncratic DILI is increasingly driven by the burgeoning popularity of herbal and dietary supplements, as well as tyrosine kinase inhibitors and immune checkpoint inhibitors used to treat cancer.

Sebastian Kaulitzki/Science Photo Library

The guidelines, which represent an update from 2014, are published in The American Journal of Gastroenterology.

DILI is commonly seen by gastroenterologists and hepatologists, but it is challenging to diagnose because there are many potential causes, and no objective diagnostic tests. Its incidence in the general population is low, but it must be considered when facing unexplained liver injury. Its potential presence should also be considered when prescribing gastrointestinal medications like azathioprine, anti–tumor necrosis factor agents, and sulfonamides.

DILI can be characterized as intrinsic or idiosyncratic. Intrinsic DILI is somewhat predictable, based on human or animal studies that have revealed the potential for liver toxicity at higher doses. The best-known example is acetaminophen. Idiosyncratic DILI is rarer and shows up in individuals with a preexisting susceptibility. Clinical signs of idiosyncratic DILI are more diverse than intrinsic DILI. The ACG guideline focuses on idiosyncratic DILI, since guidelines are already available for intrinsic DILI.

Idiosyncratic DILI diagnosis can have a wide range of presentations, including asymptomatic liver biochemistry, jaundice, liver failure, and chronic hepatitis. Diagnosis is made by eliminating other potential causes.

In the presence of hepatocellular jaundice, mortality can reach 10%. DILI patients who develop progressive jaundice, regardless of concomitant coagulopathy, should be sent to a tertiary center and may be a candidate for liver transplantation.

Corticosteroids may be considered when there is uncertainty if a liver injury is from DILI or autoimmune hepatitis, but this remains controversial because some studies have shown benefit, while others have not, according to Bubu Banini, MD, PhD, assistant professor of medicine and research director of the metabolic health and weight management program at Yale University, New Haven, Conn. “Large-scale randomized controlled trials are needed for further elucidation of the role of steroids in DILI. For now, the guideline recommends consideration of steroid therapy, particularly in patients with features of autoimmune hepatitis,” she added.

An important factor driving DILI is the increasing popularity of herbal supplements, as well as increased use of some cancer therapies. “With the advent of immune checkpoint inhibitors as effective therapies for a variety of malignancies, physicians need to be aware of the potential side effects of these agents and the possibility of immune checkpoint inhibitor–related drug induced liver injury,” Dr. Banini said. The updated ACG guideline summarizes current FDA-approved immune checkpoint inhibitors and their potential to cause DILI. The drugs can also lead to reactivation of hepatitis B infection. Studies have shown liver enzyme elevation occurs in about 30% of patients treated with immune checkpoint inhibitors.

The guidelines recommend assessing DILI patients for hepatitis B and C, and treating patients prior to, or in combination with, immune checkpoint inhibitors or other chemotherapy drugs. The recommendations are in line with preliminary data from the ICI field, according to Dr. Banini.

Dr. Banini also noted there has been an increase in the use of herbal and dietary supplements in the United States over the past decade, and these now account for about one-fifth of DILI cases. The guidelines recommend that severe cholestatic disease from these agents should be managed similarly to cases caused by prescription drugs, and patients should be considered for liver transplant if necessary.

A web-based 6-month mortality calculator for suspected DILI is available. It uses Model for End-Stage Liver Disease, Charlson comorbidity Index, and serum albumin data. Those variables predict mortality in liver disease, and an independent analysis showed they predict 6-month mortality in DILI.

DILI is difficult to diagnose, but physicians should keep it in mind when faced with a case of liver enzyme abnormality, where other possibilities have been excluded. “With over a thousand medications potentially causing DILI, physicians should be familiar with LiverTox as a very useful and practical resource. The DILI mortality calculator can serve as a clinical tool to predict 6-month mortality in patients with suspected DILI,” Dr. Banini said.

Some authors disclosed relationships with several pharmaceutical companies. Dr. Banini reports having nothing to disclose.

New guidelines from the American College of Gastroenterology on idiosyncratic drug-induced liver injury (DILI) emphasize that idiosyncratic DILI is increasingly driven by the burgeoning popularity of herbal and dietary supplements, as well as tyrosine kinase inhibitors and immune checkpoint inhibitors used to treat cancer.

Sebastian Kaulitzki/Science Photo Library

The guidelines, which represent an update from 2014, are published in The American Journal of Gastroenterology.

DILI is commonly seen by gastroenterologists and hepatologists, but it is challenging to diagnose because there are many potential causes, and no objective diagnostic tests. Its incidence in the general population is low, but it must be considered when facing unexplained liver injury. Its potential presence should also be considered when prescribing gastrointestinal medications like azathioprine, anti–tumor necrosis factor agents, and sulfonamides.

DILI can be characterized as intrinsic or idiosyncratic. Intrinsic DILI is somewhat predictable, based on human or animal studies that have revealed the potential for liver toxicity at higher doses. The best-known example is acetaminophen. Idiosyncratic DILI is rarer and shows up in individuals with a preexisting susceptibility. Clinical signs of idiosyncratic DILI are more diverse than intrinsic DILI. The ACG guideline focuses on idiosyncratic DILI, since guidelines are already available for intrinsic DILI.

Idiosyncratic DILI diagnosis can have a wide range of presentations, including asymptomatic liver biochemistry, jaundice, liver failure, and chronic hepatitis. Diagnosis is made by eliminating other potential causes.

In the presence of hepatocellular jaundice, mortality can reach 10%. DILI patients who develop progressive jaundice, regardless of concomitant coagulopathy, should be sent to a tertiary center and may be a candidate for liver transplantation.

Corticosteroids may be considered when there is uncertainty if a liver injury is from DILI or autoimmune hepatitis, but this remains controversial because some studies have shown benefit, while others have not, according to Bubu Banini, MD, PhD, assistant professor of medicine and research director of the metabolic health and weight management program at Yale University, New Haven, Conn. “Large-scale randomized controlled trials are needed for further elucidation of the role of steroids in DILI. For now, the guideline recommends consideration of steroid therapy, particularly in patients with features of autoimmune hepatitis,” she added.

An important factor driving DILI is the increasing popularity of herbal supplements, as well as increased use of some cancer therapies. “With the advent of immune checkpoint inhibitors as effective therapies for a variety of malignancies, physicians need to be aware of the potential side effects of these agents and the possibility of immune checkpoint inhibitor–related drug induced liver injury,” Dr. Banini said. The updated ACG guideline summarizes current FDA-approved immune checkpoint inhibitors and their potential to cause DILI. The drugs can also lead to reactivation of hepatitis B infection. Studies have shown liver enzyme elevation occurs in about 30% of patients treated with immune checkpoint inhibitors.

The guidelines recommend assessing DILI patients for hepatitis B and C, and treating patients prior to, or in combination with, immune checkpoint inhibitors or other chemotherapy drugs. The recommendations are in line with preliminary data from the ICI field, according to Dr. Banini.

Dr. Banini also noted there has been an increase in the use of herbal and dietary supplements in the United States over the past decade, and these now account for about one-fifth of DILI cases. The guidelines recommend that severe cholestatic disease from these agents should be managed similarly to cases caused by prescription drugs, and patients should be considered for liver transplant if necessary.

A web-based 6-month mortality calculator for suspected DILI is available. It uses Model for End-Stage Liver Disease, Charlson comorbidity Index, and serum albumin data. Those variables predict mortality in liver disease, and an independent analysis showed they predict 6-month mortality in DILI.

DILI is difficult to diagnose, but physicians should keep it in mind when faced with a case of liver enzyme abnormality, where other possibilities have been excluded. “With over a thousand medications potentially causing DILI, physicians should be familiar with LiverTox as a very useful and practical resource. The DILI mortality calculator can serve as a clinical tool to predict 6-month mortality in patients with suspected DILI,” Dr. Banini said.

Some authors disclosed relationships with several pharmaceutical companies. Dr. Banini reports having nothing to disclose.

While liver transplant outcomes were historically poor in people coinfected with HIV and hepatitis C virus (HCV), they have improved significantly in the era of direct-acting antiviral (DAA) therapy, a recent analysis of U.S. organ transplant data showed.

The availability of highly potent DAA therapy should change how transplant specialists view patients coinfected with HIV/HCV who need a liver transplant, according to researcher Jennifer Wang, MD, chief gastroenterology fellow at the University of Chicago, who presented the results of the analysis at the annual Digestive Disease Week® (DDW). Cumulative graft survival rates since the introduction of DAAs are comparable between transplant recipients with HIV/HCV coinfection and recipients who are both HIV and HCV negative, according to the study.

“Having hepatitis C no longer confers worse patient survival in the DAA era, and this is the main takeaway from our study,” Dr. Wang said.

The study also showed that the number of liver transplants among HIV-infected patients has increased over the past 4-5 years. However, the absolute number remains low at 64 cases in 2019, or less than 1% of all liver transplants that year, and only about one-third of those HIV-positive recipients had HCV coinfection, according to Dr. Wang.

Moreover, relatively few centers are performing liver transplants for patients who are HIV/HCV coinfected, and there is significant geographic variation in where the procedures are done, she said in her presentation.
 

Reassuring data that should prompt referral

Taken together, these results should offer reassurance to transplant centers that patients coinfected with HIV/HCV are no longer at increased risk for poor outcomes after transplantation, said Christine M. Durand, MD, associate professor of medicine at Johns Hopkins University, Baltimore.

“The additional call for action should be beyond the transplantation community to ensure that referrals for liver transplant are where they should be,” Dr. Durand said in an interview.

“With a number of only 64 transplants a year, we’re not doing enough, and there are more patients that could benefit from liver transplants,” added Dr. Durand, who is principal investigator of HOPE in Action, a prospective, multicenter, clinical trial evaluating the safety and survival outcomes of HIV-positive deceased donor liver transplants in HIV-positive recipients.
 

Impact of the HOPE Act

Liver transplantation for HIV-positive patients has increased since the signing of the HIV Organ Policy Equity (HOPE) Act in 2013, according to Dr. Wang.

The HOPE act expanded the donor pool to include HIV-positive deceased donors, which not only increased the donor supply overall, but specifically helped HIV-positive individuals, who experience a higher rate of waiting-list mortality, according to a review on the topic authored by Dr. Durand and coauthors.

However, some transplant centers may be reluctant to do liver transplants in HIV-positive patients coinfected with HCV. That’s because, in previous studies that were conducted before the DAA era, outcomes after liver transplant in HIV/HCV-coinfected patients were inferior to those in patients with HIV but no HCV infection, Dr. Wang said.

Accordingly, Dr. Wang and colleagues analyzed Organ Procurement and Transplantation Network (OPTN) data on adult patients who underwent liver transplants between 2008 and 2019 to see if the introduction of DAAs had leveled the playing field for those with HCV coinfection.
 

Progress in a still-underserved population

The practice of liver transplant in the HIV population has been increasing since the HOPE Act, according to Dr. Wang.

Overall, out of 70,125 liver transplant recipients over the 2008-2019 period, 416 (0.6%) were HIV infected, the data show.

In 2014, 28 liver transplants (0.5%) were performed in HIV-infected individuals, which increased to 64 transplants (0.8%) in 2019, data show. Of those 64 HIV-positive liver transplant recipients in 2019, 23 (35.9%) were coinfected with HCV.

Graft survival has greatly improved, from a 3-year survival of only 58% in patients transplanted before the availability of DAAs to 82% in the DAA era, a difference that was statistically significant, Dr. Wang said.

In the DAA era, there was no significant difference in graft failure outcomes when comparing HIV/HCV-coinfected recipients with uninfected recipients, she added.

The largest proportion of liver transplantations in HIV/HCV-coinfected recipients have been done in OPTN Region 9 (New York), both in the pre- and post-DAA eras, according to Dr. Wang. Several regions have very low numbers or have performed no liver transplants in HIV/HCV-coinfected patients in either era.

“The number of transplant centers participating in liver transplant for coinfected patients is still quite low, so this is a very underserved patient population,” Dr. Wang said.

Dr. Wang provided no financial disclosures related to the research. Dr. Durand receives grants to the institution from Abbvie and GlaxoSmithKline and she receives honoraria from Gilead Sciences for serving on a grant review committee.

While liver transplant outcomes were historically poor in people coinfected with HIV and hepatitis C virus (HCV), they have improved significantly in the era of direct-acting antiviral (DAA) therapy, a recent analysis of U.S. organ transplant data showed.

The availability of highly potent DAA therapy should change how transplant specialists view patients coinfected with HIV/HCV who need a liver transplant, according to researcher Jennifer Wang, MD, chief gastroenterology fellow at the University of Chicago, who presented the results of the analysis at the annual Digestive Disease Week® (DDW). Cumulative graft survival rates since the introduction of DAAs are comparable between transplant recipients with HIV/HCV coinfection and recipients who are both HIV and HCV negative, according to the study.

“Having hepatitis C no longer confers worse patient survival in the DAA era, and this is the main takeaway from our study,” Dr. Wang said.

The study also showed that the number of liver transplants among HIV-infected patients has increased over the past 4-5 years. However, the absolute number remains low at 64 cases in 2019, or less than 1% of all liver transplants that year, and only about one-third of those HIV-positive recipients had HCV coinfection, according to Dr. Wang.

Moreover, relatively few centers are performing liver transplants for patients who are HIV/HCV coinfected, and there is significant geographic variation in where the procedures are done, she said in her presentation.
 

Reassuring data that should prompt referral

Taken together, these results should offer reassurance to transplant centers that patients coinfected with HIV/HCV are no longer at increased risk for poor outcomes after transplantation, said Christine M. Durand, MD, associate professor of medicine at Johns Hopkins University, Baltimore.

“The additional call for action should be beyond the transplantation community to ensure that referrals for liver transplant are where they should be,” Dr. Durand said in an interview.

“With a number of only 64 transplants a year, we’re not doing enough, and there are more patients that could benefit from liver transplants,” added Dr. Durand, who is principal investigator of HOPE in Action, a prospective, multicenter, clinical trial evaluating the safety and survival outcomes of HIV-positive deceased donor liver transplants in HIV-positive recipients.
 

Impact of the HOPE Act

Liver transplantation for HIV-positive patients has increased since the signing of the HIV Organ Policy Equity (HOPE) Act in 2013, according to Dr. Wang.

The HOPE act expanded the donor pool to include HIV-positive deceased donors, which not only increased the donor supply overall, but specifically helped HIV-positive individuals, who experience a higher rate of waiting-list mortality, according to a review on the topic authored by Dr. Durand and coauthors.

However, some transplant centers may be reluctant to do liver transplants in HIV-positive patients coinfected with HCV. That’s because, in previous studies that were conducted before the DAA era, outcomes after liver transplant in HIV/HCV-coinfected patients were inferior to those in patients with HIV but no HCV infection, Dr. Wang said.

Accordingly, Dr. Wang and colleagues analyzed Organ Procurement and Transplantation Network (OPTN) data on adult patients who underwent liver transplants between 2008 and 2019 to see if the introduction of DAAs had leveled the playing field for those with HCV coinfection.
 

Progress in a still-underserved population

The practice of liver transplant in the HIV population has been increasing since the HOPE Act, according to Dr. Wang.

Overall, out of 70,125 liver transplant recipients over the 2008-2019 period, 416 (0.6%) were HIV infected, the data show.

In 2014, 28 liver transplants (0.5%) were performed in HIV-infected individuals, which increased to 64 transplants (0.8%) in 2019, data show. Of those 64 HIV-positive liver transplant recipients in 2019, 23 (35.9%) were coinfected with HCV.

Graft survival has greatly improved, from a 3-year survival of only 58% in patients transplanted before the availability of DAAs to 82% in the DAA era, a difference that was statistically significant, Dr. Wang said.

In the DAA era, there was no significant difference in graft failure outcomes when comparing HIV/HCV-coinfected recipients with uninfected recipients, she added.

The largest proportion of liver transplantations in HIV/HCV-coinfected recipients have been done in OPTN Region 9 (New York), both in the pre- and post-DAA eras, according to Dr. Wang. Several regions have very low numbers or have performed no liver transplants in HIV/HCV-coinfected patients in either era.

“The number of transplant centers participating in liver transplant for coinfected patients is still quite low, so this is a very underserved patient population,” Dr. Wang said.

Dr. Wang provided no financial disclosures related to the research. Dr. Durand receives grants to the institution from Abbvie and GlaxoSmithKline and she receives honoraria from Gilead Sciences for serving on a grant review committee.

While liver transplant outcomes were historically poor in people coinfected with HIV and hepatitis C virus (HCV), they have improved significantly in the era of direct-acting antiviral (DAA) therapy, a recent analysis of U.S. organ transplant data showed.

The availability of highly potent DAA therapy should change how transplant specialists view patients coinfected with HIV/HCV who need a liver transplant, according to researcher Jennifer Wang, MD, chief gastroenterology fellow at the University of Chicago, who presented the results of the analysis at the annual Digestive Disease Week® (DDW). Cumulative graft survival rates since the introduction of DAAs are comparable between transplant recipients with HIV/HCV coinfection and recipients who are both HIV and HCV negative, according to the study.

“Having hepatitis C no longer confers worse patient survival in the DAA era, and this is the main takeaway from our study,” Dr. Wang said.

The study also showed that the number of liver transplants among HIV-infected patients has increased over the past 4-5 years. However, the absolute number remains low at 64 cases in 2019, or less than 1% of all liver transplants that year, and only about one-third of those HIV-positive recipients had HCV coinfection, according to Dr. Wang.

Moreover, relatively few centers are performing liver transplants for patients who are HIV/HCV coinfected, and there is significant geographic variation in where the procedures are done, she said in her presentation.
 

Reassuring data that should prompt referral

Taken together, these results should offer reassurance to transplant centers that patients coinfected with HIV/HCV are no longer at increased risk for poor outcomes after transplantation, said Christine M. Durand, MD, associate professor of medicine at Johns Hopkins University, Baltimore.

“The additional call for action should be beyond the transplantation community to ensure that referrals for liver transplant are where they should be,” Dr. Durand said in an interview.

“With a number of only 64 transplants a year, we’re not doing enough, and there are more patients that could benefit from liver transplants,” added Dr. Durand, who is principal investigator of HOPE in Action, a prospective, multicenter, clinical trial evaluating the safety and survival outcomes of HIV-positive deceased donor liver transplants in HIV-positive recipients.
 

Impact of the HOPE Act

Liver transplantation for HIV-positive patients has increased since the signing of the HIV Organ Policy Equity (HOPE) Act in 2013, according to Dr. Wang.

The HOPE act expanded the donor pool to include HIV-positive deceased donors, which not only increased the donor supply overall, but specifically helped HIV-positive individuals, who experience a higher rate of waiting-list mortality, according to a review on the topic authored by Dr. Durand and coauthors.

However, some transplant centers may be reluctant to do liver transplants in HIV-positive patients coinfected with HCV. That’s because, in previous studies that were conducted before the DAA era, outcomes after liver transplant in HIV/HCV-coinfected patients were inferior to those in patients with HIV but no HCV infection, Dr. Wang said.

Accordingly, Dr. Wang and colleagues analyzed Organ Procurement and Transplantation Network (OPTN) data on adult patients who underwent liver transplants between 2008 and 2019 to see if the introduction of DAAs had leveled the playing field for those with HCV coinfection.
 

Progress in a still-underserved population

The practice of liver transplant in the HIV population has been increasing since the HOPE Act, according to Dr. Wang.

Overall, out of 70,125 liver transplant recipients over the 2008-2019 period, 416 (0.6%) were HIV infected, the data show.

In 2014, 28 liver transplants (0.5%) were performed in HIV-infected individuals, which increased to 64 transplants (0.8%) in 2019, data show. Of those 64 HIV-positive liver transplant recipients in 2019, 23 (35.9%) were coinfected with HCV.

Graft survival has greatly improved, from a 3-year survival of only 58% in patients transplanted before the availability of DAAs to 82% in the DAA era, a difference that was statistically significant, Dr. Wang said.

In the DAA era, there was no significant difference in graft failure outcomes when comparing HIV/HCV-coinfected recipients with uninfected recipients, she added.

The largest proportion of liver transplantations in HIV/HCV-coinfected recipients have been done in OPTN Region 9 (New York), both in the pre- and post-DAA eras, according to Dr. Wang. Several regions have very low numbers or have performed no liver transplants in HIV/HCV-coinfected patients in either era.

“The number of transplant centers participating in liver transplant for coinfected patients is still quite low, so this is a very underserved patient population,” Dr. Wang said.

Dr. Wang provided no financial disclosures related to the research. Dr. Durand receives grants to the institution from Abbvie and GlaxoSmithKline and she receives honoraria from Gilead Sciences for serving on a grant review committee.

The risk for serious liver injury with obeticholic acid (Ocaliva, Intercept Pharmaceuticals) has prompted the U.S. Food and Drug Administration to restrict its use in patients with primary biliary cholangitis (PBC) and advanced cirrhosis.  

The agency has added a new contraindication to the obeticholic acid prescribing information and patient medication guide stating that the drug should not be used in patients with PBC and advanced cirrhosis. 

The boxed warning on the label has also been revised to include this information.

For patients with PBC who do not have advanced cirrhosis, the FDA believes the benefits of Ocaliva outweigh the risks, based on the original clinical trials.

Five years ago, the FDA granted accelerated approval to obeticholic acid in combination with ursodeoxycholic acid (UDCA) in adults who fail to respond adequately to UDCA, or as a monotherapy in adults who cannot tolerate UDCA.  

Since then, the FDA has identified 25 cases of serious liver injury leading to liver decompensation or liver failure in patients with PBC and cirrhosis who were taking obeticholic acid at recommended doses.

According to the FDA, 18 of the cases happened in patients with PBC and compensated cirrhosis who experienced liver injury that led to decompensation. Ten of these patients had evidence or suspicion of portal hypertension at baseline; in the other eight patients, it was unclear whether portal hypertension was present.

PBC was not expected to progress rapidly in these patients, yet they experienced accelerated clinical deterioration within months of starting obeticholic acid, the FDA said.

The median time to liver decompensation after initiating treatment was 4 months (range, 2 weeks to 10 months). Four patients with PBC and compensated cirrhosis needed a liver transplant within 1.3 years after starting obeticholic acid, and one patient died from liver failure.

The other seven cases of serious liver injury occurred in patients with PBC and decompensated cirrhosis, two of whom died. 

Although there was a temporal relationship between starting obeticholic acid and liver injury, it is difficult to distinguish a drug-induced effect from disease progression in the patients with advanced baseline liver disease, the FDA cautioned.

The median time to a new decompensation event after starting the drug was 2.5 months (range, 10 days to 8 months).

Before starting obeticholic acid, clinicians should determine whether a patient with PBC has advanced cirrhosis as the drug is now contraindicated in these patients, the FDA said.

During obeticholic acid treatment, patients should be routinely monitored for progression of PBC with laboratory and clinical assessments to determine whether the drug needs to be discontinued.

The medication should be permanently discontinued in patients with cirrhosis who progress to advanced cirrhosis.

Patients should also be monitored for clinically significant liver-related adverse reactions that may manifest as development of acute-on-chronic liver disease with nausea, vomiting, diarrhea, jaundice, scleral icterus, and/or dark urine.

Obeticholic acid should be stopped permanently in any patient who develops these symptoms, the FDA advised.

Health care professionals are encouraged to report adverse events or side effects related to the use of obeticholic acid to MedWatch, FDA’s adverse event reporting site.

A version of this article first appeared on Medscape.com.

The risk for serious liver injury with obeticholic acid (Ocaliva, Intercept Pharmaceuticals) has prompted the U.S. Food and Drug Administration to restrict its use in patients with primary biliary cholangitis (PBC) and advanced cirrhosis.  

The agency has added a new contraindication to the obeticholic acid prescribing information and patient medication guide stating that the drug should not be used in patients with PBC and advanced cirrhosis. 

The boxed warning on the label has also been revised to include this information.

For patients with PBC who do not have advanced cirrhosis, the FDA believes the benefits of Ocaliva outweigh the risks, based on the original clinical trials.

Five years ago, the FDA granted accelerated approval to obeticholic acid in combination with ursodeoxycholic acid (UDCA) in adults who fail to respond adequately to UDCA, or as a monotherapy in adults who cannot tolerate UDCA.  

Since then, the FDA has identified 25 cases of serious liver injury leading to liver decompensation or liver failure in patients with PBC and cirrhosis who were taking obeticholic acid at recommended doses.

According to the FDA, 18 of the cases happened in patients with PBC and compensated cirrhosis who experienced liver injury that led to decompensation. Ten of these patients had evidence or suspicion of portal hypertension at baseline; in the other eight patients, it was unclear whether portal hypertension was present.

PBC was not expected to progress rapidly in these patients, yet they experienced accelerated clinical deterioration within months of starting obeticholic acid, the FDA said.

The median time to liver decompensation after initiating treatment was 4 months (range, 2 weeks to 10 months). Four patients with PBC and compensated cirrhosis needed a liver transplant within 1.3 years after starting obeticholic acid, and one patient died from liver failure.

The other seven cases of serious liver injury occurred in patients with PBC and decompensated cirrhosis, two of whom died. 

Although there was a temporal relationship between starting obeticholic acid and liver injury, it is difficult to distinguish a drug-induced effect from disease progression in the patients with advanced baseline liver disease, the FDA cautioned.

The median time to a new decompensation event after starting the drug was 2.5 months (range, 10 days to 8 months).

Before starting obeticholic acid, clinicians should determine whether a patient with PBC has advanced cirrhosis as the drug is now contraindicated in these patients, the FDA said.

During obeticholic acid treatment, patients should be routinely monitored for progression of PBC with laboratory and clinical assessments to determine whether the drug needs to be discontinued.

The medication should be permanently discontinued in patients with cirrhosis who progress to advanced cirrhosis.

Patients should also be monitored for clinically significant liver-related adverse reactions that may manifest as development of acute-on-chronic liver disease with nausea, vomiting, diarrhea, jaundice, scleral icterus, and/or dark urine.

Obeticholic acid should be stopped permanently in any patient who develops these symptoms, the FDA advised.

Health care professionals are encouraged to report adverse events or side effects related to the use of obeticholic acid to MedWatch, FDA’s adverse event reporting site.

A version of this article first appeared on Medscape.com.

The risk for serious liver injury with obeticholic acid (Ocaliva, Intercept Pharmaceuticals) has prompted the U.S. Food and Drug Administration to restrict its use in patients with primary biliary cholangitis (PBC) and advanced cirrhosis.  

The agency has added a new contraindication to the obeticholic acid prescribing information and patient medication guide stating that the drug should not be used in patients with PBC and advanced cirrhosis. 

The boxed warning on the label has also been revised to include this information.

For patients with PBC who do not have advanced cirrhosis, the FDA believes the benefits of Ocaliva outweigh the risks, based on the original clinical trials.

Five years ago, the FDA granted accelerated approval to obeticholic acid in combination with ursodeoxycholic acid (UDCA) in adults who fail to respond adequately to UDCA, or as a monotherapy in adults who cannot tolerate UDCA.  

Since then, the FDA has identified 25 cases of serious liver injury leading to liver decompensation or liver failure in patients with PBC and cirrhosis who were taking obeticholic acid at recommended doses.

According to the FDA, 18 of the cases happened in patients with PBC and compensated cirrhosis who experienced liver injury that led to decompensation. Ten of these patients had evidence or suspicion of portal hypertension at baseline; in the other eight patients, it was unclear whether portal hypertension was present.

PBC was not expected to progress rapidly in these patients, yet they experienced accelerated clinical deterioration within months of starting obeticholic acid, the FDA said.

The median time to liver decompensation after initiating treatment was 4 months (range, 2 weeks to 10 months). Four patients with PBC and compensated cirrhosis needed a liver transplant within 1.3 years after starting obeticholic acid, and one patient died from liver failure.

The other seven cases of serious liver injury occurred in patients with PBC and decompensated cirrhosis, two of whom died. 

Although there was a temporal relationship between starting obeticholic acid and liver injury, it is difficult to distinguish a drug-induced effect from disease progression in the patients with advanced baseline liver disease, the FDA cautioned.

The median time to a new decompensation event after starting the drug was 2.5 months (range, 10 days to 8 months).

Before starting obeticholic acid, clinicians should determine whether a patient with PBC has advanced cirrhosis as the drug is now contraindicated in these patients, the FDA said.

During obeticholic acid treatment, patients should be routinely monitored for progression of PBC with laboratory and clinical assessments to determine whether the drug needs to be discontinued.

The medication should be permanently discontinued in patients with cirrhosis who progress to advanced cirrhosis.

Patients should also be monitored for clinically significant liver-related adverse reactions that may manifest as development of acute-on-chronic liver disease with nausea, vomiting, diarrhea, jaundice, scleral icterus, and/or dark urine.

Obeticholic acid should be stopped permanently in any patient who develops these symptoms, the FDA advised.

Health care professionals are encouraged to report adverse events or side effects related to the use of obeticholic acid to MedWatch, FDA’s adverse event reporting site.

A version of this article first appeared on Medscape.com.

While colorectal cancer may be the most common and deadly gastrointestinal malignancy, liver and gastric cancers account for some of the most consistent racial and ethnic disparities, a recent retrospective, cross-sectional analysis of U.S. data suggested.

Liver and gastric cancer incidence and mortality were significantly higher for all racial and ethnic minority groups in the study, compared with non-Hispanic Whites, according to the analysis. Notably, however, non-Hispanic Blacks represented the only group to also have elevated incidence and mortality for pancreatic and colorectal, compared with non-Hispanic Whites, according to investigator Aileen Bui, MD, with the University of California, Los Angeles Health.

These study results highlights the need to address modifiable cancer risk factors and overcome barriers to cancer prevention and care in medically underserved minority populations, Dr. Bui said in a virtual presentation of the results at the annual Digestive Disease Week® (DDW).

“While we cannot infer causation or determine risk factors for certain malignancies from the results of our study, there’s little data to support a strong role of biological or genetic differences between racial and ethnic groups to account for the observed disparities in incidence and mortality for GI cancers,” she said in her presentation.
 

Setting out to explore disparities

Gastrointestinal cancer incidence and mortality remain on the rise, despite significant progress in some areas, including colorectal cancer screening and the introduction of effective treatments for hepatitis C virus, Dr. Bui said.

Incidence and mortality from gastrointestinal cancers are set to increase by 34% and 43%, respectively, by the year 2040, and will remain a significant contributor to cancer incidence and mortality in the United States, according to the researcher.

Gastrointestinal cancer incidence and mortality are known to vary by race and ethnicity, so Dr. Bui and colleagues sought to assess the extent of racial and ethnic disparities for individual gastrointestinal cancer types. They identified more than 140,000 incident cases of colorectal, pancreatic, liver, esophageal, and gastric cancers in the Surveillance, Epidemiology, and End Results database from 2013 to 2017. They also incorporated nearly 185,000 mortality cases for those same types of malignancy from National Center for Health Statistics data from the years 2014 to 2018.
 

Breaking down the numbers

Overall, the incidence of colorectal cancer was highest, at 36.9 (cases per 100,000), followed by pancreatic cancer at 11.0, gastric cancer at 7.1, esophageal cancer at 4.1, and liver cancer at 3.0, Dr. Bui’s data show. The mortality rate was again highest for colorectal cancer, followed by pancreatic, liver, esophageal and gastric cancer.

When compared with non-Hispanic Whites, all racial ethnic minority groups had significantly higher incidence of both liver and gastric cancers, according to Dr. Bui.

The researchers calculated rate ratios for gastrointestinal cancer incidence and mortality, with ratios above 1 indicating a higher incidence relative to non-Hispanic Whites.

Among Hispanics, the incidence rate ratios were 1.83 for both liver and gastric cancers, according to the analysis. Similarly, non-Hispanic Asian Pacific Islanders had IRRs of 2.00 for liver cancer and 1.9 for gastric cancer. Non-Hispanic American Indians and Alaska Natives had IRRs of 2.09 for liver cancer and 1.51 for gastric cancer.

By contrast, non-Hispanic Blacks had significantly higher IRRs not only for liver and gastric cancers, at 1.64 and 1.8, respectively, but also for pancreatic cancer, at 1.18, and colorectal cancer at 1.17, Dr. Bui said.

Similar trends were seen in mortality in the presented data, with all racial and ethnic groups exhibiting significantly increased mortality RRs for liver and gastric cancer, compared with non-Hispanic Whites, but with non-Hispanic Blacks showing significantly increases in RRs for liver (1.66), gastric (2.36), pancreatic (1.22), and colorectal (1.36) cancers.

Esophageal cancer rates of incidence and mortality were both lower in racial and ethnic minority groups, compared with non-Hispanic whites, according to Dr. Bui.
 

Increasing screening and surveillance

While the esophageal cancer data is encouraging, these data otherwise clearly highlight the need to step up efforts to help level gastrointestinal cancer disparities, according to Byron Cryer, MD, professor of internal medicine and associate dean for the office of faculty diversity and development at the University of Texas Southwestern Medical Center, Dallas.

AGA Institute

“Clearly more work needs to be done for the other four cancers,” Dr. Cryer said in an interview.

Screening and surveillance may be key to addressing those disparities, not only for colorectal cancer, but for the liver and gastric cancers for which disparities were seen throughout racial and ethnic groups in this study.

“We know that if we get rid of hepatitis C virus early, you can prevent those downstream complications such as cancer,” Dr. Cryer said. “It’s same thing with the gastric cancer – if we get rid of Helicobacter pylori early on in the infection, we decrease the burden of cancer down downstream years later.”

Dr. Bui provided no financial disclosures related to the research. Dr. Cryer has nothing to disclose.

While colorectal cancer may be the most common and deadly gastrointestinal malignancy, liver and gastric cancers account for some of the most consistent racial and ethnic disparities, a recent retrospective, cross-sectional analysis of U.S. data suggested.

Liver and gastric cancer incidence and mortality were significantly higher for all racial and ethnic minority groups in the study, compared with non-Hispanic Whites, according to the analysis. Notably, however, non-Hispanic Blacks represented the only group to also have elevated incidence and mortality for pancreatic and colorectal, compared with non-Hispanic Whites, according to investigator Aileen Bui, MD, with the University of California, Los Angeles Health.

These study results highlights the need to address modifiable cancer risk factors and overcome barriers to cancer prevention and care in medically underserved minority populations, Dr. Bui said in a virtual presentation of the results at the annual Digestive Disease Week® (DDW).

“While we cannot infer causation or determine risk factors for certain malignancies from the results of our study, there’s little data to support a strong role of biological or genetic differences between racial and ethnic groups to account for the observed disparities in incidence and mortality for GI cancers,” she said in her presentation.
 

Setting out to explore disparities

Gastrointestinal cancer incidence and mortality remain on the rise, despite significant progress in some areas, including colorectal cancer screening and the introduction of effective treatments for hepatitis C virus, Dr. Bui said.

Incidence and mortality from gastrointestinal cancers are set to increase by 34% and 43%, respectively, by the year 2040, and will remain a significant contributor to cancer incidence and mortality in the United States, according to the researcher.

Gastrointestinal cancer incidence and mortality are known to vary by race and ethnicity, so Dr. Bui and colleagues sought to assess the extent of racial and ethnic disparities for individual gastrointestinal cancer types. They identified more than 140,000 incident cases of colorectal, pancreatic, liver, esophageal, and gastric cancers in the Surveillance, Epidemiology, and End Results database from 2013 to 2017. They also incorporated nearly 185,000 mortality cases for those same types of malignancy from National Center for Health Statistics data from the years 2014 to 2018.
 

Breaking down the numbers

Overall, the incidence of colorectal cancer was highest, at 36.9 (cases per 100,000), followed by pancreatic cancer at 11.0, gastric cancer at 7.1, esophageal cancer at 4.1, and liver cancer at 3.0, Dr. Bui’s data show. The mortality rate was again highest for colorectal cancer, followed by pancreatic, liver, esophageal and gastric cancer.

When compared with non-Hispanic Whites, all racial ethnic minority groups had significantly higher incidence of both liver and gastric cancers, according to Dr. Bui.

The researchers calculated rate ratios for gastrointestinal cancer incidence and mortality, with ratios above 1 indicating a higher incidence relative to non-Hispanic Whites.

Among Hispanics, the incidence rate ratios were 1.83 for both liver and gastric cancers, according to the analysis. Similarly, non-Hispanic Asian Pacific Islanders had IRRs of 2.00 for liver cancer and 1.9 for gastric cancer. Non-Hispanic American Indians and Alaska Natives had IRRs of 2.09 for liver cancer and 1.51 for gastric cancer.

By contrast, non-Hispanic Blacks had significantly higher IRRs not only for liver and gastric cancers, at 1.64 and 1.8, respectively, but also for pancreatic cancer, at 1.18, and colorectal cancer at 1.17, Dr. Bui said.

Similar trends were seen in mortality in the presented data, with all racial and ethnic groups exhibiting significantly increased mortality RRs for liver and gastric cancer, compared with non-Hispanic Whites, but with non-Hispanic Blacks showing significantly increases in RRs for liver (1.66), gastric (2.36), pancreatic (1.22), and colorectal (1.36) cancers.

Esophageal cancer rates of incidence and mortality were both lower in racial and ethnic minority groups, compared with non-Hispanic whites, according to Dr. Bui.
 

Increasing screening and surveillance

While the esophageal cancer data is encouraging, these data otherwise clearly highlight the need to step up efforts to help level gastrointestinal cancer disparities, according to Byron Cryer, MD, professor of internal medicine and associate dean for the office of faculty diversity and development at the University of Texas Southwestern Medical Center, Dallas.

AGA Institute

“Clearly more work needs to be done for the other four cancers,” Dr. Cryer said in an interview.

Screening and surveillance may be key to addressing those disparities, not only for colorectal cancer, but for the liver and gastric cancers for which disparities were seen throughout racial and ethnic groups in this study.

“We know that if we get rid of hepatitis C virus early, you can prevent those downstream complications such as cancer,” Dr. Cryer said. “It’s same thing with the gastric cancer – if we get rid of Helicobacter pylori early on in the infection, we decrease the burden of cancer down downstream years later.”

Dr. Bui provided no financial disclosures related to the research. Dr. Cryer has nothing to disclose.

While colorectal cancer may be the most common and deadly gastrointestinal malignancy, liver and gastric cancers account for some of the most consistent racial and ethnic disparities, a recent retrospective, cross-sectional analysis of U.S. data suggested.

Liver and gastric cancer incidence and mortality were significantly higher for all racial and ethnic minority groups in the study, compared with non-Hispanic Whites, according to the analysis. Notably, however, non-Hispanic Blacks represented the only group to also have elevated incidence and mortality for pancreatic and colorectal, compared with non-Hispanic Whites, according to investigator Aileen Bui, MD, with the University of California, Los Angeles Health.

These study results highlights the need to address modifiable cancer risk factors and overcome barriers to cancer prevention and care in medically underserved minority populations, Dr. Bui said in a virtual presentation of the results at the annual Digestive Disease Week® (DDW).

“While we cannot infer causation or determine risk factors for certain malignancies from the results of our study, there’s little data to support a strong role of biological or genetic differences between racial and ethnic groups to account for the observed disparities in incidence and mortality for GI cancers,” she said in her presentation.
 

Setting out to explore disparities

Gastrointestinal cancer incidence and mortality remain on the rise, despite significant progress in some areas, including colorectal cancer screening and the introduction of effective treatments for hepatitis C virus, Dr. Bui said.

Incidence and mortality from gastrointestinal cancers are set to increase by 34% and 43%, respectively, by the year 2040, and will remain a significant contributor to cancer incidence and mortality in the United States, according to the researcher.

Gastrointestinal cancer incidence and mortality are known to vary by race and ethnicity, so Dr. Bui and colleagues sought to assess the extent of racial and ethnic disparities for individual gastrointestinal cancer types. They identified more than 140,000 incident cases of colorectal, pancreatic, liver, esophageal, and gastric cancers in the Surveillance, Epidemiology, and End Results database from 2013 to 2017. They also incorporated nearly 185,000 mortality cases for those same types of malignancy from National Center for Health Statistics data from the years 2014 to 2018.
 

Breaking down the numbers

Overall, the incidence of colorectal cancer was highest, at 36.9 (cases per 100,000), followed by pancreatic cancer at 11.0, gastric cancer at 7.1, esophageal cancer at 4.1, and liver cancer at 3.0, Dr. Bui’s data show. The mortality rate was again highest for colorectal cancer, followed by pancreatic, liver, esophageal and gastric cancer.

When compared with non-Hispanic Whites, all racial ethnic minority groups had significantly higher incidence of both liver and gastric cancers, according to Dr. Bui.

The researchers calculated rate ratios for gastrointestinal cancer incidence and mortality, with ratios above 1 indicating a higher incidence relative to non-Hispanic Whites.

Among Hispanics, the incidence rate ratios were 1.83 for both liver and gastric cancers, according to the analysis. Similarly, non-Hispanic Asian Pacific Islanders had IRRs of 2.00 for liver cancer and 1.9 for gastric cancer. Non-Hispanic American Indians and Alaska Natives had IRRs of 2.09 for liver cancer and 1.51 for gastric cancer.

By contrast, non-Hispanic Blacks had significantly higher IRRs not only for liver and gastric cancers, at 1.64 and 1.8, respectively, but also for pancreatic cancer, at 1.18, and colorectal cancer at 1.17, Dr. Bui said.

Similar trends were seen in mortality in the presented data, with all racial and ethnic groups exhibiting significantly increased mortality RRs for liver and gastric cancer, compared with non-Hispanic Whites, but with non-Hispanic Blacks showing significantly increases in RRs for liver (1.66), gastric (2.36), pancreatic (1.22), and colorectal (1.36) cancers.

Esophageal cancer rates of incidence and mortality were both lower in racial and ethnic minority groups, compared with non-Hispanic whites, according to Dr. Bui.
 

Increasing screening and surveillance

While the esophageal cancer data is encouraging, these data otherwise clearly highlight the need to step up efforts to help level gastrointestinal cancer disparities, according to Byron Cryer, MD, professor of internal medicine and associate dean for the office of faculty diversity and development at the University of Texas Southwestern Medical Center, Dallas.

AGA Institute

“Clearly more work needs to be done for the other four cancers,” Dr. Cryer said in an interview.

Screening and surveillance may be key to addressing those disparities, not only for colorectal cancer, but for the liver and gastric cancers for which disparities were seen throughout racial and ethnic groups in this study.

“We know that if we get rid of hepatitis C virus early, you can prevent those downstream complications such as cancer,” Dr. Cryer said. “It’s same thing with the gastric cancer – if we get rid of Helicobacter pylori early on in the infection, we decrease the burden of cancer down downstream years later.”

Dr. Bui provided no financial disclosures related to the research. Dr. Cryer has nothing to disclose.

Those of us treating nonalcoholic fatty liver disease (NAFLD) often find ourselves having similar conversations with our patients. After diagnosis, our next step is usually describing to them how they can improve their outcomes through a healthy diet and exercise.

Westend61/Getty Images

We can point to the latest data espousing the benefits of moderate weight reduction. The recently released American Gastroenterological Association (AGA) Clinical Practice Update gives us compelling evidence of what can be achieved with specific thresholds of total body weight loss: >5% can decrease hepatic steatosis, >7% potentially leads to resolution of nonalcoholic steatohepatitis, and >10% possibly allows for regression or stability of fibrosis.

More often than not, our patients then ask us, “What diet do you recommend?”

The AGA’s Clinical Practice Update recommends that people with NAFLD follow the Mediterranean diet, minimize saturated fatty acid intake (specifically red and processed meat), and limit or eliminate consumption of commercially produced fructose.

It’s a tried-and-true, evidence-based recommendation. Yet, recent data suggest that modifying the Mediterranean diet so that it’s further enriched with specific green polyphenols may yield even more benefits to at-risk patients.
 

The upside of a greener Mediterranean diet

In a recently published study, investigators behind the DIRECT-PLUS clinical trial randomly assigned 294 participants with abdominal obesity/dyslipidemia into three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean, and the so-called green Mediterranean diet.

Both Mediterranean diet groups were calorie restricted and called for 28 g/day of walnuts (+440 mg/day polyphenols provided). However, the green Mediterranean diet was further supplemented with 3-4 cups/day of green tea and 100 g/day of Mankai (a Wolffia globosa aquatic plant strain) in the form of frozen cubes turned into a green shake that replaced dinner (+1,240 mg/day total polyphenols provided). The percent change in intrahepatic fat content was quantified continuously by proton magnetic resonance spectroscopy. NAFLD was defined as an intrahepatic fat content of >5%.

After 18 months, the prevalence of NAFLD declined to 54.8% in the HDG group, 47.9% in the standard Mediterranean group, and 31.5% in the green Mediterranean group. Both Mediterranean groups achieved similar moderate weight loss and had significantly higher total plasma polyphenol levels versus the HDG group. However, the green Mediterranean group achieved significantly greater proportional intrahepatic fat content loss (-38.9%) than both the standard Mediterranean (-19.6; P = .023) and HDG (-12.2%; P < .001) groups.

In isolating the individual components of the diets, researchers determined that the degree of intrahepatic fat content loss was significantly associated with increased Mankai and walnut intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, and changes in microbiome composition and specific bacteria.

The authors suggest that the mechanisms by which polyphenols reduced steatosis and prevented liver injury may include reduced de novo lipogenesis, increased fatty acid oxidation, and reduced oxidative stress.

In an additional analysis, DIRECT-PLUS investigators also revealed the beneficial effects of the green Mediterranean diet on cardiometabolic health. Although both Mediterranean diets achieved similar weight loss (-6.2 kg for green Mediterranean and -5.4 kg for standard Mediterranean), which was superior to that observed in the HDG group (-1.5 kg; P < .001), the green Mediterranean group had a greater reduction in waist circumference than the standard Mediterranean group (-8.6 vs. -6.8 cm, respectively; P = .033). Within 6 months, the green Mediterranean group also achieved a greater decrease in low-density lipoprotein cholesterol levels, diastolic blood pressure, and insulin resistance.
 

A new dietary tool for combating obesity

The rising global incidence of NAFLD has made it even more urgent to identify new and improved ways of preventing the onset of obesity-related complications. To aid those efforts, we’ve been equipped with useful tools for educating our patients and their families, such as the 2020-2025 Dietary Guidelines for Americans from the U.S. Department of Agriculture (USDA), which makes a clear case for the disease-combating effects of healthy eating patterns.

This message does not appear to be making the impact it should, however, particularly among teens and young adults. It was recently reported that in 2017, only 7% of U.S. high school students consumed recommended amounts of fruits and only 2% consumed enough vegetables to meet USDA recommendations.

Novel approaches, including enhanced school and community programs, will be required to address this issue, but so will presenting patients with satisfactory dietary alternatives. Compellingly, DIRECT-PLUS investigators reported an 89.8% retention rate at 18 months among volunteers, who were able to comply with the dietary regimen with no significant complaints regarding taste. This signals that even though the “green” modification is more stringent than the typical Mediterranean regimen, it is one to which participants can adhere.

Although the real-world applicability of this diet remains to be seen, DIRECT-PLUS gives us encouraging evidence that a Mediterranean diet amplified with green plant-based proteins/polyphenols can lead to twice the intrahepatic fat loss, as compared to other nutritional strategies, and reduce the rate of NAFLD.

And as we know, having another dietary option to offer our patients is always a welcome addition to the menu.

Dr. Balistreri is with the department of hepatology & nutrition at Cincinnati Children’s Hospital Medical Center. He has disclosed no relevant financial relationships.

Iris Shai, PhD, one of the authors of the study, “Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial,” is an adviser to Hinoman, which markets Mankai. Ilan Youngster, MD, another author of that study, is medical adviser for MyBiotics.

A version of this article first appeared on Medscape.com.

This article was updated May 21, 2021.

Those of us treating nonalcoholic fatty liver disease (NAFLD) often find ourselves having similar conversations with our patients. After diagnosis, our next step is usually describing to them how they can improve their outcomes through a healthy diet and exercise.

Westend61/Getty Images

We can point to the latest data espousing the benefits of moderate weight reduction. The recently released American Gastroenterological Association (AGA) Clinical Practice Update gives us compelling evidence of what can be achieved with specific thresholds of total body weight loss: >5% can decrease hepatic steatosis, >7% potentially leads to resolution of nonalcoholic steatohepatitis, and >10% possibly allows for regression or stability of fibrosis.

More often than not, our patients then ask us, “What diet do you recommend?”

The AGA’s Clinical Practice Update recommends that people with NAFLD follow the Mediterranean diet, minimize saturated fatty acid intake (specifically red and processed meat), and limit or eliminate consumption of commercially produced fructose.

It’s a tried-and-true, evidence-based recommendation. Yet, recent data suggest that modifying the Mediterranean diet so that it’s further enriched with specific green polyphenols may yield even more benefits to at-risk patients.
 

The upside of a greener Mediterranean diet

In a recently published study, investigators behind the DIRECT-PLUS clinical trial randomly assigned 294 participants with abdominal obesity/dyslipidemia into three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean, and the so-called green Mediterranean diet.

Both Mediterranean diet groups were calorie restricted and called for 28 g/day of walnuts (+440 mg/day polyphenols provided). However, the green Mediterranean diet was further supplemented with 3-4 cups/day of green tea and 100 g/day of Mankai (a Wolffia globosa aquatic plant strain) in the form of frozen cubes turned into a green shake that replaced dinner (+1,240 mg/day total polyphenols provided). The percent change in intrahepatic fat content was quantified continuously by proton magnetic resonance spectroscopy. NAFLD was defined as an intrahepatic fat content of >5%.

After 18 months, the prevalence of NAFLD declined to 54.8% in the HDG group, 47.9% in the standard Mediterranean group, and 31.5% in the green Mediterranean group. Both Mediterranean groups achieved similar moderate weight loss and had significantly higher total plasma polyphenol levels versus the HDG group. However, the green Mediterranean group achieved significantly greater proportional intrahepatic fat content loss (-38.9%) than both the standard Mediterranean (-19.6; P = .023) and HDG (-12.2%; P < .001) groups.

In isolating the individual components of the diets, researchers determined that the degree of intrahepatic fat content loss was significantly associated with increased Mankai and walnut intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, and changes in microbiome composition and specific bacteria.

The authors suggest that the mechanisms by which polyphenols reduced steatosis and prevented liver injury may include reduced de novo lipogenesis, increased fatty acid oxidation, and reduced oxidative stress.

In an additional analysis, DIRECT-PLUS investigators also revealed the beneficial effects of the green Mediterranean diet on cardiometabolic health. Although both Mediterranean diets achieved similar weight loss (-6.2 kg for green Mediterranean and -5.4 kg for standard Mediterranean), which was superior to that observed in the HDG group (-1.5 kg; P < .001), the green Mediterranean group had a greater reduction in waist circumference than the standard Mediterranean group (-8.6 vs. -6.8 cm, respectively; P = .033). Within 6 months, the green Mediterranean group also achieved a greater decrease in low-density lipoprotein cholesterol levels, diastolic blood pressure, and insulin resistance.
 

A new dietary tool for combating obesity

The rising global incidence of NAFLD has made it even more urgent to identify new and improved ways of preventing the onset of obesity-related complications. To aid those efforts, we’ve been equipped with useful tools for educating our patients and their families, such as the 2020-2025 Dietary Guidelines for Americans from the U.S. Department of Agriculture (USDA), which makes a clear case for the disease-combating effects of healthy eating patterns.

This message does not appear to be making the impact it should, however, particularly among teens and young adults. It was recently reported that in 2017, only 7% of U.S. high school students consumed recommended amounts of fruits and only 2% consumed enough vegetables to meet USDA recommendations.

Novel approaches, including enhanced school and community programs, will be required to address this issue, but so will presenting patients with satisfactory dietary alternatives. Compellingly, DIRECT-PLUS investigators reported an 89.8% retention rate at 18 months among volunteers, who were able to comply with the dietary regimen with no significant complaints regarding taste. This signals that even though the “green” modification is more stringent than the typical Mediterranean regimen, it is one to which participants can adhere.

Although the real-world applicability of this diet remains to be seen, DIRECT-PLUS gives us encouraging evidence that a Mediterranean diet amplified with green plant-based proteins/polyphenols can lead to twice the intrahepatic fat loss, as compared to other nutritional strategies, and reduce the rate of NAFLD.

And as we know, having another dietary option to offer our patients is always a welcome addition to the menu.

Dr. Balistreri is with the department of hepatology & nutrition at Cincinnati Children’s Hospital Medical Center. He has disclosed no relevant financial relationships.

Iris Shai, PhD, one of the authors of the study, “Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial,” is an adviser to Hinoman, which markets Mankai. Ilan Youngster, MD, another author of that study, is medical adviser for MyBiotics.

A version of this article first appeared on Medscape.com.

This article was updated May 21, 2021.

Those of us treating nonalcoholic fatty liver disease (NAFLD) often find ourselves having similar conversations with our patients. After diagnosis, our next step is usually describing to them how they can improve their outcomes through a healthy diet and exercise.

Westend61/Getty Images

We can point to the latest data espousing the benefits of moderate weight reduction. The recently released American Gastroenterological Association (AGA) Clinical Practice Update gives us compelling evidence of what can be achieved with specific thresholds of total body weight loss: >5% can decrease hepatic steatosis, >7% potentially leads to resolution of nonalcoholic steatohepatitis, and >10% possibly allows for regression or stability of fibrosis.

More often than not, our patients then ask us, “What diet do you recommend?”

The AGA’s Clinical Practice Update recommends that people with NAFLD follow the Mediterranean diet, minimize saturated fatty acid intake (specifically red and processed meat), and limit or eliminate consumption of commercially produced fructose.

It’s a tried-and-true, evidence-based recommendation. Yet, recent data suggest that modifying the Mediterranean diet so that it’s further enriched with specific green polyphenols may yield even more benefits to at-risk patients.
 

The upside of a greener Mediterranean diet

In a recently published study, investigators behind the DIRECT-PLUS clinical trial randomly assigned 294 participants with abdominal obesity/dyslipidemia into three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean, and the so-called green Mediterranean diet.

Both Mediterranean diet groups were calorie restricted and called for 28 g/day of walnuts (+440 mg/day polyphenols provided). However, the green Mediterranean diet was further supplemented with 3-4 cups/day of green tea and 100 g/day of Mankai (a Wolffia globosa aquatic plant strain) in the form of frozen cubes turned into a green shake that replaced dinner (+1,240 mg/day total polyphenols provided). The percent change in intrahepatic fat content was quantified continuously by proton magnetic resonance spectroscopy. NAFLD was defined as an intrahepatic fat content of >5%.

After 18 months, the prevalence of NAFLD declined to 54.8% in the HDG group, 47.9% in the standard Mediterranean group, and 31.5% in the green Mediterranean group. Both Mediterranean groups achieved similar moderate weight loss and had significantly higher total plasma polyphenol levels versus the HDG group. However, the green Mediterranean group achieved significantly greater proportional intrahepatic fat content loss (-38.9%) than both the standard Mediterranean (-19.6; P = .023) and HDG (-12.2%; P < .001) groups.

In isolating the individual components of the diets, researchers determined that the degree of intrahepatic fat content loss was significantly associated with increased Mankai and walnut intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, and changes in microbiome composition and specific bacteria.

The authors suggest that the mechanisms by which polyphenols reduced steatosis and prevented liver injury may include reduced de novo lipogenesis, increased fatty acid oxidation, and reduced oxidative stress.

In an additional analysis, DIRECT-PLUS investigators also revealed the beneficial effects of the green Mediterranean diet on cardiometabolic health. Although both Mediterranean diets achieved similar weight loss (-6.2 kg for green Mediterranean and -5.4 kg for standard Mediterranean), which was superior to that observed in the HDG group (-1.5 kg; P < .001), the green Mediterranean group had a greater reduction in waist circumference than the standard Mediterranean group (-8.6 vs. -6.8 cm, respectively; P = .033). Within 6 months, the green Mediterranean group also achieved a greater decrease in low-density lipoprotein cholesterol levels, diastolic blood pressure, and insulin resistance.
 

A new dietary tool for combating obesity

The rising global incidence of NAFLD has made it even more urgent to identify new and improved ways of preventing the onset of obesity-related complications. To aid those efforts, we’ve been equipped with useful tools for educating our patients and their families, such as the 2020-2025 Dietary Guidelines for Americans from the U.S. Department of Agriculture (USDA), which makes a clear case for the disease-combating effects of healthy eating patterns.

This message does not appear to be making the impact it should, however, particularly among teens and young adults. It was recently reported that in 2017, only 7% of U.S. high school students consumed recommended amounts of fruits and only 2% consumed enough vegetables to meet USDA recommendations.

Novel approaches, including enhanced school and community programs, will be required to address this issue, but so will presenting patients with satisfactory dietary alternatives. Compellingly, DIRECT-PLUS investigators reported an 89.8% retention rate at 18 months among volunteers, who were able to comply with the dietary regimen with no significant complaints regarding taste. This signals that even though the “green” modification is more stringent than the typical Mediterranean regimen, it is one to which participants can adhere.

Although the real-world applicability of this diet remains to be seen, DIRECT-PLUS gives us encouraging evidence that a Mediterranean diet amplified with green plant-based proteins/polyphenols can lead to twice the intrahepatic fat loss, as compared to other nutritional strategies, and reduce the rate of NAFLD.

And as we know, having another dietary option to offer our patients is always a welcome addition to the menu.

Dr. Balistreri is with the department of hepatology & nutrition at Cincinnati Children’s Hospital Medical Center. He has disclosed no relevant financial relationships.

Iris Shai, PhD, one of the authors of the study, “Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial,” is an adviser to Hinoman, which markets Mankai. Ilan Youngster, MD, another author of that study, is medical adviser for MyBiotics.

A version of this article first appeared on Medscape.com.

This article was updated May 21, 2021.

It’s more evidence that Americans drank more alcohol during the COVID-19 lockdown. Rates of liver and gastrointestinal diseases associated with drinking alcohol rose after the COVID-19 pandemic started, compared with the same period in 2019.

Interestingly, while the overall number of people seeking GI or liver specialist care dropped by 27%, the proportion of consults for alcohol-related GI and liver diseases jumped by nearly 60%, researchers reported.

“We do believe that the lockdown of the pandemic has a direct effect on patients’ alcohol consumption,” senior study author Waihong Chung, MD, said during Digestive Disease Week® (DDW) 2021 preview media briefing on May 13.

“We urge primary care physicians and GI doctors and hepatologists to double down on questioning patients about alcohol use and to identify people who might need help sooner rather than later,” added Dr. Chung, gastroenterologist at Lifespan/Brown University in Providence, R.I.

“You have to ask. If you don’t ask, you don’t know,” Dr. Chung said in an interview when asked how to broach the subject.

Symptoms of alcohol-related GI and liver diseases, especially acute alcoholic hepatitis, can include fatigue, abdominal pain, loss of appetite, and even jaundice in more severe cases. “I want to stress that some of these symptoms appear much later during the course of the disease,” Dr. Chung said. “At the early phase, people might be asymptomatic. By the time people develop symptoms it might be too late. That’s why it’s important to ask.”

“I really believe that physicians of all specialties should make it routine when you have a patient encounter to include assessment for alcohol use,” he added.

Creating a clinical environment where patients feel safe to disclose their alcohol use is likewise essential.

Suggested questions include: Do you drink alcohol? How much did you drink in the past week?

“A few people will be offended by me asking this way, but it helps people who might think they have an alcohol problem open up [about it],” he said.

After Dr. Chung and colleagues noticed an increase in patients with alcohol-related GI and liver diseases, they conducted a hospital system–wide audit. They evaluated 558 inpatient GI consults during a lockdown phase from March 23 to May 10, 2020, and another 713 consults during a reopening phase from June 1 to July 19, 2020. They also compared results with consults from similar periods in 2019.

At the same time, consults for non–alcohol-related liver diseases, such as biliary obstruction/injury, inflammatory bowel disease, and gastrointestinal bleeding, did not change significantly. Also, during reopening the total volume of consults rebounded to 101% of the volume during the same period in 2019.

However, reopening also saw the proportion of these alcohol-related conditions remain elevated by 79%. Patients diagnosed with alcoholic hepatitis increased by 127%, for example. At the same time, patients in this population requiring inpatient endoscopy nearly tripled from 14% to 35%.

Alcohol-related GI and liver diseases included acute alcoholic hepatitis, alcoholic cirrhosis, alcoholic gastritis, alcoholic esophagitis, and pancreatitis. Most patients (70%) were men. Median ages were 56 years during the lockdown phase and 51 years during the reopening phase.

“I think it’s interesting. It fits into what people have anecdotally been suggesting,” said Loren Laine, MD, chief of the section of digestive diseases at Yale University in New Haven, Conn., and moderator of the media briefing.

“It is [also] interesting to see how COVID has changed so many different things over the past year,” he added when asked his opinion of the findings.

Dr. Chung added that not all patients with alcohol use disorders are admitted to a hospital, “so we believe that the health problems related to increased alcohol use may be even higher in the community.”

Although the study was conducted in one health system in one state, Dr. Chung said, “we do believe that the result of our study is an accurate reflection of what’s happening in many other urban and suburban cities in the United States.”

A version of this article first appeared on Medscape.com.

It’s more evidence that Americans drank more alcohol during the COVID-19 lockdown. Rates of liver and gastrointestinal diseases associated with drinking alcohol rose after the COVID-19 pandemic started, compared with the same period in 2019.

Interestingly, while the overall number of people seeking GI or liver specialist care dropped by 27%, the proportion of consults for alcohol-related GI and liver diseases jumped by nearly 60%, researchers reported.

“We do believe that the lockdown of the pandemic has a direct effect on patients’ alcohol consumption,” senior study author Waihong Chung, MD, said during Digestive Disease Week® (DDW) 2021 preview media briefing on May 13.

“We urge primary care physicians and GI doctors and hepatologists to double down on questioning patients about alcohol use and to identify people who might need help sooner rather than later,” added Dr. Chung, gastroenterologist at Lifespan/Brown University in Providence, R.I.

“You have to ask. If you don’t ask, you don’t know,” Dr. Chung said in an interview when asked how to broach the subject.

Symptoms of alcohol-related GI and liver diseases, especially acute alcoholic hepatitis, can include fatigue, abdominal pain, loss of appetite, and even jaundice in more severe cases. “I want to stress that some of these symptoms appear much later during the course of the disease,” Dr. Chung said. “At the early phase, people might be asymptomatic. By the time people develop symptoms it might be too late. That’s why it’s important to ask.”

“I really believe that physicians of all specialties should make it routine when you have a patient encounter to include assessment for alcohol use,” he added.

Creating a clinical environment where patients feel safe to disclose their alcohol use is likewise essential.

Suggested questions include: Do you drink alcohol? How much did you drink in the past week?

“A few people will be offended by me asking this way, but it helps people who might think they have an alcohol problem open up [about it],” he said.

After Dr. Chung and colleagues noticed an increase in patients with alcohol-related GI and liver diseases, they conducted a hospital system–wide audit. They evaluated 558 inpatient GI consults during a lockdown phase from March 23 to May 10, 2020, and another 713 consults during a reopening phase from June 1 to July 19, 2020. They also compared results with consults from similar periods in 2019.

At the same time, consults for non–alcohol-related liver diseases, such as biliary obstruction/injury, inflammatory bowel disease, and gastrointestinal bleeding, did not change significantly. Also, during reopening the total volume of consults rebounded to 101% of the volume during the same period in 2019.

However, reopening also saw the proportion of these alcohol-related conditions remain elevated by 79%. Patients diagnosed with alcoholic hepatitis increased by 127%, for example. At the same time, patients in this population requiring inpatient endoscopy nearly tripled from 14% to 35%.

Alcohol-related GI and liver diseases included acute alcoholic hepatitis, alcoholic cirrhosis, alcoholic gastritis, alcoholic esophagitis, and pancreatitis. Most patients (70%) were men. Median ages were 56 years during the lockdown phase and 51 years during the reopening phase.

“I think it’s interesting. It fits into what people have anecdotally been suggesting,” said Loren Laine, MD, chief of the section of digestive diseases at Yale University in New Haven, Conn., and moderator of the media briefing.

“It is [also] interesting to see how COVID has changed so many different things over the past year,” he added when asked his opinion of the findings.

Dr. Chung added that not all patients with alcohol use disorders are admitted to a hospital, “so we believe that the health problems related to increased alcohol use may be even higher in the community.”

Although the study was conducted in one health system in one state, Dr. Chung said, “we do believe that the result of our study is an accurate reflection of what’s happening in many other urban and suburban cities in the United States.”

A version of this article first appeared on Medscape.com.

It’s more evidence that Americans drank more alcohol during the COVID-19 lockdown. Rates of liver and gastrointestinal diseases associated with drinking alcohol rose after the COVID-19 pandemic started, compared with the same period in 2019.

Interestingly, while the overall number of people seeking GI or liver specialist care dropped by 27%, the proportion of consults for alcohol-related GI and liver diseases jumped by nearly 60%, researchers reported.

“We do believe that the lockdown of the pandemic has a direct effect on patients’ alcohol consumption,” senior study author Waihong Chung, MD, said during Digestive Disease Week® (DDW) 2021 preview media briefing on May 13.

“We urge primary care physicians and GI doctors and hepatologists to double down on questioning patients about alcohol use and to identify people who might need help sooner rather than later,” added Dr. Chung, gastroenterologist at Lifespan/Brown University in Providence, R.I.

“You have to ask. If you don’t ask, you don’t know,” Dr. Chung said in an interview when asked how to broach the subject.

Symptoms of alcohol-related GI and liver diseases, especially acute alcoholic hepatitis, can include fatigue, abdominal pain, loss of appetite, and even jaundice in more severe cases. “I want to stress that some of these symptoms appear much later during the course of the disease,” Dr. Chung said. “At the early phase, people might be asymptomatic. By the time people develop symptoms it might be too late. That’s why it’s important to ask.”

“I really believe that physicians of all specialties should make it routine when you have a patient encounter to include assessment for alcohol use,” he added.

Creating a clinical environment where patients feel safe to disclose their alcohol use is likewise essential.

Suggested questions include: Do you drink alcohol? How much did you drink in the past week?

“A few people will be offended by me asking this way, but it helps people who might think they have an alcohol problem open up [about it],” he said.

After Dr. Chung and colleagues noticed an increase in patients with alcohol-related GI and liver diseases, they conducted a hospital system–wide audit. They evaluated 558 inpatient GI consults during a lockdown phase from March 23 to May 10, 2020, and another 713 consults during a reopening phase from June 1 to July 19, 2020. They also compared results with consults from similar periods in 2019.

At the same time, consults for non–alcohol-related liver diseases, such as biliary obstruction/injury, inflammatory bowel disease, and gastrointestinal bleeding, did not change significantly. Also, during reopening the total volume of consults rebounded to 101% of the volume during the same period in 2019.

However, reopening also saw the proportion of these alcohol-related conditions remain elevated by 79%. Patients diagnosed with alcoholic hepatitis increased by 127%, for example. At the same time, patients in this population requiring inpatient endoscopy nearly tripled from 14% to 35%.

Alcohol-related GI and liver diseases included acute alcoholic hepatitis, alcoholic cirrhosis, alcoholic gastritis, alcoholic esophagitis, and pancreatitis. Most patients (70%) were men. Median ages were 56 years during the lockdown phase and 51 years during the reopening phase.

“I think it’s interesting. It fits into what people have anecdotally been suggesting,” said Loren Laine, MD, chief of the section of digestive diseases at Yale University in New Haven, Conn., and moderator of the media briefing.

“It is [also] interesting to see how COVID has changed so many different things over the past year,” he added when asked his opinion of the findings.

Dr. Chung added that not all patients with alcohol use disorders are admitted to a hospital, “so we believe that the health problems related to increased alcohol use may be even higher in the community.”

Although the study was conducted in one health system in one state, Dr. Chung said, “we do believe that the result of our study is an accurate reflection of what’s happening in many other urban and suburban cities in the United States.”

A version of this article first appeared on Medscape.com.