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Noninvasive tests may provide prognostic value in NAFLD
Fibrosis stages and liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE) through FibroScan were significant predictors of event-free survival, said Ferenc Mozes, DPhil, a postdoctoral research assistant at the University of Oxford, England, who has worked on biomarker evaluation of nonalcoholic steatohepatitis (NASH) as a member of the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) consortium.
“Liver histology is highly prognostic of liver-related outcomes in patients with NAFLD and NASH,” he said. “Not just that, but liver histology is also accepted, and furthermore mandated by the FDA, as a surrogate endpoint in pharmaceutical trials for NASH.”
However, liver histology is disadvantaged by sampling- and observer-dependent errors, he noted, as well as nonzero risk for patients. In recent years, researchers have hypothesized that noninvasive surrogate endpoints could be used as a way to speed up the development of new pharmaceutical treatments.
Dr. Mozes and colleagues evaluated the prognostic performance of histologically assessed liver fibrosis and three noninvasive tests (NITs): LSM-VCTE, Fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS). They conducted an individual participant data meta-analysis, which first established the diagnostic performance of NITs in identifying patients with NAFLD who had advanced fibrosis (stages F3 and F4). The research team then expanded the search by reaching out to authors to ask for outcomes data and including studies with baseline LSM-VCTE and liver histology performed within 6 months, as well as at least 1 year of follow-up data.
The composite endpoint included all-cause mortality or liver-related outcomes such as decompensation of cirrhosis, hepatocellular cancer, liver transplantation, a model of end-stage liver disease (MELD) score higher than 14, or histological progression to cirrhosis. Participants were censored at the last follow-up time or at the occurrence of the first liver-related event.
Based on Kaplan-Meier survival analysis, participants were stratified into groups based on thresholds derived from the literature: fibrosis stage 0-2 (F0-2), F3, F4; LSM less than 10 kPa, LSM equal to or more than 10 kPa and less than 20 kPa, and LSM equal to or more than 20 kPa; FIB4 less than 1.3, FIB equal to or more than 1.3 and less than 2.67, and FIB4 equal to or more than 2.67; and NFS less than –1.455, NFS equal to or more than –1.455 and less than 0.676, and NFS equal to or more than 0.676.
The research team included 13 studies from Europe and Asia with data on 1,796 patients. The median follow-up time was 64 months, both from biopsy and LSM-VCTE. The fibrosis stages were typical of what would be seen in tertiary care.
Overall, 125 patients (7%) reached the composite endpoint. They tended to be older and more likely to have type 2 diabetes, higher fibrosis stages, and cirrhosis. Among those, 80 participants died, including 25 from liver-related mortality. In addition, 23 had ascites, 28 had hepatocellular cancer, and 31 progressed to cirrhosis or a MELD score greater than 14.
On the Kaplan-Meier curves, both the histology and noninvasive tests showed significant differences among the three strata for event-free survival probability.
Based on univariable Cox proportional hazard modeling, fibrosis stages F3 and F4 and continuous LSM-VCTE were significantly predictive of event-free survival probability. In multivariable models, fibrosis stage 4 and the two higher strata of LSM-VCTE were significantly predictive.
The study had several limitations, Dr. Mozes noted, by using cohort studies that weren’t initially designed to evaluate prognostic performance. They also couldn’t account for treatment effects and had no central histology reading. In addition, there may have been geographical variation in practice, as well as changes in practice over time as FibroScan technology improved in recent years.
“It turns out that stratifying patients by NIT score ranges can predict event-free survival probability,” he said. “This could pave the way into considering noninvasive tests as surrogate endpoints in clinical trials.”
In the ongoing study, Dr. Mozes and colleagues plan to look at additional aspects, such as MELD differentiation, histologic progression, and whether the NIT cutoffs differ from the current factors used to define advanced fibrosis. Future research should include longitudinal data and prospective studies, he added.
The study was sponsored by the LITMUS consortium, which has received funding from the Innovative Medicines Initiative 2 Joint Undertaking and the European Union’s Horizon 2020 research and innovation program. Dr. Mozes disclosed no relevant financial relationships.
Fibrosis stages and liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE) through FibroScan were significant predictors of event-free survival, said Ferenc Mozes, DPhil, a postdoctoral research assistant at the University of Oxford, England, who has worked on biomarker evaluation of nonalcoholic steatohepatitis (NASH) as a member of the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) consortium.
“Liver histology is highly prognostic of liver-related outcomes in patients with NAFLD and NASH,” he said. “Not just that, but liver histology is also accepted, and furthermore mandated by the FDA, as a surrogate endpoint in pharmaceutical trials for NASH.”
However, liver histology is disadvantaged by sampling- and observer-dependent errors, he noted, as well as nonzero risk for patients. In recent years, researchers have hypothesized that noninvasive surrogate endpoints could be used as a way to speed up the development of new pharmaceutical treatments.
Dr. Mozes and colleagues evaluated the prognostic performance of histologically assessed liver fibrosis and three noninvasive tests (NITs): LSM-VCTE, Fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS). They conducted an individual participant data meta-analysis, which first established the diagnostic performance of NITs in identifying patients with NAFLD who had advanced fibrosis (stages F3 and F4). The research team then expanded the search by reaching out to authors to ask for outcomes data and including studies with baseline LSM-VCTE and liver histology performed within 6 months, as well as at least 1 year of follow-up data.
The composite endpoint included all-cause mortality or liver-related outcomes such as decompensation of cirrhosis, hepatocellular cancer, liver transplantation, a model of end-stage liver disease (MELD) score higher than 14, or histological progression to cirrhosis. Participants were censored at the last follow-up time or at the occurrence of the first liver-related event.
Based on Kaplan-Meier survival analysis, participants were stratified into groups based on thresholds derived from the literature: fibrosis stage 0-2 (F0-2), F3, F4; LSM less than 10 kPa, LSM equal to or more than 10 kPa and less than 20 kPa, and LSM equal to or more than 20 kPa; FIB4 less than 1.3, FIB equal to or more than 1.3 and less than 2.67, and FIB4 equal to or more than 2.67; and NFS less than –1.455, NFS equal to or more than –1.455 and less than 0.676, and NFS equal to or more than 0.676.
The research team included 13 studies from Europe and Asia with data on 1,796 patients. The median follow-up time was 64 months, both from biopsy and LSM-VCTE. The fibrosis stages were typical of what would be seen in tertiary care.
Overall, 125 patients (7%) reached the composite endpoint. They tended to be older and more likely to have type 2 diabetes, higher fibrosis stages, and cirrhosis. Among those, 80 participants died, including 25 from liver-related mortality. In addition, 23 had ascites, 28 had hepatocellular cancer, and 31 progressed to cirrhosis or a MELD score greater than 14.
On the Kaplan-Meier curves, both the histology and noninvasive tests showed significant differences among the three strata for event-free survival probability.
Based on univariable Cox proportional hazard modeling, fibrosis stages F3 and F4 and continuous LSM-VCTE were significantly predictive of event-free survival probability. In multivariable models, fibrosis stage 4 and the two higher strata of LSM-VCTE were significantly predictive.
The study had several limitations, Dr. Mozes noted, by using cohort studies that weren’t initially designed to evaluate prognostic performance. They also couldn’t account for treatment effects and had no central histology reading. In addition, there may have been geographical variation in practice, as well as changes in practice over time as FibroScan technology improved in recent years.
“It turns out that stratifying patients by NIT score ranges can predict event-free survival probability,” he said. “This could pave the way into considering noninvasive tests as surrogate endpoints in clinical trials.”
In the ongoing study, Dr. Mozes and colleagues plan to look at additional aspects, such as MELD differentiation, histologic progression, and whether the NIT cutoffs differ from the current factors used to define advanced fibrosis. Future research should include longitudinal data and prospective studies, he added.
The study was sponsored by the LITMUS consortium, which has received funding from the Innovative Medicines Initiative 2 Joint Undertaking and the European Union’s Horizon 2020 research and innovation program. Dr. Mozes disclosed no relevant financial relationships.
Fibrosis stages and liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE) through FibroScan were significant predictors of event-free survival, said Ferenc Mozes, DPhil, a postdoctoral research assistant at the University of Oxford, England, who has worked on biomarker evaluation of nonalcoholic steatohepatitis (NASH) as a member of the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) consortium.
“Liver histology is highly prognostic of liver-related outcomes in patients with NAFLD and NASH,” he said. “Not just that, but liver histology is also accepted, and furthermore mandated by the FDA, as a surrogate endpoint in pharmaceutical trials for NASH.”
However, liver histology is disadvantaged by sampling- and observer-dependent errors, he noted, as well as nonzero risk for patients. In recent years, researchers have hypothesized that noninvasive surrogate endpoints could be used as a way to speed up the development of new pharmaceutical treatments.
Dr. Mozes and colleagues evaluated the prognostic performance of histologically assessed liver fibrosis and three noninvasive tests (NITs): LSM-VCTE, Fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS). They conducted an individual participant data meta-analysis, which first established the diagnostic performance of NITs in identifying patients with NAFLD who had advanced fibrosis (stages F3 and F4). The research team then expanded the search by reaching out to authors to ask for outcomes data and including studies with baseline LSM-VCTE and liver histology performed within 6 months, as well as at least 1 year of follow-up data.
The composite endpoint included all-cause mortality or liver-related outcomes such as decompensation of cirrhosis, hepatocellular cancer, liver transplantation, a model of end-stage liver disease (MELD) score higher than 14, or histological progression to cirrhosis. Participants were censored at the last follow-up time or at the occurrence of the first liver-related event.
Based on Kaplan-Meier survival analysis, participants were stratified into groups based on thresholds derived from the literature: fibrosis stage 0-2 (F0-2), F3, F4; LSM less than 10 kPa, LSM equal to or more than 10 kPa and less than 20 kPa, and LSM equal to or more than 20 kPa; FIB4 less than 1.3, FIB equal to or more than 1.3 and less than 2.67, and FIB4 equal to or more than 2.67; and NFS less than –1.455, NFS equal to or more than –1.455 and less than 0.676, and NFS equal to or more than 0.676.
The research team included 13 studies from Europe and Asia with data on 1,796 patients. The median follow-up time was 64 months, both from biopsy and LSM-VCTE. The fibrosis stages were typical of what would be seen in tertiary care.
Overall, 125 patients (7%) reached the composite endpoint. They tended to be older and more likely to have type 2 diabetes, higher fibrosis stages, and cirrhosis. Among those, 80 participants died, including 25 from liver-related mortality. In addition, 23 had ascites, 28 had hepatocellular cancer, and 31 progressed to cirrhosis or a MELD score greater than 14.
On the Kaplan-Meier curves, both the histology and noninvasive tests showed significant differences among the three strata for event-free survival probability.
Based on univariable Cox proportional hazard modeling, fibrosis stages F3 and F4 and continuous LSM-VCTE were significantly predictive of event-free survival probability. In multivariable models, fibrosis stage 4 and the two higher strata of LSM-VCTE were significantly predictive.
The study had several limitations, Dr. Mozes noted, by using cohort studies that weren’t initially designed to evaluate prognostic performance. They also couldn’t account for treatment effects and had no central histology reading. In addition, there may have been geographical variation in practice, as well as changes in practice over time as FibroScan technology improved in recent years.
“It turns out that stratifying patients by NIT score ranges can predict event-free survival probability,” he said. “This could pave the way into considering noninvasive tests as surrogate endpoints in clinical trials.”
In the ongoing study, Dr. Mozes and colleagues plan to look at additional aspects, such as MELD differentiation, histologic progression, and whether the NIT cutoffs differ from the current factors used to define advanced fibrosis. Future research should include longitudinal data and prospective studies, he added.
The study was sponsored by the LITMUS consortium, which has received funding from the Innovative Medicines Initiative 2 Joint Undertaking and the European Union’s Horizon 2020 research and innovation program. Dr. Mozes disclosed no relevant financial relationships.
FROM THE LIVER MEETING
Low-carb diet aids weight loss in liver transplant recipients with obesity
A low-carbohydrate diet appears to be an effective weight-loss intervention in liver transplant recipients with obesity as compared with a calorie-restrictive diet, according to interim findings presented at the annual meeting of the American Association for the Study of Liver Diseases.
In particular, the intervention showed significant improvements in the metabophenotype profile, including visceral adipose tissue and abdominal subcutaneous adipose tissue, said Mohammad Siddiqui, MD, a gastroenterologist and liver transplant specialist at Virginia Commonwealth University, Richmond.
“Weight gain and obesity after liver transplantation is common,” he said. “Posttransplant obesity is associated with increased cardiometabolic risk burden, increased risk of cardiovascular disease and mortality, and overall mortality.”
Previously, Dr. Siddiqui and colleagues have shown that posttransplant weight loss is difficult because of metabolic inflexibility and mitochondrial inefficiency. By specifically targeting carbohydrate utilization, metabolic flexibility could be restored in liver transplant recipients, he noted.
Dr. Siddiqui and colleagues conducted a randomized controlled trial of 27 adult liver transplant recipients with obesity for 24 weeks. The primary endpoint was change in weight, and the secondary endpoints involved metabophenotype, metabolic flexibility, mitochondrial function, and metabolic risk. The research team excluded patients with end-stage disease, terminal disease, use of weight-loss medications, pregnancy, or uncontrolled psychiatric illness that could interfere with adherence.
Among the participants, 13 were randomized to a calorie restrictive diet of less than 1,200-1,500 calories per day, and 14 were randomized to a low-carbohydrate diet of 20 grams or less per day. At enrollment, the participants underwent dietary, activity, skeletal muscle, and body composition assessments, as well as metabophenotype measurements of visceral adipose tissue, abdominal subcutaneous adipose tissue, muscle fat infiltration, fat-free muscle volume, and proton density fat fraction.
All participants were advised to maintain the same level of physical activity, which was measured through 7-day accelerometry. In addition, the patients were contacted every 2 weeks throughout the 24-week study period.
“We wanted to reinforce the dietary advice. We wanted to identify factors that may lead to compliance,” Dr. Siddiqui said. “Multiple studies have documented that the more contact that patients have during weight-loss studies with medical personnel, the more effective those strategies are.”
Overall, the dietary interventions were well tolerated, and neither group showed a significant change in renal function.
The average weight loss was –7.6 kg over 6 months in the low-carbohydrate group, as compared with –0.6 kg in the calorie-restrictive group.
The low carbohydrate diet also positively affected participants’ metabophenotype profile, particularly fat deposits. As compared with the calorie-restrictive group, the low-carbohydrate group showed statistically significant improvements in visceral adipose tissue, abdominal subcutaneous adipose tissue, and muscle fat infiltration.
The liver proton density fat fraction, which is associated with fatty liver disease, decreased by 0.53% in the low-carbohydrate group and increased by 0.46% in the calorie-restrictive group, but the difference didn’t reach statistical significance.
The fat-free muscle volume decreased by about 5% in the low-carbohydrate group. Dr. Siddiqui noted that the researchers don’t know yet whether this translates to a decrease in muscle function.
In terms of metabolic risk, the low-carbohydrate diet did not affect serum lipids (such as triglycerides or cholesterol measures), renal function (such as serum creatinine, glomerular filtration rate, or blood urea nitrogen), or insulin resistance (through glucose or hemoglobin A1c). At the same time, among patients taking insulin at the time of enrollment, about 90% of patients randomized to the low-carbohydrate group were able to reduce insulin to zero during the study.
Upon completion of the current study, Dr. Siddiqui and colleagues hope to provide foundational safety and efficacy data for carbohydrate restriction in liver transplant recipients. In the ongoing study, the researchers are further investigating the dietary intervention impacts on metabolic flexibility, skeletal muscle mitochondrial function, atherogenic lipoproteins, and vascular function.
“Are we actually, on a molecular level, fixing the fundamental problem that liver transplant recipients have to improve outcomes?” he said. “We’re doing very detailed profiling of these patients, so we will have data that shows how this actually affects them.”
Dr. Siddiqui was asked about the sustainability of the low-carbohydrate diet, particularly with a restrictive parameter of 20 grams per day. During the COVID-19 pandemic, Dr. Siddiqui noted, the study was slowed and the research team was able to collect follow-up data.
“Surprisingly, we have a high rate of compliance, even after 6 months of therapy, and I think this has to do with a patient population that’s been through cirrhosis and has almost died,” he said. “They’re far more compliant, and we’re seeing that. We’re also changing the physiology and improving mitochondrial function, which improves the weight loss and weight maintenance, though I don’t know how long that’s going to last.”
The study sponsorship was not disclosed. Dr. Siddiqui reported no relevant conflicts of interest.
A low-carbohydrate diet appears to be an effective weight-loss intervention in liver transplant recipients with obesity as compared with a calorie-restrictive diet, according to interim findings presented at the annual meeting of the American Association for the Study of Liver Diseases.
In particular, the intervention showed significant improvements in the metabophenotype profile, including visceral adipose tissue and abdominal subcutaneous adipose tissue, said Mohammad Siddiqui, MD, a gastroenterologist and liver transplant specialist at Virginia Commonwealth University, Richmond.
“Weight gain and obesity after liver transplantation is common,” he said. “Posttransplant obesity is associated with increased cardiometabolic risk burden, increased risk of cardiovascular disease and mortality, and overall mortality.”
Previously, Dr. Siddiqui and colleagues have shown that posttransplant weight loss is difficult because of metabolic inflexibility and mitochondrial inefficiency. By specifically targeting carbohydrate utilization, metabolic flexibility could be restored in liver transplant recipients, he noted.
Dr. Siddiqui and colleagues conducted a randomized controlled trial of 27 adult liver transplant recipients with obesity for 24 weeks. The primary endpoint was change in weight, and the secondary endpoints involved metabophenotype, metabolic flexibility, mitochondrial function, and metabolic risk. The research team excluded patients with end-stage disease, terminal disease, use of weight-loss medications, pregnancy, or uncontrolled psychiatric illness that could interfere with adherence.
Among the participants, 13 were randomized to a calorie restrictive diet of less than 1,200-1,500 calories per day, and 14 were randomized to a low-carbohydrate diet of 20 grams or less per day. At enrollment, the participants underwent dietary, activity, skeletal muscle, and body composition assessments, as well as metabophenotype measurements of visceral adipose tissue, abdominal subcutaneous adipose tissue, muscle fat infiltration, fat-free muscle volume, and proton density fat fraction.
All participants were advised to maintain the same level of physical activity, which was measured through 7-day accelerometry. In addition, the patients were contacted every 2 weeks throughout the 24-week study period.
“We wanted to reinforce the dietary advice. We wanted to identify factors that may lead to compliance,” Dr. Siddiqui said. “Multiple studies have documented that the more contact that patients have during weight-loss studies with medical personnel, the more effective those strategies are.”
Overall, the dietary interventions were well tolerated, and neither group showed a significant change in renal function.
The average weight loss was –7.6 kg over 6 months in the low-carbohydrate group, as compared with –0.6 kg in the calorie-restrictive group.
The low carbohydrate diet also positively affected participants’ metabophenotype profile, particularly fat deposits. As compared with the calorie-restrictive group, the low-carbohydrate group showed statistically significant improvements in visceral adipose tissue, abdominal subcutaneous adipose tissue, and muscle fat infiltration.
The liver proton density fat fraction, which is associated with fatty liver disease, decreased by 0.53% in the low-carbohydrate group and increased by 0.46% in the calorie-restrictive group, but the difference didn’t reach statistical significance.
The fat-free muscle volume decreased by about 5% in the low-carbohydrate group. Dr. Siddiqui noted that the researchers don’t know yet whether this translates to a decrease in muscle function.
In terms of metabolic risk, the low-carbohydrate diet did not affect serum lipids (such as triglycerides or cholesterol measures), renal function (such as serum creatinine, glomerular filtration rate, or blood urea nitrogen), or insulin resistance (through glucose or hemoglobin A1c). At the same time, among patients taking insulin at the time of enrollment, about 90% of patients randomized to the low-carbohydrate group were able to reduce insulin to zero during the study.
Upon completion of the current study, Dr. Siddiqui and colleagues hope to provide foundational safety and efficacy data for carbohydrate restriction in liver transplant recipients. In the ongoing study, the researchers are further investigating the dietary intervention impacts on metabolic flexibility, skeletal muscle mitochondrial function, atherogenic lipoproteins, and vascular function.
“Are we actually, on a molecular level, fixing the fundamental problem that liver transplant recipients have to improve outcomes?” he said. “We’re doing very detailed profiling of these patients, so we will have data that shows how this actually affects them.”
Dr. Siddiqui was asked about the sustainability of the low-carbohydrate diet, particularly with a restrictive parameter of 20 grams per day. During the COVID-19 pandemic, Dr. Siddiqui noted, the study was slowed and the research team was able to collect follow-up data.
“Surprisingly, we have a high rate of compliance, even after 6 months of therapy, and I think this has to do with a patient population that’s been through cirrhosis and has almost died,” he said. “They’re far more compliant, and we’re seeing that. We’re also changing the physiology and improving mitochondrial function, which improves the weight loss and weight maintenance, though I don’t know how long that’s going to last.”
The study sponsorship was not disclosed. Dr. Siddiqui reported no relevant conflicts of interest.
A low-carbohydrate diet appears to be an effective weight-loss intervention in liver transplant recipients with obesity as compared with a calorie-restrictive diet, according to interim findings presented at the annual meeting of the American Association for the Study of Liver Diseases.
In particular, the intervention showed significant improvements in the metabophenotype profile, including visceral adipose tissue and abdominal subcutaneous adipose tissue, said Mohammad Siddiqui, MD, a gastroenterologist and liver transplant specialist at Virginia Commonwealth University, Richmond.
“Weight gain and obesity after liver transplantation is common,” he said. “Posttransplant obesity is associated with increased cardiometabolic risk burden, increased risk of cardiovascular disease and mortality, and overall mortality.”
Previously, Dr. Siddiqui and colleagues have shown that posttransplant weight loss is difficult because of metabolic inflexibility and mitochondrial inefficiency. By specifically targeting carbohydrate utilization, metabolic flexibility could be restored in liver transplant recipients, he noted.
Dr. Siddiqui and colleagues conducted a randomized controlled trial of 27 adult liver transplant recipients with obesity for 24 weeks. The primary endpoint was change in weight, and the secondary endpoints involved metabophenotype, metabolic flexibility, mitochondrial function, and metabolic risk. The research team excluded patients with end-stage disease, terminal disease, use of weight-loss medications, pregnancy, or uncontrolled psychiatric illness that could interfere with adherence.
Among the participants, 13 were randomized to a calorie restrictive diet of less than 1,200-1,500 calories per day, and 14 were randomized to a low-carbohydrate diet of 20 grams or less per day. At enrollment, the participants underwent dietary, activity, skeletal muscle, and body composition assessments, as well as metabophenotype measurements of visceral adipose tissue, abdominal subcutaneous adipose tissue, muscle fat infiltration, fat-free muscle volume, and proton density fat fraction.
All participants were advised to maintain the same level of physical activity, which was measured through 7-day accelerometry. In addition, the patients were contacted every 2 weeks throughout the 24-week study period.
“We wanted to reinforce the dietary advice. We wanted to identify factors that may lead to compliance,” Dr. Siddiqui said. “Multiple studies have documented that the more contact that patients have during weight-loss studies with medical personnel, the more effective those strategies are.”
Overall, the dietary interventions were well tolerated, and neither group showed a significant change in renal function.
The average weight loss was –7.6 kg over 6 months in the low-carbohydrate group, as compared with –0.6 kg in the calorie-restrictive group.
The low carbohydrate diet also positively affected participants’ metabophenotype profile, particularly fat deposits. As compared with the calorie-restrictive group, the low-carbohydrate group showed statistically significant improvements in visceral adipose tissue, abdominal subcutaneous adipose tissue, and muscle fat infiltration.
The liver proton density fat fraction, which is associated with fatty liver disease, decreased by 0.53% in the low-carbohydrate group and increased by 0.46% in the calorie-restrictive group, but the difference didn’t reach statistical significance.
The fat-free muscle volume decreased by about 5% in the low-carbohydrate group. Dr. Siddiqui noted that the researchers don’t know yet whether this translates to a decrease in muscle function.
In terms of metabolic risk, the low-carbohydrate diet did not affect serum lipids (such as triglycerides or cholesterol measures), renal function (such as serum creatinine, glomerular filtration rate, or blood urea nitrogen), or insulin resistance (through glucose or hemoglobin A1c). At the same time, among patients taking insulin at the time of enrollment, about 90% of patients randomized to the low-carbohydrate group were able to reduce insulin to zero during the study.
Upon completion of the current study, Dr. Siddiqui and colleagues hope to provide foundational safety and efficacy data for carbohydrate restriction in liver transplant recipients. In the ongoing study, the researchers are further investigating the dietary intervention impacts on metabolic flexibility, skeletal muscle mitochondrial function, atherogenic lipoproteins, and vascular function.
“Are we actually, on a molecular level, fixing the fundamental problem that liver transplant recipients have to improve outcomes?” he said. “We’re doing very detailed profiling of these patients, so we will have data that shows how this actually affects them.”
Dr. Siddiqui was asked about the sustainability of the low-carbohydrate diet, particularly with a restrictive parameter of 20 grams per day. During the COVID-19 pandemic, Dr. Siddiqui noted, the study was slowed and the research team was able to collect follow-up data.
“Surprisingly, we have a high rate of compliance, even after 6 months of therapy, and I think this has to do with a patient population that’s been through cirrhosis and has almost died,” he said. “They’re far more compliant, and we’re seeing that. We’re also changing the physiology and improving mitochondrial function, which improves the weight loss and weight maintenance, though I don’t know how long that’s going to last.”
The study sponsorship was not disclosed. Dr. Siddiqui reported no relevant conflicts of interest.
FROM THE LIVER MEETING