Andrew D. Bowser

BOSTON – Treatment of persons who inject drugs, updates in pangenotypic direct-acting antiviral therapy, the benefits of sustained virologic response, and preemptive therapy in donor-positive organ transplantation topped the list of notable hepatitis C–related abstracts this year at the annual meeting of the American Association for the Study of Liver Diseases.

That’s according to Marc Ghany, MD, of the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, who gave a hepatitis C debrief to attendees on the final day of the meeting. Here are some of the meeting highlights as summarized by Dr. Ghany in this well-attended last-day session.
 

Treatment of HCV in people who inject drugs

Emerging data suggest it is feasible to treat hepatitis C virus (HCV) infection in persons who inject drugs (PWIDs); however, overcoming adherence issues remains a challenge, Dr. Ghany told attendees.

According to one study presented at AASLD by Dhiman and coauthors (Abstract 0165), decentralized care of PWIDs using direct-acting antiviral (DAA) therapy was safe and effective, even in those with cirrhosis. Authors demonstrated an “impressive” rate of sustained virologic response at 12 weeks (SVR12) of 91% by a modified intention-to-treat analysis, Dr. Ghany said; however, treatment interruptions were frequent and reduced the overall SVR rate in the study to 78%.

Other studies at the meeting looked at strategies to improve DAA efficacy in this population of patients at high risk of nonadherence, including use of a digital medicine program (Abstract 1554) and a model of care in which an internist-addiction medicine specialist evaluated opiate-dependent patients for HCV infection in a hepatology clinic (Abstract 1589).

Reinfection remains a focus of research in PWIDs. At this meeting, Janjua and coauthors reported that DAA-treated PWIDs in British Columbia had a threefold higher rate of reinfection versus non-PWIDs; however, there were no detected reinfections among PWIDs who had received uninterrupted opioid agonist therapy. “These data suggested that opioid agonist therapy should be given before and after HCV treatment in persons who inject drugs to prevent the infection,” Dr. Ghany said in his presentation.
 

Updates on pangenotypic DAA therapy

Jonas and coauthors (Abstract 1551) reported on the safety and efficacy of glecaprevir/pibrentasvir for 8 weeks in children with chronic HCV infection enrolled in the ongoing phase 2/3 DORA study. The SVR12 was high, according to Dr. Ghany, at 96% overall, and consistent across age cohorts from 3 to less than 12 years of age.

“In the near future, we should have a safe and effective regimen (approved) for children 3 years or older,” Dr. Ghany said. “I think this will serve us well, as we try to eliminate HCV in children, who number up to 5 million cases worldwide.”

A short course of glecaprevir/pibrentasvir is approved for patients with HCV and compensated cirrhosis, and data to support that was presented last year at The Liver Meeting; however, data were not presented on patients with genotype 3, the most difficult-to-treat genotype, Dr. Ghany said. That gap was filled at this year’s meeting with a report (Abstract LP9) showing SVR12 rates of 98.4% per protocol and 95.2% in intention-to-treat analysis.
 

Relationship of SVR to clinical outcomes

While the impact of sustained virologic response (SVR) on all-cause mortality is clear in patients with HCV, less is known about the effect of SVR on liver-related mortality and other outcomes, Dr. Ghany said. In one study presented here (Abstract 0039), based on analysis of a Veterans Affairs database of patients with chronic HCV infection, SVR was linked to a significant reduction in liver-related mortality, while in another report (Abstract 0037), SVR was associated with significant reductions in acute coronary syndromes, end-stage renal disease, and ischemic stroke.

Similarly, a multinational, propensity score–matched analysis (Abstract 0040) demonstrated that SVR had an impact on 5-year overall survival and liver-related survival in patients with HCV-related hepatocellular carcinoma (HCC). “For HCC patients who are candidates for HCC therapy, consideration should also be given to treating these individuals (with DAA therapy) because of the impact on overall survival,” Dr. Ghany said.
 

Preemptive DAA therapy in organ transplantation

Exciting new data show that preemptive therapy, given for short durations, appears to either prevent or cure HCV infection after organ transplant, said Dr. Ghany.

A retrospective analysis by Wijarnpreecha and colleagues (Abstract 0003) showed that 12 or 24 weeks of direct-acting antiviral (DAA) therapy resulted in an SVR12 for 24 out of 24 HCV-seropositive to HCV-seronegative liver transplants, while Durand and colleagues (Abstract 0042) showed that just 4 weeks of pre- and postexposure DAA prophylaxis resulted in SVR12s for 9 out of 9 HCV donor-positive, recipient-negative kidney transplants. Finally, Feld and coauthors (Abstract 0038) showed that preemptive ezetimibe with DAA therapy for 7 days prevented or rapidly cured infection in an experience that included 16 HCV-positive organ donors and 25 HCV-negative recipients.

“While these data are very encouraging, I think we do need to have long-term follow-up of these patients for graft survival, as well as the effect on wait times,” Dr. Ghany said.

Dr. Ghany reported no disclosures related to his presentation.

BOSTON – Treatment of persons who inject drugs, updates in pangenotypic direct-acting antiviral therapy, the benefits of sustained virologic response, and preemptive therapy in donor-positive organ transplantation topped the list of notable hepatitis C–related abstracts this year at the annual meeting of the American Association for the Study of Liver Diseases.

That’s according to Marc Ghany, MD, of the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, who gave a hepatitis C debrief to attendees on the final day of the meeting. Here are some of the meeting highlights as summarized by Dr. Ghany in this well-attended last-day session.
 

Treatment of HCV in people who inject drugs

Emerging data suggest it is feasible to treat hepatitis C virus (HCV) infection in persons who inject drugs (PWIDs); however, overcoming adherence issues remains a challenge, Dr. Ghany told attendees.

According to one study presented at AASLD by Dhiman and coauthors (Abstract 0165), decentralized care of PWIDs using direct-acting antiviral (DAA) therapy was safe and effective, even in those with cirrhosis. Authors demonstrated an “impressive” rate of sustained virologic response at 12 weeks (SVR12) of 91% by a modified intention-to-treat analysis, Dr. Ghany said; however, treatment interruptions were frequent and reduced the overall SVR rate in the study to 78%.

Other studies at the meeting looked at strategies to improve DAA efficacy in this population of patients at high risk of nonadherence, including use of a digital medicine program (Abstract 1554) and a model of care in which an internist-addiction medicine specialist evaluated opiate-dependent patients for HCV infection in a hepatology clinic (Abstract 1589).

Reinfection remains a focus of research in PWIDs. At this meeting, Janjua and coauthors reported that DAA-treated PWIDs in British Columbia had a threefold higher rate of reinfection versus non-PWIDs; however, there were no detected reinfections among PWIDs who had received uninterrupted opioid agonist therapy. “These data suggested that opioid agonist therapy should be given before and after HCV treatment in persons who inject drugs to prevent the infection,” Dr. Ghany said in his presentation.
 

Updates on pangenotypic DAA therapy

Jonas and coauthors (Abstract 1551) reported on the safety and efficacy of glecaprevir/pibrentasvir for 8 weeks in children with chronic HCV infection enrolled in the ongoing phase 2/3 DORA study. The SVR12 was high, according to Dr. Ghany, at 96% overall, and consistent across age cohorts from 3 to less than 12 years of age.

“In the near future, we should have a safe and effective regimen (approved) for children 3 years or older,” Dr. Ghany said. “I think this will serve us well, as we try to eliminate HCV in children, who number up to 5 million cases worldwide.”

A short course of glecaprevir/pibrentasvir is approved for patients with HCV and compensated cirrhosis, and data to support that was presented last year at The Liver Meeting; however, data were not presented on patients with genotype 3, the most difficult-to-treat genotype, Dr. Ghany said. That gap was filled at this year’s meeting with a report (Abstract LP9) showing SVR12 rates of 98.4% per protocol and 95.2% in intention-to-treat analysis.
 

Relationship of SVR to clinical outcomes

While the impact of sustained virologic response (SVR) on all-cause mortality is clear in patients with HCV, less is known about the effect of SVR on liver-related mortality and other outcomes, Dr. Ghany said. In one study presented here (Abstract 0039), based on analysis of a Veterans Affairs database of patients with chronic HCV infection, SVR was linked to a significant reduction in liver-related mortality, while in another report (Abstract 0037), SVR was associated with significant reductions in acute coronary syndromes, end-stage renal disease, and ischemic stroke.

Similarly, a multinational, propensity score–matched analysis (Abstract 0040) demonstrated that SVR had an impact on 5-year overall survival and liver-related survival in patients with HCV-related hepatocellular carcinoma (HCC). “For HCC patients who are candidates for HCC therapy, consideration should also be given to treating these individuals (with DAA therapy) because of the impact on overall survival,” Dr. Ghany said.
 

Preemptive DAA therapy in organ transplantation

Exciting new data show that preemptive therapy, given for short durations, appears to either prevent or cure HCV infection after organ transplant, said Dr. Ghany.

A retrospective analysis by Wijarnpreecha and colleagues (Abstract 0003) showed that 12 or 24 weeks of direct-acting antiviral (DAA) therapy resulted in an SVR12 for 24 out of 24 HCV-seropositive to HCV-seronegative liver transplants, while Durand and colleagues (Abstract 0042) showed that just 4 weeks of pre- and postexposure DAA prophylaxis resulted in SVR12s for 9 out of 9 HCV donor-positive, recipient-negative kidney transplants. Finally, Feld and coauthors (Abstract 0038) showed that preemptive ezetimibe with DAA therapy for 7 days prevented or rapidly cured infection in an experience that included 16 HCV-positive organ donors and 25 HCV-negative recipients.

“While these data are very encouraging, I think we do need to have long-term follow-up of these patients for graft survival, as well as the effect on wait times,” Dr. Ghany said.

Dr. Ghany reported no disclosures related to his presentation.

BOSTON – Treatment of persons who inject drugs, updates in pangenotypic direct-acting antiviral therapy, the benefits of sustained virologic response, and preemptive therapy in donor-positive organ transplantation topped the list of notable hepatitis C–related abstracts this year at the annual meeting of the American Association for the Study of Liver Diseases.

That’s according to Marc Ghany, MD, of the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, who gave a hepatitis C debrief to attendees on the final day of the meeting. Here are some of the meeting highlights as summarized by Dr. Ghany in this well-attended last-day session.
 

Treatment of HCV in people who inject drugs

Emerging data suggest it is feasible to treat hepatitis C virus (HCV) infection in persons who inject drugs (PWIDs); however, overcoming adherence issues remains a challenge, Dr. Ghany told attendees.

According to one study presented at AASLD by Dhiman and coauthors (Abstract 0165), decentralized care of PWIDs using direct-acting antiviral (DAA) therapy was safe and effective, even in those with cirrhosis. Authors demonstrated an “impressive” rate of sustained virologic response at 12 weeks (SVR12) of 91% by a modified intention-to-treat analysis, Dr. Ghany said; however, treatment interruptions were frequent and reduced the overall SVR rate in the study to 78%.

Other studies at the meeting looked at strategies to improve DAA efficacy in this population of patients at high risk of nonadherence, including use of a digital medicine program (Abstract 1554) and a model of care in which an internist-addiction medicine specialist evaluated opiate-dependent patients for HCV infection in a hepatology clinic (Abstract 1589).

Reinfection remains a focus of research in PWIDs. At this meeting, Janjua and coauthors reported that DAA-treated PWIDs in British Columbia had a threefold higher rate of reinfection versus non-PWIDs; however, there were no detected reinfections among PWIDs who had received uninterrupted opioid agonist therapy. “These data suggested that opioid agonist therapy should be given before and after HCV treatment in persons who inject drugs to prevent the infection,” Dr. Ghany said in his presentation.
 

Updates on pangenotypic DAA therapy

Jonas and coauthors (Abstract 1551) reported on the safety and efficacy of glecaprevir/pibrentasvir for 8 weeks in children with chronic HCV infection enrolled in the ongoing phase 2/3 DORA study. The SVR12 was high, according to Dr. Ghany, at 96% overall, and consistent across age cohorts from 3 to less than 12 years of age.

“In the near future, we should have a safe and effective regimen (approved) for children 3 years or older,” Dr. Ghany said. “I think this will serve us well, as we try to eliminate HCV in children, who number up to 5 million cases worldwide.”

A short course of glecaprevir/pibrentasvir is approved for patients with HCV and compensated cirrhosis, and data to support that was presented last year at The Liver Meeting; however, data were not presented on patients with genotype 3, the most difficult-to-treat genotype, Dr. Ghany said. That gap was filled at this year’s meeting with a report (Abstract LP9) showing SVR12 rates of 98.4% per protocol and 95.2% in intention-to-treat analysis.
 

Relationship of SVR to clinical outcomes

While the impact of sustained virologic response (SVR) on all-cause mortality is clear in patients with HCV, less is known about the effect of SVR on liver-related mortality and other outcomes, Dr. Ghany said. In one study presented here (Abstract 0039), based on analysis of a Veterans Affairs database of patients with chronic HCV infection, SVR was linked to a significant reduction in liver-related mortality, while in another report (Abstract 0037), SVR was associated with significant reductions in acute coronary syndromes, end-stage renal disease, and ischemic stroke.

Similarly, a multinational, propensity score–matched analysis (Abstract 0040) demonstrated that SVR had an impact on 5-year overall survival and liver-related survival in patients with HCV-related hepatocellular carcinoma (HCC). “For HCC patients who are candidates for HCC therapy, consideration should also be given to treating these individuals (with DAA therapy) because of the impact on overall survival,” Dr. Ghany said.
 

Preemptive DAA therapy in organ transplantation

Exciting new data show that preemptive therapy, given for short durations, appears to either prevent or cure HCV infection after organ transplant, said Dr. Ghany.

A retrospective analysis by Wijarnpreecha and colleagues (Abstract 0003) showed that 12 or 24 weeks of direct-acting antiviral (DAA) therapy resulted in an SVR12 for 24 out of 24 HCV-seropositive to HCV-seronegative liver transplants, while Durand and colleagues (Abstract 0042) showed that just 4 weeks of pre- and postexposure DAA prophylaxis resulted in SVR12s for 9 out of 9 HCV donor-positive, recipient-negative kidney transplants. Finally, Feld and coauthors (Abstract 0038) showed that preemptive ezetimibe with DAA therapy for 7 days prevented or rapidly cured infection in an experience that included 16 HCV-positive organ donors and 25 HCV-negative recipients.

“While these data are very encouraging, I think we do need to have long-term follow-up of these patients for graft survival, as well as the effect on wait times,” Dr. Ghany said.

Dr. Ghany reported no disclosures related to his presentation.

Among children with atopic dermatitis, genetic variants associated with skin barrier dysfunction vary significantly by race and by their influence on disease persistence, according to authors of a cohort study.

In the study, which was based on data from a pediatric eczema registry, white children with atopic dermatitis (AD) were more than twice as likely as black children to have a filaggrin gene (FLG) loss-of-function (LoF) variant. The investigators remarked on “profound” differences by race in the study, which used a high-throughput sequencing method to identify FLG LoF variants, some of which were common in white children but not so frequently seen in black children.

Conversely, some variants common in black children were completely absent in the white children, according to the investigators, led by David J. Margolis, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia. The study was published in JAMA Dermatology.

These findings imply that any genetic tests developed for AD should be “inclusive,” they wrote, and shouldn’t simply rely on the most common variants associated with patients of European ancestry, namely p.R501*, c.2282del4[p.S761fs], p.S3247*, and p.R2447*.

“Relying on the classic 4 FLG LoF variants would result in approximately 8% of white children and 64% of black children with an FLG LoF variant being improperly classified,” Dr. Margolis and coinvestigators wrote.

Their comprehensive analysis of FLG LoF variants was based on a U.S. cohort of 741 children with mild to moderate AD in the Pediatric Eczema Elective Registry (PEER), enrolled from 2005 to 2017. The mean age of onset of AD among the children was almost 2 years. Using massively parallel sequencing, the investigators identified a total of 23 FLG LoF variants in 177 children, or 23.9% of the overall cohort.

White children had a higher frequency of FLG LoF variants, according to the investigators. The prevalence of variants was 31.5% in white and 15.3% in black participants, translating into an odds ratio of 2.44 for carrying any variant in a white versus black child (95% confidence interval, 1.76-3.39).

In previous studies, FLG LoF variants are seen in 25%-30% of people with AD who have European and Asian ancestry; by contrast, they are “uncommonly” exhibited in individuals of African ancestry, the investigators wrote.

Persistent AD was more likely among children with FLG LoF variants, with an odds ratio of 0.67 (95% CI, 0.56-0.80), according to Dr. Margolis and coauthors. However, the black children in this cohort had more persistent disease, compared with white children, regardless of whether they had FLG LoF variants or not.

Exon 3 FLG LoF are known to be the most common variants linked to skin barrier dysfunction, the investigators noted.

“However, all FLG LoF variants might not confer an increased risk of AD, and further, they may not all have the same effect on the persistence of AD over time,” they added in a discussion of their results.

The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The PEER cohort is funded by Valeant Pharmaceuticals. Dr. Margolis reported receiving research funding as the principal investigator via the trustees of the University of Pennsylvania, and receiving funding from the National Institutes of Health and Valeant; disclosures not related to the study included consulting activities primarily as a member of a data monitoring or scientific advisory boards for several pharmaceutical companies.

SOURCE: Margolis DJ et al. JAMA Dermatol. 2019 Jul 31. doi: 10.1011/jamadermatol.2019.1946.

Among children with atopic dermatitis, genetic variants associated with skin barrier dysfunction vary significantly by race and by their influence on disease persistence, according to authors of a cohort study.

In the study, which was based on data from a pediatric eczema registry, white children with atopic dermatitis (AD) were more than twice as likely as black children to have a filaggrin gene (FLG) loss-of-function (LoF) variant. The investigators remarked on “profound” differences by race in the study, which used a high-throughput sequencing method to identify FLG LoF variants, some of which were common in white children but not so frequently seen in black children.

Conversely, some variants common in black children were completely absent in the white children, according to the investigators, led by David J. Margolis, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia. The study was published in JAMA Dermatology.

These findings imply that any genetic tests developed for AD should be “inclusive,” they wrote, and shouldn’t simply rely on the most common variants associated with patients of European ancestry, namely p.R501*, c.2282del4[p.S761fs], p.S3247*, and p.R2447*.

“Relying on the classic 4 FLG LoF variants would result in approximately 8% of white children and 64% of black children with an FLG LoF variant being improperly classified,” Dr. Margolis and coinvestigators wrote.

Their comprehensive analysis of FLG LoF variants was based on a U.S. cohort of 741 children with mild to moderate AD in the Pediatric Eczema Elective Registry (PEER), enrolled from 2005 to 2017. The mean age of onset of AD among the children was almost 2 years. Using massively parallel sequencing, the investigators identified a total of 23 FLG LoF variants in 177 children, or 23.9% of the overall cohort.

White children had a higher frequency of FLG LoF variants, according to the investigators. The prevalence of variants was 31.5% in white and 15.3% in black participants, translating into an odds ratio of 2.44 for carrying any variant in a white versus black child (95% confidence interval, 1.76-3.39).

In previous studies, FLG LoF variants are seen in 25%-30% of people with AD who have European and Asian ancestry; by contrast, they are “uncommonly” exhibited in individuals of African ancestry, the investigators wrote.

Persistent AD was more likely among children with FLG LoF variants, with an odds ratio of 0.67 (95% CI, 0.56-0.80), according to Dr. Margolis and coauthors. However, the black children in this cohort had more persistent disease, compared with white children, regardless of whether they had FLG LoF variants or not.

Exon 3 FLG LoF are known to be the most common variants linked to skin barrier dysfunction, the investigators noted.

“However, all FLG LoF variants might not confer an increased risk of AD, and further, they may not all have the same effect on the persistence of AD over time,” they added in a discussion of their results.

The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The PEER cohort is funded by Valeant Pharmaceuticals. Dr. Margolis reported receiving research funding as the principal investigator via the trustees of the University of Pennsylvania, and receiving funding from the National Institutes of Health and Valeant; disclosures not related to the study included consulting activities primarily as a member of a data monitoring or scientific advisory boards for several pharmaceutical companies.

SOURCE: Margolis DJ et al. JAMA Dermatol. 2019 Jul 31. doi: 10.1011/jamadermatol.2019.1946.

Among children with atopic dermatitis, genetic variants associated with skin barrier dysfunction vary significantly by race and by their influence on disease persistence, according to authors of a cohort study.

In the study, which was based on data from a pediatric eczema registry, white children with atopic dermatitis (AD) were more than twice as likely as black children to have a filaggrin gene (FLG) loss-of-function (LoF) variant. The investigators remarked on “profound” differences by race in the study, which used a high-throughput sequencing method to identify FLG LoF variants, some of which were common in white children but not so frequently seen in black children.

Conversely, some variants common in black children were completely absent in the white children, according to the investigators, led by David J. Margolis, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia. The study was published in JAMA Dermatology.

These findings imply that any genetic tests developed for AD should be “inclusive,” they wrote, and shouldn’t simply rely on the most common variants associated with patients of European ancestry, namely p.R501*, c.2282del4[p.S761fs], p.S3247*, and p.R2447*.

“Relying on the classic 4 FLG LoF variants would result in approximately 8% of white children and 64% of black children with an FLG LoF variant being improperly classified,” Dr. Margolis and coinvestigators wrote.

Their comprehensive analysis of FLG LoF variants was based on a U.S. cohort of 741 children with mild to moderate AD in the Pediatric Eczema Elective Registry (PEER), enrolled from 2005 to 2017. The mean age of onset of AD among the children was almost 2 years. Using massively parallel sequencing, the investigators identified a total of 23 FLG LoF variants in 177 children, or 23.9% of the overall cohort.

White children had a higher frequency of FLG LoF variants, according to the investigators. The prevalence of variants was 31.5% in white and 15.3% in black participants, translating into an odds ratio of 2.44 for carrying any variant in a white versus black child (95% confidence interval, 1.76-3.39).

In previous studies, FLG LoF variants are seen in 25%-30% of people with AD who have European and Asian ancestry; by contrast, they are “uncommonly” exhibited in individuals of African ancestry, the investigators wrote.

Persistent AD was more likely among children with FLG LoF variants, with an odds ratio of 0.67 (95% CI, 0.56-0.80), according to Dr. Margolis and coauthors. However, the black children in this cohort had more persistent disease, compared with white children, regardless of whether they had FLG LoF variants or not.

Exon 3 FLG LoF are known to be the most common variants linked to skin barrier dysfunction, the investigators noted.

“However, all FLG LoF variants might not confer an increased risk of AD, and further, they may not all have the same effect on the persistence of AD over time,” they added in a discussion of their results.

The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The PEER cohort is funded by Valeant Pharmaceuticals. Dr. Margolis reported receiving research funding as the principal investigator via the trustees of the University of Pennsylvania, and receiving funding from the National Institutes of Health and Valeant; disclosures not related to the study included consulting activities primarily as a member of a data monitoring or scientific advisory boards for several pharmaceutical companies.

SOURCE: Margolis DJ et al. JAMA Dermatol. 2019 Jul 31. doi: 10.1011/jamadermatol.2019.1946.

BOSTON – For treatment of nonalcoholic fatty liver disease, cotadutide, licogliflozin, tropifexor, saroglitazar, and PF-05221304 are just a few of the drugs with promising data, Kathleen E. Corey, MD, MPH, said at the annual meeting of the American Association for the Study of Liver Diseases.

Andrew D. Bowser/MDedge News

By contrast, selonsertib and emricasan did not achieve their endpoints in studies described here at the meeting, “but we have a lot to learn from them,” said Dr. Corey, director of the Mass General Fatty Liver Clinic and assistant professor at Harvard Medical School, Boston.

“This is an exciting time,” Dr. Corey said in a special debriefing oral session held on the final day of the conference. “There are many novel mechanisms of action out there, as well as some known mechanisms of action, with a considerable amount of promise.”
 

Cotadutide (MEDI0382)

Narha and coauthors (Abstract 35) described the effects of cotadutide, a GLP-1/glucagon receptor dual agonist on biomarkers of nonalcoholic steatohepatitis (NASH) at 26 weeks in overweight or obese patients with type 2 diabetes mellitus. In the randomized, phase 2b study, cotadutide produced superior reductions versus liraglutide, the GLP-1 receptor agonist, in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and body weight, which investigators said supported prospective trials of the drug for a potential indication in NASH.

“The adverse events were fairly typical for what we see with the GLP-1s – GI side effects that usually over 8 weeks improve,” Dr. Corey told attendees at the debrief session.
 

Licogliflozin (LIK066)

Interim analysis of a 12-week, randomized, placebo-controlled, phase 2a study showed that this SGLT1/2 inhibitor produced “robust” decreases in ALT and improvements in markers of hepatic and metabolic health in patients with NASH, according to Zhang and coauthors (Abstract L07).

Some 67% of those who received licogliflozin had at least a 30% decrease in their liver fat, while decreases in weight and hemoglobin A_1c were also reported, according to Dr. Corey. “It was associated with diarrhea in about 97%, but this was considered mild, and certainly, we’re seeing good metabolic effects overall,” she said.
 

Tropifexor

Treatment for 12 weeks with this potent FXR agonist resulted in robust, dose-dependent reductions in hepatic fat and serum ALT in patients with fibrotic NASH, according to investigators in a phase 2 randomized, placebo-controlled trial known as FLIGHT-FXR (Abstract L04).

A total of 65% of patients achieved a 30% or greater reduction in liver fat, and decreases in weight and insulin resistance were reported. “Similar to other FXRs, they did have this concerning although potentially manageable increase in low-density lipoprotein (LDL)-cholesterol, and the adverse event of pruritis,” said Dr. Corey.
 

Saroglitazar

Gawrieh and coauthors presented results from EVIDENCES IV, a phase 2, double-blind, randomized, placebo-controlled study of saroglitazar, a novel dual peroxisome proliferator activated receptor (PPAR) alpha/gamma agonist, in patients with NAFLD or NASH (Abstract LO10).

The investigators found that 41% of patients achieved a 30% or greater relative reduction in liver fat, as well as reductions in hemoglobin A_1c and lipids, but the treatment was “weight neutral,” Dr. Corey said, adding that no serious adverse events were reported.
 

PF-05221304

This liver-targeted acetyl-CoA carboxylase inhibitor (ACCI) demonstrated robust reduction in liver fat and ALT in a 16-week phase 2a, dose-ranging study in adults with NAFLD, according to Amin and coinvestigators (Abstract 31).

There was a “dramatic” decrease in liver fat in this study, said Dr. Corey, with 90% of treated patients experiencing a 30% or greater decrease. Side effects included a “significant” increase in triglycerides, she added, as well as transient increases in ALT and AST.
 

Selonsertib and emricasan

One agent not meeting study endpoints was selonsertib, an apoptosis signal-regulating kinase 1 (ASK1) inhibitor. While safe and well tolerated, the drug was nevertheless not effective as monotherapy in phase 3 double-blind, placebo-controlled trials including patients with advanced fibrosis due to NASH, investigators said (Abstract 64). Currently, the agent is being evaluated in combination with firsocostat – an ACCI – in a phase 2 study called ATLAS, according to the authors.

Emricasan, an oral pan-caspase inhibitor that suppresses apoptosis, did not improve fibrosis or resolve NASH in a multicenter, double-blind, placebo-controlled randomized trial, and may have even worsened histology, according to Dr. Corey. Investigators said further evaluation of the mechanisms underlying findings could provide insights into the role of necro-apoptosis in NASH pathophysiology (Abstract 61).

Dr. Corey provided disclosures related to BMS, Novo Nordisk, Boehringer Ingelheim, and Gilead.

BOSTON – For treatment of nonalcoholic fatty liver disease, cotadutide, licogliflozin, tropifexor, saroglitazar, and PF-05221304 are just a few of the drugs with promising data, Kathleen E. Corey, MD, MPH, said at the annual meeting of the American Association for the Study of Liver Diseases.

Andrew D. Bowser/MDedge News

By contrast, selonsertib and emricasan did not achieve their endpoints in studies described here at the meeting, “but we have a lot to learn from them,” said Dr. Corey, director of the Mass General Fatty Liver Clinic and assistant professor at Harvard Medical School, Boston.

“This is an exciting time,” Dr. Corey said in a special debriefing oral session held on the final day of the conference. “There are many novel mechanisms of action out there, as well as some known mechanisms of action, with a considerable amount of promise.”
 

Cotadutide (MEDI0382)

Narha and coauthors (Abstract 35) described the effects of cotadutide, a GLP-1/glucagon receptor dual agonist on biomarkers of nonalcoholic steatohepatitis (NASH) at 26 weeks in overweight or obese patients with type 2 diabetes mellitus. In the randomized, phase 2b study, cotadutide produced superior reductions versus liraglutide, the GLP-1 receptor agonist, in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and body weight, which investigators said supported prospective trials of the drug for a potential indication in NASH.

“The adverse events were fairly typical for what we see with the GLP-1s – GI side effects that usually over 8 weeks improve,” Dr. Corey told attendees at the debrief session.
 

Licogliflozin (LIK066)

Interim analysis of a 12-week, randomized, placebo-controlled, phase 2a study showed that this SGLT1/2 inhibitor produced “robust” decreases in ALT and improvements in markers of hepatic and metabolic health in patients with NASH, according to Zhang and coauthors (Abstract L07).

Some 67% of those who received licogliflozin had at least a 30% decrease in their liver fat, while decreases in weight and hemoglobin A_1c were also reported, according to Dr. Corey. “It was associated with diarrhea in about 97%, but this was considered mild, and certainly, we’re seeing good metabolic effects overall,” she said.
 

Tropifexor

Treatment for 12 weeks with this potent FXR agonist resulted in robust, dose-dependent reductions in hepatic fat and serum ALT in patients with fibrotic NASH, according to investigators in a phase 2 randomized, placebo-controlled trial known as FLIGHT-FXR (Abstract L04).

A total of 65% of patients achieved a 30% or greater reduction in liver fat, and decreases in weight and insulin resistance were reported. “Similar to other FXRs, they did have this concerning although potentially manageable increase in low-density lipoprotein (LDL)-cholesterol, and the adverse event of pruritis,” said Dr. Corey.
 

Saroglitazar

Gawrieh and coauthors presented results from EVIDENCES IV, a phase 2, double-blind, randomized, placebo-controlled study of saroglitazar, a novel dual peroxisome proliferator activated receptor (PPAR) alpha/gamma agonist, in patients with NAFLD or NASH (Abstract LO10).

The investigators found that 41% of patients achieved a 30% or greater relative reduction in liver fat, as well as reductions in hemoglobin A_1c and lipids, but the treatment was “weight neutral,” Dr. Corey said, adding that no serious adverse events were reported.
 

PF-05221304

This liver-targeted acetyl-CoA carboxylase inhibitor (ACCI) demonstrated robust reduction in liver fat and ALT in a 16-week phase 2a, dose-ranging study in adults with NAFLD, according to Amin and coinvestigators (Abstract 31).

There was a “dramatic” decrease in liver fat in this study, said Dr. Corey, with 90% of treated patients experiencing a 30% or greater decrease. Side effects included a “significant” increase in triglycerides, she added, as well as transient increases in ALT and AST.
 

Selonsertib and emricasan

One agent not meeting study endpoints was selonsertib, an apoptosis signal-regulating kinase 1 (ASK1) inhibitor. While safe and well tolerated, the drug was nevertheless not effective as monotherapy in phase 3 double-blind, placebo-controlled trials including patients with advanced fibrosis due to NASH, investigators said (Abstract 64). Currently, the agent is being evaluated in combination with firsocostat – an ACCI – in a phase 2 study called ATLAS, according to the authors.

Emricasan, an oral pan-caspase inhibitor that suppresses apoptosis, did not improve fibrosis or resolve NASH in a multicenter, double-blind, placebo-controlled randomized trial, and may have even worsened histology, according to Dr. Corey. Investigators said further evaluation of the mechanisms underlying findings could provide insights into the role of necro-apoptosis in NASH pathophysiology (Abstract 61).

Dr. Corey provided disclosures related to BMS, Novo Nordisk, Boehringer Ingelheim, and Gilead.

BOSTON – For treatment of nonalcoholic fatty liver disease, cotadutide, licogliflozin, tropifexor, saroglitazar, and PF-05221304 are just a few of the drugs with promising data, Kathleen E. Corey, MD, MPH, said at the annual meeting of the American Association for the Study of Liver Diseases.

Andrew D. Bowser/MDedge News

By contrast, selonsertib and emricasan did not achieve their endpoints in studies described here at the meeting, “but we have a lot to learn from them,” said Dr. Corey, director of the Mass General Fatty Liver Clinic and assistant professor at Harvard Medical School, Boston.

“This is an exciting time,” Dr. Corey said in a special debriefing oral session held on the final day of the conference. “There are many novel mechanisms of action out there, as well as some known mechanisms of action, with a considerable amount of promise.”
 

Cotadutide (MEDI0382)

Narha and coauthors (Abstract 35) described the effects of cotadutide, a GLP-1/glucagon receptor dual agonist on biomarkers of nonalcoholic steatohepatitis (NASH) at 26 weeks in overweight or obese patients with type 2 diabetes mellitus. In the randomized, phase 2b study, cotadutide produced superior reductions versus liraglutide, the GLP-1 receptor agonist, in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and body weight, which investigators said supported prospective trials of the drug for a potential indication in NASH.

“The adverse events were fairly typical for what we see with the GLP-1s – GI side effects that usually over 8 weeks improve,” Dr. Corey told attendees at the debrief session.
 

Licogliflozin (LIK066)

Interim analysis of a 12-week, randomized, placebo-controlled, phase 2a study showed that this SGLT1/2 inhibitor produced “robust” decreases in ALT and improvements in markers of hepatic and metabolic health in patients with NASH, according to Zhang and coauthors (Abstract L07).

Some 67% of those who received licogliflozin had at least a 30% decrease in their liver fat, while decreases in weight and hemoglobin A_1c were also reported, according to Dr. Corey. “It was associated with diarrhea in about 97%, but this was considered mild, and certainly, we’re seeing good metabolic effects overall,” she said.
 

Tropifexor

Treatment for 12 weeks with this potent FXR agonist resulted in robust, dose-dependent reductions in hepatic fat and serum ALT in patients with fibrotic NASH, according to investigators in a phase 2 randomized, placebo-controlled trial known as FLIGHT-FXR (Abstract L04).

A total of 65% of patients achieved a 30% or greater reduction in liver fat, and decreases in weight and insulin resistance were reported. “Similar to other FXRs, they did have this concerning although potentially manageable increase in low-density lipoprotein (LDL)-cholesterol, and the adverse event of pruritis,” said Dr. Corey.
 

Saroglitazar

Gawrieh and coauthors presented results from EVIDENCES IV, a phase 2, double-blind, randomized, placebo-controlled study of saroglitazar, a novel dual peroxisome proliferator activated receptor (PPAR) alpha/gamma agonist, in patients with NAFLD or NASH (Abstract LO10).

The investigators found that 41% of patients achieved a 30% or greater relative reduction in liver fat, as well as reductions in hemoglobin A_1c and lipids, but the treatment was “weight neutral,” Dr. Corey said, adding that no serious adverse events were reported.
 

PF-05221304

This liver-targeted acetyl-CoA carboxylase inhibitor (ACCI) demonstrated robust reduction in liver fat and ALT in a 16-week phase 2a, dose-ranging study in adults with NAFLD, according to Amin and coinvestigators (Abstract 31).

There was a “dramatic” decrease in liver fat in this study, said Dr. Corey, with 90% of treated patients experiencing a 30% or greater decrease. Side effects included a “significant” increase in triglycerides, she added, as well as transient increases in ALT and AST.
 

Selonsertib and emricasan

One agent not meeting study endpoints was selonsertib, an apoptosis signal-regulating kinase 1 (ASK1) inhibitor. While safe and well tolerated, the drug was nevertheless not effective as monotherapy in phase 3 double-blind, placebo-controlled trials including patients with advanced fibrosis due to NASH, investigators said (Abstract 64). Currently, the agent is being evaluated in combination with firsocostat – an ACCI – in a phase 2 study called ATLAS, according to the authors.

Emricasan, an oral pan-caspase inhibitor that suppresses apoptosis, did not improve fibrosis or resolve NASH in a multicenter, double-blind, placebo-controlled randomized trial, and may have even worsened histology, according to Dr. Corey. Investigators said further evaluation of the mechanisms underlying findings could provide insights into the role of necro-apoptosis in NASH pathophysiology (Abstract 61).

Dr. Corey provided disclosures related to BMS, Novo Nordisk, Boehringer Ingelheim, and Gilead.

BOSTON – While about one-third of overweight patients with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) slimmed down after a weight-loss intervention, about 20% gained weight back within the next few years, according to results from a large, long-term observational cohort study.

Effectively, that meant about one-quarter of overweight subjects enrolled in the TARGET-NASH study were able to lose weight and keep it off, said investigator Miguel H. Malespin, MD, a transplant hepatologist at Tampa General Hospital.

These findings illustrate how challenging lifestyle interventions can be for patients with NAFLD and NASH, and have clinical implications for identifying those individuals who are more or less likely to respond to weight-loss intervention as an initial treatment, Dr. Malespin said.

“I think we as providers need to better identify what are the barriers for weight loss for these patients, and try to use data, such as this data from TARGET-NASH, to help our clinical judgment and to learn strategies to be able to help these patients optimize their weight loss,” he added in an interview.

With no approved pharmacologic treatments for NAFLD and NASH, weight reduction remains one of the mainstays of treatment, Dr. Malespin said.

However, there are few studies evaluating structured programs designed to achieve such weight loss, and the long-term sustainability of this approach remains in question, according to Dr. Malespin, who presented findings of TARGET-NASH at the annual meeting of the American Association for the Study of Liver Diseases.

To date, more than 4,500 patients have been enrolled in TARGET-NASH at 59 U.S. centers. The present analysis, which Dr. Malespin described in an oral abstract presentation, included 2,037 patients with a body mass index of at least 25 kg/m² and no decompensated cirrhosis, bariatric surgery, weight-loss medication use, or cancer diagnoses.

In sum, 34% of patients had 5% or more weight loss over about 3 years of follow-up, while about 10% had a 10% or greater weight loss, Dr. Malespin reported.

It took patients about 18 months, on average, to achieve 5% or greater weight loss. Those who achieved weight loss tended to be older, according to the investigator, and were about 1.5 times as likely to be obese class II or III, as opposed to just being overweight.

Patients were significantly more likely to lose weight, Dr. Malespin and coauthors found, if they had cirrhosis or comorbid medical conditions such as diabetes, osteoarthritis, or cardiovascular disease.

“All these factors essentially imply that these patients are hopefully being seen by multiple providers,” Dr. Malespin said, “so hopefully they’re getting the message [on the need for lifestyle modifications] from multiple different providers, and this is contributing to why we’re seeing some of this weight loss.”

However, weight loss did not persist in all patients, with 20.2% regaining weight back up to baseline or greater, according to the report. The median time to weight regain was 24-31 months, depending on initial weight class.

TARGET-NASH, sponsored by TARGET PharmaSolutions, is a 5-year longitudinal observational study with an enrollment goal of 15,000 patients with NAFLD or NASH and an estimated study completion date of 2021, according to a ClinicalTrials.gov listing.

Dr. Malespin reported disclosures with Gilead (speaker board), Intercept (speaker board, advisory committee), and TARGET PharmaSolutions (research grant paid to institution).

SOURCE: Malespin MH et al. The Liver Meeting 2019, Abstract 240.

BOSTON – While about one-third of overweight patients with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) slimmed down after a weight-loss intervention, about 20% gained weight back within the next few years, according to results from a large, long-term observational cohort study.

Effectively, that meant about one-quarter of overweight subjects enrolled in the TARGET-NASH study were able to lose weight and keep it off, said investigator Miguel H. Malespin, MD, a transplant hepatologist at Tampa General Hospital.

These findings illustrate how challenging lifestyle interventions can be for patients with NAFLD and NASH, and have clinical implications for identifying those individuals who are more or less likely to respond to weight-loss intervention as an initial treatment, Dr. Malespin said.

“I think we as providers need to better identify what are the barriers for weight loss for these patients, and try to use data, such as this data from TARGET-NASH, to help our clinical judgment and to learn strategies to be able to help these patients optimize their weight loss,” he added in an interview.

With no approved pharmacologic treatments for NAFLD and NASH, weight reduction remains one of the mainstays of treatment, Dr. Malespin said.

However, there are few studies evaluating structured programs designed to achieve such weight loss, and the long-term sustainability of this approach remains in question, according to Dr. Malespin, who presented findings of TARGET-NASH at the annual meeting of the American Association for the Study of Liver Diseases.

To date, more than 4,500 patients have been enrolled in TARGET-NASH at 59 U.S. centers. The present analysis, which Dr. Malespin described in an oral abstract presentation, included 2,037 patients with a body mass index of at least 25 kg/m² and no decompensated cirrhosis, bariatric surgery, weight-loss medication use, or cancer diagnoses.

In sum, 34% of patients had 5% or more weight loss over about 3 years of follow-up, while about 10% had a 10% or greater weight loss, Dr. Malespin reported.

It took patients about 18 months, on average, to achieve 5% or greater weight loss. Those who achieved weight loss tended to be older, according to the investigator, and were about 1.5 times as likely to be obese class II or III, as opposed to just being overweight.

Patients were significantly more likely to lose weight, Dr. Malespin and coauthors found, if they had cirrhosis or comorbid medical conditions such as diabetes, osteoarthritis, or cardiovascular disease.

“All these factors essentially imply that these patients are hopefully being seen by multiple providers,” Dr. Malespin said, “so hopefully they’re getting the message [on the need for lifestyle modifications] from multiple different providers, and this is contributing to why we’re seeing some of this weight loss.”

However, weight loss did not persist in all patients, with 20.2% regaining weight back up to baseline or greater, according to the report. The median time to weight regain was 24-31 months, depending on initial weight class.

TARGET-NASH, sponsored by TARGET PharmaSolutions, is a 5-year longitudinal observational study with an enrollment goal of 15,000 patients with NAFLD or NASH and an estimated study completion date of 2021, according to a ClinicalTrials.gov listing.

Dr. Malespin reported disclosures with Gilead (speaker board), Intercept (speaker board, advisory committee), and TARGET PharmaSolutions (research grant paid to institution).

SOURCE: Malespin MH et al. The Liver Meeting 2019, Abstract 240.

BOSTON – While about one-third of overweight patients with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) slimmed down after a weight-loss intervention, about 20% gained weight back within the next few years, according to results from a large, long-term observational cohort study.

Effectively, that meant about one-quarter of overweight subjects enrolled in the TARGET-NASH study were able to lose weight and keep it off, said investigator Miguel H. Malespin, MD, a transplant hepatologist at Tampa General Hospital.

These findings illustrate how challenging lifestyle interventions can be for patients with NAFLD and NASH, and have clinical implications for identifying those individuals who are more or less likely to respond to weight-loss intervention as an initial treatment, Dr. Malespin said.

“I think we as providers need to better identify what are the barriers for weight loss for these patients, and try to use data, such as this data from TARGET-NASH, to help our clinical judgment and to learn strategies to be able to help these patients optimize their weight loss,” he added in an interview.

With no approved pharmacologic treatments for NAFLD and NASH, weight reduction remains one of the mainstays of treatment, Dr. Malespin said.

However, there are few studies evaluating structured programs designed to achieve such weight loss, and the long-term sustainability of this approach remains in question, according to Dr. Malespin, who presented findings of TARGET-NASH at the annual meeting of the American Association for the Study of Liver Diseases.

To date, more than 4,500 patients have been enrolled in TARGET-NASH at 59 U.S. centers. The present analysis, which Dr. Malespin described in an oral abstract presentation, included 2,037 patients with a body mass index of at least 25 kg/m² and no decompensated cirrhosis, bariatric surgery, weight-loss medication use, or cancer diagnoses.

In sum, 34% of patients had 5% or more weight loss over about 3 years of follow-up, while about 10% had a 10% or greater weight loss, Dr. Malespin reported.

It took patients about 18 months, on average, to achieve 5% or greater weight loss. Those who achieved weight loss tended to be older, according to the investigator, and were about 1.5 times as likely to be obese class II or III, as opposed to just being overweight.

Patients were significantly more likely to lose weight, Dr. Malespin and coauthors found, if they had cirrhosis or comorbid medical conditions such as diabetes, osteoarthritis, or cardiovascular disease.

“All these factors essentially imply that these patients are hopefully being seen by multiple providers,” Dr. Malespin said, “so hopefully they’re getting the message [on the need for lifestyle modifications] from multiple different providers, and this is contributing to why we’re seeing some of this weight loss.”

However, weight loss did not persist in all patients, with 20.2% regaining weight back up to baseline or greater, according to the report. The median time to weight regain was 24-31 months, depending on initial weight class.

TARGET-NASH, sponsored by TARGET PharmaSolutions, is a 5-year longitudinal observational study with an enrollment goal of 15,000 patients with NAFLD or NASH and an estimated study completion date of 2021, according to a ClinicalTrials.gov listing.

Dr. Malespin reported disclosures with Gilead (speaker board), Intercept (speaker board, advisory committee), and TARGET PharmaSolutions (research grant paid to institution).

SOURCE: Malespin MH et al. The Liver Meeting 2019, Abstract 240.

“Do you vape?” may be one of the most important questions health care can providers can ask patients who present with respiratory symptoms this winter.

mauro grigollo/Thinkstock

Vaping-related lung injuries cause symptoms such as fever, cough, headache, and fatigue, making it challenging to differentiate them from influenza or respiratory infections, according to the Centers for Disease Control and Prevention.

Accordingly, providers need to ask patients with respiratory, gastrointestinal, or constitutional symptoms about their use of e-cigarette or vaping products, according to one several new CDC recommendations that appear in the Morbidity and Mortality Weekly Review.

“E-cigarette or vaping product use–associated lung injury (EVALI) remains a diagnosis of exclusion because, at present, no specific test or marker exists for its diagnosis, and evaluation should be guided by clinical judgment,” the CDC report reads.

As of Nov. 13, there have been 2,172 cases of EVALI reported to CDC, of which 42 (1.9%) have been fatal. Most of the patients with EVALI have been white (79%), male (68%), and under the age of 35 years (77%), according to CDC data.

Although vitamin E acetate was recently implicated as a potential cause of EVALI, the agency said evidence is “not sufficient” at this point in their investigation to rule out other chemicals of potential concern.

“Many different substances and product sources are still under investigation, and it might be that there is more than one cause of this outbreak,” CDC said.

Further recommendations

Beyond asking about vape use, providers should evaluate suspected EVALI with pulse oximetry and chest imaging, and should consider outpatient management for patients who are clinically stable, according to the recommendations.

The agency said influenza testing should be “strongly considered,” especially during influenza season, given that EVALI is a diagnosis of exclusion and that it may co-occur with other respiratory illnesses. Antimicrobials (including antivirals) should be given as warranted, they added.

Corticosteroids may be helpful in treating EVALI, but may worsen respiratory infections typically seen in outpatients, and so should be prescribed with caution in the outpatient setting, the CDC recommended.

Behavioral counseling, addiction treatment services, and Food and Drug Administration–approved cessation medications are recommended to help patients quit vaping or e-cigarette products, CDC said.

Health care providers should emphasize the importance of an annual flu shot for all patients 6 months of age or older, including those who use e-cigarette or vaping products, according to the agency.

“It is not known whether patients with EVALI are at higher risk for severe complications of influenza or other respiratory infections,” the report reads.

Blame it on vitamin E? THC? Other?

The report details how, as previously reported, vitamin E acetate was detected in bronchoalveolar lavage fluid samples from 29 patients with EVALI. Although other chemicals could contribute to EVALI, that finding provided “direct evidence” of vitamin E acetate at the primary site of injury, according to CDC.

Most patients with EVALI, 83%, have reported using a tetrahydrocannabinol (THC)-containing e-cigarette or vaping product, according to CDC, while 61% reported using a nicotine-containing product.

Based on that, CDC recommended that people avoid using THC-containing products. However, the agency cautioned that the specific cause or causes of EVALI remain to be elucidated.

“The only way for persons to assure that they are not at risk is to consider refraining from use of all e-cigarette, or vaping, products while this investigation continues,” CDC said in the report.

The need for this additional clinical guidance was assessed in anticipation of the seasonal uptick in influenza and other respiratory infections, according to the CDC, which said the recommendations were based in part on individual clinical perspectives from nine national experts who participated in a previously published clinical guidance on managing patients with EVALI.

SOURCES: Jatlaoui TC et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 19. doi. 10.15585/mmwr.mm6846e2; Chatham-Stephens K et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 19. doi. 10.15585/mmwr.mm6846e1.

“Do you vape?” may be one of the most important questions health care can providers can ask patients who present with respiratory symptoms this winter.

mauro grigollo/Thinkstock

Vaping-related lung injuries cause symptoms such as fever, cough, headache, and fatigue, making it challenging to differentiate them from influenza or respiratory infections, according to the Centers for Disease Control and Prevention.

Accordingly, providers need to ask patients with respiratory, gastrointestinal, or constitutional symptoms about their use of e-cigarette or vaping products, according to one several new CDC recommendations that appear in the Morbidity and Mortality Weekly Review.

“E-cigarette or vaping product use–associated lung injury (EVALI) remains a diagnosis of exclusion because, at present, no specific test or marker exists for its diagnosis, and evaluation should be guided by clinical judgment,” the CDC report reads.

As of Nov. 13, there have been 2,172 cases of EVALI reported to CDC, of which 42 (1.9%) have been fatal. Most of the patients with EVALI have been white (79%), male (68%), and under the age of 35 years (77%), according to CDC data.

Although vitamin E acetate was recently implicated as a potential cause of EVALI, the agency said evidence is “not sufficient” at this point in their investigation to rule out other chemicals of potential concern.

“Many different substances and product sources are still under investigation, and it might be that there is more than one cause of this outbreak,” CDC said.

Further recommendations

Beyond asking about vape use, providers should evaluate suspected EVALI with pulse oximetry and chest imaging, and should consider outpatient management for patients who are clinically stable, according to the recommendations.

The agency said influenza testing should be “strongly considered,” especially during influenza season, given that EVALI is a diagnosis of exclusion and that it may co-occur with other respiratory illnesses. Antimicrobials (including antivirals) should be given as warranted, they added.

Corticosteroids may be helpful in treating EVALI, but may worsen respiratory infections typically seen in outpatients, and so should be prescribed with caution in the outpatient setting, the CDC recommended.

Behavioral counseling, addiction treatment services, and Food and Drug Administration–approved cessation medications are recommended to help patients quit vaping or e-cigarette products, CDC said.

Health care providers should emphasize the importance of an annual flu shot for all patients 6 months of age or older, including those who use e-cigarette or vaping products, according to the agency.

“It is not known whether patients with EVALI are at higher risk for severe complications of influenza or other respiratory infections,” the report reads.

Blame it on vitamin E? THC? Other?

The report details how, as previously reported, vitamin E acetate was detected in bronchoalveolar lavage fluid samples from 29 patients with EVALI. Although other chemicals could contribute to EVALI, that finding provided “direct evidence” of vitamin E acetate at the primary site of injury, according to CDC.

Most patients with EVALI, 83%, have reported using a tetrahydrocannabinol (THC)-containing e-cigarette or vaping product, according to CDC, while 61% reported using a nicotine-containing product.

Based on that, CDC recommended that people avoid using THC-containing products. However, the agency cautioned that the specific cause or causes of EVALI remain to be elucidated.

“The only way for persons to assure that they are not at risk is to consider refraining from use of all e-cigarette, or vaping, products while this investigation continues,” CDC said in the report.

The need for this additional clinical guidance was assessed in anticipation of the seasonal uptick in influenza and other respiratory infections, according to the CDC, which said the recommendations were based in part on individual clinical perspectives from nine national experts who participated in a previously published clinical guidance on managing patients with EVALI.

SOURCES: Jatlaoui TC et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 19. doi. 10.15585/mmwr.mm6846e2; Chatham-Stephens K et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 19. doi. 10.15585/mmwr.mm6846e1.

“Do you vape?” may be one of the most important questions health care can providers can ask patients who present with respiratory symptoms this winter.

mauro grigollo/Thinkstock

Vaping-related lung injuries cause symptoms such as fever, cough, headache, and fatigue, making it challenging to differentiate them from influenza or respiratory infections, according to the Centers for Disease Control and Prevention.

Accordingly, providers need to ask patients with respiratory, gastrointestinal, or constitutional symptoms about their use of e-cigarette or vaping products, according to one several new CDC recommendations that appear in the Morbidity and Mortality Weekly Review.

“E-cigarette or vaping product use–associated lung injury (EVALI) remains a diagnosis of exclusion because, at present, no specific test or marker exists for its diagnosis, and evaluation should be guided by clinical judgment,” the CDC report reads.

As of Nov. 13, there have been 2,172 cases of EVALI reported to CDC, of which 42 (1.9%) have been fatal. Most of the patients with EVALI have been white (79%), male (68%), and under the age of 35 years (77%), according to CDC data.

Although vitamin E acetate was recently implicated as a potential cause of EVALI, the agency said evidence is “not sufficient” at this point in their investigation to rule out other chemicals of potential concern.

“Many different substances and product sources are still under investigation, and it might be that there is more than one cause of this outbreak,” CDC said.

Further recommendations

Beyond asking about vape use, providers should evaluate suspected EVALI with pulse oximetry and chest imaging, and should consider outpatient management for patients who are clinically stable, according to the recommendations.

The agency said influenza testing should be “strongly considered,” especially during influenza season, given that EVALI is a diagnosis of exclusion and that it may co-occur with other respiratory illnesses. Antimicrobials (including antivirals) should be given as warranted, they added.

Corticosteroids may be helpful in treating EVALI, but may worsen respiratory infections typically seen in outpatients, and so should be prescribed with caution in the outpatient setting, the CDC recommended.

Behavioral counseling, addiction treatment services, and Food and Drug Administration–approved cessation medications are recommended to help patients quit vaping or e-cigarette products, CDC said.

Health care providers should emphasize the importance of an annual flu shot for all patients 6 months of age or older, including those who use e-cigarette or vaping products, according to the agency.

“It is not known whether patients with EVALI are at higher risk for severe complications of influenza or other respiratory infections,” the report reads.

Blame it on vitamin E? THC? Other?

The report details how, as previously reported, vitamin E acetate was detected in bronchoalveolar lavage fluid samples from 29 patients with EVALI. Although other chemicals could contribute to EVALI, that finding provided “direct evidence” of vitamin E acetate at the primary site of injury, according to CDC.

Most patients with EVALI, 83%, have reported using a tetrahydrocannabinol (THC)-containing e-cigarette or vaping product, according to CDC, while 61% reported using a nicotine-containing product.

Based on that, CDC recommended that people avoid using THC-containing products. However, the agency cautioned that the specific cause or causes of EVALI remain to be elucidated.

“The only way for persons to assure that they are not at risk is to consider refraining from use of all e-cigarette, or vaping, products while this investigation continues,” CDC said in the report.

The need for this additional clinical guidance was assessed in anticipation of the seasonal uptick in influenza and other respiratory infections, according to the CDC, which said the recommendations were based in part on individual clinical perspectives from nine national experts who participated in a previously published clinical guidance on managing patients with EVALI.

SOURCES: Jatlaoui TC et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 19. doi. 10.15585/mmwr.mm6846e2; Chatham-Stephens K et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 19. doi. 10.15585/mmwr.mm6846e1.

BOSTON – Some of the most notable abstracts presented here at the annual meeting of the American Association for the Study of Liver Diseases dealt with key topics including the natural history of hepatitis B virus, novel treatment approaches, and prevention, according to Marc Ghany, MD.

Andrew Bowser/MDedge News

During a special hepatitis debriefing session held on the last day of the conference, Dr. Ghany reviewed his key selections in hepatitis B virus (HBV) research, including the following:
 

Natural history

Steatohepatitis may worsen HBV-related liver injury, according to results of an analysis of liver biopsies from adult patients enrolled in a North American cohort study (Abstract 162). Investigators found that steatohepatitis was associated with a 1.6-fold increased risk of advanced fibrosis.

“For all patients with hepatitis B, I think it’s important to screen and manage metabolic abnormalities to prevent liver disease progression,” said Dr. Ghany, who is with the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md.

Risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B was evaluated in two notable studies, Dr. Ghany said, including one that found no difference in risk of HCC development among white patients who received long-term entecavir versus those who received long-term tenofovir (Abstract 454). This stands in contrast to a previous and controversial finding, according to investigators, that HCC incidence was lower in Asian patients treated with tenofovir versus those treated with entecavir.

In the other study, investigators found that dual-antiplatelet therapy (DAPT) was associated with a lower risk of HCC versus aspirin monotherapy in patients with chronic hepatitis B (Abstract 934). Antiplatelet therapy was associated with a near 20% reduction in HCC risk, while DAPT as compared with aspirin monotherapy was linked to a near 30% reduction. “These are very provocative findings,” Dr. Ghany said. “Of course they need to be confirmed, but if so, may open new avenues of HCC chemoprevention.”
 

Novel therapies

Several new and promising drugs are undergoing clinical trials, including JNJ-64530440 (JNJ-0440), a novel class N capsid assembly modulator. In phase 1a data presented here at The Liver Meeting, the treatment was safe, well tolerated, and resulted in potent inhibition of viral replication (Abstract 0089). “We await further studies on its effect on functional cure,” Dr. Ghany told attendees.

Another treatment to watch is GSK3389404 (GSK404), a liver-targeted antisense oligonucleotide; in a phase 2 placebo-controlled study in patients with chronic hepatitis B on stable nucleos(t)ide therapy, this treatment had acceptable safety and produced dose-dependent declines in hepatitis B surface antigen (HBsAg), according to investigators (Abstract 0695). Dr. Ghany said this constitutes “proof of principle” that antisense oligonucleotides can decrease HBsAg levels.

In a phase 2 randomized, placebo-controlled study in virally suppressed adults with chronic hepatitis B, the toll-like receptor 8 (TLR8) agonist GS-9688 was safe and well tolerated, and resulted in dose-dependent pharmacodynamic changes, with 5% of patients experiencing a 1 log₁₀ IU/mL or greater decline in HBsAg levels or an HBsAg loss by week 24 (Abstract 0697). This is a “promising approach” that merits further study, according to Dr. Ghany.
 

Prevention: Vaccination and screening

A trivalent HBV vaccine is superior to monovalent vaccine, according to results from the double-blind, randomized, controlled, phase 3 PROTECT study presented here at the meeting (Abstract LP13). Known as Sci-B-Vac, the mammalian cell-derived trivalent vaccine had higher response rates versus the recombinant monovalent vaccine Engerix-B in difficult-to-vaccinate populations, according to Dr. Ghany.

A separate report based on a national health insurance cohort study in Korea demonstrated that regular follow-up, that is to say, every 3-6 months, significantly reduced liver cancer–related mortality (Abstract 0159). Patients compliant with screening in the study not only had a 44% reduction in risk of death from HCC, but also were more likely to receive curative treatments (23.1% versus 15.1%). “Notwithstanding the limitations or cohort studies, I think these data reinforce the need to screen patients with chronic hepatitis B,” Dr. Ghany said.

He provided no disclosures in his presentation.

BOSTON – Some of the most notable abstracts presented here at the annual meeting of the American Association for the Study of Liver Diseases dealt with key topics including the natural history of hepatitis B virus, novel treatment approaches, and prevention, according to Marc Ghany, MD.

Andrew Bowser/MDedge News

During a special hepatitis debriefing session held on the last day of the conference, Dr. Ghany reviewed his key selections in hepatitis B virus (HBV) research, including the following:
 

Natural history

Steatohepatitis may worsen HBV-related liver injury, according to results of an analysis of liver biopsies from adult patients enrolled in a North American cohort study (Abstract 162). Investigators found that steatohepatitis was associated with a 1.6-fold increased risk of advanced fibrosis.

“For all patients with hepatitis B, I think it’s important to screen and manage metabolic abnormalities to prevent liver disease progression,” said Dr. Ghany, who is with the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md.

Risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B was evaluated in two notable studies, Dr. Ghany said, including one that found no difference in risk of HCC development among white patients who received long-term entecavir versus those who received long-term tenofovir (Abstract 454). This stands in contrast to a previous and controversial finding, according to investigators, that HCC incidence was lower in Asian patients treated with tenofovir versus those treated with entecavir.

In the other study, investigators found that dual-antiplatelet therapy (DAPT) was associated with a lower risk of HCC versus aspirin monotherapy in patients with chronic hepatitis B (Abstract 934). Antiplatelet therapy was associated with a near 20% reduction in HCC risk, while DAPT as compared with aspirin monotherapy was linked to a near 30% reduction. “These are very provocative findings,” Dr. Ghany said. “Of course they need to be confirmed, but if so, may open new avenues of HCC chemoprevention.”
 

Novel therapies

Several new and promising drugs are undergoing clinical trials, including JNJ-64530440 (JNJ-0440), a novel class N capsid assembly modulator. In phase 1a data presented here at The Liver Meeting, the treatment was safe, well tolerated, and resulted in potent inhibition of viral replication (Abstract 0089). “We await further studies on its effect on functional cure,” Dr. Ghany told attendees.

Another treatment to watch is GSK3389404 (GSK404), a liver-targeted antisense oligonucleotide; in a phase 2 placebo-controlled study in patients with chronic hepatitis B on stable nucleos(t)ide therapy, this treatment had acceptable safety and produced dose-dependent declines in hepatitis B surface antigen (HBsAg), according to investigators (Abstract 0695). Dr. Ghany said this constitutes “proof of principle” that antisense oligonucleotides can decrease HBsAg levels.

In a phase 2 randomized, placebo-controlled study in virally suppressed adults with chronic hepatitis B, the toll-like receptor 8 (TLR8) agonist GS-9688 was safe and well tolerated, and resulted in dose-dependent pharmacodynamic changes, with 5% of patients experiencing a 1 log₁₀ IU/mL or greater decline in HBsAg levels or an HBsAg loss by week 24 (Abstract 0697). This is a “promising approach” that merits further study, according to Dr. Ghany.
 

Prevention: Vaccination and screening

A trivalent HBV vaccine is superior to monovalent vaccine, according to results from the double-blind, randomized, controlled, phase 3 PROTECT study presented here at the meeting (Abstract LP13). Known as Sci-B-Vac, the mammalian cell-derived trivalent vaccine had higher response rates versus the recombinant monovalent vaccine Engerix-B in difficult-to-vaccinate populations, according to Dr. Ghany.

A separate report based on a national health insurance cohort study in Korea demonstrated that regular follow-up, that is to say, every 3-6 months, significantly reduced liver cancer–related mortality (Abstract 0159). Patients compliant with screening in the study not only had a 44% reduction in risk of death from HCC, but also were more likely to receive curative treatments (23.1% versus 15.1%). “Notwithstanding the limitations or cohort studies, I think these data reinforce the need to screen patients with chronic hepatitis B,” Dr. Ghany said.

He provided no disclosures in his presentation.

BOSTON – Some of the most notable abstracts presented here at the annual meeting of the American Association for the Study of Liver Diseases dealt with key topics including the natural history of hepatitis B virus, novel treatment approaches, and prevention, according to Marc Ghany, MD.

Andrew Bowser/MDedge News

During a special hepatitis debriefing session held on the last day of the conference, Dr. Ghany reviewed his key selections in hepatitis B virus (HBV) research, including the following:
 

Natural history

Steatohepatitis may worsen HBV-related liver injury, according to results of an analysis of liver biopsies from adult patients enrolled in a North American cohort study (Abstract 162). Investigators found that steatohepatitis was associated with a 1.6-fold increased risk of advanced fibrosis.

“For all patients with hepatitis B, I think it’s important to screen and manage metabolic abnormalities to prevent liver disease progression,” said Dr. Ghany, who is with the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md.

Risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B was evaluated in two notable studies, Dr. Ghany said, including one that found no difference in risk of HCC development among white patients who received long-term entecavir versus those who received long-term tenofovir (Abstract 454). This stands in contrast to a previous and controversial finding, according to investigators, that HCC incidence was lower in Asian patients treated with tenofovir versus those treated with entecavir.

In the other study, investigators found that dual-antiplatelet therapy (DAPT) was associated with a lower risk of HCC versus aspirin monotherapy in patients with chronic hepatitis B (Abstract 934). Antiplatelet therapy was associated with a near 20% reduction in HCC risk, while DAPT as compared with aspirin monotherapy was linked to a near 30% reduction. “These are very provocative findings,” Dr. Ghany said. “Of course they need to be confirmed, but if so, may open new avenues of HCC chemoprevention.”
 

Novel therapies

Several new and promising drugs are undergoing clinical trials, including JNJ-64530440 (JNJ-0440), a novel class N capsid assembly modulator. In phase 1a data presented here at The Liver Meeting, the treatment was safe, well tolerated, and resulted in potent inhibition of viral replication (Abstract 0089). “We await further studies on its effect on functional cure,” Dr. Ghany told attendees.

Another treatment to watch is GSK3389404 (GSK404), a liver-targeted antisense oligonucleotide; in a phase 2 placebo-controlled study in patients with chronic hepatitis B on stable nucleos(t)ide therapy, this treatment had acceptable safety and produced dose-dependent declines in hepatitis B surface antigen (HBsAg), according to investigators (Abstract 0695). Dr. Ghany said this constitutes “proof of principle” that antisense oligonucleotides can decrease HBsAg levels.

In a phase 2 randomized, placebo-controlled study in virally suppressed adults with chronic hepatitis B, the toll-like receptor 8 (TLR8) agonist GS-9688 was safe and well tolerated, and resulted in dose-dependent pharmacodynamic changes, with 5% of patients experiencing a 1 log₁₀ IU/mL or greater decline in HBsAg levels or an HBsAg loss by week 24 (Abstract 0697). This is a “promising approach” that merits further study, according to Dr. Ghany.
 

Prevention: Vaccination and screening

A trivalent HBV vaccine is superior to monovalent vaccine, according to results from the double-blind, randomized, controlled, phase 3 PROTECT study presented here at the meeting (Abstract LP13). Known as Sci-B-Vac, the mammalian cell-derived trivalent vaccine had higher response rates versus the recombinant monovalent vaccine Engerix-B in difficult-to-vaccinate populations, according to Dr. Ghany.

A separate report based on a national health insurance cohort study in Korea demonstrated that regular follow-up, that is to say, every 3-6 months, significantly reduced liver cancer–related mortality (Abstract 0159). Patients compliant with screening in the study not only had a 44% reduction in risk of death from HCC, but also were more likely to receive curative treatments (23.1% versus 15.1%). “Notwithstanding the limitations or cohort studies, I think these data reinforce the need to screen patients with chronic hepatitis B,” Dr. Ghany said.

He provided no disclosures in his presentation.

Secondary surgical cytoreduction was feasible but did not extend overall survival among women with platinum-sensitive, recurrent ovarian cancer in a prospective, randomized, phase 3 clinical trial, investigators report.

Women who received platinum-based chemotherapy plus surgery had a median overall survival of about 51 months, compared with 64.7 months for women who received platinum-based chemotherapy and no surgery, according to the results of the Gynecologic Oncology Group (GOG)-0213 study, a multicenter, open-label, randomized, phase 3 trial.

These findings “call into question” the merits of surgical cytoreduction, said the authors, led by Robert L. Coleman, MD, of the department of gynecologic oncology and reproductive medicine at the University of Texas M.D. Anderson Cancer Center, Houston.

Specifically, the shorter overall survival in the surgery group vs. no-surgery group emphasizes the “importance of formally assessing the value of the procedure in clinical care,” said Dr. Coleman and coauthors in the report on GOG-0213. The study was published in the New England Journal of Medicine.

Clinical practice guidelines from the National Comprehensive Cancer Network currently cite secondary cytoreduction as an option for treatment of patients who experience a treatment-free interval of at least 6 months after a complete remission achieved on prior chemotherapy, the GOG-0213 investigators wrote.

Beyond GOG-0213, there are several other randomized trials underway in this setting, including DESKTOP III, a multicenter study comparing the efficacy of chemotherapy alone to chemotherapy plus additional tumor debulking surgery in women with recurrent platinum-sensitive ovarian cancer.

“Maturity of the DESKTOP III trial and other trials will shape the debate on the value or merit of surgery in this patient population,” wrote Dr. Coleman and colleagues.

The GOG-0213 study, conducted in 67 centers, 65 of which were in the United States, had both a chemotherapy objective and a surgical objective in patients with platinum-sensitive recurrent ovarian cancer, investigators said.

Results of the chemotherapy objective, published in 2017 in Lancet Oncology, indicated that bevacizumab added to standard chemotherapy, followed by maintenance bevacizumab until progression, improved median overall survival.

The more recently reported results focused on 485 women of who 245 were randomized to receive chemotherapy alone. While 240 were randomized to receive cytoreduction prior to chemotherapy, 15 declined surgery, leaving 225 eligible patients (94%).

The adjusted hazard ratio for death was 1.29 (95% confidence interval, 0.97-1.72; P = 0.08) for surgery, compared with no surgery, which translated into median overall survival times of 50.6 months in the surgery arm and 64.7 months in the no-surgery arm, Dr. Coleman and coauthors reported.

However, 30-day morbidity and mortality were low, at 9% (20 patients) and 0.4% (1 patient), and just 4% of cases (8 patients) were aborted, they added.

Quality of life significantly declined right after secondary cytoreduction, although after recovery no significant differences were found between groups, according to the investigators.

Taken together, those findings “did not indicate that surgery plus chemotherapy was superior to chemotherapy alone,” investigators concluded.

However, several factors in GOG-0213, including longer-than-expected survival times and substantial platinum sensitivity among women in the trial, could have diluted an independent surgical effect, they said.

Dr. Coleman reported disclosures related to several pharmaceutical companies, including Agenus, AstraZeneca, Clovis, GamaMabs, Genmab, Janssen, Medivation, Merck, Regeneron, Roche/Genentech, OncoQuest, and Tesaro.

SOURCE: Coleman RL et al. N Engl J Med. 2019;381:1929-39.

Secondary surgical cytoreduction was feasible but did not extend overall survival among women with platinum-sensitive, recurrent ovarian cancer in a prospective, randomized, phase 3 clinical trial, investigators report.

Women who received platinum-based chemotherapy plus surgery had a median overall survival of about 51 months, compared with 64.7 months for women who received platinum-based chemotherapy and no surgery, according to the results of the Gynecologic Oncology Group (GOG)-0213 study, a multicenter, open-label, randomized, phase 3 trial.

These findings “call into question” the merits of surgical cytoreduction, said the authors, led by Robert L. Coleman, MD, of the department of gynecologic oncology and reproductive medicine at the University of Texas M.D. Anderson Cancer Center, Houston.

Specifically, the shorter overall survival in the surgery group vs. no-surgery group emphasizes the “importance of formally assessing the value of the procedure in clinical care,” said Dr. Coleman and coauthors in the report on GOG-0213. The study was published in the New England Journal of Medicine.

Clinical practice guidelines from the National Comprehensive Cancer Network currently cite secondary cytoreduction as an option for treatment of patients who experience a treatment-free interval of at least 6 months after a complete remission achieved on prior chemotherapy, the GOG-0213 investigators wrote.

Beyond GOG-0213, there are several other randomized trials underway in this setting, including DESKTOP III, a multicenter study comparing the efficacy of chemotherapy alone to chemotherapy plus additional tumor debulking surgery in women with recurrent platinum-sensitive ovarian cancer.

“Maturity of the DESKTOP III trial and other trials will shape the debate on the value or merit of surgery in this patient population,” wrote Dr. Coleman and colleagues.

The GOG-0213 study, conducted in 67 centers, 65 of which were in the United States, had both a chemotherapy objective and a surgical objective in patients with platinum-sensitive recurrent ovarian cancer, investigators said.

Results of the chemotherapy objective, published in 2017 in Lancet Oncology, indicated that bevacizumab added to standard chemotherapy, followed by maintenance bevacizumab until progression, improved median overall survival.

The more recently reported results focused on 485 women of who 245 were randomized to receive chemotherapy alone. While 240 were randomized to receive cytoreduction prior to chemotherapy, 15 declined surgery, leaving 225 eligible patients (94%).

The adjusted hazard ratio for death was 1.29 (95% confidence interval, 0.97-1.72; P = 0.08) for surgery, compared with no surgery, which translated into median overall survival times of 50.6 months in the surgery arm and 64.7 months in the no-surgery arm, Dr. Coleman and coauthors reported.

However, 30-day morbidity and mortality were low, at 9% (20 patients) and 0.4% (1 patient), and just 4% of cases (8 patients) were aborted, they added.

Quality of life significantly declined right after secondary cytoreduction, although after recovery no significant differences were found between groups, according to the investigators.

Taken together, those findings “did not indicate that surgery plus chemotherapy was superior to chemotherapy alone,” investigators concluded.

However, several factors in GOG-0213, including longer-than-expected survival times and substantial platinum sensitivity among women in the trial, could have diluted an independent surgical effect, they said.

Dr. Coleman reported disclosures related to several pharmaceutical companies, including Agenus, AstraZeneca, Clovis, GamaMabs, Genmab, Janssen, Medivation, Merck, Regeneron, Roche/Genentech, OncoQuest, and Tesaro.

SOURCE: Coleman RL et al. N Engl J Med. 2019;381:1929-39.

Secondary surgical cytoreduction was feasible but did not extend overall survival among women with platinum-sensitive, recurrent ovarian cancer in a prospective, randomized, phase 3 clinical trial, investigators report.

Women who received platinum-based chemotherapy plus surgery had a median overall survival of about 51 months, compared with 64.7 months for women who received platinum-based chemotherapy and no surgery, according to the results of the Gynecologic Oncology Group (GOG)-0213 study, a multicenter, open-label, randomized, phase 3 trial.

These findings “call into question” the merits of surgical cytoreduction, said the authors, led by Robert L. Coleman, MD, of the department of gynecologic oncology and reproductive medicine at the University of Texas M.D. Anderson Cancer Center, Houston.

Specifically, the shorter overall survival in the surgery group vs. no-surgery group emphasizes the “importance of formally assessing the value of the procedure in clinical care,” said Dr. Coleman and coauthors in the report on GOG-0213. The study was published in the New England Journal of Medicine.

Clinical practice guidelines from the National Comprehensive Cancer Network currently cite secondary cytoreduction as an option for treatment of patients who experience a treatment-free interval of at least 6 months after a complete remission achieved on prior chemotherapy, the GOG-0213 investigators wrote.

Beyond GOG-0213, there are several other randomized trials underway in this setting, including DESKTOP III, a multicenter study comparing the efficacy of chemotherapy alone to chemotherapy plus additional tumor debulking surgery in women with recurrent platinum-sensitive ovarian cancer.

“Maturity of the DESKTOP III trial and other trials will shape the debate on the value or merit of surgery in this patient population,” wrote Dr. Coleman and colleagues.

The GOG-0213 study, conducted in 67 centers, 65 of which were in the United States, had both a chemotherapy objective and a surgical objective in patients with platinum-sensitive recurrent ovarian cancer, investigators said.

Results of the chemotherapy objective, published in 2017 in Lancet Oncology, indicated that bevacizumab added to standard chemotherapy, followed by maintenance bevacizumab until progression, improved median overall survival.

The more recently reported results focused on 485 women of who 245 were randomized to receive chemotherapy alone. While 240 were randomized to receive cytoreduction prior to chemotherapy, 15 declined surgery, leaving 225 eligible patients (94%).

The adjusted hazard ratio for death was 1.29 (95% confidence interval, 0.97-1.72; P = 0.08) for surgery, compared with no surgery, which translated into median overall survival times of 50.6 months in the surgery arm and 64.7 months in the no-surgery arm, Dr. Coleman and coauthors reported.

However, 30-day morbidity and mortality were low, at 9% (20 patients) and 0.4% (1 patient), and just 4% of cases (8 patients) were aborted, they added.

Quality of life significantly declined right after secondary cytoreduction, although after recovery no significant differences were found between groups, according to the investigators.

Taken together, those findings “did not indicate that surgery plus chemotherapy was superior to chemotherapy alone,” investigators concluded.

However, several factors in GOG-0213, including longer-than-expected survival times and substantial platinum sensitivity among women in the trial, could have diluted an independent surgical effect, they said.

Dr. Coleman reported disclosures related to several pharmaceutical companies, including Agenus, AstraZeneca, Clovis, GamaMabs, Genmab, Janssen, Medivation, Merck, Regeneron, Roche/Genentech, OncoQuest, and Tesaro.

SOURCE: Coleman RL et al. N Engl J Med. 2019;381:1929-39.

BOSTON – Bezafibrate was superior to placebo for ameliorating pruritus in patients with chronic cholestatic liver diseases, investigators reported at the annual meeting of the American Association for the Study of Liver Diseases.

Improvements in itch were reported by four times as many patients treated with the peroxisome proliferator-activated receptor (PPAR) agonist, compared with those treated with placebo, according to results of the FITCH (Fibrates for cholestatic ITCH) trial.

That finding from FITCH is very encouraging for patients with this “vexing” clinical issue, which can be highly distressing and is a common feature of cholestatic liver diseases, said Michael R. Charlton, MBBS, FRCP, director of the Transplant Institute and hepatology chief at the University of Chicago.

“It’s generally a misery-making condition,” Dr. Charlton said in a podium discussion of the FITCH study results at the Liver Meeting 2019. “I had a patient tell me that they felt like the subject of Edvard Munch’s ‘Scream’ painting.”

As of this meeting, bezafibrate should be considered superior to placebo for treatment of pruritus in cholangiopathies and should be “considered as first-line treatment” for pruritus in primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), added Dr. Charlton, who was not involved in the study.

Investigators in FITCH recruited a total of 74 patients – all enrolled in the Netherlands or Spain – with cholestasis-induced pruritus who reported itch with an intensity of least 5 out of 10 on a visual analogue scale (VAS). Of the 70 patients who completed the trial, 44 had PSC, 24 had PBC, and 2 had secondary sclerosing cholangitis. Patients were randomly allocated to receive bezafibrate 400 mg once daily or placebo for 21 days.

The hypothesis was that PPAR agonist treatment would relieve itch by alleviating hepatobiliary inflammation and reducing formation of a biliary itch factor, according to the investigators, led by Elsemieke de Vries, MD, of the department of gastroenterology and hepatology, Amsterdam University Medical Centers.

“Guideline-approved pharmacological strategies show limited efficacy and can provoke serious side effects,” Dr. de Vries and coauthors said in the published abstract on the study.

The primary study endpoint, a 50% reduction in pruritus VAS score, was achieved in 45% of patients in the bezafibrate treatment arm (17 of 38 patients) versus just 11% in the placebo arm (4 of 36 patients; P = .003), according to updated results presented at the meeting.

The mean VAS score, comparable at baseline, was significantly lower in the bezafibrate group vs. the placebo group at day 21 (P < .001), the results showed.

Authors of the FITCH study reported disclosures related to Intercept Pharmaceuticals, Gilead, Takeda, Tillotts, Pliant, and Dr. Falk GmbH.

SOURCE: de Vries E et al. The Liver Meeting 2019. Abstract 13.

BOSTON – Bezafibrate was superior to placebo for ameliorating pruritus in patients with chronic cholestatic liver diseases, investigators reported at the annual meeting of the American Association for the Study of Liver Diseases.

Improvements in itch were reported by four times as many patients treated with the peroxisome proliferator-activated receptor (PPAR) agonist, compared with those treated with placebo, according to results of the FITCH (Fibrates for cholestatic ITCH) trial.

That finding from FITCH is very encouraging for patients with this “vexing” clinical issue, which can be highly distressing and is a common feature of cholestatic liver diseases, said Michael R. Charlton, MBBS, FRCP, director of the Transplant Institute and hepatology chief at the University of Chicago.

“It’s generally a misery-making condition,” Dr. Charlton said in a podium discussion of the FITCH study results at the Liver Meeting 2019. “I had a patient tell me that they felt like the subject of Edvard Munch’s ‘Scream’ painting.”

As of this meeting, bezafibrate should be considered superior to placebo for treatment of pruritus in cholangiopathies and should be “considered as first-line treatment” for pruritus in primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), added Dr. Charlton, who was not involved in the study.

Investigators in FITCH recruited a total of 74 patients – all enrolled in the Netherlands or Spain – with cholestasis-induced pruritus who reported itch with an intensity of least 5 out of 10 on a visual analogue scale (VAS). Of the 70 patients who completed the trial, 44 had PSC, 24 had PBC, and 2 had secondary sclerosing cholangitis. Patients were randomly allocated to receive bezafibrate 400 mg once daily or placebo for 21 days.

The hypothesis was that PPAR agonist treatment would relieve itch by alleviating hepatobiliary inflammation and reducing formation of a biliary itch factor, according to the investigators, led by Elsemieke de Vries, MD, of the department of gastroenterology and hepatology, Amsterdam University Medical Centers.

“Guideline-approved pharmacological strategies show limited efficacy and can provoke serious side effects,” Dr. de Vries and coauthors said in the published abstract on the study.

The primary study endpoint, a 50% reduction in pruritus VAS score, was achieved in 45% of patients in the bezafibrate treatment arm (17 of 38 patients) versus just 11% in the placebo arm (4 of 36 patients; P = .003), according to updated results presented at the meeting.

The mean VAS score, comparable at baseline, was significantly lower in the bezafibrate group vs. the placebo group at day 21 (P < .001), the results showed.

Authors of the FITCH study reported disclosures related to Intercept Pharmaceuticals, Gilead, Takeda, Tillotts, Pliant, and Dr. Falk GmbH.

SOURCE: de Vries E et al. The Liver Meeting 2019. Abstract 13.

BOSTON – Bezafibrate was superior to placebo for ameliorating pruritus in patients with chronic cholestatic liver diseases, investigators reported at the annual meeting of the American Association for the Study of Liver Diseases.

Improvements in itch were reported by four times as many patients treated with the peroxisome proliferator-activated receptor (PPAR) agonist, compared with those treated with placebo, according to results of the FITCH (Fibrates for cholestatic ITCH) trial.

That finding from FITCH is very encouraging for patients with this “vexing” clinical issue, which can be highly distressing and is a common feature of cholestatic liver diseases, said Michael R. Charlton, MBBS, FRCP, director of the Transplant Institute and hepatology chief at the University of Chicago.

“It’s generally a misery-making condition,” Dr. Charlton said in a podium discussion of the FITCH study results at the Liver Meeting 2019. “I had a patient tell me that they felt like the subject of Edvard Munch’s ‘Scream’ painting.”

As of this meeting, bezafibrate should be considered superior to placebo for treatment of pruritus in cholangiopathies and should be “considered as first-line treatment” for pruritus in primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), added Dr. Charlton, who was not involved in the study.

Investigators in FITCH recruited a total of 74 patients – all enrolled in the Netherlands or Spain – with cholestasis-induced pruritus who reported itch with an intensity of least 5 out of 10 on a visual analogue scale (VAS). Of the 70 patients who completed the trial, 44 had PSC, 24 had PBC, and 2 had secondary sclerosing cholangitis. Patients were randomly allocated to receive bezafibrate 400 mg once daily or placebo for 21 days.

The hypothesis was that PPAR agonist treatment would relieve itch by alleviating hepatobiliary inflammation and reducing formation of a biliary itch factor, according to the investigators, led by Elsemieke de Vries, MD, of the department of gastroenterology and hepatology, Amsterdam University Medical Centers.

“Guideline-approved pharmacological strategies show limited efficacy and can provoke serious side effects,” Dr. de Vries and coauthors said in the published abstract on the study.

The primary study endpoint, a 50% reduction in pruritus VAS score, was achieved in 45% of patients in the bezafibrate treatment arm (17 of 38 patients) versus just 11% in the placebo arm (4 of 36 patients; P = .003), according to updated results presented at the meeting.

The mean VAS score, comparable at baseline, was significantly lower in the bezafibrate group vs. the placebo group at day 21 (P < .001), the results showed.

Authors of the FITCH study reported disclosures related to Intercept Pharmaceuticals, Gilead, Takeda, Tillotts, Pliant, and Dr. Falk GmbH.

SOURCE: de Vries E et al. The Liver Meeting 2019. Abstract 13.

BOSTON – The combination of nivolumab and ipilimumab provided a “robust” clinical benefit and had manageable hepatic adverse events in a phase 2 study of sorafenib-treated patients with advanced hepatocellular carcinoma (HCC), an investigator said at the annual meeting of the American Association for the Study of Liver Diseases.

Response rates for the combination treatment exceeded 30% in CheckMate 040, with median overall survival approaching 23 months in one arm of this randomized trial, said Bruno Sangro, MD, PhD, of Clinica Universidad de Navarra, Pamplona, Spain.

The combination had a manageable safety profile with no new safety signals, and most immune-mediated adverse events resolved, including hepatic events, Dr. Sango said in an oral abstract session.

“The favorable benefit/risk profile observed we believe warrants further investigation in patients with HCC,” Dr. Sangro said in his presentation to attendees, adding that a phase 3 study of the combination is already ongoing.

On Nov. 11, 2019, Bristol-Myers Squibb announced its application for nivolumab plus ipilimumab for previously treated advanced HCC had been accepted for priority review by the Food and Drug Administration, which had furthermore granted breakthrough therapy designation for that potential indication.

In September 2017, the FDA approved nivolumab as monotherapy for patients with HCC previously treated with sorafenib. That action was based on results from CheckMate 040 showing on overall response rate of 14% and a median overall survival of 15 months, Dr. Sangro said.

The combination of the programmed death–1 inhibitor nivolumab and the CTLA-4 inhibitor ipilimumab, which has shown durable responses in other tumor types, may promote synergistic immune activity in HCC through their distinct but complementary mechanisms, according to the investigator.

The first report on the combination of nivolumab plus ipilimumab in CheckMate 040, reported earlier this year at the annual meeting of the American Society of Clinical Oncology, indicated that the combination produced responses that were robust and durable.

Dr. Sangro reported data on 148 patients with advanced HCC previously treated with sorafenib randomized to one of three different dosing regimens with nivolumab plus ipilimumab.

Response rates ranged from 31% to 32% in the three arms, while one particular dosing regimen given every 3 weeks for four cycles had a median overall survival of 22.8 months.

“Just to give a perspective, let me remind you that patients receiving placebo post sorafenib in a number of phase 3 trials have very consistently shown median overall survivals of around 8 months,” Dr. Sangro told attendees.

Hepatic treatment-related adverse events of any grade reported within 30 days of the last dose were seen in 39% of patients in that arm, Dr. Sangro said.

Hepatic events thought to be immune mediated were typically managed with a short course of high-dose corticosteroids, according to Dr. Sangro, who said no patients rechallenged with treatment experienced a recurrence of the event.

Most of the hepatic adverse events occurred early, with a median time to onset of 5.6-8.1 weeks, he said, and most resolved at a median of 6.1-7.9 weeks.

In the ongoing phase 3 CheckMate 9DW study, patients with advanced HCC who are naive to systemic therapy are being randomized to the combination of nivolumab plus ipilimumab, or to the investigators’ choice of either sorafenib or lenvatinib, with a primary endpoint of overall survival, Dr. Sangro said.

The study was supported by Bristol-Myers Squibb and ONO Pharmaceutical. Dr. Sangro reported disclosures related to Adaptimmune, AstraZeneca, Bayer, Bristol-Myers Squibb, BTG, Merck, Onxeo, Sirtex Medical, Terumo, H3 Biomedicine, Ipsen, Lilly, Exelixis, Roche, and Ipsen.

SOURCE: Sangro B et al. The Liver Meeting 2019, Abstract 200.

BOSTON – The combination of nivolumab and ipilimumab provided a “robust” clinical benefit and had manageable hepatic adverse events in a phase 2 study of sorafenib-treated patients with advanced hepatocellular carcinoma (HCC), an investigator said at the annual meeting of the American Association for the Study of Liver Diseases.

Response rates for the combination treatment exceeded 30% in CheckMate 040, with median overall survival approaching 23 months in one arm of this randomized trial, said Bruno Sangro, MD, PhD, of Clinica Universidad de Navarra, Pamplona, Spain.

The combination had a manageable safety profile with no new safety signals, and most immune-mediated adverse events resolved, including hepatic events, Dr. Sango said in an oral abstract session.

“The favorable benefit/risk profile observed we believe warrants further investigation in patients with HCC,” Dr. Sangro said in his presentation to attendees, adding that a phase 3 study of the combination is already ongoing.

On Nov. 11, 2019, Bristol-Myers Squibb announced its application for nivolumab plus ipilimumab for previously treated advanced HCC had been accepted for priority review by the Food and Drug Administration, which had furthermore granted breakthrough therapy designation for that potential indication.

In September 2017, the FDA approved nivolumab as monotherapy for patients with HCC previously treated with sorafenib. That action was based on results from CheckMate 040 showing on overall response rate of 14% and a median overall survival of 15 months, Dr. Sangro said.

The combination of the programmed death–1 inhibitor nivolumab and the CTLA-4 inhibitor ipilimumab, which has shown durable responses in other tumor types, may promote synergistic immune activity in HCC through their distinct but complementary mechanisms, according to the investigator.

The first report on the combination of nivolumab plus ipilimumab in CheckMate 040, reported earlier this year at the annual meeting of the American Society of Clinical Oncology, indicated that the combination produced responses that were robust and durable.

Dr. Sangro reported data on 148 patients with advanced HCC previously treated with sorafenib randomized to one of three different dosing regimens with nivolumab plus ipilimumab.

Response rates ranged from 31% to 32% in the three arms, while one particular dosing regimen given every 3 weeks for four cycles had a median overall survival of 22.8 months.

“Just to give a perspective, let me remind you that patients receiving placebo post sorafenib in a number of phase 3 trials have very consistently shown median overall survivals of around 8 months,” Dr. Sangro told attendees.

Hepatic treatment-related adverse events of any grade reported within 30 days of the last dose were seen in 39% of patients in that arm, Dr. Sangro said.

Hepatic events thought to be immune mediated were typically managed with a short course of high-dose corticosteroids, according to Dr. Sangro, who said no patients rechallenged with treatment experienced a recurrence of the event.

Most of the hepatic adverse events occurred early, with a median time to onset of 5.6-8.1 weeks, he said, and most resolved at a median of 6.1-7.9 weeks.

In the ongoing phase 3 CheckMate 9DW study, patients with advanced HCC who are naive to systemic therapy are being randomized to the combination of nivolumab plus ipilimumab, or to the investigators’ choice of either sorafenib or lenvatinib, with a primary endpoint of overall survival, Dr. Sangro said.

The study was supported by Bristol-Myers Squibb and ONO Pharmaceutical. Dr. Sangro reported disclosures related to Adaptimmune, AstraZeneca, Bayer, Bristol-Myers Squibb, BTG, Merck, Onxeo, Sirtex Medical, Terumo, H3 Biomedicine, Ipsen, Lilly, Exelixis, Roche, and Ipsen.

SOURCE: Sangro B et al. The Liver Meeting 2019, Abstract 200.

BOSTON – The combination of nivolumab and ipilimumab provided a “robust” clinical benefit and had manageable hepatic adverse events in a phase 2 study of sorafenib-treated patients with advanced hepatocellular carcinoma (HCC), an investigator said at the annual meeting of the American Association for the Study of Liver Diseases.

Response rates for the combination treatment exceeded 30% in CheckMate 040, with median overall survival approaching 23 months in one arm of this randomized trial, said Bruno Sangro, MD, PhD, of Clinica Universidad de Navarra, Pamplona, Spain.

The combination had a manageable safety profile with no new safety signals, and most immune-mediated adverse events resolved, including hepatic events, Dr. Sango said in an oral abstract session.

“The favorable benefit/risk profile observed we believe warrants further investigation in patients with HCC,” Dr. Sangro said in his presentation to attendees, adding that a phase 3 study of the combination is already ongoing.

On Nov. 11, 2019, Bristol-Myers Squibb announced its application for nivolumab plus ipilimumab for previously treated advanced HCC had been accepted for priority review by the Food and Drug Administration, which had furthermore granted breakthrough therapy designation for that potential indication.

In September 2017, the FDA approved nivolumab as monotherapy for patients with HCC previously treated with sorafenib. That action was based on results from CheckMate 040 showing on overall response rate of 14% and a median overall survival of 15 months, Dr. Sangro said.

The combination of the programmed death–1 inhibitor nivolumab and the CTLA-4 inhibitor ipilimumab, which has shown durable responses in other tumor types, may promote synergistic immune activity in HCC through their distinct but complementary mechanisms, according to the investigator.

The first report on the combination of nivolumab plus ipilimumab in CheckMate 040, reported earlier this year at the annual meeting of the American Society of Clinical Oncology, indicated that the combination produced responses that were robust and durable.

Dr. Sangro reported data on 148 patients with advanced HCC previously treated with sorafenib randomized to one of three different dosing regimens with nivolumab plus ipilimumab.

Response rates ranged from 31% to 32% in the three arms, while one particular dosing regimen given every 3 weeks for four cycles had a median overall survival of 22.8 months.

“Just to give a perspective, let me remind you that patients receiving placebo post sorafenib in a number of phase 3 trials have very consistently shown median overall survivals of around 8 months,” Dr. Sangro told attendees.

Hepatic treatment-related adverse events of any grade reported within 30 days of the last dose were seen in 39% of patients in that arm, Dr. Sangro said.

Hepatic events thought to be immune mediated were typically managed with a short course of high-dose corticosteroids, according to Dr. Sangro, who said no patients rechallenged with treatment experienced a recurrence of the event.

Most of the hepatic adverse events occurred early, with a median time to onset of 5.6-8.1 weeks, he said, and most resolved at a median of 6.1-7.9 weeks.

In the ongoing phase 3 CheckMate 9DW study, patients with advanced HCC who are naive to systemic therapy are being randomized to the combination of nivolumab plus ipilimumab, or to the investigators’ choice of either sorafenib or lenvatinib, with a primary endpoint of overall survival, Dr. Sangro said.

The study was supported by Bristol-Myers Squibb and ONO Pharmaceutical. Dr. Sangro reported disclosures related to Adaptimmune, AstraZeneca, Bayer, Bristol-Myers Squibb, BTG, Merck, Onxeo, Sirtex Medical, Terumo, H3 Biomedicine, Ipsen, Lilly, Exelixis, Roche, and Ipsen.

SOURCE: Sangro B et al. The Liver Meeting 2019, Abstract 200.

BOSTON – A machine-learning model based on standard clinical and laboratory values is able to predict nonalcoholic steatohepatitis (NASH) with a sensitivity of 72%-81%, an investigator reported at the annual meeting of the American Association for the Study of Liver Diseases.

The tool, dubbed NASHmap, could serve as an initial screening tool to reveal more potential undiagnosed patients with NASH, according to Jörn M. Schattenberg, MD, with the metabolic liver research program in the department of medicine at University Medical Centre Mainz (Germany).

While not intended to replace current scoring systems, NASHmap potentially could be applied as a clinical decision support tool within electronic medical record systems, allowing greater numbers of patients with suspected NASH to be evaluated and referred to specialists for further testing, according to Dr. Schattenberg.

“To me, this is an at-risk population,” Dr. Schattenberg said in an interview. “There’s a lot of talk of increasing numbers of end-stage liver disease, and these are the cases that are waiting to happen. I think if we identify them, we can manage them better.”

“I’m not saying they should all get drugs – I’m saying they have to be informed about their condition because they may not have a clue they have liver disease,” he continued.

The machine-learning approach described here by Dr. Schattenberg included an exploratory analysis based on 704 patients with NASH or non-NASH nonalcoholic fatty liver disease (NAFLD) in the NAFLD Adult Database from the National Institute of Diabetes, Digestive, and Kidney Diseases.

The best-performing model they identified included 14 variables. Ranked by contribution to predictive power, those variables included hemoglobin A_1c, aspartate aminotransferase, alanine aminotransferase, total protein, AST/ALT ratio, body mass index, triglycerides, height, platelets, white blood cells, hematocrit, albumin, hypertension, and sex.

That 14-variable model had good performance when tested on the Optum Humedica electronic medical record database, according to Dr. Schattenberg and colleagues.

In the analysis for final evaluation, including 1,016 patients with histologically confirmed NASH, the area under the curve was 0.76, they reported.

A simplified, five-variable model including just hemoglobin A_1c, AST, ALT, total protein, and AST/ALT ratio also had good performance, with an area under the curve of 0.74, they said in their report.

Dr. Schattenberg provided disclosures related to AbbVie, Novartis, MSD, Pfizer, Boehringer Ingelheim, BMS, Intercept Pharmaceuticals, Genfit, Gilead, and Echosens. Several study coauthors reported employment with Novartis and stock ownership.

BOSTON – A machine-learning model based on standard clinical and laboratory values is able to predict nonalcoholic steatohepatitis (NASH) with a sensitivity of 72%-81%, an investigator reported at the annual meeting of the American Association for the Study of Liver Diseases.

The tool, dubbed NASHmap, could serve as an initial screening tool to reveal more potential undiagnosed patients with NASH, according to Jörn M. Schattenberg, MD, with the metabolic liver research program in the department of medicine at University Medical Centre Mainz (Germany).

While not intended to replace current scoring systems, NASHmap potentially could be applied as a clinical decision support tool within electronic medical record systems, allowing greater numbers of patients with suspected NASH to be evaluated and referred to specialists for further testing, according to Dr. Schattenberg.

“To me, this is an at-risk population,” Dr. Schattenberg said in an interview. “There’s a lot of talk of increasing numbers of end-stage liver disease, and these are the cases that are waiting to happen. I think if we identify them, we can manage them better.”

“I’m not saying they should all get drugs – I’m saying they have to be informed about their condition because they may not have a clue they have liver disease,” he continued.

The machine-learning approach described here by Dr. Schattenberg included an exploratory analysis based on 704 patients with NASH or non-NASH nonalcoholic fatty liver disease (NAFLD) in the NAFLD Adult Database from the National Institute of Diabetes, Digestive, and Kidney Diseases.

The best-performing model they identified included 14 variables. Ranked by contribution to predictive power, those variables included hemoglobin A_1c, aspartate aminotransferase, alanine aminotransferase, total protein, AST/ALT ratio, body mass index, triglycerides, height, platelets, white blood cells, hematocrit, albumin, hypertension, and sex.

That 14-variable model had good performance when tested on the Optum Humedica electronic medical record database, according to Dr. Schattenberg and colleagues.

In the analysis for final evaluation, including 1,016 patients with histologically confirmed NASH, the area under the curve was 0.76, they reported.

A simplified, five-variable model including just hemoglobin A_1c, AST, ALT, total protein, and AST/ALT ratio also had good performance, with an area under the curve of 0.74, they said in their report.

Dr. Schattenberg provided disclosures related to AbbVie, Novartis, MSD, Pfizer, Boehringer Ingelheim, BMS, Intercept Pharmaceuticals, Genfit, Gilead, and Echosens. Several study coauthors reported employment with Novartis and stock ownership.

BOSTON – A machine-learning model based on standard clinical and laboratory values is able to predict nonalcoholic steatohepatitis (NASH) with a sensitivity of 72%-81%, an investigator reported at the annual meeting of the American Association for the Study of Liver Diseases.

The tool, dubbed NASHmap, could serve as an initial screening tool to reveal more potential undiagnosed patients with NASH, according to Jörn M. Schattenberg, MD, with the metabolic liver research program in the department of medicine at University Medical Centre Mainz (Germany).

While not intended to replace current scoring systems, NASHmap potentially could be applied as a clinical decision support tool within electronic medical record systems, allowing greater numbers of patients with suspected NASH to be evaluated and referred to specialists for further testing, according to Dr. Schattenberg.

“To me, this is an at-risk population,” Dr. Schattenberg said in an interview. “There’s a lot of talk of increasing numbers of end-stage liver disease, and these are the cases that are waiting to happen. I think if we identify them, we can manage them better.”

“I’m not saying they should all get drugs – I’m saying they have to be informed about their condition because they may not have a clue they have liver disease,” he continued.

The machine-learning approach described here by Dr. Schattenberg included an exploratory analysis based on 704 patients with NASH or non-NASH nonalcoholic fatty liver disease (NAFLD) in the NAFLD Adult Database from the National Institute of Diabetes, Digestive, and Kidney Diseases.

The best-performing model they identified included 14 variables. Ranked by contribution to predictive power, those variables included hemoglobin A_1c, aspartate aminotransferase, alanine aminotransferase, total protein, AST/ALT ratio, body mass index, triglycerides, height, platelets, white blood cells, hematocrit, albumin, hypertension, and sex.

That 14-variable model had good performance when tested on the Optum Humedica electronic medical record database, according to Dr. Schattenberg and colleagues.

In the analysis for final evaluation, including 1,016 patients with histologically confirmed NASH, the area under the curve was 0.76, they reported.

A simplified, five-variable model including just hemoglobin A_1c, AST, ALT, total protein, and AST/ALT ratio also had good performance, with an area under the curve of 0.74, they said in their report.

Dr. Schattenberg provided disclosures related to AbbVie, Novartis, MSD, Pfizer, Boehringer Ingelheim, BMS, Intercept Pharmaceuticals, Genfit, Gilead, and Echosens. Several study coauthors reported employment with Novartis and stock ownership.