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Tsipora M Huisman, Douglas T Dieterich, Scott L Friedman Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USACorrespondence: Scott L FriedmanIcahn School of Medicine at Mount Sinai, Box 1123, 1425 Madison Ave, Room 1170C, New York, NY, 10025, USAEmail Scott.friedman@mssm.eduAbstract: There have been major advances in the treatment of HBV and HCV with anti-viral treatments, which is reducing the prevalence of fibrosis due to these viruses and obviating the need for anti-fibrotic therapies in these diseases. At the same time, however, the prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing, of which a substantial fraction of patients have non-alcoholic steatohepatitis (NASH), which may progress to cirrhosis. Accordingly, NASH is emerging as the leading indication for liver transplantation in North America and Europe. Progress in uncovering pathogenic determinants of fibrosis in NASH include metabolic dysregulation in hepatocytes that induce inflammation and cytokine secretion leading to cell injury and apoptosis, among others. These pathogenic events converge upon hepatic stellate cells, which are the primary fibrogenic cell in liver, and represent a target of new therapeutic candidates that are currently being evaluated in animal models and clinical trials. This review highlights key experimental and investigational therapies for NASH fibrosis, whose evaluation will be accelerated as new non-invasive markers of fibrosis are established. While no drugs are approved yet for NASH fibrosis, there is growing optimism that new pharmacotherapies are likely to emerge within the next 3 years that will favorably alter the natural history of disease.Keywords: liver fibrosis, novel treatments, NASH, pharmacotherapies, antifibrotic therapy, cirrhosis, hepatic stellate cell

Objectives Pegylated-interferon/ribavirin dual therapy for hepatitis C virus ( HCV) infection has a lower sustained virological response ( SVR) rate in HIV/ HCV-coinfected patients than in HCV monoinfected patients, but little is known about the relative effectiveness of teleprevir-based triple therapy in the two groups. Methods Data on 33 coinfected and 116 monoinfected patients were analysed on an intention-to-treat basis. SVR12 was defined as undetectable HCV RNA at week 12 post-end-of-treatment, severe anaemia as haemoglobin ≤ 89 g/L or a drop of ≥ 45 g/L, and advanced fibrosis/cirrhosis as Fib-4 ≥ 3.25. All coinfected patients had well controlled HIV infection. Results The groups were similar in age, gender, percentage with Fib-4 ≥ 3.25 and HCV viral load, but differed in previous treatment response, with more coinfected patients being nonresponders or treatment-intolerant (75.8% vs. 50.0% for monoinfected patients; P < 0.01). During treatment, the percentages of patients with undetectable HCV RNA were similar, but, surprisingly, this percentage tended to be higher in coinfected patients. SVR12 rates were 60.6% in coinfected patients vs. 42.2% in monoinfected patients ( P = 0.06). In multivariable analysis, SVR12 was associated with HIV infection [odds ratio ( OR) 3.55; P < 0.01], African American race ( OR 0.37; P = 0.03) and previous treatment response ( OR 0.46; P = 0.03). Rates of severe anaemia (45.5 vs. 58.6% in coinfected and monoinfected patients, respectively; P = 0.18) were similar in the two groups, but rash (15.2 vs. 34.5%, respectively; P = 0.03) and rectal symptoms (12.1 vs. 43.1%, respectively; P < 0.01) were less common in coinfected patients. Conclusions Virological responses of coinfected and monoinfected patients did not differ significantly, but tended to be higher in coinfected patients, who had a 60.6% SVR12 rate. Telaprevir-based triple therapy is a promising option for coinfected patients with well-controlled HIV infection. [ABSTRACT FROM AUTHOR]

Although the number of new hepatitis C virus (HCV) infections has dropped dramatically during the past 15 years, millions of Americans remain infected and at risk for fatal liver disease. Persons who require testing include health care workers with needlestick in-juries and children born to HCV-infected women. Consider testing patients who have injected illicit drugs, received clotting factor concentrates before 1987 or blood transfusions or organ transplants before July 1992, undergone long-term hemodialysis, had unexplained increases in alanine aminotransferase or aspartate aminotransferase levels, or who are infected with HIV. Liver biopsy remains the best method of assessing disease severity. Combination therapy with pegylated interferon alfa and ribavirin produces a sustained viral response rate of about 50% of patients with genotype 1 disease and more than 75% of those with genotype 2 or 3 infection. Therapy is associated with serious side effects and must be carefully monitored. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) frequently co-exist due to shared routes of transmission. In the past, the impact of HCV on overall morbidity and mortality of coinfected patients was minimal due to the poor prognosis of HIV. However, since the introduction of highly active antiretroviral therapy (HAART), HCV has become a significant pathogen in this population. HIV clearly exacerbates HCV infection and accelerates progression to cirrhosis, end-stage liver disease, and hepatocellular carcinoma. There is debate over whether HCV influences the natural history of HIV. Given the high prevalence of coinfection and the accelerated liver damage, HCV treatment has become a priority in these patients. There are new data on pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy for HCV in coinfected patients. The therapy is well tolerated and safe, although it appears to be slightly less effective than in monoinfected patients. The risk of HAART-related hepatotoxicity is greater in coinfected patients and therefore requires special consideration and close monitoring. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection is highly prevalent and is associated with substantial morbidity and mortality among persons infected with the human immunodeficiency virus (HIV). We compared the efficacy and safety of pegylated interferon alfa-2a (peginterferon alfa-2a) plus either ribavirin or placebo with those of interferon alfa-2a plus ribavirin for the treatment of chronic HCV infection in patients who were also infected with HIV.Methods: A total of 868 persons who were infected with both HIV and HCV and who had not previously been treated with interferon or ribavirin were randomly assigned to receive one of three regimens: peginterferon alfa-2a (180 microg per week) plus ribavirin (800 mg per day), peginterferon alfa-2a plus placebo, or interferon alfa-2a (3 million IU three times a week) plus ribavirin. Patients were treated for 48 weeks and followed for an additional 24 weeks. The primary end point was a sustained virologic response (defined as a serum HCV RNA level below 50 IU per milliliter at the end of follow-up, at week 72).Results: The overall rate of sustained virologic response was significantly higher among the recipients of peginterferon alfa-2a plus ribavirin than among those assigned to interferon alfa-2a plus ribavirin (40 percent vs. 12 percent, P<0.001), or peginterferon alfa-2a plus placebo (40 percent vs. 20 percent, P<0.001). Among patients infected with HCV genotype 1, the rates of sustained virologic response were 29 percent with peginterferon alfa-2a plus ribavirin, 14 percent with peginterferon alfa-2a plus placebo, and 7 percent with interferon alfa-2a plus ribavirin. The corresponding rates among patients infected with HCV genotype 2 or 3 were 62 percent, 36 percent, and 20 percent. Neutropenia and thrombocytopenia were more common among patients treated with regimens that contained peginterferon alfa-2a, and anemia was more common among patients treated with regimens containing ribavirin.Conclusions: Among patients infected with both HIV and HCV, the combination of peginterferon alfa-2a plus ribavirin was significantly more effective than either interferon alfa-2a plus ribavirin or peginterferon alfa-2a monotherapy. [ABSTRACT FROM AUTHOR]

Primary sclerosing cholangitis is a heterogenous immune-mediated disorder characterized by chronic inflammation and stricturing of the bile ducts. Though the driving pathophysiologic mechanisms remain elusive, there are several observed clinical phenotypes of the disease. The distribution of bile duct involvement, presence of concomitant inflammatory bowel disease, significant infiltration of IgG4-positive plasma cells, and overlapping features with other autoimmune disease has significant implications for prognosis and treatment. As there remains no pathognomonic finding for primary sclerosing cholangitis, a broad differential diagnosis and extensive evaluation of other underlying causes is critical to appropriate management., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background & Aims: The investigational first-generation core inhibitor vebicorvir (VBR) demonstrated safety and antiviral activity over 24 weeks in two phase IIa studies in patients with chronic HBV infection. In this long-term extension study, patients received open-label VBR with nucleos(t)ide reverse transcriptase inhibitors (NrtIs)., Methods: Patients in this study (NCT03780543) previously received VBR + NrtI or placebo + NrtI in parent studies 201 (NCT03576066) or 202 (NCT03577171). After receiving VBR + NrtI for ≥52 weeks, stopping criteria (based on the treatment history and hepatitis B e antigen status in the parent studies) were applied, and patients either discontinued both VBR + NrtI, discontinued VBR only, or continued both VBR + NrtI. The primary efficacy endpoint was the proportion of patients with HBV DNA <20 IU/ml at 24 weeks off treatment., Results: Ninety-two patients entered the extension study and received VBR + NrtI. Long-term VBR + NrtI treatment led to continued suppression of HBV nucleic acids and, to a lesser extent, HBV antigens. Forty-three patients met criteria to discontinue VBR + NrtI, with no patients achieving the primary endpoint; the majority of virologic rebound occurred ≥4 weeks off treatment. Treatment was generally well tolerated, with few discontinuations due to adverse events (AEs). There were no deaths. Most AEs and laboratory abnormalities were related to elevations in alanine aminotransferase and occurred during the off-treatment or NrtI-restart phases. No drug-drug interactions between VBR + NrtI and no cases of treatment-emergent resistance among patients who adhered to treatment were observed., Conclusions: Long-term VBR + NrtI was safe and resulted in continued reductions in HBV nucleic acids following completion of the 24-week parent studies. Following treatment discontinuation, virologic relapse was observed in all patients. This first-generation core inhibitor administered with NrtI for at least 52 weeks was not sufficient for HBV cure., Clinical Trial Number: NCT03780543., Impact and Implications: Approved treatments for chronic hepatitis B virus infection (cHBV) suppress viral replication, but viral rebound is almost always observed after treatment discontinuation, highlighting an unmet need for improved therapies with finite treatment duration producing greater therapeutic responses that can be sustained off treatment. First-generation core inhibitors, such as vebicorvir, have mechanisms of action orthogonal to standard-of-care therapies that deeply suppress HBV viral replication during treatment; however, to date, durable virologic responses have not been observed after treatment discontinuation. The results reported here will help researchers with the design and interpretation of future studies investigating core inhibitors as possible components of finite treatment regimens for patients with cHBV. It is possible that next-generation core inhibitors with enhanced potency may produce deeper and more durable antiviral activity than first-generation agents, including vebicorvir., Competing Interests: M-FY reports being an advisor/consultant for AbbVie, AiCuris, Aligos Therapeutics, Antios Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, Fujirebio Incorporation, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Roche, Sysmex Corporation, Tune Therapeutics, Vir Biotechnology, and Visirna Therapeutics and receiving grant/research support from AbbVie, Arrowhead Pharmaceuticals, Assembly Biosciences, Fujirebio Incorporation, Gilead Sciences, Immunocore, Roche, and Sysmex Corporation. SF reports receiving fees for speaking and teaching and/or serving on advisory committees for AbbVie, Assembly Biosciences, Gilead Sciences, Janssen, Lupin, Novo Nordisk, Pfizer, and Springbank Pharma. XM reports being a consultant and being on the speakers' bureau for Gilead Sciences. TTN reports receiving research grant support from Assembly Biosciences and Gilead Sciences. TH reports being on the advisory committee, review panel, or consulting for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Mallinckrodt Pharmaceuticals, Merck, and Organovo and receiving research support from AbbVie, Allergan, Assembly Biosciences, Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, CARA, Cytodyn, DURECT Corporation, Enanta Pharmaceuticals, Galectin Therapeutics, Gilead Sciences, Grifols, Intercept Pharmaceuticals, Janssen, Merck, Mirum, Novartis, Novo Nordisk, Nucorion Pharmaceuticals, Pfizer, Salix Pharmaceuticals, Sonic Incytes, Terns Pharmaceuticals, and Valeant. H-WH reports serving on the National Advisory Board and receives research grant support from Gilead Sciences. ME reports receiving grants from AbbVie, Bristol-Myers Squibb, Eisai, Gilead Sciences, and Roche and serving on advisory boards for AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Merck. RGN reports having served on advisory boards and as a speaker for Gilead Sciences, Janssen, and Merck and having conducted research for AbbVie, Gilead Sciences, Janssen, and Merck. JSP reports receiving research grants from Assembly Biosciences and GlaxoSmithKline and consulting fees from Gilead Sciences. IMJ reports being a consultant or on advisory boards for AbbVie, Aligos Therapeutics, Arbutus Biopharma, Gilead Sciences, Intercept Pharmaceuticals, Janssen, and Roche; having conducted research (all payments to institution) for Assembly Biosciences, Bristol-Myers Squibb, Cymabay, Eli Lilly, Enanta Pharmaceuticals, Genfit, Gilead Sciences, Intercept, Janssen, Merck, and Novo Nordisk; receiving payment from the Chronic Liver Disease Foundation for manuscript preparation; and participating on a Data Monitoring Committee for Altimmune, Arrowhead Pharmaceuticals, Galmed, GlaxoSmithKline, and Takeda. WSA reports being a member of the speaking bureau for Gilead Sciences and Intercept Pharmaceuticals and has received research grants from Genfit, GlaxoSmithKline, Intercept Pharmaceuticals, Ipsen, Madrigal, Mirum, Pfizer, and Zydus. S-HH reports being a consultant and being on the speakers' bureau for Gilead Sciences. EJG reports serving on advisory boards for AbbVie, Aligos Therapeutics, Assembly Biosciences, Gilead Sciences, GlaxoSmithKline, Intellia, Janssen, Roche, Vir Biotechnology, and Virion and having served as a speaker for Abbott Diagnostics, AbbVie, and Gilead Sciences. KZ, RY, and SJK report being employees of and holding stock interest in Assembly Biosciences. JM and LMS report being former employees of and holding stock interest in Assembly Biosciences. MBo reports being a member of the speaking bureau for AbbVie, Gilead Sciences, and Intercept Pharmaceuticals and has received research support from Assembly Biosciences, Boehringer Ingelheim, Gilead Sciences, Intercept Pharmaceuticals, Inventiva, and Viking Therapeutics. FW reports being a study investigator for AbbVie. AR reports receiving grant support, lecture fees, and advisory board fees from AbbVie, Celgene, Gilead Sciences, Intercept Pharmaceuticals, Merck, and Novartis. MBe reports having no conflicts of interest. NR reports advising, being on the speakers’ bureau for, and receiving grants from AbbVie and Gilead Sciences; being on the speakers’ bureau for Onyx and Salix; and having received grants from Bristol-Myers Squibb and Merck. SC reports receiving clinical trial–related payments from Assembly Biosciences. DTD reports being a consultant for Gilead Sciences and Intercept Pharmaceuticals. PYK reports being an advisor/consultant for AbbVie, Aligos Therapeutics, Antios Therapeutics, Enanta Pharmaceuticals, Gilead Sciences, and Janssen and receives grant/research supports from Altimmune, Arrowhead Pharmaceuticals, Assembly Biosciences, Bristol-Myers Squibb, Eiger Biopharmaceuticals, and Target Registries. ERS reports receiving research and grant support from Assembly Biosciences, Celgene, the University of Florida (TARGET), and Vir Biotechnology and receives royalties from the Schiff Diseases of the Liver, 12th edition. HSB reports having consultancy agreements with and receiving research support from Bristol-Myers Squibb and Gilead Sciences. JL reports having no conflicts of interest. KA reports being on the advisory board, a consultant, and a speaker for AbbVie, Aligos, Arbutus Biopharma, Assembly Biosciences, Bristol-Myers Squibb, Gilead Sciences, Immunocore, Janssen, Merck, Novartis, Roche, Shinogi, Sobi, and Vir Biotechnology and receiving grants from Bristol-Myers Squibb, Gilead Sciences, and Roche. MSS reports receiving grants from AbbVie, Assembly Biosciences, GlaxoSmithKline, Janssen, the National Institutes of Health, and Vir Biotechnology and receiving personal fees from AbbVie, Antios Therapeutics, Arbutus Biopharma, Atea Pharmaceuticals, Gilead Sciences, GlaxoSmithKline, F2G, Immunocore, Precision Biosciences, and Virion Therapeutics. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2024 The Authors.)

Background & Aims: Nucleos(t)ide reverse transcriptase inhibitors do not completely suppress HBV DNA in chronic HBV infection (cHBV). Vebicorvir (VBR) is an investigational core inhibitor that interferes with multiple aspects of HBV replication. This phase II trial evaluated the safety and efficacy of VBR in combination with entecavir (ETV) in treatment-naïve patients with cHBV., Methods: HBeAg-positive, treatment-naïve patients without cirrhosis were randomised 1:1 in a double-blind manner to once-daily VBR 300 mg+ETV 0.5 mg or placebo (PBO)+ETV 0.5 mg for 24 weeks. The primary endpoint was change in mean log 10 HBV DNA from Baseline to Week 12 and 24., Results: All patients in both treatment groups (PBO+ETV: 12/12; VBR+ETV: 13/13) completed the study. At Week 12, VBR+ETV led to a greater mean (SD) reduction from Baseline in log 10 IU/ml HBV DNA (-4.45 [1.03]) vs. PBO+ETV (-3.30 [1.18]; p = 0.0077). At Week 24, VBR+ETV led to a greater reduction from Baseline in log 10 IU/ml HBV DNA (-5.33 [1.59]) vs. PBO+ETV (-4.20 [0.98]; p = 0.0084). Greater mean reductions in pregenomic RNA were observed at Week 12 and 24 in patients receiving VBR+ETV vs. PBO+ETV (p <0.0001 and p <0.0001). Changes in viral antigens were similar in both groups. No drug interaction between VBR and ETV was observed. Two patients experienced HBV DNA rebound during treatment, with no resistance breakthrough detected. The safety of VBR+ETV was similar to PBO+ETV. All treatment-emergent adverse events and laboratory abnormalities were Grade 1/2. There were no deaths, serious adverse events, or evidence of drug-induced liver injury., Conclusions: In this 24-week study, VBR+ETV provided additive antiviral activity over PBO+ETV in treatment-naïve patients with cHBV, with a favourable safety and tolerability profile., Clinical Trial Number: NCT03577171 LAY SUMMARY: Hepatitis B is a long-lasting viral infection of the liver. Current treatments can suppress hepatitis B virus but do not offer the opportunity of cure, hence, new treatment approaches are required. Herein, we show that the combination of the novel core inhibitor vebicorvir with an existing antiviral (entecavir) in treatment-naïve patients chronically infected with hepatitis B virus demonstrated greater antiviral activity than entecavir alone. Additionally, vebicorvir was safe and well tolerated. Thus, further studies evaluating its potential role in the treatment of chronic hepatitis B are warranted., Competing Interests: Conflict of interest Mark S. Sulkowski reports receiving grants from AbbVie, Assembly Biosciences, Gilead Sciences, Janssen, and the National Institutes of Health; and receiving personal fees from AbbVie, Antios Therapeutics, Arbutus Biopharma, Atea Pharmaceuticals, Gilead Sciences, FH360, and Immunocore. Kosh Agarwal reports being on the advisory board, a consultant, and a speaker for AbbVie, Assembly Biosciences, Aligos, Arbutus, Bristol-Myers Squibb, Gilead Sciences, Immunocore, Janssen, Merck, Novartis, Roche, Sobi, Shinoigi, and Vir; and receiving grants from Bristol-Myers Squibb, Gilead Sciences, and Roche. Xiaoli Ma reports being a consultant and being on the speakers bureau for Gilead Sciences. Tuan T. Nguyen reports receiving research grant support from Gilead Sciences and Assembly Biosciences. Eugene R. Schiff reports receiving research and grant support from Assembly Biosciences, Celgene, and the University of Florida (TARGET) and receives royalties from the Schiff Diseases of the Liver, 12th edition. Hie-Won L. Hann reports serving on the National Advisory Board and receives research grant support from Gilead Sciences. Douglas T. Dieterich reports being a consultant for Gilead Sciences and Intercept Pharmaceuticals. Ronald G. Nahass reports having served on advisory boards and as a speaker for Gilead Sciences, Merck, and Janssen; and having conducted research for Gilead Sciences, Merck, Janssen, and AbbVie. James S. Park reports receiving research grants from Assembly Biosciences and GlaxoSmithKline and consulting fees from Gilead Sciences. Sing Chan reports receiving clinical trial–related payments from Assembly Biosciences. Steven-Huy Han reports being a consultant and being on the speakers bureau for Gilead Sciences. Edward J. Gane reports serving on advisory boards for AbbVie, Aligos Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Avilia Therapeutics, Clear B Therapeutics, Dicerna, Enanta Pharmaceuticals, Finch Therapeutics, Gilead Sciences, GlaxoSmithKline, Immunocore, Janssen, Roche, Silverback, and Vir Bio; and having served as a speaker for Gilead Sciences, AbbVie, and Roche. Michael Bennett reports having no conflicts of interest. Katia Alves reports being a former employee of and holding stock interest in Assembly Biosciences. Marc Evanchik reports having been an employee of and holding stock interest in Assembly Biosciences and is currently an employee of Edgewise Therapeutics. Ran Yan reports being an employee of and holding stock interest in Assembly Biosciences. Qi Huang reports being an employee of and holding stock interest in Assembly Biosciences. Uri Lopatin reports being a former employee and holding stock interest in Assembly Biosciences. Richard Colonno reports being an employee of and holding stock interest in Assembly Biosciences. Julie Ma reports being an employee of and holding stock interest in Assembly Biosciences. Steven J. Knox reports being an employee of and holding stock interest in Assembly Biosciences. Luisa M. Stamm reports being an employee of and holding stock interest in Assembly Biosciences. Maurizio Bonacini reports being a member of the speaking bureau for Intercept Pharmaceuticals, Gilead Sciences, and AbbVie and has received research support from Assembly Biosciences, Intercept Pharmaceuticals, Viking Therapeutics, and Boehringer Ingelheim. Ira M. Jacobson reports being a consultant or on advisory boards for AbbVie, Aligos Therapeutics, Arbutus Biopharma, Gilead Sciences, Janssen, Madrigal and Virion; having conducted research (all payments to institution) for Assembly Biosciences, Bristol-Myers Squib, Eli Lilly, Enanta Pharmaceuticals, Gilead Sciences, Janssen, Merck, and Novo Nordisk; receiving payment from the Chronic Liver Disease Foundation for manuscript preparation; and reports participation on a Data Safety Monitoring Board for GSK, Redhill, Galmed, NeuroBo, and Arrowhead Pharmaceuticals. Walid S. Ayoub reports being a member of the speaking bureau for both Gilead Sciences and Intercept Pharmaceuticals and has conducted research for Assembly Biosciences, Intercept Pharmaceuticals, Enanta Pharmaceuticals, and Gilead Sciences. Frank Weilert reports being a study investigator for AbbVie. Natarajan Ravendhran reports advising, being on the speakers’ bureau for, and receiving grants from Gilead Sciences and AbbVie; being on the speakers' bureau for Salix and Onyx; and having received grants from Bristol-Myers Squibb and Merck. Alnoor Ramji reports receiving grant support, lecture fees, and advisory board fees from AbbVie, Celgene, Gilead Sciences, Intercept Pharmaceuticals, Novartis, and Merck. Paul Yien Kwo reports being an advisor/consultant for AbbVie, Aligos Therapeutics, Antios Therapeutics, Enanta Pharmaceuticals, Gilead Sciences, Janssen, and receives grant/research supports from Assembly Biosciences, Arrowhead Pharmaceuticals, Eiger Biopharmaceuticals, Bristol-Myers Squibb, Altimmune, and Target Registries. Magdy Elkhashab reports receiving grants from AbbVie, Bristol-Myers Squibb, Eisai, Gilead Sciences, and Roche; and serving on advisory boards for AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Merck. Tarek Hassanein reports being on the advisory committee, review panel, or consulting for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Mallinckrodt Pharmaceuticals, Merck, and Organovo and receiving research support from AbbVie, Allergan, Cytodyn, Assembly Biosciences, Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, CARA, DURECT Corporation, Enanta Pharmaceuticals, Galectin Therapeutics, Gilead Sciences, Grifols, Intercept Pharmaceuticals, Janssen, Merck, Mirum, Novartis, Novo Nordisk, Nucorion Pharmaceuticals, Pfizer, Salix Pharmaceuticals, Sonic Incytes, Terns Pharmaceuticals, and Valeant. Ho S. Bae reports having consultancy agreements with and receiving research support from Bristol-Myers Squibb and Gilead Sciences. Jacob P. Lalezari reports having no conflicts of interest. Scott K. Fung reports receiving fees for speaking and teaching and/or serving on advisory committees for AbbVie, Assembly Biosciences, Gilead Sciences, Janssen, and Springbank Pharma. Man-Fung Yuen reports being an advisor/consultant for and/or having received grant/research support from AbbVie, Aligos Therapeutics, Antios Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Bristol-Myers Squibb, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, Fujirebio Incorporation, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Merck Sharp and Dohme, Roche, Springbank Pharmaceuticals, Silverback Therapeutics, Sysmex Corporation and Vir Biotechnology. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The Diabetes Prevention Program (DPP) is the gold standard lifestyle modification program that reduces incident type 2 diabetes mellitus. Patients with prediabetes and patients with non-alcoholic fatty liver disease (NAFLD) often share metabolic features; we hypothesized that the DPP could be adapted and used to improve outcomes in patients with NAFLD., Methods: NAFLD patients were recruited into a 1 year modified DPP. Demographics, medical comorbidities, and clinical laboratory values were collected at baseline, 6 and 12 months. The primary endpoint was change in weight at 12 months. Secondary endpoints were changes in hepatic steatosis, metabolic comorbidities, and liver enzymes (per-protocol basis) and retention at 6 and 12 months., Results: Fourteen NAFLD patients enrolled; three dropped out before 6 months. From baseline to 12 months, hepatic steatosis ( p  = 0.03), alanine aminotransferase ( p  = 0.02), aspartate aminotransferase ( p = 0.02), high-density lipoprotein ( p  = 0.01) and NAFLD fibrosis score ( p  < 0.001) improved, but low-density lipoprotein worsened ( p  = 0.04)., Conclusion: Seventy-nine percent of patients completed the modified DPP. Patients lost weight and had improvements in five out of six indicators of liver injury and lipid metabolism., Clinical Trial Registry Number: NCT04988204., Competing Interests: The authors declare no other conflict of interest., (© 2022 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Background & Aims: HBV nucleos(t)ide reverse transcriptase inhibitors (NrtIs) do not completely suppress HBV replication. Previous reports indicate persistent viremia during NrtI treatment despite HBV DNA being undetectable. HBV core inhibitors may enhance viral suppression when combined with NrtIs. This phase II trial (NCT03576066) evaluated the efficacy and safety of the investigational core inhibitor, vebicorvir (VBR), in virologically- suppressed patients on NrtIs., Methods: Non-cirrhotic, NrtI-suppressed patients with chronic HBV were randomised to VBR 300 mg once daily or matching placebo (PBO) for 24 weeks. Treatment was stratified by hepatitis B e antigen (HBeAg) status. The primary endpoint was change from Baseline in serum HBeAg or hepatitis B surface antigen (HBsAg) after 24 weeks., Results: Of 73 patients enrolled, 47 were HBeAg positive and 26 were HBeAg negative. In HBeAg-positive and -negative patients, there were no differences in the change from Baseline at Week 24 for HBsAg or HBeAg. Using a novel, high-sensitivity assay to detect HBV DNA, a greater proportion of patients with detectable HBV DNA at Baseline achieved undetectable HBV DNA at Week 24 in the VBR+NrtI vs. PBO+NrtI group. In HBeAg-positive patients, a greater change from Baseline in HBV pregenomic (pg)RNA was observed at Week 24 with VBR+NrtI vs. PBO+NrtI. Treatment-emergent adverse events (TEAEs) in VBR+NrtI patients included upper respiratory tract infection, nausea, and pruritus. No serious adverse events, Grade 4 TEAEs, or deaths were reported., Conclusions: In this 24-week study, VBR+NrtI demonstrated a favourable safety and tolerability profile. While there were no significant changes in viral antigen levels, enhanced viral suppression was demonstrated by greater changes in DNA and pgRNA with the addition of VBR compared to NrtI alone., Clinical Trials Number: NCT03576066., Lay Summary: Core inhibitors represent a novel approach for the treatment of chronic hepatitis B virus (HBV) infection, with mechanisms of action distinct from existing treatments. In this study, vebicorvir added to existing therapy reduced HBV replication to a greater extent than existing treatment and was generally safe and well tolerated., Competing Interests: Conflict of interest Man-Fung Yuen reports being an advisor/consultant for and/or having received grant/research support from AbbVie, Aligos Therapeutics, Antios Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Bristol-Myers Squibb, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, Fujirebio Incorporation, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Merck Sharp and Dohme, Roche, Springbank Pharmaceuticals, Silverback Therapeutics, Sysmex Corporation, and Vir Biotechnology. Kosh Agarwal reports being on the advisory board, a consultant, and a speaker for AbbVie, Assembly Biosciences, Aligos, Arbutus, Bristol-Myers Squibb, Gilead Sciences, Immunocore, Janssen, Merck, Novartis, Roche, Sobi, Shinoigi, and Vir; and receiving grants from Bristol-Myers Squibb, Gilead Sciences, and Roche. Xiaoli Ma reports being a consultant and being on the speakers bureau for Gilead Sciences. Tuan T. Nguyen reports receiving research grant support from Gilead Sciences and Assembly Biosciences. Eugene R. Schiff reports receiving research and grant support from Assembly Biosciences, Celgene, and the University of Florida (TARGET) and receives royalties from the Schiff Diseases of the Liver, 12th edition. Hie-Won L. Hann reports serving on the National Advisory Board and receives research grant support from Gilead Sciences. Douglas T. Dieterich reports being a consultant for Gilead Sciences and Intercept Pharmaceuticals. Ronald G. Nahass reports having served on advisory boards and as a speaker for Gilead Sciences, Merck, and Janssen; and having conducted research for Gilead Sciences, Merck, Janssen, and AbbVie. James S. Park reports receiving research grants from Assembly Biosciences and GlaxoSmithKline and consulting fees from Gilead Sciences. Sing Chan reports receiving clinical trial-related payments from Assembly Biosciences. Steven-Huy Han reports being a consultant and being on the speakers bureau for Gilead Sciences. Edward J. Gane reports serving on advisory boards for AbbVie, Aligos Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Avilia Therapeutics, Clear B Therapeutics, Dicerna, Enanta Pharmaceuticals, Finch Therapeutics, Gilead Sciences, GlaxoSmithKline, Immunocore, Janssen, Roche, Silverback, and Vir Bio. and having served as a speaker for Gilead Sciences, AbbVie, and Roche. Michael Bennett reports having no conflicts of interest. Katia Alves reports being a former employee of and holding stock interest in Assembly Biosciences. Marc Evanchik reports having been an employee of and holding stock interest in Assembly Biosciences and is currently an employee of Edgewise Therapeutics. Ran Yan reports being an employee of and holding stock interest in Assembly Biosciences. Qi Huang reports being an employee of and holding stock interest in Assembly Biosciences. Uri Lopatin reports being a former employee and holding stock interest in Assembly Biosciences. Richard Colonno reports being an employee of and holding stock interest in Assembly Biosciences. Julie Ma reports being an employee of and holding stock interest in Assembly Biosciences. Steven J. Knox reports being an employee of and holding stock interest in Assembly Biosciences. Luisa M. Stamm reports being an employee of and holding stock interest in Assembly Biosciences. Maurizio Bonacini reports being a member of the speaking bureau for Intercept Pharmaceuticals, Gilead Sciences, and AbbVie and has received research support from Assembly Biosciences, Intercept Pharmaceuticals, Viking Therapeutics, and Boehringer Ingelheim. Ira M. Jacobson reports being a consultant or on advisory boards for AbbVie, Aligos Therapeutics, Arbutus Biopharma, Gilead Sciences, Janssen, Madrigal and Virion; having conducted research (all payments to institution) for Assembly Biosciences, Bristol-Myers Squib, Eli Lilly, Enanta Pharmaceuticals, Gilead Sciences, Janssen, Merck, and Novo Nordisk; receiving payment from the Chronic Liver Disease Foundation for manuscript preparation; and reports participation on a Data Safety Monitoring Board for GSK, Redhill, Galmed, NeuroBo, and Arrowhead Pharmaceuticals. Walid S. Ayoub reports being a member of the speaking bureau for both Gilead Sciences and Intercept Pharmaceuticals and has conducted research for Assembly Biosciences, Intercept Pharmaceuticals, Enanta Pharmaceuticals, and Gilead Sciences. Frank Weilert reports being a study investigator for AbbVie. Natarajan Ravendhran reports advising, being on the speakers’ bureau for, and receiving grants from Gilead Sciences and AbbVie; being on the speakers' bureau for Salix and Onyx; and having received grants from Bristol-Myers Squibb and Merck. Alnoor Ramji reports receiving grant support, lecture fees, and advisory board fees from AbbVie, Celgene, Gilead Sciences, Intercept Pharmaceuticals, Novartis, and Merck. Paul Yien Kwo reports being an advisor/consultant for AbbVie, Aligos Therapeutics, Antios Therapeutics, Enanta Pharmaceuticals, Gilead Sciences, Janssen, and receives grant/research support from Assembly Biosciences, Arrowhead Pharmaceuticals, Eiger Biopharmaceuticals, Bristol Myer Squibb, Altimmune, and Target Registries. Magdy Elkhashab reports receiving grants from AbbVie, Bristol-Myers Squibb, Eisai, Gilead Sciences, and Roche; and serving on advisory boards for AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Merck. Tarek Hassanein reports being on the advisory committee, review panel, or consulting for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Mallinckrodt Pharmaceuticals, Merck, and Organovo and receiving research support from AbbVie, Allergan, Cytodyn, Assembly Biosciences, Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, CARA, DURECT Corporation, Enanta Pharmaceuticals, Galectin Therapeutics, Gilead Sciences, Grifols, Intercept Pharmaceuticals, Janssen, Merck, Mirum, Novartis, Novo Nordisk, Nucorion Pharmaceuticals, Pfizer, Salix Pharmaceuticals, Sonic Incytes, Terns Pharmaceuticals, and Valeant. Ho S. Bae reports having consultancy agreements with and receiving research support from Bristol-Myers-Squibb and Gilead Sciences. Jacob P. Lalezari reports having no conflicts of interest. Scott K. Fung reports receiving fees for speaking & teaching and/or serving on advisory committees for AbbVie, Assembly Biosciences, Gilead Sciences, Janssen, and Springbank Pharma. Mark S. Sulkowski reports receiving grants from AbbVie, Assembly Biosciences, Gilead Sciences, Janssen, and the National Institutes of Health; and receiving personal fees from AbbVie, Antios Therapeutics, Arbutus Biopharma, Atea Pharmaceuticals, Gilead Sciences, FH360, and Immunocore. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Chronic hepatitis B (CHB) infection remains the most frequent etiology of hepatocellular carcinoma globally as well as a major cause of cirrhosis. Despite vaccination, substantial numbers of persons have already been infected with hepatitis B virus and remain at risk of progressive liver disease., Methods: In 2004, a CHB management algorithm was developed by a panel of North American hepatologists, which was subsequently updated in 2006, 2008, and 2015. Since the most recent version, several developments have altered the management of CHB. Tenofovir alafenamide, with a more favorable safety profile than tenofovir disoproxil fumarate, has been introduced as an initial antiviral choice as well as an alternative for long-term therapy. Quantitation of hepatitis B surface antigen is becoming more widely available in clinical practice, with implications for monitoring response to treatment. Additionally, there has been a shift in how the natural history of CHB is perceived, as newer evidence has challenged the concept that during the immunotolerant phase of infection disease progression is not a concern. Finally, recent analyses indicate that in the United States, the average age of patients with CHB has increased, implying that the presence of comorbidities, including metabolic liver disease, increasing use of biologics associated with aging will increasingly affect disease management., Results: This updated algorithm is intended to serve as a guide to manage CHB while new antiviral strategies are developed., Conclusions: Recommendations have been based on evidence from the scientific literature, when possible, as well as clinical experience and consensus expert opinion. Points of continued debate and areas of research need are also described., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Thrombocytopenia is the most common haematological abnormality in patients with chronic liver disease in the United States. Severe thrombocytopenia (platelet count <50 × 10 9 /L) can complicate the management of patients with chronic liver disease by significantly increasing the potential risk of bleeding during or after invasive procedures. The current standard-of-care treatment for severe thrombocytopenia is platelet transfusion. Novel agents that target the thrombopoietin pathway, including receptor agonists avatrombopag and lusutrombopag, have recently shown promise in clinical trials as alternatives to platelet transfusion., Aim: To review treatment options for severe thrombocytopenia, including platelet transfusion and thrombopoietin-receptor agonists, with the aim of producing a simplified treatment algorithm., Methods: Five liver disease specialists were assigned sections of the manuscript to research and present at a consensus meeting in April 2019, with the goal of creating an easy-to-use, effective treatment plan for severe thrombocytopenia in patients with chronic liver disease., Results: Through discussion and collaborative decision making, a simplified algorithm was developed to provide guidance to healthcare professionals on treating severe thrombocytopenia in patients with chronic liver disease undergoing elective medical procedures in the United States. As part of these guidelines, we outline the use of the US Food and Drug Administration-approved thrombopoietin receptor agonists avatrombopag and lusutrombopag as well tolerated and effective alternatives to platelet transfusion., Conclusions: This algorithm provides guidance for the management of severe thrombocytopenia to reduce bleeding risks in patients with chronic liver disease undergoing elective procedures, while reducing requirement for platelet transfusion., (© 2020 John Wiley & Sons Ltd.)

Patient-reported outcomes (PROs) are important measures of quality of life. Direct-acting antiviral (DAA) drugs for hepatitis C virus (HCV) improved PROs in clinical trials. We prospectively evaluated the impact of DAA-based HCV cure on PROs and liver-related outcomes in real-world patients at a large urban medical center. The short form (SF)-36 and three additional validated instruments were used. F3-4 fibrosis was defined as > 9.6 kPa by transient elastography (TE); S2-3 steatosis was defined as > 270 dB/m by TE-controlled attenuation parameter (CAP). Data were analysed by paired and unpaired t tests. Patients (n = 16) who did not achieve a sustained virologic response at 12 weeks (SVR12) were excluded. The study achieved its primary endpoint and showed a significant 30% improvement in the SF-36 vitality score, measured baseline to SVR12: 63 versus 82, P < .001 (n = 111). Scores in 24 of 25 PRO domains improved at SVR12 (P < .05). Nearly all gains exceeded 5%, indicating their clinical significance. Transaminase values and liver stiffness improved (decreased) significantly, baseline to SVR12 (P < .005), but steatosis was unchanged (P = .58). Patients with baseline F0-2 fibrosis and those with F3-F4 fibrosis both improved in 22 domains. Patients with baseline S0-S1 steatosis improved in more domains (23) than patients with S2-S3 steatosis (19). At baseline, patients with F3-F4 fibrosis and patients with S2-3 steatosis had worse scores in certain PRO domains than patients with F0-2 fibrosis or S0-S1 steatosis, but this difference resolved by SVR12. HCV cure led to meaningful gains in PROs, and these findings may encourage patients to seek treatment., (© 2019 John Wiley & Sons Ltd.)

Liver disease in human immunodeficiency virus (HIV) remains a main cause of morbidity and mortality. Liver-related morbidity and mortality can be caused by multiple etiologic factors, including opportunistic infections, direct and indirect effects of antiretrovirals, direct and indirect effects of HIV, and viral hepatitides. These factors present with varied liver pathophysiologic mechanisms that lead to abnormalities in liver enzymes and synthetic function test, followed by distinct clinical presentations. This article elucidates the direct effects on HIV in the liver and explores the diagnostic and management challenges in patients with HIV in the era of highly active antiretroviral treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Elimination of hepatitis C virus (HCV) infection as a public health threat is a goal of the World Health Organization. Official treatment guidelines are comprehensive and may be most appropriate for experienced treaters of HCV; however, global elimination of HCV infection will require the engagement of frontline health care providers (HCPs) to increase the capacity to treat patients. Thus, a simplified treatment algorithm is needed to provide guidance to non-HCV specialists. To accomplish this, a panel of 13 HCV specialists held a consensus meeting in September 2018 to create an easy-to-use, effective, safe, and scalable algorithm for the management and treatment of HCV infection through discussion and collective decision-making. The algorithm begins with universal HCV screening and diagnosis by testing for HCV antibody with reflex to polymerase chain reaction to detect HCV RNA. The pretreatment evaluation uses platelet-based stratification to initially assess fibrosis, and the pan-genotypic regimens glecaprevir/pibrentasvir or sofosbuvir/velpatasvir are recommended for treatment. Unless clinically indicated, on-treatment monitoring is optional. Confirmation of cure (undetectable HCV RNA 12 weeks posttreatment) is followed by harm-reduction measures, as well as surveillance for hepatocellular carcinoma every 6 months in patients with advanced fibrosis/cirrhosis. This algorithm provides guidance for management of uncomplicated cases of HCV by frontline HCPs and indicates when referral to an HCV specialist is warranted. The algorithm was created to enable more HCPs to screen for and manage HCV infection, and thus contribute to its elimination., Competing Interests: Disclaimer This supplement is supported by Gilead Sciences. Support of this supplement does not imply the supporter’s agreement with the views expressed herein. Every effort has been made to ensure that drug usage and other information are presented accurately; however, the ultimate responsibility rests with the prescribing physician. Gastro-Hep Communications, Inc., the supporter, and the participants shall not be held responsible for errors or for any consequences arising from the use of information contained herein. Readers are strongly urged to consult any relevant primary literature. No claims or endorsements are made for any drug or compound at present under clinical investigation., (Copyright © 2019, Gastro-Hep Communications, Inc.)

Introduction: Hepatitis C contributes to significant morbidity and mortality worldwide. AHCV is defined as documented infection within 6 months of exposure. Treating acute hepatitis C virus (AHCV) with direct-acting antiviral agents in persons who inject drugs, HIV-positive men who have sex with men, and patients who acquire HCV nosocomially can contribute to the elimination of disease globally, preclude the morbidity and mortality of chronic disease, and prevent further transmission. Areas covered: In this review, we describe the epidemiology of AHCV, its natural history, the considerations involved in the decision of whether to treat AHCV, and the most current DAA therapy guidelines. PubMed was queried using key words and bibliographies were evaluated for relevant articles. Expert commentary: Despite the obvious benefits of AHCV treatment, clinical management is limited by the ability to identify asymptomatic cases and the absence of fully supported guidelines. However, clinical research is advancing and identifying specific regimens, decreasing treatment durations, and creating strategies to target at risk groups and screen for AHCV.

Objective The primary study objective is to determine which measures of depression are associated with early discontinuation of hepatitis C virus infection treatment and to determine which measure best characterizes the depression that develops during treatment. Methods Seventy-eight treatment-naïve subjects who initiated pegylated interferon/ribavirin treatment for hepatitis C virus infection were included. Baseline depression was assessed with the Structured Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), the Hamilton Depression Rating Scale, and the Beck Depression Inventory-II. The latter two measures were repeated at treatment weeks 12 and 24. Results Depression scores, as measured by the three instruments, lacked adequate consistency. Baseline depression as measured by the Beck Depression Inventory-II, but not by the other scales, was associated with early treatment discontinuation at weeks 12 and 24. Changes in depression during treatment were restricted to somatic symptoms. Of those who completed treatment, those who were not depressed at baseline tended to demonstrate significant depression increases during treatment. Conclusion The Beck Depression Inventory-II is recommended to assess depression prior to hepatitis C virus infection treatment. Somatic symptoms of depression should be monitored during treatment. Baseline depression as measured by the Beck Depression Inventory-II was associated with early treatment discontinuation. The Beck Depression Inventory-II, Structured Interview for DSM-IV, and Hamilton Depression Rating Scale yielded results that were not consistent with each other in this sample. Future research should focus on standardizing depression assessment in medically ill populations to identify measures that predict treatment discontinuation.

The number of transplants caused by nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) has been progressively increasing and this is expected to become the most common indication for liver transplant in the United States. Patients with NASH show many features of the metabolic syndrome and, as a result, are at higher risk for postoperative cardiovascular morbidity and mortality. Despite this, patients with NASH have long-term graft and patient survival rates comparable with other causes of chronic liver disease. Posttransplant metabolic syndrome is a common occurrence that increases the risk of steatosis in the graft liver., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: To assess the real-world effectiveness and cost of simeprevir (SMV), and/or sofosbuvir (SOF)-based therapy for chronic hepatitis C virus (HCV) infection., Methods: The real-world performance of patients treated with SMV/SOF ± ribavirin (RBV), SOF/RBV, and SOF/RBV with pegylated-interferon (PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response - the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response (SVR) 12] - were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic regression., Results: SVR12 rates were as follows: 86% (95%CI: 80%-91%) among 178 patients on SMV/SOF ± RBV; 62% (95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78% (95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR12 were $174442 (standard deviation: ± $18588) for SMV/SOF ± RBV; $223003 (± $77946) for SOF/RBV; and $126496 (± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio (OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin (OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR12 (OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV., Conclusion: SVR12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs., Competing Interests: Conflict-of-interest statement: Dr. Kian Bichoupan is a paid consultant for Gilead Sciences and Janssen Pharmaceuticals, Inc. Neeta Tandon is an employee of Johnson and Johnson. Dr. Andrea D Branch received research support from Gilead Sciences and Janssen Pharmaceuticals, Inc. Dr. Douglas T Dieterich serves as a paid lecturer, consultant and is a member on scientific advisory boards of companies which either develop or assess medicines used for the treatment of viral hepatitis. These companies include Gilead Sciences, Abbvie, Achillion, Bristol-Myers Squibb, Merck, and Janssen Pharmaceuticals, Inc. Dr. Thomas D Schiano is a paid consultant for Salix, Merck, Gilead, BMS, Novartis and Janssen and received research support from Mass biologics, Gilead, Merck, Biotest and Genentech. Michel Ng is a paid member of AbbVie’s Speakers bureau. Dr. Ponni V Perumalswami receives research support from Gilead Sciences. Dr. Keith M Sigel has served on an advisory board for Gilead Sciences. Dr. James Crismale, Dr Meena B Bansal, Dr. Joshua Hartman, Dr. Sweta Chekuri, Alyson Harty, Dr. Joseph A Odin, Dr. Priya Grewal, Dr. Nancy Bach, Dr. Lawrence Liu, Dr. Charissa Y Chang, Dr. Gene Y Im, Dr. Jennifer Leong, Dr. David Del Bello, Dr. Neal M Patel and Dr. Scott L Friedman do not have any relevant disclosures.

Chronic liver diseases (CLDs), due to chronic hepatitis C; hepatitis B; nonalcoholic fatty liver diseases (NAFLD); and alcoholic liver disease, are a leading cause of morbidity and mortality globally. Early identification of patients with cirrhosis at high risk of progression to liver-related complications may facilitate timely care and improve outcomes. With risks and misclassification associated with invasive tests, such as liver biopsy, noninvasive imaging modalities for liver fibrosis assessment have gained popularity. Therefore, the American Gastroenterological Association prioritized clinical guidelines on the role of elastography in CLDs, focusing on vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE). To inform these clinical guidelines, the current technical review was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for diagnostic accuracy studies. This technical review addresses focused questions related to: (1) comparative diagnostic performance of VCTE and MRE relative to nonproprietary, serum-based fibrosis markers for detection of cirrhosis in patients with hepatitis C virus (HCV), hepatitis B virus (HBV), NAFLD, and alcoholic liver diseases; (2) performance of specific VCTE-defined liver stiffness cutoffs as a test replacement strategy (to replace liver biopsy) in making key decisions in the management of patients with CLDs; and (3) performance of specific VCTE-defined liver stiffness cutoffs as a triage test to identify patients with low likelihood of harboring high-risk esophageal varices (EVs) or having clinically significant portal hypertension (for presurgical risk stratification). This technical review does not address performance of other noninvasive modalities for assessing fibrosis (eg, acoustic radiation force pulse imaging or shear wave elastography) or steatosis (controlled attenuation parameter or magnetic resonance imaging-estimated proton density fat fraction)., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate new therapies for hepatitis C virus (HCV), data about real-world outcomes are needed., Methods: Outcomes of 223 patients with genotype 1 HCV who started telaprevir- or boceprevir-based triple therapy (May 2011-March 2012) at the Mount Sinai Medical Center were analyzed. Human immunodeficiency virus-positive patients and patients who received a liver transplant were excluded. Factors associated with sustained virological response (SVR24) and relapse were analyzed by univariable and multivariable logistic regression as well as classification and regression trees. Fast virological response (FVR) was defined as undetectable HCV RNA at week-4 (telaprevir) or week-8 (boceprevir)., Results: The median age was 57 years, 18% were black, 44% had advanced fibrosis/cirrhosis (FIB-4 ≥ 3.25). Only 42% (94/223) of patients achieved SVR24 on an intention-to-treat basis. In a model that included platelets, SVR24 was associated with white race [odds ratio (OR) = 5.92, 95% confidence interval (CI): 2.34-14.96], HCV sub-genotype 1b (OR = 2.81, 95%CI: 1.45-5.44), platelet count (OR = 1.10, per x 10 4 cells/μL, 95%CI: 1.05-1.16), and IL28B CC genotype (OR = 3.54, 95%CI: 1.19-10.53). Platelet counts > 135 x 10 3 /μL were the strongest predictor of SVR by classification and regression tree. Relapse occurred in 25% (27/104) of patients with an end-of-treatment response and was associated with non-FVR (OR = 4.77, 95%CI: 1.68-13.56), HCV sub-genotype 1a (OR = 5.20; 95%CI: 1.40-18.97), and FIB-4 ≥ 3.25 (OR = 2.77; 95%CI: 1.07-7.22)., Conclusion: The SVR rate was 42% with telaprevir- or boceprevir-based triple therapy in real-world practice. Low platelets and advanced fibrosis were associated with treatment failure and relapse., Competing Interests: Conflict-of-interest statement: Kian Bichoupan is a paid consultant for Gilead Sciences and Janssen Pharmaceuticals, Inc. Dr. Andrea D Branch is a paid consultant for Gilead Sciences and Janssen Pharmaceuticals, Inc. Dr. Douglas T Dieterich serves as a paid lecturer, consultant and is a member on scientific advisory boards of companies which either develop or assess medicines used for the treatment of viral hepatitis. These companies include Gilead Sciences, Abbvie, Achillion, Bristol-Myers Squibb, Merck, and Janssen Pharmaceuticals, Inc. Dr. Thomas D Schiano is a paid consultant for Salix, Merck, Gilead, BMS, Novartis and Janssen and received research support from Mass biologics, Gilead, Merck, Biotest and Genentech. Michel Ng is a paid member of AbbVie’s Speakers bureau. Viktoriya Khaitova is a paid member of a scientific advisory board for Abbvie, and Johnson & Johnson. Dr. Valerie Martel-Lafferiere, Dr. Emily A Schonfeld, Dr. James Crismale, Alicia Stivala, Donald Gardenier, Dr. David Sachs, Dr. Joseph A. Odin, Dr. Lawrence Liu, Dr. Neal M Patel, and Dr. Ponni V Perumalswami do not have any disclosures.

The human immunodeficiency virus (HIV), hepatitis C virus (HCV), and the treatment of HCV with pegylated interferon and ribavirin (IFN/RBV) have been associated with neurocognitive and psychiatric abnormalities. The goal of this research was to prospectively evaluate neurocognitive functioning among a group of HCV mono-infected and HIV/HCV co-infected patients during the first 24 weeks of IFN/RBV treatment while accounting for practice effects, normal variations in change over time, and variations in IFN/RBV treatment exposure. Forty-four HCV mono-infected and 30 HIV/HCV co-infected patients were enrolled in a prospective study of patients beginning on IFN/RBV for chronic HCV infection. Patients were administered a depression inventory, a measure of fatigue, a structured psychiatric interview, and a neurocognitive battery at baseline and 24 weeks after initiation of treatment. Analyses were conducted to explore possible associations between neurocognitive functioning and the following: HIV/HCV co-infection vs. HCV mono-infection, IFN and RBV treatment exposure, psychiatric status, liver disease stage, and other medical characteristics. At baseline, there were no significant differences between the two groups' neuropsychiatric or neurocognitive function other than the mono-infected group had significantly higher reports of fatigue (p = 0.033). Over the course of 24 weeks of treatment after controlling for practice effects, the HIV/HCV co-infected patients experienced significantly greater declines in memory (t(56) = 2.14, p = 0.037) and global neurocognitive functioning (t(53) = 2.28, p = 0.027). In a well-characterized sample of mono-infected and co-infected patients, it appears that persons with HIV/HCV co-infection are potentially more vulnerable to neurocognitive sequalae during HCV treatment.

Background: There is an international epidemic of hepatitis C virus (HCV) infection among HIV-infected men who have sex with men. We previously showed that adding telaprevir to pegylated interferon (IFN) and ribavirin (RBV) both shortened treatment and increased the cure rate of early HCV in these men. Whether shortening treatment of early HCV using IFN-free regimens would be similarly successful has not yet been demonstrated., Methods: We performed a pilot study of treatment with sofosbuvir (SOF) + RBV for 12 weeks in early genotype 1 HCV infection in HIV-infected men. The primary endpoint was SVR 12., Results: Twelve men were treated with 12 weeks SOF + RBV and 11 (92%) achieved SVR 12. Most (63%) were actively using recreational drugs, mostly methamphetamine. The one man who failed had laboratory results more characteristic of chronic than of early HCV infection. The overall safety profile was similar to that known for SOF + RBV., Conclusions: The success of this short-duration IFN-free treatment in early HCV infection is proof in principle that enhanced treatment responsiveness is an inherent characteristic of early HCV infection and not a function of IFN treatment itself. Future studies should now be done with more potent regimens to try to further shorten therapy. In the mean time, in clinical practice early HCV infection should be treated immediately after detection to take advantage of short-duration treatments, as well as to decrease further HCV transmission among HIV-infected MSM.

Early data regarding the "real-world" experience with novel therapies for hepatitis C (HCV) are encouraging. Data are still limited, however, regarding real-world rates of sustained virologic response (SVR) for ledipasvir-sofosbuvir (LDV-SOF), particularly for patients with prior treatment failure. We performed a retrospective cohort study of 1597 patients with chronic genotype 1 HCV who were treated using 12 weeks of the following regimens LDV-SOF±ribavirin (RBV) (n=1521 without RBV, n=76 with RBV). The primary outcome was SVR-determined at 12 weeks in an intention-to-treat design. Prescription according to Food and Drug Administration (FDA) approved labelling (adding RBV for patients with cirrhosis and treatment failure) was assessed in multivariate models. The study population was aged 60 years on average (range 19-89), 60% male, 50% Caucasian, 43% cared for at an academic centre and 30% cirrhotic. Overall, LDV-SOF resulted in a 94% SVR rate. Only 44 (2.9%) patients relapsed. LDV-SOF+RBV yielded SVR in 97% with 0 viral relapses. While cirrhosis and thrombocytopenia were associated with lower odds of SVR, in a multivariable regression model, only treatment at an academic centre and prescriptions contrary to FDA labelling were significantly associated with lower SVR-odds ratios, 0.56 95% CI (0.35-0.87) and 0.29 95% CI(0.12-0.68), respectively. The real-world experience with LDV-SOF mirrors the SVR rates observed in clinical trials. Efforts to promote prescription within FDA recommendations are warranted., (© 2016 John Wiley & Sons Ltd.)

Many patients with chronic hepatitis C virus (HCV) are on prolonged proton-pump inhibitor (PPI) therapy and wish to remain on PPI therapy once treatment for HCV starts. A preliminary report recently suggested decrease rates of sustained virological response (SVR) for patients taking concomitant PPI and ledipasvir/sofosbuvir (LDV/SOF). We sought to determine the effect of PPI use on the rate of SVR in a real-world cohort of 1,979 patients with chronic HCV treated with LDV/SOF. We collected clinical data and pharmacy dispensing records on patients taking 8, 12, or 24 weeks of LDV/SOF ± ribavirin (RBV). The primary outcome was sustained virological response at 12 weeks after treatment completion (SVR12) in a per-protocol analysis in order to determine the effect of PPI use adjusted for confounders. Statistical adjustment was performed in propensity-matched analysis. Among treatment completers, SVR12 was achieved in 441 (97.1%) of PPI recipients compared with 1,497 (98.2%) in PPI nonrecipients (P = 0.19). Neither low- nor high-dose PPI was associated with decreased SVR, although patients taking twice-daily PPI achieved a lower SVR12 rate (91.2%; 95% confidence interval [CI], 77.0-97.0; P = 0.046). After propensity matching for PPI use, there were no significant associations between SVR12 and any dose or frequency of PPI use. However, in a sensitivity analysis focusing on patients with cirrhosis, twice-daily PPI use was associated with lower odds ratio for SVR12 (0.11; 95% CI, 0.02-0.59)., Conclusion: These data from a cohort of real-world patients receiving hepatitis C antibody therapy with LDF/SOF ± RBV support the prescription labeling suggesting that patients take no more than low-dose (20-mg omeprazole equivalents) PPI daily. (Hepatology 2016;64:1893-1899)., (© 2016 by the American Association for the Study of Liver Diseases.)

To conduct surveillance and determine the safety profile of new hepatitis C virus treatments in real-world clinical practice. Hepatic decompensation and other serious adverse events were investigated in an observational cohort study of 511 patients treated with regimens containing sofosbuvir, December 2013-June 2014. Among 499 previously stable patients (no history of hepatic decompensation during the previous 12 months), a nested case-control study was performed to identify predictors of decompensation/serious adverse event. Cases and controls were matched 1:5 based on treatment regimen and duration. Matched conditional logistic regression was used for analysis. Providers scored the likelihood that events were treatment-related (scale = 0-4). The cumulative incidence of decompensation/events was 6.4% for the total cohort. Among 499 previously stable patients, the incidence of decompensation/events was 4.5%; the mortality rate was 0.6%. Sixteen of the 499 experienced one or more serious complications considered to be at least potentially treatment-related, and the sustained virological response rate was 7/16 (44%). Two cases, both on sofosbuvir/simeprevir (without interferon or ribavirin), had complications consistent with autoimmune events (score 3, 'likely treatment-related'), and one experienced a flare of autoimmune hepatitis. Compared to controls, cases had higher baseline median model for end-stage liver disease scores (14 vs 8, P < 0.01). Decompensation/events was independently associated with lower baseline albumin (OR = 0.12/g/dL, P = 0.01) and higher total bilirubin (OR = 4.31/mg/dL, P = 0.01). Reduced hepatic function at baseline increased the risk of liver decompensation/events., (© 2016 John Wiley & Sons Ltd.)

Background and Aim: To investigate the impact of a sustained virological response (SVR) to hepatitis C virus (HCV) treatment on liver stiffness (LS)., Methods: LS, measured by transient elastography (FibroScan), demographic and laboratory data of patients treated with interferon (IFN)-containing or IFN-free regimens who had an SVR24 (undetectable HCV viral load 24 weeks after the end of treatment) were analyzed using two-tailed paired t-tests, Mann-Whitney Wilcoxon Signed-rank tests and linear regression. Two time intervals were investigated: pre-treatment to SVR24 and SVR24 to the end of follow-up. LS scores ≥ 12.5 kPa indicated LS-defined cirrhosis. A p-value below 0.05 was considered statistically significant., Results: The median age of the patients (n = 100) was 60 years [IQR (interquartile range) 54-64); 72% were male; 60% were Caucasian; and 42% had cirrhosis pre-treatment according to the FibroScan measurement. The median LS score dropped from 10.40 kPa (IQR: 7.25-18.60) pre-treatment to 7.60 kPa (IQR: 5.60-12.38) at SVR24, p <0.01. Among the 42 patients with LS-defined cirrhosis pre-treatment, 25 (60%) of patients still had LS scores ≥ 12.5 kPa at SVR24, indicating the persistence of cirrhosis. The median change in LS was similar in patients receiving IFN-containing and IFN-free regimens: -1.95 kPa (IQR: -5.75 --0.38) versus -2.40 kPa (IQR: -7.70 --0.23), p = 0.74. Among 56 patients with a post-SVR24 LS measurement, the LS score changed by an additional -0.90 kPa (IQR: -2.98-0.5) during a median follow-up time of 1.17 (IQR: 0.88-1.63) years, which was not a statistically significant decrease (p = 0.99)., Conclusions: LS decreased from pre-treatment to SVR24, but did not decrease significantly during additional follow-up. Earlier treatment may be needed to reduce the burden of liver disease.

Background: Patients with hepatitis C virus (HCV) with or without human immunodeficiency virus (HIV) achieve high sustained virological response (SVR) rates on sofosbuvir (SOF)-containing regimens in clinical trials. Real world data on patients coinfected with HCV and HIV treated with SOF-based regimens are lacking., Methods: This observational cohort study included HIV/HCV-coinfected adults with genotype 1 HCV who initiated treatment with a SOF-containing regimen between December 2013 and December 2014 (n = 89) at the Mount Sinai Hospital or the Brooklyn Hospital Center. The primary outcome was SVR at 12 weeks after the end of treatment. The secondary outcomes were risk factors for treatment failure, serious adverse events, and side effects. A post hoc per protocol analysis of SVR was performed on patients who completed treatment and follow-up., Results: In an intention-to-treat analysis, SVR rates were 76% (31/41) for simeprevir (SMV)/SOF, 94% (16/17) for SMV/SOF/ribavirin (RBV), and 52% (16/31) for SOF/RBV. The SVR rates of SMV/SOF/RBV and SMV/SOF did not differ significantly in this small study (P = .15). However the SVR rate of SMV/SOF/RBV was higher than that of SOF/RBV (P < .01). In a per protocol analysis, SMV/SOF/RBV had a higher SVR rate than SOF/RBV: 100% (16/16) vs 57% (16/28) (P < .01). The most commonly reported adverse effects were rash, pruritus, fatigue, and insomnia. One patient who had decompensated cirrhosis prior to treatment initiation died after receiving SMV/SOF., Conclusions: SMV/SOF ± RBV is an effective option with minimal adverse effects for most HIV-positive patients with genotype 1 HCV. SMV should be used with caution in patients with decompensated cirrhosis., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Sub-Saharan African nations have among the highest rates of chronic hepatitis B virus (HBV) infection worldwide, but little is known about HBV infection in African-born persons in the United States., Methods: From October 2011 to July 2013, community-based HBV screenings were conducted targeting persons originating from Africa in New York City. Persons were identified as currently HBV infected (HBsAg positive) or exposed (HBcAb positive)., Results: Overall, 955 persons were screened for HBV; the median age was 45 years (interquartile range, 35-54 years) and 75.5% were men. Of these, 919 persons had no history of liver disease, of whom 9.6% (n = 88) had current HBV infection and 73.9% (n = 679) had exposure. In logistic regression, older age (odds ratio [OR], 0.97; 95% confidence interval [CI], .94-.99; P < .01) and female sex (OR, 0.35; 95% CI, .14-.75; P < .01) were less likely to be associated with HBV infection, whereas having a mother with hepatitis was associated with infection (OR, 18.8; 95% CI, 2.72-164.65; P < .01). HBV exposure was associated with older age (OR, 1.03; 95% CI, 1.01-1.04; P < .01), whereas female sex (OR, 0.46; 95% CI, .33-.66; P < .01) and history of blood transfusion (OR, 0.43; 95% CI, .22-.83; P = .01) were negatively associated. A patient navigator linked 97% of infected persons to care. Eleven persons were recommended for treatment, of whom 9 (82%) started therapy. Three persons were diagnosed with hepatocellular carcinoma on the first screening ultrasound., Conclusions: The high burden of HBV infection among African immigrants in the United States underscores a need for continued screening and linkage to care in this at-risk population., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Despite the clinical success in the real-world of all oral hepatitis C virus (HCV) therapy with response rates approaching that seen in the clinical trials, access has been limited by many payers with discussion of prioritization of treatment based upon AASLD guidelines. We evaluated patients in the TRIO network who were prescribed sofosbuvir (SOF)-based regimens to determine reasons for not starting treatment. Trio Health is a disease management company that works in partnership with academic medical centres, community physicians and specialty pharmacies in the United States to optimize care for HCV. Data for 3841 patients prescribed a sofosbuvir-containing regimen between December 2013 and September 2014 were obtained through this programme. Of the entire group, 315 (8%) patients did not start the prescribed sofosbuvir-containing therapy. A total of 141 (45%) of the nonstart patients had a commercial plan as their primary insurance, 137 (44%) were primarily covered by Medicaid, 17 (5%) were primarily covered by Medicare, and 20 (6%) were either without coverage or coverage was not specified. Reasons for nonstarts were varied and overlapping. Only 15 patients (5% of nonstarts) did not start because they were unreachable or failed to complete required testing. Another 39 patients who did not start (12%) were following their physicians' direction to either wait for new treatment options or to hold treatment for an unspecified reason. Insurance-related processes and financial reasons accounted for 254 (81%) of the 315 nonstarts. The remaining 7 (2%) patients did not have a specified reason for not starting treatment. Nonstart rates were highest in the Medicaid-covered population at 35%. Medicare and Commercial nonstart rates were 2% and 6%, respectively. In a matched comparison, patients with commercial coverage were 6.5 times as likely to start SOF-based therapy compared to patients with Medicaid. Despite high SVR rates of SOF-based regimens in clinical practice, there are still barriers to access to care. In fact, almost half of the nonstart patients had advanced fibrosis scores (F3 or F4) and should have been prioritized to start treatment. As better treatment for HCV with high efficacy and low side effect rates become available, the disparity in access to treatment, as evidenced by the high nonstart rate in the Medicaid-covered group, must be resolved., (© 2016 John Wiley & Sons Ltd.)

Chronic hepatitis B and C infection are the leading causes of hepatocellular carcinoma and liver related death in the world and in the United States respectively. Screening guidelines have been developed based on estimated prevalence determined by NHANES data. However, individuals with the most risk of chronic infection (incarcerated, homeless, immigrants, nursing home residents, and hospitalized persons) are underrepresented in this cohort leading to an underestimation of the true prevalence of chronic hepatitis B and C infection. This has led to recent updates in the screening guidelines. This review examines the change in the guidelines, the likely true seroprevalence of hepatitis B and C virus, as well as the burden of chronic infection in this population.

Background: In the era of combination therapy for human immunodeficiency virus (HIV), liver disease, and hepatocellular carcinoma (HCC) are major causes of death for patients coinfected with HIV and hepatitis B virus (HBV). This study compared HIV provider and hepatologist awareness of and adherence to the American Association for the Study of Liver Diseases (AASLD) practice guidelines for chronic HBV management. The primary endpoint of HIV provider adherence to HCC screening recommendations was compared to that of hepatologists at a large metropolitan academic medical center., Methods: Medical record database searches by ICD-9 codes were used to identify HIV/HBV coinfected (n = 144) and HBV monoinfected (n = 225) patients who were seen at least twice over a 2-year period in outpatient clinics. Adherence to AASLD guidelines was assessed by chart review. Provider awareness was evaluated through a voluntary anonymous survey with knowledge-based questions., Results: Over a 2-year period, only 36.0% of HIV/HBV coinfected patients seen in HIV practices completed HCC screening compared to 81.8% of HBV monoinfected patients in hepatology practices (P < .00001). Similarly, HIV providers less frequently monitored HBV viral load (P < .0001), HBeAg/anti-HBe (P < .00001), HBsAg/anti-HBs (P < .00001) than hepatologists but screened more often for hepatitis A immunity (P = .028). Self-reported adherence and knowledge scores were similar among 19 HIV providers and 16 hepatologists., Conclusions: HIV providers ordered significantly fewer HCC screening and HBV monitoring tests than hepatologists within a single academic medical center. In the setting of increased reliance on quality indicators for care, both patients and providers will benefit from greater adherence to established guidelines., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Chronic hepatitis B (CHB) continues to be an important public health problem worldwide, including in the United States. An algorithm for managing CHB was developed by a panel of United States hepatologists in 2004 and subsequently updated in 2006 and 2008. Since 2008, additional data on long-term safety and efficacy of licensed therapies have become available and have better defined therapeutic options for CHB. The evidence indicates that potent antiviral therapy can lead to regression of extensive fibrosis or even cirrhosis, thus potentially altering the natural history of CHB. In addition, appropriate choice of antiviral agent can minimize the risk of resistance. This updated algorithm for managing CHB is based primarily on evidence from the scientific literature. Where data were lacking, the panel relied on clinical experience and consensus expert opinion. The primary aim of antiviral therapy for CHB is durable suppression of serum hepatitis B virus (HBV) DNA to low or undetectable levels. CHB patients who have HBV DNA >2000 IU/mL, elevated alanine aminotransferase level, and any degree of fibrosis should receive antiviral therapy regardless of their hepatitis B e antigen status. CHB patients with HBV DNA >2000 IU/mL and elevated alanine aminotransferase level but no evidence of fibrosis may also be considered for antiviral therapy. Approved antiviral therapies for CHB are interferon alfa-2b, peginterferon alfa-2a, lamivudine, adefovir, entecavir, telbivudine, and tenofovir, although the preferred first-line treatment choices are peginterferon alfa-2a, entecavir, and tenofovir. In determining choice of therapy, considerations include efficacy, safety, rate of resistance, method of administration, duration, and cost., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Nonalcoholic fatty liver disease is a common cause of chronic liver disease and has been an increasingly studied topic of research as the obesity epidemic has been growing. There is a significant morbidity and mortality with uncontrolled steatohepatitis, which can progress to fibrosis, cirrhosis and hepatocellular carcinoma. The prevalence of this disease has been estimated to be roughly one-third of the western population, thought to be largely due to diet and sedentary lifestyle. Several treatments have been studied including vitamin E, insulin-sensitizing agents and ursodeoxycholic acid; however, the only treatment shown to improve the histologic changes of nonalcoholic fatty liver disease is weight loss. Given the proven benefit of weight loss, there may be reason to screen at-risk populations; however, limited availability of other disease-modifying treatments may limit the cost-benefit ratios. A better understanding of the diagnosis and management of this condition is required to alter the course of this modifiable disease.

Between 15% and 30% of patients infected with HIV in the United States and Europe are coinfected with hepatitis C virus (HCV), and rates of acute HCV infection have been increasing in some populations of HIV-positive patients. Liver disease is now a leading cause of death in HIV-infected patients. Patients with HIV/HCV coinfection have lower rates of spontaneous acute HCV clearance, poorer response to treatment of chronic HCV in the pre-direct-acting antiviral era, more rapid progression to cirrhosis, and increased risk of hepatocellular carcinoma. This article will summarize data on management of HIV/HCV coinfection, discuss the epidemic of acute HCV infection in HIV-infected patients, and examine the many new HCV treatment regimens on the horizon with data on coinfected patients.

Background: Hepatic encephalopathy (HE) represents a significant burden to the healthcare system. The aim of this study was to determine factors influencing the hospital length of stay among patients hospitalized with HE., Methods: A data warehouse query was performed to identify 316 patients with a first hospitalization during which HE occurred, between April 2010 and February 2012. Baseline and hospitalization characteristics were collected with IRB approval. A negative binomial multivariable model was used to control for potential confounders on the length of hospitalization., Results: Median age was 59 years, and 60.4% of admitted patients were male. The median MELD score was 22 (IQR: 17-28). Median length of stay was 8 days (IQR: 3.25-14.25). After controlling for MELD score, female gender (2.2 days; p = 0.04), being initially admitted for a reason other than HE (liver-related: 7.6 days; p < 0.01 and non liver-related 10.7 days; p < 0.01) and receiving antibiotics other than rifaximin (10.5 days; p < 0.01) were associated with longer length of stay whereas hepatitis C (-3.1 days; p < 0.01) was associated with a shorter length of stay., Conclusions: MELD score, gender, use of antibiotics other than rifaximin, reason for admission and hepatitis C are predictors readily available in clinic that can help identify patients at risk for longer length of stay.

Unlabelled: In registration trials, triple therapy with telaprevir (TVR), pegylated interferon (Peg-IFN), and ribavirin (RBV) achieved sustained virological response (SVR) rates between 64% and 75%, but the clinical effectiveness and economic burdens of this treatment in real-world practice remain to be determined. Records of 147 patients who initiated TVR-based triple therapy at the Mount Sinai Medical Center (May-December 2011) were reviewed. Direct medical costs for pretreatment, on-treatment, and posttreatment care were calculated using data from Medicare reimbursement databases, RED Book, and the Healthcare Cost and Utilization Project database. Costs are presented in 2012 U.S. dollars. SVR (undetectable hepatitis C virus [HCV] RNA 24 weeks after the end of treatment) was determined on an intention-to-treat basis. Cost per SVR was calculated by dividing the median cost by the SVR rate. Median age of the 147 patients was 56 years (interquartile range [IQR] = 51-61), 68% were male, 19% were black, 11% had human immunodeficiency virus/HCV coinfection, 36% had advanced fibrosis/cirrhosis (FIB-4 scores ≥3.25), and 44% achieved an SVR. The total cost of care was $11.56 million. Median cost of care was $83,721 per patient (IQR = $66,652-$98,102). The median cost per SVR was $189,338 (IQR = $150,735-$221,860). Total costs were TVR (61%), IFN (24%), RBV (4%), adverse event management (8%), professional fees (2%), and laboratory tests (1%)., Conclusions: TVR and Peg-IFN accounted for 85% of costs. Pharmaceutical prices and the low (44%) SVR rate, in this real-world study, were major contributors to the high cost per SVR., (© 2014 by the American Association for the Study of Liver Diseases.)

Introduction: Liver disease is a major burden in patients co-infected with HIV and hepatitis C virus (HCV). From the time of its approval, pegylated-IFNα-2a (pegIFN-α2a) has played a major role in treatment of HCV in HIV/HCV co-infection., Areas Covered: This article briefly summarizes the epidemiology of HCV/HIV co-infection, the pharmacokinetic, and pharmacodynamic properties of pegIFN-α2a. Results from clinical trials investigating therapies containing pegIFN-α2a for HIV/HCV co-infected patients will be discussed with a focus on efficacy and safety., Expert Opinion: PegIFN-α2a has improved rates of sustained virologic response for co-infected patients. In combination with direct-acting antivirals (DAA), the disparity between mono- and co-infected patients is beginning to disappear. For the first time, IFN-free regimens are available in clinical practice. It is unlikely that pegIFN-α2a will continue to be a critical component in treatments for HCV in the general co-infected population.