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Background & Aims Non‐alcoholic fatty liver disease (NAFLD) affects about 25% of the general population worldwide. Although epidemiology of NAFLD is well studied in the United States, there is paucity of data for the Asian Americans. Our aim was to assess the prevalence and risk factors for NAFLD among Asian Americans. Methods We utilized NHANES data for 2011‐2016. We defined NAFLD using recently derived US‐FLI. Relative risks (RRs) and population attributable fractions (PAFs) of metabolic components on atherosclerotic cardiovascular disease (ASCVD) and advanced fibrosis were calculated for Asian Americans, and these rates were compared to non‐Hispanic whites. Results NAFLD prevalence was 18.3% among Asian Americans and 28.4% among non‐Hispanic whites. Asian Americans with NAFLD had lower BMI and waist circumference than non‐Hispanic whites with NAFLD and were less likely to have metabolic syndrome, cardiovascular disease (CVD), chronic obstructive pulmonary disease, cancer and incident ASCVD (P < 0.05). Hyperlipidaemia had the highest attributable fraction (76.6%) for risk of ASCVD among Asian Americans with NAFLD, followed by diabetes (24.0%), current smoking (9.2%), and obesity (3.7%). Advanced fibrosis in Asian American with NAFLD was independently associated with presence of type 2 diabetes (RR = 2.70, 95% CI: 1.00‐7.27). Conclusions Asian Americans have lower prevalence of NAFLD than non‐Hispanic whites. However, Asian Americans with NAFLD have similar risk factors for advanced fibrosis and ASCVD than non‐Hispanic Whites.

OBJECTIVES:Data from the United States are lacking regarding the impact of entecavir (ETV) on the risk of hepatocellular carcinoma (HCC). Our aim is to determine whether treatment with ETV is associated with a reduced HCC risk by calculating the expected HCC incidence based on the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) model and comparing it with the observed HCC incidence. METHODS:The incidence of HCC in US patients treated with ETV between 2005 and 2013 in a retrospective cohort was obtained. The predicted HCC incidence was calculated using the REACH-B model. The standardized incidence ratios (SIRs) were calculated as a ratio of observed over predicted HCC cases. RESULTS:Of 841 patients, 646 (65% male, 84% Asian, median age 47 years, 36% hepatitis B e antigen positive, 9.4% with cirrhosis) met the inclusion criteria. Over a median follow-up of 4 years, 17 (2.6%) cases of HCC were diagnosed, including 8 out of 61 (13.1%) patients with cirrhosis and 9 out of 585 (1.5%) without cirrhosis. Compared with those without HCC, the 17 patients with HCC were older at 53 years vs. 47 years and more likely to have cirrhosis at 47.1% vs. 8.4%. Among patients without cirrhosis, the observed HCC incidence was signifi cantly lower than predicted by the fourth year (SIR, 0.37; 95% confi dence interval: 0.166-0.82). A sensitivity analysis that comprised all patients, including those with cirrhosis, showed that at the maximum follow-up time of 8.2 years, a signifi cantly lower than predicted HCC incidence was noted with an SIR of 0.56 (95% confi dence interval: 0.35-0.905).CONCLUSIONS: Based on the REACH-B model, long-term ETV therapy was associated with a lower than predicted HCC incidence. However, the risk of HCC persisted, and careful HCC surveillance remains warranted despite the anti-viral treatment.SUPPLEMENTARY MATERIAL is linked to the online version of the paper at

Objectives: Preclinical data suggest histone deacetylase inhibitors improve the therapeutic index of sorafenib. A phase I study was initiated to establish the recommended phase 2 dose of sorafenib combined with vorinostat in patients with unresectable hepatocellular carcinoma. Materials and Methods: Patients received vorinostat (200 to 400 mg by mouth once daily, 5 of 7 d) and sorafenib at standard or reduced doses (400 mg [cohort A] or 200 mg [cohort B] by mouth twice daily). Patients who received 14 days of vorinostat in cycle 1 were evaluable for dose-limiting toxicity (DLT). Results: Sixteen patients were treated. Thirteen patients were evaluable for response. Three patients experienced DLTs, 2 in cohort A (grade [gr] 3 hypokalemia; gr 3 maculopapular rash) and 1 in cohort B (gr 3 hepatic failure; gr 3 hypophosphatemia; gr 4 thrombocytopenia). Eleven patients required dose reductions or omissions for non-DLTtoxicity. Ten patients (77%) had stable disease (SD). The median treatment duration was 4.7 months for response-evaluable patients. One patient with SD was on treatment for 29.9 months, and another patient, also with SD, was on treatment for 18.7 months. Another patient electively stopped therapy after 15 months and remains without evidence of progression 3 years later. Conclusions: Although some patients had durable disease control, the addition of vorinostat to sorafenib led to toxicities in most patients, requiring dose modifications that prevented determination of the recommended phase 2 dose. The combination is not recommended for further exploration with this vorinostat schedule in this patient population.

It is estimated that two billion people worldwide have been infected with hepatitis B virus (HBV) with more than 350 million with chronic infection. AbstractThe management of chronic hepatitis B (CHB) during pregnancy remains a challenge and involves various aspects of maternal-fetal care. Despite the standard immunoprophylaxis, a significant portion of infants born to highly viremic mothers remain infected with hepatitis B virus (HBV). Emerging data suggest that antiviral therapy in the third trimester can prevent immunoprophylaxis failure. To minimize fetal exposure to antiviral agents, antiviral therapy during pregnancy should be reserved for mothers with advanced disease or who are at risk for hepatic decompensation. Current safety data suggest that lamivudine, telbivudine, or tenofovir may be used during pregnancy. However, the timing in initiating antiviral therapy requires careful assessment of risks and benefit. The authors provide a systematic review of the features of HBV during pregnancy, risk factors for vertical transmission, and evidence-based data on antiviral use during pregnancy. They propose an algorithm to assess the need of antiviral treatment and monitor mothers with CHB.

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Background and Aims Gut microbiota, including bacteria and phages, are altered in cirrhosis, but their role during infections and spontaneous bacterial peritonitis (SBP) prophylaxis is unclear. Our aim was determine metagenomic changes in gut bacteria; phages and their linkages centered around Gram‐negative and Gram‐positive pathobionts in patients with cirrhosis with/without infections or SBP prophylaxis. Approach and Results We included uninfected (n = 231) and infected (n = 30, SBP n = 19 and urinary tract infection n = 11 before antibiotics) patients who gave stool for bacterial and phage metagenomics. We matched uninfected to infected patients 1:1 on a model for end‐stage liver disease (MELD). We also analyzed subgroups of patients with ascites matched on an MELD (n = 73) to patients on SBP prophylaxis (n = 7) and then to SBP infection. Phage and bacterial taxa differences (DESeq2) and correlation networks centered around Escherichia coli and Enterococcus faecium were analyzed. Infections were mostly due to Enterobacteriaceae and Enterococcus spp. On metagenomics, higher fold changes of Enterobacteriaceae members, Enterococcus and Streptococcus spp., and Escherichia phages were seen in infected patients. Correlation networks showed more complex bacteria‐phage linkages in infected patients compared with uninfected ones overall and centered around E. coli and E. faecium. SBP prophylaxis induced higher Gram‐positive bacteria. In SBP, Enterococcus and Escherichia were higher versus ascites. Correlation networks around E. coli were complex in ascites but sparse with SBP prophylaxis, whereas the reverse was seen with E. faecium. Lytic phages and those associated with antibiotic resistance were correlated with E. faecium. Conclusion In cirrhosis, there are significant changes in phage‐bacterial linkages in infected patients and those on SBP prophylaxis compared to the remaining patients. SBP prophylaxis enriches complexity of E. faecium–centered but induces a collapse in E. coli–centered phage‐bacterial correlations.

Representatives from academia, industry, regulatory agencies, and patient advocacy groups convened under the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) in June 2022 with the primary goal of achieving consensus on chronic HBV and HDV treatment endpoints to guide clinical trials aiming to “cure” HBV and HDV. Conference participants reached an agreement on some key points. The preferred primary endpoint for phase II/III trials evaluating finite treatments for chronic hepatitis B (CHB) is a “functional” cure, defined as sustained HBsAg loss and HBV DNA less than the lower limit of quantitation (LLOQ) 24 weeks off-treatment. An alternate endpoint would be “partial cure” defined as sustained HBsAg level < 100 IU/mL and HBV DNA < LLOQ 24 weeks off-treatment. Clinical trials should initially focus on patients with HBeAg positive or negative CHB, who are treatment-naive or virally suppressed on nucleos(t)ide analogs. Hepatitis flares may occur during curative therapy and should be promptly investigated and outcomes reported. HBsAg loss would be the preferred endpoint for chronic hepatitis D, but HDV RNA < LLOQ 24 weeks off-treatment is a suitable alternate primary endpoint of phase II/III trials assessing finite strategies. For trials assessing maintenance therapy, the primary endpoint should be HDV RNA < LLOQ assessed at on-treatment week 48. An alternate endpoint would be ≥2 log reduction in HDV RNA combined with normalization of alanine aminotransferase level. Suitable candidates for phase II/III trials would be treatment-naiive or experienced patients with quantifiable HDV RNA. Novel biomarkers (hepatitis B core–related antigen [HBcrAg] and HBV RNA) remain exploratory, while nucleos(t)ide analogs and pegylated interferon still have a role in combination with novel agents. Importantly, patient input is encouraged early on in drug development under the FDA/EMA patient–focused drug development programs.