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In the United States, non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and associated with higher mortality according to data from earlier National Health and Nutrition Examination Survey (NHANES) 1988-1994. Our goal was to determine the NAFLD prevalence in the recent 1999-2012 NHANES, risk factors for advanced fibrosis (stage 3-4) and mortality. NAFLD was defined as having a United States Fatty Liver Index (USFLI) > 30 in the absence of heavy alcohol use and other known liver diseases. The probability of low/high risk of having advanced fibrosis was determined by the NAFLD Fibrosis Score (NFS). In total, 6000 persons were included; of which, 30.0% had NAFLD and 10.3% of these had advanced fibrosis. Five and eight-year overall mortality in NAFLD subjects with advanced fibrosis was significantly higher than subjects without NAFLD ((18% and 35% vs. 2.6% and 5.5%, respectively) but not NAFLD subjects without advanced fibrosis (1.1% and 2.8%, respectively). NAFLD with advanced fibrosis (but not those without) is an independent predictor for mortality on multivariate analysis (HR = 3.13, 95% CI 1.93-5.08, p<0.001). In conclusion, in this most recent NHANES, NAFLD prevalence remains at 30% with 10.3% of these having advanced fibrosis. NAFLD per se was not a risk factor for increased mortality, but NAFLD with advanced fibrosis was. Mexican American ethnicity was a significant risk factor for NAFLD but not for advanced fibrosis or increased mortality.

Previous studies, mostly small and single center, have shown gaps in the evaluation and monitoring of patients with chronic hepatitis B (CHB) virus infection. We aimed to examine the rates and predictors of adherence to guidelines for CHB care in a large nationwide cohort. We identified adult patients with CHB infection from the Truven MarketScan databases of commercially insured and Medicare patients with private insurance supplement (2007-2014) using International Classification of Diseases, Ninth Revision, Clinical Modification codes. The initial evaluation cohort had at least 6 months follow-up, whereas at least 12 months was required for the long-term monitoring cohort. We analyzed 55,317 eligible patients with CHB infection: mean age 46 ± 12 years, 58% men, and 14.8% with cirrhosis. Over a mean follow-up of 3.2 ± 2.3 years, 55.8% had specialist (gastroenterology or infectious diseases) visits. For initial evaluation, 59% of patients received both alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA tests, whereas only 33% had ALT, HBV DNA, and hepatitis B e antigen tests, with higher frequencies among patients with specialist visits. For long-term monitoring, only 25% had both ALT and HBV DNA tests performed annually. Among patients at higher risk of developing hepatocellular carcinoma (patients with cirrhosis, male patients without cirrhosis older than 40 years, and female patients without cirrhosis older than 50), less than 40% underwent annual hepatocellular carcinoma surveillance, with 25% never receiving surveillance during the study period. Predictors of optimal initial evaluation and long-term monitoring were compensated cirrhosis (odds ratio: 1.60 and 1.47, respectively) and specialist visits (odds ratio: 1.86 and 1.31, respectively) (both P < 0.001). In this large cohort of patients with CHB infection with private insurance or Medicare with private insurance supplement, we observed poor adherence to the recommended initial evaluation and long-term monitoring. Among the predictors of adherence were specialist visits. Further efforts are needed to identify barriers and improve access to care.

Nonalcoholic fatty liver disease (NAFLD) and infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) are major causes of liver disease in adults. However, data for children and adolescents are limited. Our study aimed to characterize the prevalence, trend, and risk factors of infection of HBV and HCV and possible NAFLD for this population. We analyzed 6,647 children and adolescents (aged 6-21 years) from the 1999-2016 National Health and Nutrition Examination Survey. Among individuals aged 6-21 years, HBV prevalence decreased after 2011, from 0.72% in 1999-2004 and 0.85% in 2005-2010 to 0.27% in 2011-2016 (P < 0.001), whereas HCV prevalence increased to 0.26% in 2011-2016 after an initial decline from 0.15% in 1999-2004 to 0.02% in 2005-2010 (P = 0.01). Possible NAFLD prevalence also increased by approximately 40% in individuals aged 12-21 years, from 8.54% in 1999-2004 to 10.1% in 2005-2010 and then 11.8% in 2011-2016 (P = 0.033), with most possible NAFLD individuals being male, being obese, or having higher glucose, fasting insulin, hemoglobin A1c, homeostatic model assessment of insulin resistance, liver enzymes, lipids, and uric acid (all P < 0.01). On multivariate logistic regression, hypertension (odds ratio 4.79, 95% confidence interval 1.44-15.9) and dyslipidemia (odds ratio 11.6, 95% confidence interval 5.65-23.9) increased risk for possible NAFLD but not income:poverty ratio, hours spent on computer use, or added sugars. Although HBV prevalence has decreased in recent years among US children and adolescents, HCV and possible NAFLD have increased. Public health efforts must seek further understanding of the driving factors of this increase so that age-appropriate interventions can be developed and implemented.

BackgroundNAFLD is increasing in Asia including Japan, despite its lower obesity rate than the West. However, NAFLD can occur in lean people, but data are limited. We aimed to investigate the epidemiology of NAFLD in Japan with a focus on lean NAFLD.MethodsWe searched PubMed, Cochrane Library, EMBASE, Web of Science, and the Japan Medical Abstracts Society (inception to 5/15/2019) and included 73 eligible full-text original research studies (n = 258,531). We used random-effects model for pooled estimates, Bayesian modeling for trend and forecasting, contacted authors for individual patient data and analyzed 14,887 (7752 NAFLD; 7135 non-NAFLD—8 studies) patients.ResultsThe overall NAFLD prevalence was 25.5%, higher in males (p < 0.001), varied by regions (p < 0.001), and increased over time (p = 0.015), but not by per-person income or gross prefectural productivity, which increased by 0.64% per year (1983–2012) and is forecasted to reach 39.3% in 2030 and 44.8% in 2040. The incidence of NAFLD, HCC, and overall mortality were 23.5, 7.6 and 5.9 per 1000 person-years, respectively. Individual patient-level data showed a lean NAFLD prevalence of 20.7% among the NAFLD population, with lean NAFLD persons being older and with a higher all-cause mortality rate (8.3 vs. 5.6 per 1000 person-years for non-lean NAFLD, p = 0.02). Older age, male sex, diabetes, and FIB-4 were independent predictors of mortality, but not lean NAFLD.ConclusionNAFLD prevalence has increased in Japan and may affect half of the population by 2040. Lean NAFLD individuals makeup 20% of the NAFLD population, were older, and had higher mortality.

BackgroundGenotype 3 (GT3) is a common chronic hepatitis C (CHC) genotype in Asia. Direct-acting antiviral (DAA) regimens have high cure rates, but real-world results are limited for Asia.AimTo determine the real-world effectiveness of DAAs for patients with CHC GT3 in Asia.MethodsA systematic search was performed in PubMed (including MEDLINE), Embase, and selected international meeting abstract repositories. Eligible studies were postmarketing observational studies from Asia with the primary outcome of sustained virological response 12 weeks after completion of treatment (SVR12).ResultsA total of 15 studies with 4230 patients yielded a pooled SVR12 of 92.7%. High heterogeneity (I2=93.2%, P<0.0001) was noted. In subgroup analyses, patients with cirrhosis had 10.9% lower SVR12 than non-cirrhotic patients (88.6% vs 98.9%; P<0.0001) and contributed 69.5% of the heterogeneity. Prior treatment failure did not reduce the pooled SVR12 (treatment-naïve: 94.6%, 95% CI 91.3% to 96.7% vs treatment-experienced: 94.0%, 95% CI 77.5% to 98.6%; P=0.89). Twenty-four weeks of sofosbuvir+ribavirin dual therapy was the most commonly used regimen which led to similar SVR12 (OR=1.1, P=0.73) but lower adverse event rate than 12 weeks of sofosbuvir+ribavirin+pegylated interferon triple therapy.ConclusionSofosbuvir+ribavirin for 24 weeks is the most widely used and generally well-tolerated DAA therapy in Asia. However, its effectiveness is not optimal in GT3 patients with cirrhosis.

BackgroundSofosbuvir plus ribavirin (SOF+RBV) for 12 weeks is the standard treatment for chronic hepatitis C (CHC) genotype 2 (GT2) in most of Asia despite availability of new CHC medications. SOF-RBV real-world effectiveness has only been reported in small and/or single-centre studies. Our goal was to determine the real-world effectiveness of 12-week SOF+RBV therapy for CHC GT2 in Asia.MethodsA systematic search on PubMed and Embase was conducted through 30 June 2017. We identified full articles and conference proceedings of at least 10 adult patients with CHC GT2 treated with SOF+RBV for 12 weeks under real-world setting in Asia.ResultsA total of 2208 patients from 13 studies were included. The pooled sustained virological response 12 weeks after the end of treatment (SVR12) was 95.8% (95% CI 94.6% to 96.9%) with non-significant heterogeneity (I2=34.4%). Anaemia (27.9%) was the most common adverse event (AE), with serious AEs in 2.0% and only 0.7% discontinued therapy prematurely. In subgroup analyses, patients with cirrhosis had 8.7% lower SVR12 than non-cirrhotic patients (P<0.0001), and treatment-experienced patients had 7.2% lower SVR12 than treatment-naïve patients (P=0.0002). Cirrhotic treatment-experienced patients had the lowest SVR12 at 84.5%. There were no significant differences in pooled SVR12 among patient subgroups: RBV dose reduction versus no dose reduction (P=0.30); hepatocellular carcinoma (HCC) versus no HCC (P=0.10); GT 2a versus 2b (P=0.86); and <65 vs ≥65 years of age (P=0.20).ConclusionsSOF+RBV for 12 weeks was safe and effective for patients with CHC GT2 in Asia, although those with cirrhosis and prior treatment failure had a lower pooled SVR12 rate.Trial registration numberCRD42017067928.

The World Health Assembly has called for the elimination of hepatitis B and C by 2030. As hepatitis B has no cure, the US strategy to eliminate hepatitis B has focused on prevention through vaccination. However, there are limited data on the trend in vaccine-associated immunity since the US implementation of universal infant hepatitis B vaccination. To compare self-reported hepatitis B vaccination coverage among children and adolescents with serologic evidence of immunity and infection in the US from 1999 to 2016. This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016. US-born persons aged 2 to 18 years without missing hepatitis B serologic test results and with reported vaccination history were included. Data were analyzed from September 2017 to June 2018. The proportion of participants who reported complete vaccination for hepatitis B and who had positive serologic test results indicating immunity. Of 21 873 children and adolescents, 51.2%% were male, and the mean (SD) age was 10.6 (4.6) years. The survey reported that hepatitis B vaccination coverage increased significantly from 1999 to 2016 (from 62.6% [95% CI, 58.6%-66.4%] to 86.3% [95% CI, 82.9%-89.2%]; P < .001). Vaccine-associated immunity also increased from 1999 to 2016 among children aged 2 to 5 years (from 60.7% [95% CI, 48.8%-71.4%] to 65.2% [95% CI, 57.4%-72.3%]; P = .001) but decreased among children aged 6 to 10 years (from 64.6% [95% CI, 57.7%-70.9%] to 46.5% [95% CI, 39.1%-54.0%]; P < .001), adolescents aged 11 to 13 years (from 68.8% [95% CI, 58.1%-77.8%] to 26.2% [95% CI, 18.6%-35.5%]; P < .001), and adolescents aged 14 to 18 years (from 68.5% [95% CI, 62.9%-73.6%] to 15.6% [95% CI, 12.2%-19.8%]; P < .001). By birth year, serologic evidence of vaccine-associated immunity significantly decreased in the 1994-2003 NHANES birth cohort but not among those born between 1988 and 1993. Non-US-born children and adolescents did not show the same decreasing trend in immunity. In this cross-sectional study, decreasing hepatitis B immunity was observed among US-born children and adolescents in the 1994-2003 NHANES birth cohort despite increasing rates of hepatitis B vaccination coverage. These findings suggest a possible need for surveillance and a booster vaccine dose for hepatitis B as those without serologic evidence of immunity become young adults and may engage in behaviors associated with an increased risk for infection.

Abstract Background Global metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is estimated at 30% and projected to reach 55.7% by 2040. In the Veterans Affairs (VA) healthcare system, an estimated 1.8 million veterans have metabolic dysfunction-associated steatohepatitis (MASH). Methods Adult patients at risk for MASLD in a VA healthcare system underwent Fibrosis-4 (FIB-4) and Enhanced Liver Fibrosis (ELF®) testing. Referral rates and cost savings were compared among 6 noninvasive testing (NIT) strategies using these 2 tests independently or sequentially at various cutoffs. Results Enrolled patients (N = 254) had a mean age of 65.3 ± 9.3 years and mean body mass index (BMI) of 31.7 ± 6, 87.4% male: 78.3% were non-Hispanic/Latino, and 96.5% had type 2 diabetes mellitus (T2DM). Among the 6 evaluated strategies, using FIB-4 followed by ELF at a 9.8 cutoff yielded the highest proportion of patients retained in primary care without need of referral to hepatology clinic (165/227; 72.7%), and was associated with the lowest costs ($407.62). Compared to the FIB-4 only strategy, FIB-4/ELF with a 9.8 cutoff strategy resulted in 26% fewer referrals and 8.47% lower costs. In the subgroup of patients with BMI >32, there were 25.17% fewer referrals and costs were 8.31% lower. Conclusions Our study suggests that sequential use of ELF with a 9.8 cutoff following indeterminate FIB-4 tests results in lower referral rates and lower care costs in a veteran population at risk of MASLD. Adding ELF as a sequential test after indeterminate FIB-4 might help reduce the number of referrals and overall cost of care.

Purpose of ReviewChronic hepatitis B (CHB) remains a major global contributor to liver related morbidity and mortality. Currently available first line therapies offer all oral, highly effective, and safe treatment options for suppression of hepatitis B virus (HBV) and reduce long-term CHB-related complications. This review summarizes some of the more recent real-world data on the safety and effectiveness of oral nucleos(t)ide analogs in the treatment of CHB.Recent FindingsCurrent first line CHB oral treatment options include entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF). Recent real-world evidence continues to emphasize the highly effective nature of these therapies in suppressing HBV DNA and normalization of alanine aminotransferase. While all of these oral nucleos(t)ide analogs are relatively safe and well-tolerated, we include some recent data illustrating the potential benefit of TAF among CHB patients at risk for chronic kidney disease or osteopenia/osteoporosis.SummaryWhile highly effective and safe oral antiviral therapies are available for CHB treatment, disparities in timely CHB diagnosis and linkage to care and treatment remain. Improvements in HBV screening for early CHB diagnosis as well as effective programs to link known CHB patients into care and treatment are urgently needed.