Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression, and outcomes of NAFLD and nonalcoholic steatohepatitis (NASH). PubMed/MEDLINE were searched from 1989 to 2015 for terms involving epidemiology and progression of NAFLD. Exclusions included selected groups (studies that exclusively enrolled morbidly obese or diabetics or pediatric) and no data on alcohol consumption or other liver diseases. Incidence of hepatocellular carcinoma (HCC), cirrhosis, overall mortality, and liver-related mortality were determined. NASH required histological diagnosis. All studies were reviewed by three independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication, and study population. We used random-effects models to provide point estimates (95% confidence interval [CI]) of prevalence, incidence, mortality and incidence rate ratios, and metaregression with subgroup analysis to account for heterogeneity. Of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. . Fibrosis progression proportion, and mean annual rate of progression in NASH were 40.76% (95% CI: 34.69-47.13) and 0.09 (95% CI: 0.06-0.12). HCC incidence among NAFLD patients was 0.44 per 1,000 person-years (range, 0.29-0.66). Liver-specific mortality and overall mortality among NAFLD and NASH were 0.77 per 1,000 (range, 0.33-1.77) and 11.77 per 1,000 person-years (range, 7.10-19.53) and 15.44 per 1,000 (range, 11.72-20.34) and 25.56 per 1,000 person-years (range, 6.29-103.80). Incidence risk ratios for liver-specific and overall mortality for NAFLD were 1.94 (range, 1.28-2.92) and 1.05 (range, 0.70-1.56). Conclusions: As the global epidemic of obesity fuels metabolic conditions, the clinical and economic burden of NAFLD will become enormous. (HEPATOLOGY 2016;64:73-84)

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Chronic hepatitis C (CHC) affects over 185 million individuals worldwide, approximately 3% of the world's population. CHC can lead to quality of life impairment, cirrhosis, hepatocellular carcinoma (HCC), liver failure and liver-related death. While CHC has been associated with increases in HCC, liver-related mortality and all-cause mortality, being cured of CHC is associated with improvement in these outcomes. Older interferon-based regimens were complex and toxic and required 6-12 months of therapy, with cure rates averaging around 40-45% for HCV genotype 1. Newer interferon-free regimens are now available in the US, Europe, Japan and in other countries. These regimens have short durations, minimal side effects, low pill burden and efficacy approaching 90-100%. We may eventually see single-tablet regimens lasting no more than 4-6 weeks. This review will summarize the data regarding these interferon-free regimens, including Gilead's Harvoni (sofosbuvir/ledipasvir), AbbVie's Viekira Pak (paritaprevir/ritonavir/ombitasvir with dasabuvir), and Janssen's Olysio (simeprevir) with sofosbuvir. Some practical considerations as we move into an interferon-free era will also be discussed, such as patient adherence and drug-drug interactions.

Nonalcoholic steatohepatitis (NASH) can lead to complications such as liver failure, cirrhosis and hepatocellular carcinoma. The diagnostic gold standard for NASH is liver biopsy; however, other noninvasive methods have been developed. In this article, the authors evaluate current methods in NASH screening and diagnosis. Routine radiologic modalities were found to detect hepatic steatosis accurately, but were unable to establish the diagnosis of NASH or stage of fibrosis. Newly developed elastography based techniques seem promising to estimate liver fibrosis. Other noninvasive tests such as FibroTest, ELF, Hepascore, FIB-4, NFS, FLI and ION (biochemical panels) have AUROCs ranging between 0.80-0.98 for detecting advanced fibrosis but lack specificity for detecting mild fibrosis. Noninvasive tools, especially elastography, identify NASH associated advanced fibrosis potentially reducing liver biopsies. More research is needed to validate the clinical utility of these tests.

In trials enrolling more than 3000 patients, LDV/SOF is well tolerated with a good safety and side-effect profile in diverse cohorts, including previous direct-acting antiviral (DAA) treatment failures, liver transplant recipients, decompensated cirrhosis and HIV/HCV co-infection. As with all DAAs, the potential for drug-drug interactions must be carefully evaluated, as demonstrated by recent post-marketing reports of symptomatic bradycardia when LDV/SOF is co-administered with amiodarone. Currently, dose recommendations cannot be given for patients with advanced renal disease. Trials in this population are ongoing, more study is warranted. When surveying the DAA regimens available, efficacy, safety and tolerability of LDV/SOF is comparable or better, and LDV/SOF provides an option with convenient single-tablet, once daily, ribavirin-free dosing with relatively few significant drug-drug interactions.

The human leukocyte antigen (HLA) genes may play a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH). The aim of this study was to assess the association of HLA class I and II alleles with NASH and its histological features. Deoxyribonucleic acid (DNA) was extracted from 140 subjects (85 biopsy-proven NAFLD and 55 controls) and genotyped for HLA (-A, -B, -C, -DR1, -DR3, -DQ, and -DP). Liver biopsies were assessed for presence of NASH, degree of fibrosis and inflammation. Multivariate analysis was performed to assess associations between HLA genes and different histologic features of NAFLD. Our data for HLA class I showed that HLA-C∗4 was associated with lower risk for histologic NASH and HLA-C∗6 was protective against portal fibrosis. Conversely, HLA-B∗27 was associated with high-grade hepatic steatosis, while HLA-A∗31 was associated with increased risk for advanced fibrosis. Among HLA class II alleles, HLA-DQA1∗01 was associated with lower risk for NASH while HLA-DRB1∗03 was associated with increased risk for NASH. Our findings indicate that HLA class I and II gene polymorphism may be associated with susceptibility to NASH, fibrosis and other pathologic features and may be involved in the pathogenesis of NAFLD.

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