Linda Henry

Global epidemiology of nonalcoholic fatty liver disease—Meta‐analytic assessment of prevalence, incidence, and outcomes

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. Global prevalence of NAFLD is 25.24% (95% CI: 22.10‐28.65) with highest prevalence in the Middle East and South America and lowest in Africa. Metabolic comorbidities associated with NAFLD included obesity (51.34%; 95% CI: 41.38‐61.20), type 2 diabetes (22.51%; 95% CI: 17.92‐27.89), hyperlipidemia (69.16%; 95% CI: 49.91‐83.46%), hypertension (39.34%; 95% CI: 33.15‐45.88), and metabolic syndrome (42.54%; 95% CI: 30.06‐56.05). 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)

Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009

Hepatocellular carcinoma (HCC) is increasingly reported in patients with nonalcoholic fatty liver disease (NAFLD). Our aim was to assess the prevalence and mortality of patients with NAFLD‐HCC. We examined Surveillance, Epidemiology and End Results (SEER) registries (2004‐2009) with Medicare‐linkage files for HCC, which was identified by the International Classification of Diseases for Oncology, third edition codes using topography and morphology codes 8170‐8175. Medicare‐linked data was used to identify NAFLD, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic liver disease (ALD), and other liver disease using International Classification of Diseases, Ninth Revision, Clinical Modification codes. NAFLD was also defined by clinical diagnosis (cryptogenic cirrhosis, obese‐diabetics with cryptogenic liver disease). A logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of HCC. In addition, adjusted hazard ratios for 1‐year mortality were estimated by Coxs proportional hazard regression. A total of 4,929 HCC cases and 14,937 controls without HCC were included. Of the HCC cases, 54.9% were related to HCV, 16.4% to ALD, 14.1% to NAFLD, and 9.5% to HBV. Across the 6‐year period (2004 to 2009), the number of NAFLD‐HCC showed a 9% annual increase. NAFLD‐HCC were older, had shorter survival time, more heart disease, and were more likely to die from their primary liver cancer (all P < 0.0001). Of those who received a transplant after HCC (n = 488), only 5% were related to NAFLD‐HCC. In multivariate analysis, NAFLD increased the risk of 1‐year mortality (OR, 1.21; 95% CI: 1.01‐1.45). Additionally, older age, lower income, unstaged HCC increased risk of 1‐year mortality while receiving a liver transplant (LT), and having localized tumor stage were protective (all P < 0.05). Conclusions: NAFLD is becoming a major cause of HCC in the United States. NAFLD HCC is associated with shorter survival time, more advanced tumor stage, and lower possibility of receiving a LT. (Hepatology 2015;62:1723–1730)

The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. There is uncertainty around the economic burden of NAFLD. We constructed a steady‐state prevalence model to quantify this burden in the United States and Europe. Five models were constructed to estimate the burden of NAFLD in the United States and four European countries. Models were built using a series of interlinked Markov chains, each representing age increments of the NAFLD and the general populations. Incidence and remission rates were calculated by calibrating against real‐world prevalence rates. The data were validated using a computerized disease model called DisMod II. NAFLD patients transitioned between nine health states (nonalcoholic fatty liver, nonalcoholic steatohepatitis [NASH], NASH‐fibrosis, NASH‐compensated cirrhosis, NASH‐decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, post‐liver transplant, and death). Transition probabilities were sourced from the literature and calibrated against real‐world data. Utilities were obtained from NAFLD patients using the Short Form‐6D. Costs were sourced from the literature and local fee schedules. In the United States, over 64 million people are projected to have NAFLD, with annual direct medical costs of about

Extrahepatic Manifestations of Hepatitis C: A Meta-analysis of Prevalence, Quality of Life, and Economic Burden

103 billion (

Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention

1,613 per patient). In the Europe‐4 countries (Germany, France, Italy, and United Kingdom), there are ∼52 million people with NAFLD with an annual cost of about €35 billion (from €354 to €1,163 per patient). Costs are highest in patients aged 45‐65. The burden is significantly higher when societal costs are included. Conclusion: The analysis quantifies the enormity of the clinical and economic burdens of NAFLD, which will likely increase as the incidence of NAFLD continues to rise. (Hepatology 2016;64:1577‐1586)

Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patients

BACKGROUND & AIMS Hepatitis C virus (HCV) infection has hepatic and extrahepatic manifestations with various costs and impairments to health-related quality of life (HRQL). We performed a meta-analysis to determine the prevalence of extrahepatic manifestations in patients with HCV infection, how these impair HRQL, and their costs. METHODS We performed systematic reviews of the literature using MEDLINE, CINAHL, and the Cochrane Systematic Review Database, from 1996 through December 2014, to identify studies of the following extrahepatic manifestations of HCV infection: mixed cryoglobulinemia, chronic kidney or end-stage renal disease, type 2 diabetes, B-cell lymphoma, lichen planus, Sjögrens syndrome, porphyria cutanea tarda, rheumatoid-like arthritis, or depression. We performed a separate meta-analysis for each condition to determine prevalence rates of extrahepatic manifestations of HCV infection and their effects on HRQL. We determined the annual costs (inpatient, outpatient, and pharmacy) associated with extrahepatic manifestations of HCV infection. RESULTS In an analysis of data from 102 studies, we found the most common extrahepatic manifestations to be diabetes (in 15% of patients) and depression (in 25% of patients). HRQL data showed that HCV infection had negative effects on overall physical and mental health. Total direct medical costs of extrahepatic manifestations of HCV infection, in 2014 US dollars, were estimated to be

Improvement of health-related quality of life and work productivity in chronic hepatitis C patients with early and advanced fibrosis treated with ledipasvir and sofosbuvir

1506 million (range,

Effects of Sofosbuvir-Based Treatment, With and Without Interferon, on Outcome and Productivity of Patients With Chronic Hepatitis C

922 million-

Strict versus liberal target range for perioperative glucose in patients undergoing coronary artery bypass grafting: A prospective randomized controlled trial

2208 million in sensitivity analysis). CONCLUSIONS In a systematic review and meta-analysis we determined the prevalence, risks, and costs associated with extrahepatic manifestations of HCV infection. These estimates should be added to the liver-related burden of disease to obtain a more accurate assessment of the total burden of chronic HCV infection. Prospective, real-world studies are needed to increase our understanding of the total clinical and economic effects of HCV infection and treatment on patients and society.

Systematic review with meta‐analysis: non‐alcoholic steatohepatitis ‐ a case for personalised treatment based on pathogenic targets

NAFLD is one of the most important causes of liver disease worldwide and will probably emerge as the leading cause of end-stage liver disease in the coming decades, with the disease affecting both adults and children. The epidemiology and demographic characteristics of NAFLD vary worldwide, usually parallel to the prevalence of obesity, but a substantial proportion of patients are lean. The large number of patients with NAFLD with potential for progressive liver disease creates challenges for screening, as the diagnosis of NASH necessitates invasive liver biopsy. Furthermore, individuals with NAFLD have a high frequency of metabolic comorbidities and could place a growing strain on health-care systems from their need for management. While awaiting the development effective therapies, this disease warrants the attention of primary care physicians, specialists and health policy makers.