obeticholic-acid and 2-4-thiazolidinedione

Non-alcoholic fatty liver disease (NAFLD) is a major national and international health burden. It is one of the most common liver diseases worldwide and the most common cause of abnormal liver enzymes in many developed countries. Non-alcoholic fatty liver disease is also known as an important cause of cryptogenic cirrhosis and second leading cause for liver transplantation. It is commonly associated with metabolic syndrome. Non-alcoholic steatohepatitis (NASH) is the progressive phenotype of NAFLD. In spite of promising performance of non-invasive tools, liver biopsy remains the gold standard test for NASH diagnosis. Over decades, many drugs have been investigated in phase 2 and 3; however, no approved therapy to date. Despite the alarming global rates of NAFLD, there are no local community-based studies on the prevalence of NAFLD or local practice guidelines on its management; this expert review aims to fill this gap.

Topics: Bariatric Surgery; Biomarkers; Biopsy; Chalcones; Chenodeoxycholic Acid; Diagnostic Imaging; Healthy Lifestyle; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Liver; Liver Transplantation; Mass Screening; Non-alcoholic Fatty Liver Disease; Pioglitazone; Prevalence; Propionates; Thiazolidinediones; Vitamin E

Topics: Adolescent; Asia; Bariatric Surgery; Carcinoma, Hepatocellular; Chenodeoxycholic Acid; Child; Diet; Exercise; Fatty Acids, Omega-3; Gastroenterology; Humans; Liver Neoplasms; Liver Transplantation; Non-alcoholic Fatty Liver Disease; Obesity; Pacific Islands; Practice Guidelines as Topic; Risk; Systematic Reviews as Topic; Thiazolidinediones; Vitamin E

The prevalence of nonalcoholic fatty liver disease (NAFLD) has significantly increased over the last decades. Despite existence of several interventions, there remains unclear which interventions work the best.. A systematic review and network meta-analysis of randomized trials comparing efficacy of all treatment options in NAFLD were performed to determine comparative efficacy and safety of interventions in the management of NAFLD. Several electronic databases were searched up to Nov 15, 2015. Outcomes include liver histological outcomes (i.e., fibrosis), all-cause mortality, cirrhosis, and safety. A network meta-analysis was applied to estimate pooled risk ratios (RR). Quality of evidence was assessed using GRADE criteria.. A total of 44 studies (n = 3802) were eligible. When compared with placebo, obeticholic acid (OCA) was the only intervention that significantly improved fibrosis with RR (95% CI) of 1.91 (1.15, 3.16), while pentoxyfylline (PTX) demonstrated improved fibrosis without statistical significance with RR (95% CI) of 2.27 (0.81, 6.36). Only thiazolidinedione (TZD) and vitamin E use resulted in significant increase in resolution of NASH, while OCA, TZD, and vitamin E significantly improved other outcomes including NAS, steatosis, ballooning, and inflammation outcomes. Quality of evidence varied from very low (i.e., metformin, PTX on mean change of ballooning grade) to high (OCA, TZD, vitamin E on improving histological outcomes). Limitations of this study were lack of relevant long-term outcomes (e.g., cirrhosis, death, safety), possible small study effect, and few head-to-head studies.. Our study suggests potential efficacy of OCA, TZD, and vitamin E in improving histologic endpoints in NAFLD. These findings are however based on a small number of studies. Additional studies are awaited to strengthen this network meta-analysis.

Topics: Antioxidants; Chenodeoxycholic Acid; Humans; Non-alcoholic Fatty Liver Disease; Pentoxifylline; Thiazolidinediones; Treatment Outcome; Vitamin E