title: Nonalcoholic steatohepatitis:  the therapeutic challenge of a global epidemic.
abstract: OBJECTIVE
  Nonalcoholic fatty liver (NAFL) and especially its inflammatory variant nonalcoholic steatohepatitis (NASH) have become a major challenge to healthcare systems worldwide because of the increasing prevalence of its major risk factors obesity and type 2 diabetes, which are closely linked to overeating, physical inactivity, and the metabolic syndrome.
  
  
  RESULTS
  Between 10 and 20% of patients with NAFL develop NASH, which can progress to cirrhosis, end-stage liver disease, and hepatocellular carcinoma. The overall mortality in these patients is significantly increased because of both cardiovascular and liver-related complications. Sustained weight loss by diet and exercise, which is the most effective therapeutic measure, is only achieved by a minority of patients, having led to a great yet unmet need for medical therapies of NASH.
  
  
  CONCLUSIONS
  Pharmacological therapies should target the underlying pathophysiology that involves insulin resistance, enhanced peripheral lipolysis and release of free fatty acids, oxidative stress, accumulation of toxic lipids, adipose tissue inflammation, sensitization of hepatocytes toward apoptotic cell death, and fibrogenesis. However, pharmacological therapy that is well tolerated, cost-effective, and poses an acceptable risk-to-benefit ratio has still to be identified. This review summarizes the current and promising treatment options and their implications for future research and clinical practice.
authors: Department of Medicine I bCenter for Molecular and Translational Medicine, University Medical Center of the Johannes Gutenberg University, Langenbeckstraße 1, Mainz, Germany.
authors: Jörn M
authors: JM
authors: Schattenberg
authors: Detlef
authors: D
authors: Schuppan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000627:therapeutic use; D004038:Diet, Reducing; D058872:Epidemics; D005234:Fatty Liver / Q000453:epidemiology / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic
chemical_list: D000893:Anti-Inflammatory Agents; D001647:Bile Acids and Salts; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents