The challenge of developing novel pharmacological therapies for non-alcoholic steatohepatitis.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term for a series of hepatic pathologies that begin with relatively benign steatosis and can, with appropriate triggers, lead to the serious entity of non-alcoholic steatohepatitis (NASH). This sets the stage for liver fibrosis and finally the development of cirrhosis in up to 20% of patients with NASH. NAFLD, already among the most common diseases in industrialized countries, is increasing in prevalence and roughly affects 30% of US adults and 10% of US children alone. NAFLD is strongly associated with insulin resistance (IR) and represents the hepatic manifestation of the metabolic syndrome. Indeed, treatments aimed at reducing IR are the current mainstay of therapeutic approaches to NAFLD. While lifestyle interventions may produce limited degrees of success, there remains an urgent need for improved pharmacological therapies. Emerging diagnostic and therapeutic opportunities as well as future developments in NAFLD, NASH and liver fibrosis were discussed by a panel of experts and are presented herein. Promising novel therapeutic targets include inhibitors of dipeptidyl peptidase 4 and the renin-angiotensin system. However, improved non-invasive technologies to diagnose and stage NAFLD are needed. Combined with a better understanding of the pathophysiological processes that underlie the mechanisms of hepatic fibrogenesis in NASH, rapid clinical validation of novel therapies is expected.

• Authors: Detlef Schuppan, Mark D Gorrell, Thomas Klein, Michael Mark, Nezam H Afdhal
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 30 Issue 6 Pg. 795-808 (Jul 2010) ISSN: 1478-3231 [Electronic] United States
• PMID: 20624207 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Dipeptidyl-Peptidase IV Inhibitors

Topics

• Angiotensin II Type 1 Receptor Blockers (chemistry, therapeutic use)
• Animals
• Consensus Development Conferences as Topic
• Dipeptidyl-Peptidase IV Inhibitors (chemistry, therapeutic use)
• Disease Models, Animal
• Drug Design
• Fatty Liver (complications, diagnosis, drug therapy)
• Humans
• Liver Cirrhosis (etiology, prevention & control)
• Predictive Value of Tests
• Renin-Angiotensin System (drug effects)
• Risk Reduction Behavior
• Severity of Illness Index
• Treatment Outcome