title: Nonalcoholic Steatohepatitis and Endpoints in Clinical Trials.
abstract: Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in developed countries, and the rates of NAFLD continue to rise in conjunction with the obesity pandemic. While the majority of patients with isolated steatosis generally have a benign course, a diagnosis of nonalcoholic steatohepatitis (NASH) carries a significantly higher risk for progression of disease, cirrhosis, and death. Pharmacologic therapeutic interventions in NASH have largely proven to be ineffective or unappealing due to long-term side-effect profiles, and the majority of patients cannot achieve or sustain targeted weight loss goals, necessitating an urgent need for therapeutic trials and drug development. The complex molecular mechanisms leading to NASH and the long duration of time to develop complications of disease are challenges to developing meaningful clinical endpoints. Because of these challenges, surrogate endpoints that are linked to all-cause mortality, liver-related death, and complications of cirrhosis are much more likely to be beneficial in the majority of patients.
authors.affiliation: Dr Hannah is an associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Maryland and the Department of Medicine at the San Antonio Military Medical Center in Joint Base San Antonio-Fort Sam Houston, Texas. Dr Torres is an associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Maryland and the Division of Gastroenterology in the Department of Medicine at the Walter Reed National Military Medical Center in Bethesda, Maryland. Dr Harrison is a visiting professor of hepatology in the Radcliffe Department of Medicine at the University of Oxford in Oxford, United Kingdom.
authors.forename: William N
authors.initials: WN
authors.lastname: Hannah
authors.affiliation: Dr Hannah is an associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Maryland and the Department of Medicine at the San Antonio Military Medical Center in Joint Base San Antonio-Fort Sam Houston, Texas. Dr Torres is an associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Maryland and the Division of Gastroenterology in the Department of Medicine at the Walter Reed National Military Medical Center in Bethesda, Maryland. Dr Harrison is a visiting professor of hepatology in the Radcliffe Department of Medicine at the University of Oxford in Oxford, United Kingdom.
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Torres
authors.affiliation: Dr Hannah is an associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Maryland and the Department of Medicine at the San Antonio Military Medical Center in Joint Base San Antonio-Fort Sam Houston, Texas. Dr Torres is an associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Maryland and the Division of Gastroenterology in the Department of Medicine at the Walter Reed National Military Medical Center in Bethesda, Maryland. Dr Harrison is a visiting professor of hepatology in the Radcliffe Department of Medicine at the University of Oxford in Oxford, United Kingdom.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Harrison
keywords: Nonalcoholic steatohepatitis; cirrhosis; endpoints; surrogate marker