Hannah William N, Torres Dawn M, Harrison Stephen A
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.
Gastroenterol Hepatol (N Y). 2016 Dec;12(12):756-763.
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.
非酒精性脂肪性肝病（NAFLD）现已成为发达国家肝病的主要病因，并且随着肥胖症的流行，NAFLD的发病率持续上升。虽然大多数单纯性脂肪肝患者通常病程良性，但非酒精性脂肪性肝炎（NASH）的诊断意味着疾病进展、肝硬化和死亡的风险显著更高。由于长期副作用，NASH的药物治疗干预在很大程度上已被证明无效或缺乏吸引力，并且大多数患者无法实现或维持目标体重减轻目标，因此迫切需要进行治疗试验和药物研发。导致NASH的复杂分子机制以及疾病并发症发生所需的长时间是开发有意义的临床终点的挑战。由于这些挑战，与全因死亡率、肝脏相关死亡和肝硬化并发症相关的替代终点在大多数患者中更有可能有益。
