Division of Gastroenterology and Hepatology, Saint Louis University, St Louis, Missouri.
Gastroenterology. 2020 May;158(7):1984-1998.e3. doi: 10.1053/j.gastro.2020.01.051. Epub 2020 Feb 13.
Lifestyle modifications focused on healthy eating and regular exercise are the primary recommendations for patients with nonalcoholic steatohepatitis (NASH). However, for multiple societal, psychological, physical, genetic, and epigenetic reasons, the ability of people to adopt and sustain such changes is challenging and typically not successful. To end the epidemic of NASH and prevent its complications, including cirrhosis and hepatocellular carcinoma, pharmacological interventions are now being evaluated in clinical trials. Treatments include drugs targeting energy intake, energy disposal, lipotoxic liver injury, and the resulting inflammation and fibrogenesis that lead to cirrhosis. It is likely that patients develop the phenotype of NASH by multiple mechanisms, and thus the optimal treatments of NASH will likely evolve to personalized therapy once we understand the mechanistic underpinnings of NASH in each patient. Reviewed here is the treatment landscape in this rapidly evolving field with an emphasis on drugs in Phase 2 and Phase 3 trials.
生活方式的改变,侧重于健康饮食和有规律的运动,是非酒精性脂肪性肝炎(NASH)患者的主要推荐治疗方法。然而,由于多种社会、心理、身体、遗传和表观遗传原因,人们采用和维持这些改变的能力具有挑战性,通常也不成功。为了终结 NASH 的流行并预防其并发症,包括肝硬化和肝细胞癌,目前正在临床试验中评估药理学干预措施。治疗方法包括针对能量摄入、能量消耗、脂毒性肝损伤以及由此导致的炎症和纤维化导致肝硬化的药物。患者可能通过多种机制发展为 NASH 表型,因此一旦我们了解每个患者 NASH 的机制基础,NASH 的最佳治疗方法可能会演变为个性化治疗。本文重点介绍了处于第 2 阶段和第 3 阶段临床试验中的药物,对这一快速发展领域的治疗前景进行了综述。