Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA; Gastroenterology Department, Hospital de Santa Maria, CHLN, Lisbon, Portugal.
Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
J Hepatol. 2018 Mar;68(3):550-562. doi: 10.1016/j.jhep.2017.10.017. Epub 2017 Oct 26.
Liver disease remains a leading cause of mortality worldwide despite recent successes in the field of viral hepatitis, because increases in alcohol consumption and obesity are fuelling an epidemic of chronic fatty liver disease for which there are currently no effective medical therapies. About 20% of individuals with chronic liver injury ultimately develop end-stage liver disease due to cirrhosis. Hence, treatments to prevent and reverse cirrhosis in individuals with ongoing liver injury are desperately needed. The development of successful treatments requires an improved understanding of the mechanisms controlling liver disease progression. The liver responds to diverse insults with a conserved wound healing response, suggesting that it might be generally beneficial to optimise pathways that are crucial for effective liver repair. The Hedgehog pathway has emerged as a potential target based on compelling preclinical and clinical data, which demonstrate that it critically regulates the liver's response to injury. Herein, we will summarise evidence of the Hedgehog pathway's role in liver disease and discuss how modulating pathway activity might be applied to improve liver disease outcomes.
尽管在病毒性肝炎领域取得了近期的成功，但肝脏疾病仍然是全球主要的死亡原因，因为酒精消费和肥胖的增加正在引发慢性脂肪肝疾病的流行，而目前尚无有效的医学疗法。约 20%的慢性肝损伤患者最终因肝硬化而发展为终末期肝病。因此，迫切需要预防和逆转持续肝损伤患者的肝硬化的治疗方法。成功治疗方法的开发需要对控制肝病进展的机制有更好的理解。肝脏对各种损伤的反应具有保守的伤口愈合反应，这表明优化对有效肝脏修复至关重要的途径可能通常是有益的。基于令人信服的临床前和临床数据，Hedgehog 通路已成为一个潜在的治疗靶点，这些数据表明它对肝脏对损伤的反应具有关键的调节作用。本文将总结 Hedgehog 通路在肝脏疾病中的作用的证据，并讨论调节通路活性如何应用于改善肝脏疾病的结果。
