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.

中文翻译：

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肝脏病理生理学中的刺猬信号

尽管最近在病毒性肝炎领域取得了成功，但肝病仍然是世界范围内死亡的主要原因，因为饮酒和肥胖的增加正在助长慢性脂肪肝的流行，目前尚无有效的药物治疗方法。大约 20% 的慢性肝损伤患者最终会因肝硬化而发展为终末期肝病。因此，迫切需要在持续肝损伤的个体中预防和逆转肝硬化的治疗。开发成功的治疗方法需要更好地了解控制肝病进展的机制。肝脏以保守的伤口愈合反应对各种损伤作出反应，这表明优化对有效肝脏修复至关重要的途径通常可能是有益的。基于令人信服的临床前和临床数据，Hedgehog 通路已成为潜在的靶点，这表明它可以严格调节肝脏对损伤的反应。在此，我们将总结 Hedgehog 通路在肝病中作用的证据，并讨论如何应用调节通路活性来改善肝病结果。