Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark.
Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, Sydney NSW 2145, Australia.
World J Gastroenterol. 2020 Jun 14;26(22):2931-2947. doi: 10.3748/wjg.v26.i22.2931.
More than five years ago, the treatment of hepatitis C virus infection was revolutionized with the introduction of all-oral direct-acting antiviral (DAA) drugs. They proved highly efficient in curing patients with chronic hepatitis C (CHC), including patients with cirrhosis. The new DAA treatments were alleged to induce significant improvements in clinical outcome and prognosis, but the exact cause of the expected benefit was unclear. Further, little was known about how the underlying liver disease would be affected during and after viral clearance. In this review, we describe and discuss the liver-related effects of the new treatments in regards to both pathophysiological aspects, such as macrophage activation, and the time-dependent effects of therapy, with specific emphasis on inflammation, structural liver changes, and liver function, as these factors are all related to morbidity and mortality in CHC patients. It seems clear that antiviral therapy, especially the achievement of a sustained virologic response has several beneficial effects on liver-related parameters in CHC patients with advanced liver fibrosis or cirrhosis. There seems to be a time-dependent effect of DAA therapy with viral clearance and the resolution of liver inflammation followed by more discrete changes in structural liver lesions. These improvements lead to favorable effects on liver function, followed by an improvement in cognitive dysfunction and portal hypertension. Overall, the data provide knowledge on the several beneficial effects of DAA therapy on liver-related parameters in CHC patients suggesting short- and long-term improvements in the underlying disease with the promise of an improved long-term prognosis.
五年多以前，随着全口服直接作用抗病毒药物（DAA）的引入，丙型肝炎病毒感染的治疗发生了革命性变化。它们被证明在治愈慢性丙型肝炎（CHC）患者方面非常有效，包括肝硬化患者。新的 DAA 治疗据称可显著改善临床结果和预后，但确切的获益原因尚不清楚。此外，对于在病毒清除期间和之后，潜在的肝脏疾病将如何受到影响，人们知之甚少。在这篇综述中，我们描述和讨论了新疗法在以下方面对肝脏的影响，包括病理生理学方面，如巨噬细胞激活，以及治疗的时间依赖性效应，特别强调炎症、结构性肝改变和肝功能，因为这些因素都与 CHC 患者的发病率和死亡率有关。很明显，抗病毒治疗，尤其是实现持续病毒学应答，对纤维化或肝硬化程度较高的 CHC 患者的肝脏相关参数有多种有益影响。DAA 治疗具有清除病毒和消除肝脏炎症的时间依赖性效应，随后是结构性肝病变的更离散变化。这些改善导致肝功能的有利影响，随后认知功能障碍和门静脉高压症得到改善。总的来说，这些数据提供了关于 DAA 治疗对 CHC 患者肝脏相关参数的多种有益影响的知识，表明在潜在疾病方面有短期和长期的改善，并有望改善长期预后。
