Nakagawa Mina, Asahina Yasuhiro, Kakinuma Sei, Okamoto Ryuichi
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
Institute of Education, Tokyo Medical and Dental University, Tokyo, Japan.
J Gastroenterol. 2023 Apr;58(4):299-310. doi: 10.1007/s00535-022-01940-1. Epub 2022 Dec 30.
Hepatitis C virus infection is characterized by chronic liver inflammation and fibrogenesis, leading to end-stage liver failure and hepatocellular carcinoma over the course of 20 to 30 years. It seems not only the chronicity of hepatitis C but also the presence of the virus in non-hepatic tissues creates a favorable environment for the potential development of pathogenic impacts on extrahepatic systems and organs. Numerous extra-hepatic manifestations have been reported in association with HCV infection, all of which can substantially affect morbidity, mortality, and quality of life. With the recent development of DAAs, antiviral treatment can cure almost all patients with HCV infection, even those intolerant of or unresponsive to IFN treatment, and several large multicenter studies have confirmed the association of DAA-induced SVR with reductions in liver-related and liver-unrelated complications, such as cardiovascular events, end stage renal disease, and so on. Because, in addition to liver-related diseases, extrahepatic lesions are threatening for patients, it is important to eradicate the virus before these progress and affect life prognosis; in other words, patients should be treated before reaching the point of no return. Tailored surveillance with biomarkers such as M2BPGi and Ang-2, which can be used to identify patients with an elevated risk of EHM, and early prevention or treatment for these patients could improve the morbidity, mortality and QOL. Advancement of both basic and clinical research in this field including the development of more precise biomarkers is highly anticipated.
丙型肝炎病毒感染的特征是慢性肝脏炎症和纤维化,在20至30年的病程中会导致终末期肝衰竭和肝细胞癌。似乎不仅丙型肝炎的慢性化,而且病毒在非肝脏组织中的存在为肝外系统和器官潜在的致病性影响创造了有利环境。与丙型肝炎病毒感染相关的肝外表现已被大量报道,所有这些表现都会严重影响发病率、死亡率和生活质量。随着直接抗病毒药物(DAAs)的最新发展,抗病毒治疗几乎可以治愈所有丙型肝炎病毒感染患者,甚至包括那些对干扰素治疗不耐受或无反应的患者,并且几项大型多中心研究已经证实DAAs诱导的持续病毒学应答(SVR)与肝脏相关和肝脏无关并发症(如心血管事件、终末期肾病等)的减少有关。因为除了肝脏相关疾病外,肝外病变也对患者构成威胁,所以在这些病变进展并影响生命预后之前根除病毒很重要;换句话说,患者应在不可挽回之前接受治疗。使用诸如M2BPGi和血管生成素-2(Ang-2)等生物标志物进行针对性监测,可用于识别发生肝外表现(EHM)风险升高的患者,对这些患者进行早期预防或治疗可改善发病率、死亡率和生活质量。人们高度期待该领域基础研究和临床研究的进展,包括开发更精确的生物标志物。