Baumert Thomas F, Jühling Frank, Ono Atsushi, Hoshida Yujin
Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.
Université de Strasbourg, Strasbourg, France.
BMC Med. 2017 Mar 14;15(1):52. doi: 10.1186/s12916-017-0815-7.
Hepatitis C virus infection is a major cause of hepatocellular carcinoma worldwide. Interferon has been the major antiviral treatment, yielding viral clearance in approximately half of patients. New direct-acting antivirals substantially improved the cure rate to above 90%. However, access to therapies remains limited due to the high costs and under-diagnosis of infection in specific subpopulations, e.g., baby boomers, inmates, and injection drug users, and therefore, hepatocellular carcinoma incidence is predicted to increase in the next decades even in high-resource countries. Moreover, cancer risk persists even after 10 years of viral cure, and thus a clinical strategy for its monitoring is urgently needed. Several risk-predictive host factors, e.g., advanced liver fibrosis, older age, accompanying metabolic diseases such as diabetes, persisting hepatic inflammation, and elevated alpha-fetoprotein, as well as viral factors, e.g., core protein variants and genotype 3, have been reported. Indeed, a molecular signature in the liver has been associated with cancer risk even after viral cure. Direct-acting antivirals may affect cancer development and recurrence, which needs to be determined in further investigation.
丙型肝炎病毒感染是全球肝细胞癌的主要病因。干扰素一直是主要的抗病毒治疗药物，约半数患者可实现病毒清除。新型直接抗病毒药物大幅提高了治愈率，使其超过90%。然而，由于成本高昂以及特定亚人群（如婴儿潮一代、囚犯和注射吸毒者）感染诊断不足，治疗的可及性仍然有限，因此，即使在资源丰富的国家，预计未来几十年肝细胞癌发病率仍将上升。此外，即使在病毒治愈10年后，癌症风险依然存在，因此迫切需要一种临床监测策略。已经报道了几种风险预测宿主因素，如晚期肝纤维化、高龄、伴有糖尿病等代谢性疾病、持续的肝脏炎症以及甲胎蛋白升高，以及病毒因素，如核心蛋白变体和基因3型。事实上，即使在病毒治愈后肝脏中的分子特征也与癌症风险相关。直接抗病毒药物可能会影响癌症的发生和复发，这需要进一步研究来确定。
