Du Yan, Su Tong, Ding Yibo, Cao Guangwen
Department of Epidemiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China.
Hepat Mon. 2012 Oct;12(10 HCC):e6031. doi: 10.5812/hepatmon.6031. Epub 2012 Oct 20.
Hepatocellular carcinoma (HCC) is a fatal disease. Chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection is the major cause of HCC. High viral replication rate and related hepatic/systematic inflammation are the major risk factors in HCC recurrence after hepatectomy or liver transplantation.
Some of the carcinogenesis-related HBV mutations are also associated with poor prognosis for HCC patients. Antiviral therapy is an option for improving HCC prognosis after surgery. In case of HBV-associated HCC, treatment with interferon and nucleos(t)ide analogues (NAs), especially interferon, is effective in improving the prognosis. However, long-term use of NAs increases the possibility of developing drug-resistant viral mutations such as the HBV rtA181T/sW172 mutation, which increases the risk of HCC recurrence.
In cases of HCV-associated HCC, standard interferon with or without ribavirin therapy is effective in improving the prognosis of HCV-associated HCC; however, some HCV mutations, such as the amino acid substitution M91L, are associated with treatment failure and a poor prognosis. Therapeutic efficacy needs to be confirmed using largescale, randomized, placebo-controlled clinical trials.
Surveillance of viral mutations during antiviral treatment and a better understanding of the associations of HCC recurrence with viral load, inflammation-associated signaling, and environmental factors can aid the development of more effective strategies for the prevention of HCC recurrence after surgery.
肝细胞癌(HCC)是一种致命疾病。慢性乙型肝炎病毒(HBV)和/或丙型肝炎病毒(HCV)感染是HCC的主要病因。高病毒复制率及相关的肝脏/全身炎症是肝切除或肝移植后HCC复发的主要危险因素。
一些与致癌作用相关的HBV突变也与HCC患者的不良预后相关。抗病毒治疗是改善术后HCC预后的一种选择。对于HBV相关的HCC,使用干扰素和核苷(酸)类似物(NAs)进行治疗,尤其是干扰素,对改善预后有效。然而,长期使用NAs会增加出现耐药性病毒突变的可能性,如HBV rtA181T/sW172突变,这会增加HCC复发的风险。
对于HCV相关的HCC,标准干扰素联合或不联合利巴韦林治疗对改善HCV相关HCC的预后有效;然而,一些HCV突变,如氨基酸替代M91L,与治疗失败和不良预后相关。需要通过大规模、随机、安慰剂对照的临床试验来证实治疗效果。
在抗病毒治疗期间监测病毒突变,以及更好地了解HCC复发与病毒载量、炎症相关信号和环境因素之间的关联,有助于制定更有效的策略来预防术后HCC复发。