Akuta Norio, Kobayashi Masahiro, Suzuki Fumitaka, Sezaki Hitomi, Fujiyama Shunichiro, Kawamura Yusuke, Hosaka Tetsuya, Kobayashi Mariko, Saitoh Satoshi, Suzuki Yoshiyuki, Arase Yasuji, Ikeda Kenji, Kumada Hiromitsu
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Oncology. 2016;91(6):341-347. doi: 10.1159/000450551. Epub 2016 Oct 1.
Predictive factors for hepatocarcinogenesis following eradication of hepatitis C virus (HCV) RNA by antiviral therapy with direct-acting antivirals are unknown. Especially the impact of treatment with or without interferon on hepatocarcinogenesis is not clear.
A total of 958 patients with HCV genotype 1-related chronic liver disease and a sustained virological response defined as negative HCV RNA 24 weeks after cessation of antiviral therapy with direct-acting antivirals (triple therapy of NS3/4A protease inhibitor/peginterferon/ribavirin or all-oral combination therapy with NS3/4A protease inhibitor plus NS5A inhibitor) were included in a retrospective study. None of the patients had hepatocellular carcinoma before and during antiviral therapy.
In all, 14 patients developed hepatocellular carcinoma during follow-up, and the development rate per 1,000 person-years was 7.35. The cumulative hepatocarcinogenesis rates were 4.2 and 4.2% at the end of 5 and 7 years, respectively. Multivariate analysis identified fibrosis 4 (FIB4) index (≥2.7) and body mass index (≥23.0) as determinants of hepatocarcinogenesis, but they did not identify the treatment regimen. In patients with a FIB4 index ≥2.7, the hepatocarcinogenesis rates with the interferon regimen were not different from those for the regimen without interferon, regardless of gender.
Liver fibrosis and body mass index, but not treatment regimen, are important predictors of hepatocarcinogenesis following eradication of HCV RNA by direct-acting antivirals.
直接作用抗病毒药物抗病毒治疗清除丙型肝炎病毒（HCV）RNA后肝癌发生的预测因素尚不清楚。尤其是干扰素治疗与否对肝癌发生的影响尚不明确。
一项回顾性研究纳入了958例基因型1相关的慢性丙型肝炎患者，这些患者在使用直接作用抗病毒药物（NS3/4A蛋白酶抑制剂/聚乙二醇干扰素/利巴韦林三联疗法或NS3/4A蛋白酶抑制剂加NS5A抑制剂的全口服联合疗法）抗病毒治疗停止后24周，HCV RNA持续呈阴性，即获得持续病毒学应答。所有患者在抗病毒治疗前及治疗期间均无肝细胞癌。
总共14例患者在随访期间发生肝细胞癌，每1000人年的发生率为7.35。5年和7年末的累积肝癌发生率分别为4.2%和4.2%。多因素分析确定FIB4指数（≥2.7）和体重指数（≥23.0）为肝癌发生的决定因素，但未确定治疗方案。在FIB4指数≥2.7的患者中，无论性别，干扰素治疗方案组的肝癌发生率与无干扰素治疗方案组并无差异。
肝纤维化和体重指数而非治疗方案是直接作用抗病毒药物清除HCV RNA后肝癌发生的重要预测因素。
