丙型肝炎病毒患者接受直接抗病毒药物治疗后发生的肝细胞癌

Hepatocellular carcinoma after direct-acting antiviral drug treatment in patients with hepatitis C virus.

作者信息

Kogiso Tomomi, Sagawa Takaomi, Kodama Kazuhisa, Taniai Makiko, Katagiri Satoshi, Egawa Hiroto, Yamamoto Masakazu, Tokushige Katsutoshi

机构信息

Department of Internal Medicine, Institute of Gastroenterology Tokyo Women's Medical University Tokyo Japan.

Department of Surgery Tokyo Women's Medical University, Yachiyo Medical Center Yachiyo Japan.

出版信息

JGH Open. 2018 Nov 9;3(1):52-60. doi: 10.1002/jgh3.12105. eCollection 2019 Feb.

BACKGROUND AND AIM

Given the use of direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV), their effects on hepatocarcinogenesis should be determined.

METHODS

This study enrolled 349 patients with HCV who underwent DAA treatment at our hospital between 2014 and 2018. Their median age was 65 years, and 184 were male; 301 cases were of HCV serotype 1, and 48 were of serotype 2. The DAA treatment was daclatasvir/asunaprevir in 107 cases, sofosbuvir (SOF)/ledipasvir in 147 cases, ritonavir-boosted ombitasvir/paritaprevir in 28 cases, elbasvir/grazoprevir in 19 cases, and SOF/ribavirin in 48 cases. The patients' histories included hepatocellular carcinoma (HCC) in 45 cases, liver transplant (LT) in 10 cases, and kidney transplant (KT) in 17 cases.

RESULTS

Sustained virological responses occurred in 335 cases (96%). DAA treatment was initiated a median of 16.3 months after HCC treatment. After DAA treatment, 15 cases (33%) had recurrence of HCC after a median of 11.6 months, and 3 cases (1%) developed HCC. Six LT patients and one KT patient had HCC; however, no HCC was observed after DAA. The incidence of HCC was significantly higher in patients with multiple HCC treatments in the Cox hazard model (hazard ratio 1.664, 95% confidence interval 1.134-2.441, < 0.01). Surgical resection or LT reduced the risk of HCC.

CONCLUSIONS

DAA did not increase the rate of HCC, even in immunosuppressed patients. However, careful follow-up for HCC recurrence is required in previously treated cases.

背景与目的

鉴于直接抗病毒药物（DAAs）用于治疗丙型肝炎病毒（HCV），应确定其对肝癌发生的影响。

方法

本研究纳入了2014年至2018年间在我院接受DAA治疗的349例HCV患者。他们的中位年龄为65岁，男性184例；301例为HCV 1型，48例为2型。107例患者接受达卡他韦/阿舒瑞韦DAA治疗，147例接受索磷布韦（SOF）/来迪派韦治疗，28例接受利托那韦增强的奥比他韦/帕立普韦治疗，19例接受艾尔巴韦/格拉瑞韦治疗，48例接受SOF/利巴韦林治疗。患者病史包括45例肝细胞癌（HCC）、10例肝移植（LT）和17例肾移植（KT）。

结果

335例（96%）出现持续病毒学应答。DAA治疗在HCC治疗后中位16.3个月开始。DAA治疗后，15例（33%）在中位11.6个月后出现HCC复发，3例（1%）发生HCC。6例LT患者和1例KT患者发生HCC；然而，DAA治疗后未观察到HCC。在Cox风险模型中，接受多次HCC治疗的患者HCC发生率显著更高（风险比1.664，95%置信区间1.134 - 2.441，P < 0.01）。手术切除或LT降低了HCC风险。