慢性丙型肝炎病毒清除后肝细胞癌的晚期发展：需要持续监测。

Late development of hepatocellular carcinoma after viral clearance in patients with chronic hepatitis C: A need for continual surveillance.

机构信息

Liver Center, Huntington Medical Research Institutes, Pasadena, California, USA.

Pfleger Liver Institute and the Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, California, USA.

出版信息

J Dig Dis. 2018 Jul;19(7):411-420. doi: 10.1111/1751-2980.12615. Epub 2018 Jul 19.

DOI:10.1111/1751-2980.12615

PMID:29889353

Abstract

OBJECTIVE

Eradication of chronic hepatitis C (CHC) infection decreases the incidence of hepatocellular carcinoma (HCC), but a risk remains. We aimed to investigate HCC development-associated factors in CHC patients with sustained virological response (SVR) after antiviral therapies.

METHODS

We compared CHC patients achieving SVR from 1996-2016 who did and did not develop HCC. Their median follow-up period was 8.01 years.

RESULTS

Compared with 164 non-HCC SVR patients, 22 who developed HCC were older at SVR (P = 0.032), had a higher incidence of diabetes (P = 0.013) and higher pre-antiviral treatment alpha-fetoprotein (AFP) levels (P = 0.016), more had fibrosis stage 3 and cirrhosis (P = 0.0009) and hepatitis B core antibody (anti-HBc) positivity (P = 0.006). Eight and seven of 22 patients, respectively, developed HCC at 4-10 years and 10 years after SVR. The longest duration from SVR to HCC was 18.7 years. Independent factors associated with HCC development were anti-HBc positivity (hazard ratio [HR] 5.57, P = 0.012), age at SVR (HR 1.08, P = 0.014), higher pre-antiviral treatment AFP levels (HR 1.01, P = 0.01) and Hispanic ethnicity (HR 12.9, P = 0.002). HCC risk was significantly less in genotype 2 patients (HR 0.2, P = 0.02) or in those with higher pre-antiviral treatment albumin levels (HR 0.33, P = 0.04).

CONCLUSIONS

The risk for HCC exists in a subset of CHC patients after SVR and may occur up to 18 years after viral clearance. Indefinite HCC surveillance is necessary in SVR patients with other risk factors.

摘要

目的

根除慢性丙型肝炎（CHC）感染可降低肝细胞癌（HCC）的发病率，但仍存在风险。本研究旨在探讨抗病毒治疗后获得持续病毒学应答（SVR）的 CHC 患者中与 HCC 发展相关的因素。

方法

我们比较了 1996 年至 2016 年期间获得 SVR 且未发生 HCC 的 CHC 患者。他们的中位随访时间为 8.01 年。

结果

与 164 例非 HCC SVR 患者相比，22 例发生 HCC 的患者在获得 SVR 时年龄更大（P=0.032），糖尿病发病率更高（P=0.013），抗病毒治疗前甲胎蛋白（AFP）水平更高（P=0.016），纤维化分期 3 级和肝硬化（P=0.0009）及乙型肝炎核心抗体（抗-HBc）阳性率更高（P=0.006）。22 例 HCC 患者中，分别有 8 例和 7 例分别在 SVR 后 4-10 年和 10 年后发生 HCC。从 SVR 到 HCC 的最长时间为 18.7 年。与 HCC 发生相关的独立因素包括抗-HBc 阳性（风险比 [HR] 5.57，P=0.012）、SVR 时年龄（HR 1.08，P=0.014）、抗病毒治疗前 AFP 水平较高（HR 1.01，P=0.01）和西班牙裔（HR 12.9，P=0.002）。基因型 2 患者（HR 0.2，P=0.02）或抗病毒治疗前白蛋白水平较高的患者（HR 0.33，P=0.04）的 HCC 风险显著降低。