胰岛素抵抗对非肝硬化慢性丙型肝炎患者抗病毒治疗后肝细胞癌发生的影响
Influence of insulin resistance on the development of hepatocellular carcinoma after antiviral treatment for non-cirrhotic patients with chronic hepatitis C.
作者信息
Hayashi Takeo, Ogawa Eiichi, Furusyo Norihiro, Murata Masayuki, Hayashi Jun
机构信息
Department of General Internal Medicine, Kyushu University Hospital, Higashi-Ku, Fukuoka, 812-8582 Japan.
Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka, Japan.
出版信息
Infect Agent Cancer. 2016 Feb 24;11:9. doi: 10.1186/s13027-016-0056-y. eCollection 2016.
BACKGROUND
Insulin resistance is considered to be an important factor in the progression of fibrosis and the enhancement of the risk of hepatocellular carcinoma (HCC) for chronic hepatitis C patients. The aim of this study was to assess the effect of insulin resistance on the development of HCC by non-cirrhotic chronic hepatitis C patients treated with pegylated interferon alpha-2b (PEG-IFNα2b) and ribavirin.
METHODS
This retrospective study consisted of 474 Japanese non-cirrhotic patients with chronic hepatitis C. The cumulative incidence of HCC was estimated using the Kaplan-Meier method, according to insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR) and treatment outcome.
RESULTS
The overall sustained virological response (SVR) rate was 45.1 % (214/474, genotype 1: 35.4 % [129/364] and genotype 2: 77.3 % [85/110]). Twenty-one (4.4 %) patients developed HCC during the follow-up period. The 5-year cumulative incidence of HCC of the SVR group (2.6 %) was significantly lower than that of the non-SVR group (9.7 %) (log-rank test: P = 0.025). In multivariable logistic regression analysis, HOMA-IR (≥2.5) (hazard ratio [HR] 12.8, P = 0.0006), fibrosis status (F3) (HR 8.85, P < 0.0001), and post-treatment alanine aminotransferase (ALT) level (≥40 U/L) (HR 4.33, P = 0.036) were independently correlated to the development of HCC. Receiver operating characteristic analysis to determine the optimal threshold value of HOMA-IR for predicting the development of HCC in the non-SVR group showed that the areas under the curve was high (0.80, cutoff value: 3.0). Only three patients (1.4 %) who achieved SVR developed HCC. Two of them had severe insulin resistance and did not show improvement in HOMA-IR after achieving SVR.
CONCLUSIONS
Insulin resistance has a strong impact on the development of HCC by non-cirrhotic patients who have PEG-IFNα2b and ribavirin treatment failure.
背景
胰岛素抵抗被认为是慢性丙型肝炎患者纤维化进展及肝细胞癌（HCC）风险增加的重要因素。本研究旨在评估胰岛素抵抗对接受聚乙二醇化干扰素α-2b（PEG-IFNα2b）和利巴韦林治疗的非肝硬化慢性丙型肝炎患者发生HCC的影响。
方法
这项回顾性研究纳入了474例日本非肝硬化慢性丙型肝炎患者。根据胰岛素抵抗的稳态模型评估（HOMA-IR）和治疗结果，采用Kaplan-Meier法估计HCC的累积发病率。
结果
总体持续病毒学应答（SVR）率为45.1%（214/474，基因1型：35.4%[129/364]，基因2型：77.3%[85/110]）。21例（4.4%）患者在随访期间发生HCC。SVR组HCC的5年累积发病率（2.6%）显著低于非SVR组（9.7%）（对数秩检验：P = 0.025）。在多变量逻辑回归分析中，HOMA-IR（≥2.5）（风险比[HR] 12.8，P = 0.0006）、纤维化状态（F3）（HR 8.85，P < 0.0001）和治疗后丙氨酸转氨酶（ALT）水平（≥40 U/L）（HR 4.33，P = 0.036）与HCC的发生独立相关。通过受试者工作特征分析确定非SVR组中预测HCC发生的HOMA-IR最佳阈值，结果显示曲线下面积较高（0.80，临界值：3.0）。仅3例（1.4%）达到SVR的患者发生HCC。其中2例存在严重胰岛素抵抗，达到SVR后HOMA-IR未改善。
结论
胰岛素抵抗对接受PEG-IFNα2b和利巴韦林治疗失败的非肝硬化患者发生HCC有强烈影响。
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