Interferon therapy reduces the risk for hepatocellular carcinoma: National surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan
Interferon therapy reduces the risk for hepatocellular carcinoma: National surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan
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DOI：
10.7326/0003-4819-131-3-199908030-00003
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发表时间：
1999-08-03
影响因子：
39.2
通讯作者：
Omata, M
中科院分区：
文献类型：
--
作者：
Yoshida, H;Shiratori, Y;Omata, M
背景资料：以前关于干扰素治疗对肝细胞癌发病率的影响的研究没有充分评估肝纤维化的程度，肝纤维化是肝细胞癌的主要危险因素。目的：评估干扰素治疗对肝细胞癌发病率的影响，调整危险因素，包括肝纤维化的程度。设计：回顾性队列研究。设置：日本七所大学医院和一所地区核心医院。患者：自1986年以来接受肝活检的2890例慢性丙型肝炎患者。在这些患者中，2400人接受干扰素治疗，490人未接受治疗。测量：肝纤维化的程度从F0期（无纤维化）到F4期（肝硬化）进行评估。对干扰素的反应由病毒学和生物化学测定。在平均4.3年的随访期间，定期进行肝细胞癌的筛查。采用考克斯比例风险回归分析干扰素治疗对肝癌风险的影响。结果：89例干扰素治疗患者和59例未治疗患者发生肝癌。在未经治疗的患者中，肝细胞癌的年发病率随着肝纤维化程度而增加，从F0或F1期纤维化患者的0.5%增加到F4期纤维化患者的7.9%。F2期纤维化患者（P = 0.0128）和F3期纤维化患者（P = 0.0011）的治疗和未治疗患者的累积发生率差异显著。在多变量分析中，干扰素治疗与肝细胞癌风险降低相关（调整后的危险比，0.516 [95% CI，0.358 ~ 0.742]; P < 0.001），尤其是持续病毒学应答的患者（危险比，0.197 [CI，0.099 - 0.392]），在血清丙氨酸转氨酶水平持续正常的患者中，（风险比，0.197 [CI，0.104 ~ 0.375]），丙氨酸氨基转移酶水平低于正常上限两倍的患者中（风险比，0.358 [CI，0.206至0.622]）。干扰素治疗可显著降低肝细胞癌的风险，尤其是在病毒学或生化应答者中。
Background: Previous studies on the effect of interferon therapy on the incidence of hepatocellular carcinoma have not sufficiently assessed degree of liver fibrosis, a major risk factor for hepatocellular carcinoma.Objective: To evaluate the effect of interferon therapy on incidence of hepatocellular carcinoma, adjusting for risk factors, including the degree of liver fibrosis.Design: Retrospective cohort study.Setting: Seven university hospitals and one regional core hospital in Japan.Patients: 2890 patients with chronic hepatitis C who had undergone liver biopsy since 1986. Of these patients, 2400 received interferon and 490 were untreated.Measurements: The degree of liver fibrosis was assessed from stage F0 (no fibrosis) to stage F4 (cirrhosis). Response to interferon was determined virologically and biochemically. Screening for development of hepatocellular carcinoma was performed periodically during an average follow-up of 4.3 years. Effect of interferon therapy on the risk for hepatocellular carcinoma was analyzed by using Cox proportional hazards regression.Results: Hepatocellular carcinoma developed in 89 interferon-treated patients and in 59 untreated patients. Among untreated patients, the annual incidence of hepatocellular carcinoma increased with the degree of liver fibrosis, from 0.5% among patients with stage F0 or F1 fibrosis to 7.9% among patients with stage F4 fibrosis. The cumulative incidence in treated and untreated patients differed significantly for patients with stage F2 fibrosis (P = 0.0128) and for those with stage F3 fibrosis (P = 0.0011). In multivariate analysis, interferon therapy was associated with a reduced risk for hepatocellular carcinoma (adjusted risk ratio, 0.516 [95% CI, 0.358 to 0.742]; P < 0.001), especially among patients with sustained virologic response (risk ratio, 0.197 [CI, 0.099 to 0.392]), among those with persistently normal serum alanine aminotransferase levels (risk ratio, 0.197 [CI, 0.104 to 0.375]), and among those with alanine aminotransferase levels less than two times the upper limit of normal (risk ratio, 0.358 [CI, 0.206 to 0.622]).Conclusions: Interferon therapy significantly reduces the risk for hepatocellular carcinoma, especially among virologic or biochemical responders.