目的采用回顾性队列研究,探讨日本慢性丙肝患者停用干扰素治疗后恶性肿瘤发生的危险因素。方法纳入4302名慢性丙肝患者,均接受过干扰素抗病毒治疗并已停药。研究的主要终点是患者首诊恶性肿瘤。以Kaplan-Meier和Cox风险模型计算生存率和相关影响因素。结果患者平均随访时间为8.1年。随访期内共有606名患者发生恶性肿瘤,其中肝细胞癌393例,其他恶性肿瘤213例,主要为胃癌(36例)和结肠癌(35例)。本组患者肝癌的5、10、15年累积发病率分别为4.3%、10.5%和19.7%。研究显示,以下因素显著增加肝癌发生风险(P<0.05):肝硬化(HR=50.1)、未获得持续的病毒学应答(HR=4.93)、男性(HR=1.67)、年龄≥50岁、累计酒精摄取总量超过200 kg(HR=1.45)以及合并2型糖尿病(HR=1.73,95%CI:1.30-2.30)。对于糖尿病患者,若糖化血红蛋白水平控制在7.0%以下,在随访期内,其肝癌发生风险显著下降(危险比0.56,95%CI:0.33-0.89,P=0.015)。本组其他恶性肿瘤5、10、15年的累积发病率分别为2.4%、5.1%和9.8%。以下因素增加其他肿瘤的发生风险:年龄≥50岁、吸烟指数(每天吸烟包数×吸烟年数)≥20(HR=1.89)以及2型糖尿病(HR=1.70,95%CI:1.14-2.53)。若控制血糖使平均糖化血红蛋白低于7.0%水平,其他恶性肿瘤的发生风险下降,但差异无统计学意义(危险比0.62,P=0.170)。结论经过干扰素治疗的HCV阳性患者,若合并2型糖尿病,其罹患肝细胞癌或其他恶性肿瘤的风险约升高1.7倍。同时,这部分患者若能有效控制血糖,使糖化血红蛋白低于7%的水平,将显著降低其肝细胞癌的发生风险。 Objective To investigate the risk factors of malignant tumor after discontinuation of interferon therapy in Japanese chronic hepatitis C patients by retrospective cohort study. Methods A total of 4,302 patients with chronic hepatitis C were enrolled and received interferon antiviral therapy and were discontinued. The primary endpoint of the study was the patient’s first malignancy. Survival rates and related influencing factors were calculated using Kaplan-Meier and Cox risk models. Results The average follow-up time was 8.1 years. A total of 606 patients developed malignant tumors during the follow-up period, including 393 hepatocellular carcinoma and 213 other malignant tumors, mainly including gastric cancer (36 cases) and colon cancer (35 cases). The cumulative incidence of hepatic cancer in 5, 10, 15 years was 4.3%, 10.5% and 19.7% respectively. The study showed that the following factors significantly increased the risk of hepatocellular carcinoma (P <0.05): cirrhosis (HR = 50.1), no sustained virologic response (HR = 4.93), male (HR = 1.67) Total alcohol intake exceeded 200 kg (HR = 1.45) and type 2 diabetes mellitus (HR = 1.73, 95% CI: 1.30-2.30). For patients with diabetes, if the HbA1c level was below 7.0%, the risk of liver cancer was significantly decreased during follow-up (hazard ratio 0.56, 95% CI: 0.33-0.89, P = 0.015). The cumulative incidence of other malignant tumors at 5, 10 and 15 years was 2.4%, 5.1% and 9.8% respectively. The following factors increased the risk of other tumors: age ≥50 years, smoking index (number of packs smoked per day × years of smoking) ≥20 (HR = 1.89), and type 2 diabetes (HR = 1.70,95% CI: 1.14-2.53). The risk of other malignancies decreased if control of blood glucose resulted in mean HbA1c levels below 7.0% (hazard ratio 0.62, P = 0.170). Conclusions Interferon-treated HCV-positive patients with type 2 diabetes have a roughly 1.7-fold increased risk of developing HCC or other malignancies. At the same time, if this part of patients can effectively control blood sugar, HbA1c levels lower than 7% will significantly reduce the risk of hepatocellular carcinoma.