南方医科大学学报

南方医科大学学报 ›› 2021, Vol. 41 ›› Issue (3): 313-318.doi: 10.12122/j.issn.1673-4254.2021.03.01

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乙型肝炎肝硬化合并糖尿病时发生肝细胞癌的风险：一项随访5年的前瞻性队列研究

唐淬蓉，胡承光，周宇辰，宋杨达，李 孟，廖敏君，孙家润，钟春秀，周 琳，林志昭，周元平   

  • 出版日期:2021-03-20 发布日期:2021-04-06

Risk analysis for hepatocellular carcinoma in patients with chronic hepatitis B-associated cirrhosis complicated by type 2 diabetes mellitus: a 5-year prospective cohort study

  • Online:2021-03-20 Published:2021-04-06

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摘要： 目的 阐明乙型肝炎肝硬化（CHB-Cir）合并2型糖尿病（T2DM）时发生肝细胞癌（HCC）的风险及其协同因素。方法 以2010年6月~2019年6月在南方医院肝病中心随访的CHB-Cir患者为研究对象，依性别、年龄、HBeAg状态、HBV DNA水平基本匹配后，构成CHB-Cir合并T2DM队列（观察组）和CHB-Cir无T2DM队列（对照组），半年随访1次。取已完成2年或以上随访且数据完整的病例纳入统计分析。采用Kaplan-Meier法比较两组HCC累积发生率；以Cox比例风险回归模型分析CHB-Cir合并T2DM时发生HCC的风险及其协同因素。结果 纳入分析的467例研究对象平均随访时间为4.4±1.62年。观察组（n=203）和对照组（n=264）新发HCC病例分别为69例和48例，观察组HCC发病密度明显高于对照组（P<0.001）。观察组HCC累积发生率明显高于对照组（P<0.001），相对危险度为2.096（P<0.01）。调整年龄（≥40岁）、肝癌家族史、既往抗病毒治疗、胆固醇升高、低密度脂蛋白胆固醇升高等因素后，T2DM仍是CHB-Cir患者发生HCC的独立危险因素（P=0.000）。结论 T2DM是HCC的独立危险因素；CHB-Cir患者合并T2DM时HCC的发生风险增加2倍左右，提示及早控制糖尿病对降低CHB-Cir患者发生HCC的风险具有重要临床意义。

关键词: 慢性乙型肝炎；肝硬化；肝细胞癌；2型糖尿病；队列研究

Abstract: Objective To elucidate the risk and synergistic factors of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B-associated cirrhosis (CHB-Cir) complicated by type 2 diabetes (T2DM). Methods The patients with CHB-Cir who were followed up in Hepatology Center of Nanfang Hospital from June 2010 to June 2019 were divided based on their T2DM status into two cohorts matched for gender, age, HBeAg status and HBV DNA load: CHB-Cir with T2DM group (observation group) and CHB-Cir without T2DM group (control group). All the patients were followed up at a 6-month interval, and the cases with complete clinical data and follow-up data for more than 2 years were included in the analysis. Kaplan- Meier method was used to compare the cumulative incidence of HCC between the two groups. A Cox proportional hazard regression model was used to analyze the relationship between T2DM and the risk of HCC in these patients. Results A total of 467 patients with a mean follow-up time of 4.4±1.62 years were included in the analysis, including 203 in the observation group and 264 in the control group. Sixty-nine and forty-eight new HCC cases occurred in the observation group and control group, respectively, showing a significantly higher incidence rate of HCC in the observation group (P<0.001). The cumulative incidence of HCC in the observation group was significantly higher than that in the control group (P<0.001), with a relative risk of 2.096 (P<0.01). After adjustment for age (≥40 years), family history of liver cancer, previous antiviral therapy, elevated cholesterol and elevated LDL cholesterol, T2DM remained an independent risk factor for HCC in CHB-Cir patients (P=0.000). Conclusion T2DM is an independent risk factor for HCC, and the risk of HCC increases by more than two folds in CHB-Cir patients complicated by T2DM, suggesting the clinical significance of early interventions of diabetes to reduce the risk of HCC in CHB-Cir patients.

Key words: chronic hepatitis B; cirrhosis; hepatocellular carcinoma; type 2 diabetes mellitus; cohort study