Chinese General Practice ›› 2025, Vol. 28 ›› Issue (35): 4414-4420.DOI: 10.12114/j.issn.1007-9572.2024.0563

Special Issue: 内分泌代谢性疾病最新文章合辑

• Original Research • Previous Articles     Next Articles

Effect of Type 2 Diabetes Mellitus on the Efficacy of Nucleoside (Acid) Analogues in the Treatment of Chronic Hepatitis B

  

  1. 1. Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin 300070, China
    2. Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
    3. The Fifth Medical Center of PLA General Hospital, Beijing 100039, China
    4. Department of Infectious Disease, Tianjin Fourth Central Hospital, the Affiliated Hospital of Tianjin Medical University, Tianjin 300143, China
    5. Tianjin Research Institute of Liver Diseases, Tianjin 300192, China
  • Received:2024-11-10 Revised:2025-07-20 Published:2025-12-15 Online:2025-10-15
  • Contact: MI Yuqiang, XU Liang

2型糖尿病对核苷(酸)类似物治疗慢性乙型肝炎效果的影响研究

  

  1. 1.300070 天津市,天津医科大学第二人民医院临床学院
    2.300192 天津市第二人民医院肝病科
    3.100039 北京市,解放军总医院第五医学中心
    4.300143 天津市,天津医科大学附属第四中心医院感染性疾病科
    5.300192 天津市肝病医学研究所
  • 通讯作者: 宓余强, 徐亮
  • 作者简介:

    作者贡献:

    曾明慧负责数据收集和统计学分析、论文的起草与修订;蒯文涛负责主要研究目标的提出与论文修订;陈林、葛立颖、代容容负责数据的收集;韩家鑫负责统计学图形的绘制;徐连欣负责论文格式的修改;宓余强负责对研究的可行性进行分析,确保研究正常进行;徐亮负责文章的构思、设计、质量控制及审校,对文章整体负责,监督管理。

  • 基金资助:
    国家科技重大专项(2023ZD0508700); 天津市自然科学基金资助项目(23JCYBJC00950); 天津市第二批卫生健康行业高层次人才选拔工程入选人才项目(TJSQNYXXR-D2-145); 天津市卫生健康科技项目重点学科专项(TJWJ2022XK034); 天津市医学重点学科(专科)建设项目(TJYXZDXK-059B)

Abstract:

Background

Nucleoside (acid) analogues (NAs) have become the primary treatment for chronic hepatitis B (CHB), but the impact of type 2 diabetes (T2DM) on the efficacy was unclear.

Objective

To identify the effect of T2DM on the efficacy of NAs antiviral therapy in CHB patients.

Methods

Patients with CHB who underwent liver biopsy in Tianjin Second People's Hospital from January 2015 to June 2023 and newly treated with NAs were included (n=350) .The patients were divided into T2DM-CHB group and CHB group according to their medical history. After matching according to gender, age, HBV DNA level, HBeAg status, ALT and AST level, 238 patients were finally included (T2DM-CHB group: n=70; CHB group: n=168). The patient's medication status, as well as liver and renal function, virological indicators and other data were reviewed once every 6 months for a total of 5 years. To evaluate the effectiveness of early treatment of NAs, follow-up was conducted once at the first and third months after the initiation of antiviral therapy.

Results

After receiving NAs treatment, the serum lgHBV DNA level in T2DM-CHB group was significantly higher than that in CHB group at 1, 3, 6 and 18 months (P<0.05). The HBsAg value of T2DM-CHB group was significantly higher than that of CHB group at 12, 30 and 36 months (P<0.05). Kaplan-Meier survival curve showed that there was a significant difference between the two groups in the time to achieve complete virological response (CVR) for the first time (χ2=14.144, P<0.001), and the median time of first CVR in T2DM-CHB group and CHB group was 18.9 months and 14.3 months respectively. The cumulative clearance rate and seroconversion rate of HBeAg in T2DM-CHB group were lower than those in CHB group at 6, 12, 18, 24 and 30 months after treatment (P<0.05). In terms of liver function recovery, the accumulation rate of normal liver function in T2DM-CHB group was also lower than that in CHB group at 1, 3, 6, 12, 18 and 24 months after treatment (P<0.001). The results of multivariate Cox regression showed that T2DM (HR=0.706, 95%CI=0.584-0.854), HBV DNA (HR=0.624, 95%CI=0.534-0.730), eGFR (HR=1.197, 95%CI=1.017-1.409) were the factors influencing the time of the first CVR in patients with CHB (P<0.05) .

Conclusion

The combination of T2DM weakened the virological response of CHB patients to NAs, and prolonged the time to achieve CVR and liver function recovery.

Key words: Chronic hepatitis B, Type 2 diabetes mellitus, Nucleoside (acid) analogues, Cohort studies, Efficacy evaluation

摘要:

背景

核苷(酸)类似物(NAs)已成为慢性乙型肝炎(CHB)的主要治疗药物,而2型糖尿病(T2DM)对其疗效的影响尚不明确。

目的

探讨T2DM对CHB患者接受NAs抗病毒治疗疗效的影响。

方法

纳入2015年1月—2023年6月在天津市第二人民医院住院行肝穿病理检查,且为NAs初治的CHB患者350例,根据是否合并T2DM,将患者分为T2DM-CHB组和CHB组。按照性别、年龄、乙型肝炎病毒(lgHBV)DNA水平、乙肝病毒e抗原(HBeAg)状态、丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平进行倾向性匹配后,最终纳入患者238例(T2DM-CHB组:n=70;CHB组:n=168)。回顾性采集患者用药情况,以及肝肾功能、病毒学指标等数据,每6个月随访1次,共随访5年。为评估NAs早期治疗的有效性,在抗病毒治疗启动后的第1个月和第3个月各随访记录1次。

结果

T2DM-CHB组患者在接受NAs治疗后,其血清lgHBV DNA水平在1、3、6个月和18个月均高于CHB组(P<0.05)。T2DM-CHB组在治疗后12、30个月和36个月的乙型肝炎表面抗原(lgHBsAg)值高于CHB组(P<0.05)。Kaplan-Meier生存曲线显示,两组患者首次达到完全病毒学应答(CVR)的时间存在差异(χ2=14.144,P<0.001),T2DM-CHB组和CHB组首次发生CVR中位时间分别为18.9个月和14.3个月。T2DM-CHB组在治疗后6、12、18、24、30个月的HBeAg累积清除率和HBeAg血清学转换率均低于CHB组(P<0.05)。T2DM-CHB组治疗后1、3、6、12、18、24个月肝功能正常累积率均低于CHB组(P<0.001)。多因素Cox回归分析结果显示,T2DM(HR=0.706,95%CI=0.584~0.854)、lgHBV DNA(HR=0.624,95%CI=0.534~0.730)、估算肾小球滤过率(eGFR)(HR=1.197,95%CI=1.017~1.409)是CHB患者首次CVR发生时间的影响因素(P<0.05)。

结论

合并T2DM影响CHB患者应用NAs治疗的病毒学应答,延长达到CVR和肝功能恢复的时间。

关键词: 慢性乙型肝炎, 2型糖尿病, 核苷(酸)类似物, 队列研究, 疗效评估