肝硬化乙肝患者经有限疗程治疗后肝癌减少、HBsAg 丢失增加且生存改善。

Hepatocellular carcinoma reduced, HBsAg loss increased, and survival improved after finite therapy in hepatitis B patients with cirrhosis.

机构信息

Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan.

College of Medicine, Chang Gung University, Taiwan.

出版信息

Hepatology. 2024 Mar 1;79(3):690-703. doi: 10.1097/HEP.0000000000000575. Epub 2023 Aug 25.

DOI:10.1097/HEP.0000000000000575

PMID:37625144

Abstract

BACKGROUND AND AIMS

Long-term nucleos(t)ide analog (Nuc) treatment can reduce HCC in patients with HBV-related liver cirrhosis (HBV-LC). Earlier small cohort studies showed a comparable 5-year incidence of HCC in HBeAg-negative patients with HBV-LC who stopped and those continued Nuc therapy. This study aimed to validate these findings using a large cohort with 10-year follow-up.

APPROACH AND RESULTS

From 2 centers, 494 HBeAg-negative patients with HBV-LC who stopped (finite group) and 593 who continued (continuous group) Nuc therapy were recruited. HCC, HBsAg loss, liver-related mortality/transplantation, and overall survival rates were compared between 2 groups with 1:1 propensity score matching of sex, treatment history, types of Nuc, age, transaminases, platelet count, and HBsAg levels at end of therapy in finite group or 3-year on-therapy in continuous groups. During a median follow-up of 6.2 (3.4-8.9) years, the annual and 10-year HCC incidence were lower in finite group (1.6 vs. 3.3%/y and 10-y 15.7% vs. 26.8%, respectively; log-rank test, p <0.0001). The finite group showed greater HBsAg decline/year (-0.116 vs. -0.095 log 10 IU/mL, p =0.0026) and 7.6 times higher 10-year incidence of HBsAg loss (22.7% vs. 3%, p <0.0001). Multivariate Cox regression showed finite therapy an independent factor for HBsAg loss (adjusted HR: 11.79) but protective against HCC (adjusted HR: 0.593), liver-related mortality/transplantation (adjusted HR: 0.312), and overall mortality (adjusted HR: 0.382).

CONCLUSIONS

Finite Nuc therapy in HBeAg-negative HBV-LC may reduce HCC incidence, increase HBsAg loss, and improve survival. Greater HBsAg decline/loss may reflect enhanced immunity and contribute to the reduction of hepatic carcinogenesis.

摘要

背景和目的

长期核苷（酸）类似物（Nuc）治疗可降低 HBV 相关肝硬化（HBV-LC）患者的 HCC 发生率。早期的小队列研究表明，HBV-LC 中 HBeAg 阴性患者停止和继续 Nuc 治疗的 5 年 HCC 发生率相当。本研究旨在使用具有 10 年随访的大队列验证这些发现。

方法和结果

本研究从 2 个中心招募了 494 名停止（有限组）和 593 名继续（连续组）Nuc 治疗的 HBeAg 阴性 HBV-LC 患者。通过对有限组的性别、治疗史、Nuc 类型、年龄、转氨酶、血小板计数和治疗结束时 HBsAg 水平，或连续组的 3 年治疗中的 HBsAg 水平进行 1:1 倾向评分匹配，比较两组的 HCC、HBsAg 丢失、肝相关死亡率/移植和总生存率。中位随访 6.2（3.4-8.9）年后，有限组的 HCC 年发生率和 10 年发生率较低（1.6%比 3.3%/年和 10 年 15.7%比 26.8%；log-rank 检验，p<0.0001）。有限组的 HBsAg 下降/年更大（-0.116 比 -0.095 log 10 IU/mL，p=0.0026），10 年 HBsAg 丢失率高 7.6 倍（22.7%比 3%，p<0.0001）。多变量 Cox 回归显示，有限治疗是 HBsAg 丢失的独立因素（调整后的 HR：11.79），但可预防 HCC（调整后的 HR：0.593）、肝相关死亡率/移植（调整后的 HR：0.312）和总死亡率（调整后的 HR：0.382）。