Mohareb Amir M, Ezaz Ghideon, Kim Arthur Y, Freedberg Kenneth A, Boyd Anders, Hyle Emily P
Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
J Viral Hepat. 2025 Oct;32(10):e70079. doi: 10.1111/jvh.70079.
Discontinuing antivirals in chronic hepatitis B virus (HBV) 'e' antigen negative infection can enhance HBV surface antigen (HBsAg) loss but risks complications. We modelled the clinical impact of discontinuing antivirals in chronic HBV. We developed a Markov state model with Monte Carlo simulation of chronic HBV to compare continuation of antiviral therapy with 3 strategies of cessation and reinitiation for: (1) virologic relapse, (2) clinical relapse, or (3) hepatitis flare. We simulated the probability of virologic relapse as an exponential decay function from the time of antiviral cessation. We used literature-based estimates for input probabilities following virologic relapse: clinical relapse (60%, conditional on virologic relapse), hepatitis flare (57%, conditional on clinical relapse) and HBsAg-loss (6%-8%). We projected HBsAg loss, cirrhosis, HCC, and survival. In 10 years, cessation strategies would increase cumulative incidence of HBsAg loss from 4.6% to 12.9%-17.3% but would not appreciably change survival (from 90.6% with continuation to 88.1%-89.0%). In an undifferentiated population, continuation would be a preferred strategy to increase average life expectancy (by 0.75-1.05 years) unless HBsAg loss following treatment cessation was > 46%. Sensitivity analyses showed that the decision to continue or stop antivirals would depend on the off-treatment rates of cirrhosis and HCC for people who remain HBsAg-positive but do not fulfil retreatment criteria. Careful selection of people for antiviral cessation using quantitative HBsAg levels could improve survival compared with continuation. Clinical practice guidelines should emphasise selective application of antiviral cessation to persons most likely to lose HBsAg without experiencing liver-related complications.
在慢性乙型肝炎病毒（HBV）e抗原阴性感染中停用抗病毒药物可增加HBV表面抗原（HBsAg）丢失，但存在并发症风险。我们模拟了慢性HBV感染中停用抗病毒药物的临床影响。我们开发了一个马尔可夫状态模型，并对慢性HBV进行蒙特卡洛模拟，以比较抗病毒治疗的持续与3种停药和重新开始治疗策略：（1）病毒学复发，（2）临床复发，或（3）肝炎发作。我们将病毒学复发的概率模拟为从抗病毒药物停用时间开始的指数衰减函数。我们使用基于文献的估计值作为病毒学复发后的输入概率：临床复发（60%，以病毒学复发为条件）、肝炎发作（57%，以临床复发为条件）和HBsAg丢失（6%-8%）。我们预测了HBsAg丢失、肝硬化、肝癌和生存率。在10年中，停药策略将使HBsAg丢失的累积发生率从4.6%增加到12.9%-17.3%，但不会明显改变生存率（从持续治疗的90.6%变为88.1%-89.0%）。在未分化人群中，持续治疗将是增加平均预期寿命（增加0.75-1.05年）的首选策略，除非停药后HBsAg丢失率>46%。敏感性分析表明，继续或停止抗病毒药物治疗的决定将取决于HBsAg仍为阳性但不符合再治疗标准的人群中肝硬化和肝癌的停药后发生率。与持续治疗相比，使用定量HBsAg水平仔细选择停药人群可提高生存率。临床实践指南应强调将抗病毒药物停药选择性应用于最有可能丢失HBsAg而不发生肝脏相关并发症的人群。
