Introduction

We aimed to describe long-term clinical outcomes in chronic hepatitis B (CHB) patients after HBsAg seroclearance, and identify factors that modify disease outcomes.

Methods

CHB patients with HBsAg seroclearance occurring between 1986 and 2017 were recruited. Primary outcome was cirrhosis/hepatocellular carcinoma (HCC), and secondary outcomes were hepatic decompensation, liver-related death/transplantation, and all-cause mortality. Multivariable Cox model included demographics, prior antivirals, comorbidities, drugs (statins, metformin, proton-pump inhibitors, non-selective beta-blockers), and laboratory parameters (platelet, liver function test, prothrombin time, alpha-fetoprotein [AFP], anti-HBs). Statin users were propensity score matched (PSM) with non-users (1:2 ratio) for survival analysis of all outcomes.

Results

Of 913 patients with HBsAg seroclearance (male: 613 [67.1%]; median age: 53.4 years [18.5–87.0]), 129 (14.1%) were statin users. During median follow-up of 7.7 years (up to 29.1 years), 64/833 (7.7%) developed cirrhosis, 25/905 (2.8%) developed HCC, 3/913 (0.3%) underwent transplantation, and 76/913 (8.3%) died. Statins were associated with lower cirrhosis/HCC risk (adjusted hazard ratio [aHR]: 0.44; 95% CI 0.20–0.96; aHR for every 1-year increase in use: 0.85; 95% CI 0.75–0.97). Statin users had no hepatic decompensation or liver-related death/transplantation (vs 18/778 [2.3%] and 18/784 [2.3%] cases in statin non-users, respectively). Statins were also associated with lower all-cause mortality risk (aHR: 0.21; 95% CI 0.08–0.53). PSM yields consistent results for beneficial effects of statins (log-rank p < 0.05 for all outcomes). Other factors for cirrhosis/HCC included increasing age (aHR: 1.06), diabetes (aHR: 2.03), higher creatinine (aHR: 1.008), GGT > 50U/L (aHR: 3.25), and AFP > 9 ng/mL (aHR: 10.14).

Conclusion

Patients with HBsAg seroclearance have favorable long-term survival. However, liver-related adverse outcomes still develop, necessitating further investigations on beneficial effects of statins.

中文翻译：

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他汀类药物与 HBsAg 血清学清除的慢性乙型肝炎患者更好的临床结果相关

介绍

我们旨在描述 HBsAg 血清学清除后慢性乙型肝炎 (CHB) 患者的长期临床结果，并确定改变疾病结果的因素。

方法

招募了 1986 年至 2017 年间发生 HBsAg 血清学清除的 CHB 患者。主要结果是肝硬化/肝细胞癌 (HCC)，次要结果是肝失代偿、肝脏相关死亡/移植和全因死亡率。多变量 Cox 模型包括人口统计学、既往抗病毒药物、合并症、药物（他汀类药物、二甲双胍、质子泵抑制剂、非选择性 β 受体阻滞剂）和实验室参数（血小板、肝功能测试、凝血酶原时间、甲胎蛋白 [AFP]、抗-HBs）。他汀类药物使用者与非使用者（1:2 比例）​​进行倾向评分匹配 (PSM)，以对所有结果进行生存分析。

结果

在 913 名 HBsAg 血清学清除患者中（男性：613 [67.1%]；中位年龄：53.4 岁 [18.5–87.0]），129 名 (14.1%) 是他汀类药物使用者。在 7.7 年（最长 29.1 年）的中位随访期间，64/833 (7.7%) 发生肝硬化，25/905 (2.8%) 发生 HCC，3/913 (0.3%) 接受移植，76/913 ( 8.3%) 死亡。他汀类药物与较低的肝硬化/HCC 风险相关（调整后的风险比 [aHR]：0.44；95% CI 0.20–0.96；使用量每增加 1 年的 aHR：0.85；95% CI 0.75–0.97）。他汀类药物使用者没有肝功能失代偿或肝脏相关的死亡/移植（相比之下，他汀类药物非使用者分别为 18/778 [2.3%] 和 18/784 [2.3%]）。他汀类药物还与较低的全因死亡风险相关（aHR：0.21；95% CI 0.08–0.53）。PSM 对他汀类药物的有益作用产生了一致的结果（对数秩p < 0.05 所有结果）。肝硬化/HCC 的其他因素包括年龄增加 (aHR: 1.06)、糖尿病 (aHR: 2.03)、肌酐升高 (aHR: 1.008)、GGT > 50U/L (aHR: 3.25) 和 AFP > 9 ng/mL (aHR) : 10.14)。

结论

HBsAg 血清清除的患者具有良好的长期生存率。然而，肝脏相关的不良后果仍在发生，需要进一步研究他汀类药物的有益作用。