Background & Aims

Antiviral treatment from hepatitis B envelope antigen (HBeAg)-positive status may attenuate the integration of hepatitis B virus DNA into the host genome causing hepatocellular carcinoma (HCC). We investigated the impact of HBeAg status at the onset of antiviral treatment on the risk of HCC.

Methods

The incidence of HCC was evaluated in Korean patients with chronic hepatitis B who started entecavir or tenofovir in either HBeAg-positive or HBeAg-negative phase. The results in the Korean cohort were validated in a Caucasian PAGE-B cohort.

Results

A total of 9143 Korean patients (mean age, 49.2 years) were included: 49.1% were HBeAg-positive and 49.2% had cirrhosis. During follow-up (median, 5.1 years), 916 patients (10.0%) developed HCC. Baseline HBeAg positivity was not associated with the risk of HCC in the entire cohort or cirrhotic subcohort. However, in the non-cirrhotic subcohort, HBeAg positivity was independently associated with a lower risk of HCC in multivariable (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.26–0.66), propensity score-matching (aHR, 0.46; 95% CI, 0.28–0.76), and inverse probability weighting analyses (aHR, 0.44; 95% CI, 0.28–0.70). In the Caucasian cohort (n = 719; mean age, 51.8 years; HBeAg-positive, 20.3%; cirrhosis, 34.8%), HBeAg-positivity was not associated with the risk of HCC either in the entire cohort or cirrhotic subcohort. In the non-cirrhotic subcohort, none of the HBeAg-positive group developed HCC, although the difference failed to reach statistical significance (aHR, 0.21; 95% CI, 0.00–1.67).

Conclusions

This multinational cohort study implies that HBeAg positivity at the onset of antiviral treatment seems to be an independent factor associated with a lower risk of HCC in patients with chronic hepatitis B without cirrhosis, but not in those with cirrhosis.

中文翻译：

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HBeAg 对慢性乙型肝炎患者口服抗病毒治疗期间肝细胞癌风险的影响

背景与目标

乙型肝炎包膜抗原 (HBeAg) 阳性状态的抗病毒治疗可能会减弱乙型肝炎病毒 DNA 与宿主基因组的整合，从而导致肝细胞癌 (HCC)。我们调查了抗病毒治疗开始时 HBeAg 状态对 HCC 风险的影响。

方法

在 HBeAg 阳性或 HBeAg 阴性期开始使用恩替卡韦或替诺福韦的韩国慢性乙型肝炎患者中评估了 HCC 的发生率。韩国队列的结果在白种人 PAGE-B 队列中得到验证。

结果

共纳入 9143 名韩国患者（平均年龄 49.2 岁）：49.1% 为 HBeAg 阳性，49.2% 为肝硬化。在随访期间（中位数，5.1 年），916 名患者（10.0%）发展为 HCC。基线 HBeAg 阳性与整个队列或肝硬化亚队列的 HCC 风险无关。然而，在非肝硬化亚队列中，HBeAg 阳性与多变量（校正风险比 [aHR]，0.41；95% 置信区间 [CI]，0.26-0.66）、倾向评分匹配（ aHR，0.46；95% CI，0.28-0.76）和逆概率加权分析（aHR，0.44；95% CI，0.28-0.70）。在高加索人群（n = 719；平均年龄，51.8 岁；HBeAg 阳性，20.3%；肝硬化，34.8%）中，HBeAg 阳性与整个队列或肝硬化亚队列的 HCC 风险无关。

结论

这项多国队列研究表明，抗病毒治疗开始时的 HBeAg 阳性似乎是与无肝硬化的慢性乙型肝炎患者 HCC 风险降低相关的独立因素，但与肝硬化患者无关。