Background & Aims

The contribution of the novel biomarkers, hepatitis B virus (HBV) RNA and HBV core-related antigen (HBcrAg), to characterization of HBV-human immunodeficiency virus (HIV) coinfection is unclear. We evaluated the longitudinal dynamics of HBV RNA and HBcrAg and their association with classical HBV serum biomarkers and liver histology and viral staining.

Methods

HBV-HIV co-infected adults from 8 North American centers entered a National Institutes of Health-funded prospective cohort study. Demographic, clinical, serological, and virological data were collected at entry and every 24 to 48 weeks for up to 192 weeks. Participants with HBV RNA and HBcrAg measured ≥2 times (N = 95) were evaluated; 56 had paired liver biopsies obtained at study entry and end of follow-up.

Results

Participants had a median age of 50 years; 97% were on combination anti-viral therapy. In hepatitis B e antigen (HBeAg)+ participants, there were significant declines in HBV RNA and HBcrAg over 192 weeks that tracked with declines in HBeAg, hepatitis B surface antigen, HBV DNA, and hepatitis B core antigen (HBcAg) hepatocyte staining grade (all P < .05). In HBeAg− participants, there were not significant declines in HBV RNA (P = .49) and HBcrAg (P = .63), despite modest reductions in hepatitis B surface antigen (P < .01) and HBV DNA (P = .03). HBV serum biomarkers were not significantly related to change in hepatic activity index, Ishak fibrosis score, or hepatocyte HBcAg loss (all P > .05).

Conclusions

In HBV-HIV coinfected adults on suppressive dually active antiviral therapy, the use of novel HBV markers reveals continued improvement in suppression of HBV transcription and translation over time. The lack of further improvement in HBV serum biomarkers among HBeAg− patients suggests limits to the benefit of combination anti-viral therapy and provide rationale for additional agents with distinct mechanisms of action.

中文翻译：

---

人类免疫缺陷病毒混合感染中乙型肝炎病毒复制新标志物的前瞻性队列研究

 背景与目标

新型生物标志物乙型肝炎病毒 (HBV) RNA 和 HBV 核心相关抗原 (HBcrAg) 对 HBV-人类免疫缺陷病毒 (HIV) 共感染特征的贡献尚不清楚。我们评估了 HBV RNA 和 HBcrAg 的纵向动态及其与经典 HBV 血清生物标志物、肝脏组织学和病毒染色的关联。

 方法

来自 8 个北美中心的 HBV-HIV 共感染成年人参加了美国国立卫生研究院资助的一项前瞻性队列研究。在入组时以及每 24 至 48 周收集一次人口统计学、临床、血清学和病毒学数据，持续长达 192 周。对 HBV RNA 和 HBcrAg 测量≥2 次（N = 95）的参与者进行了评估； 56 名患者在研究开始和随访结束时进行了配对肝脏活检。

 结果

参与者的平均年龄为 50 岁； 97% 接受联合抗病毒治疗。在乙型肝炎 e 抗原 (HBeAg)+ 参与者中，192 周内 HBV RNA 和 HBcrAg 显着下降，同时 HBeAg、乙型肝炎表面抗原、HBV DNA 和乙型肝炎核心抗原 (HBcAg) 肝细胞染色等级也下降。所有P < .05）。在 HBeAg− 参与者中，尽管乙型肝炎表面抗原 ( P < .01) 和 HBV DNA ( P = .03) 略有下降，但 HBV RNA ( P = .49) 和 HBcrAg ( P = .63) 并未显着下降）。 HBV 血清生物标志物与肝活动指数、Ishak 纤维化评分或肝细胞 HBcAg 丢失的变化没有显着相关（所有P > .05）。

 结论

在接受抑制性双重活性抗病毒治疗的 HBV-HIV 共感染成人中，新型 HBV 标记物的使用揭示了随着时间的推移，对 HBV 转录和翻译的抑制持续改善。 HBeAg−患者中 HBV 血清生物标志物缺乏进一步改善，表明联合抗病毒治疗的益处有限，并为具有不同作用机制的其他药物提供了理论基础。