Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia; Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Victoria, 3004, Australia.
HIV-NAT, Thai Red Cross AIDS Research Center (TRCARC), Bangkok, 10330, Thailand.
EBioMedicine. 2024 Apr;102:105054. doi: 10.1016/j.ebiom.2024.105054. Epub 2024 Mar 21.
In people living with HIV-HBV, liver fibrosis progression can occur even with suppressive antiretroviral therapy (ART). We investigated the relationship between liver fibrosis and biomarkers of inflammation, apoptosis, and microbial translocation.
In this observational cohort study adults living with HIV-HBV already on effective ART were recruited in Australia and Thailand and followed for 3 years including 6 monthly clinical review and blood tests and annual transient elastography. Differences in clinical and laboratory predictors of liver fibrosis progression were tested followed by regression analysis adjusted for CD4+ T-cells at study entry. A linear mixed model was fitted to longitudinal data to explore changes over time.
67 participants (85% male, median age 49 y) were followed for 175 person-years. Median duration of ART was 10 years (interquartile range (IQR) 8-16 years). We found 11/59 (19%) participants during 3-years follow-up (6/100 person-years) met the primary endpoint of liver disease progression, defined as increased Metavir stage from baseline to final scan. In regression analysis, progressors compared to non-progressors had higher levels of high mobility group box 1 protein (HGMB1), (median (IQR) 3.7 (2.6-5.0) and 2.4 ng/mL (1.5-3.4) respectively, adjusted relative risk 1.47, 95% CI [1.00, 2.17]) and lower nadir CD4+ T-cell percentage (median 4% (IQR 2-8) and 11% (4-15) respectively (relative risk 0.93, 95% CI [0.88, 0.98]).
Progression in liver fibrosis occurs in people with HIV-HBV on suppressive ART. Fibrosis progression was associated with higher HMGB1 and lower percentage nadir CD4+ T-cell count, highlighting the importance of early initiation of HBV-active ART.
This work was supported by NHMRC project grant 1101836; NHMRC practitioner fellowship 1138581 and NHMRC program grant 1149990. The funder had no role in study design, data collection, data analysis, interpretation, writing of this manuscript or decision to submit for publication.
在接受抑制性抗逆转录病毒疗法（ART）的 HIV-HBV 感染者中，即使病毒得到抑制，肝纤维化也可能进展。我们研究了纤维化与炎症、凋亡和微生物易位的生物标志物之间的关系。
本观察性队列研究招募了澳大利亚和泰国已经接受有效 ART 的 HIV-HBV 感染者，对其进行了 3 年的随访，包括每 6 个月进行临床评估和血液检测，以及每年进行瞬时弹性成像检查。检验了肝纤维化进展的临床和实验室预测因素的差异，然后进行了回归分析，调整了研究入组时 CD4+ T 细胞数。对纵向数据进行线性混合模型拟合，以探讨随时间的变化。
67 名参与者（85%为男性，中位年龄 49 岁）接受了 175 人年的随访。ART 的中位持续时间为 10 年（四分位距（IQR）8-16 年）。在 3 年的随访中，我们发现 11/59（19%）名参与者（每 100 人年有 6 例）符合肝病进展的主要终点，定义为从基线到最终扫描时 Metavir 分期增加。在回归分析中，与非进展者相比，进展者的高迁移率族蛋白 B1（HMGB1）水平更高（中位数（IQR）分别为 3.7（2.6-5.0）和 2.4ng/mL（1.5-3.4），调整后的相对风险为 1.47，95%CI[1.00,2.17]），且 CD4+T 细胞最低百分比更低（中位数分别为 4%（IQR 2-8）和 11%（4-15），相对风险为 0.93，95%CI[0.88,0.98]）。
在接受抑制性 ART 的 HIV-HBV 感染者中，肝纤维化会进展。纤维化进展与更高的 HMGB1 和更低的 CD4+T 细胞最低百分比有关，这突显了早期启动针对 HBV 的积极 ART 的重要性。
本研究得到 NHMRC 项目资助（1101836）、NHMRC 研究员奖学金（1138581）和 NHMRC 项目资助（1149990）。资助者在研究设计、数据收集、数据分析、解释、本手稿的撰写或提交发表方面没有任何作用。
