Hepatitis delta coinfection in persons with HIV: misdiagnosis and disease burden in Italy

Hepatitis Delta virus (HDV) causes severe liver disease. Due to similarities in transmission routes, persons living with HIV (PLWH) are at risk of HDV infection. This analysis investigates the prevalence and the long-term clinical outcome of people with HDV in a large cohort of PLWH. We retrieved HBsAg ± anti-HDV positive PLWH enrolled from 1997 to 2015 in the multicentre, prospective ICONA study. The primary endpoint was a composite clinical outcome (CCO = having experienced ≥1 of the following: Fib4 score >3.25; diagnosis of cirrhosis; decompensation; hepatocellular carcinoma or liver-related death). Kaplan–Meier curves and unweighted and weighted Cox regression models were used for data analysis. Less than half of HBsAg positive patients had been tested for anti-HDV in clinical practice. After testing stored sera, among 617 HBV/HIV cases, 115 (19%) were anti-HDV positive; 405 (65%) HBV monoinfected; 99 (16%) undeterminate. The prevalence declined over the observation period. HDV patients were more often males, intravenous drug users, HCV coinfected. After a median of 26 months, 55/115 (48%) developed CCO among HDV+; 98/403 (24%) among HBV monoinfected; 18/99 (18%) in HDV unknown (p < 0.001). After controlling for geographical region, alcohol consumption, CD4 count, anti-HCV status and IFN-based therapies, the association with HDV retained statistical significance [HR = 1.67 (1.15, 2.95; p = 0.025)]. HDV infection among PLWH is underdiagnosed, although HDV entails an high risk of liver disease progression. Because effective drugs to treat HDV are now available, it is even more crucial to identify PLWH at an early stage of liver disease.

丁型肝炎病毒（Hepatitis Delta Virus, HDV）可引发严重肝脏疾病。由于传播途径相似，艾滋病病毒感染者（persons living with HIV, PLWH）存在感染丁型肝炎病毒的风险。本研究针对大型艾滋病病毒感染者队列中的丁型肝炎病毒感染者，分析其感染流行率与长期临床转归。本研究纳入1997年至2015年间于多中心前瞻性ICONA研究中入组的乙型肝炎表面抗原（Hepatitis B Surface Antigen, HBsAg）±抗丁型肝炎病毒抗体（anti-HDV）阳性的艾滋病病毒感染者。本研究的主要终点为复合临床结局（composite clinical outcome, CCO），即满足以下任意一项：Fib4评分＞3.25、确诊肝硬化、肝功能失代偿、肝细胞癌或肝脏相关死亡。数据分析采用Kaplan-Meier曲线、未加权与加权Cox回归模型。临床实践中，乙型肝炎表面抗原阳性患者的抗丁型肝炎病毒抗体检测率不足五成。对留存血清进行检测后，在617例乙型肝炎病毒（Hepatitis B Virus, HBV）/艾滋病病毒共感染病例中，115例（19%）抗丁型肝炎病毒抗体呈阳性，405例（65%）为乙型肝炎病毒单一感染，99例（16%）检测结果不确定。丁型肝炎病毒感染流行率随观察周期延长呈下降趋势。丁型肝炎病毒感染者多为男性、静脉注射毒品使用者，且常合并丙型肝炎病毒（Hepatitis C Virus, HCV）感染。中位随访26个月后，丁型肝炎病毒阳性组中有55例（48%）出现复合临床结局，乙型肝炎病毒单一感染组为98例（24%），丁型肝炎病毒感染状态未知组为18例（18%）（p＜0.001）。在校正地理区域、饮酒情况、CD4细胞计数、抗丙型肝炎病毒抗体状态及基于干扰素的治疗方案等混杂因素后，丁型肝炎病毒感染与复合临床结局的关联仍具有统计学意义[风险比（Hazard Ratio, HR）=1.67，95%置信区间：1.15~2.95；p=0.025]。艾滋病病毒感染者中的丁型肝炎病毒感染存在诊断不足的问题，尽管丁型肝炎病毒感染会显著增加肝脏疾病进展风险。鉴于目前已有针对丁型肝炎病毒感染的有效治疗药物，早期识别存在肝脏疾病早期表现的艾滋病病毒感染者显得尤为重要。