AP-HP, Hôpital Avicenne, Unité d'hépatologie, Université Paris 13, Bobigny; Inserm U955, équipe 18, Université Paris-Est, Créteil.
AP-HP, Hôpital Avicenne, Laboratoire de microbiologie clinique, Université Paris 13, Centre national de référence des hépatites B, C et Delta, Bobigny, Inserm U955, équipe 18, Université Paris-Est, Créteil.
J Hepatol. 2020 Nov;73(5):1046-1062. doi: 10.1016/j.jhep.2020.06.038. Epub 2020 Jul 4.
BACKGROUND & AIMS: HDV infection causes severe chronic liver disease in individuals infected with HBV. However, the factors associated with poor prognosis are largely unknown. Thus, we aimed to identify prognostic factors in patients with HDV infection.
The French National Reference Centre for HDV performed a nationwide retrospective study on 1,112 HDV-infected patients, collecting epidemiological, clinical, virological and histological data from the initial referral to the last recorded follow-up.
The median age of our cohort was 36.5 (29.9-43.2) years and 68.6% of our cohort were male. Most patients whose birthplace was known were immigrants from sub-Saharan Africa (52.5%), southern and eastern Europe (21.3%), northern Africa and the Middle East (6.2%), Asia (5.9%) and South America (0.3%). Only 150 patients (13.8%) were French native. HDV load was positive in 659 of 748 tested patients (88.1%). HDV-1 was predominant (75.9%), followed by sub-Saharan genotypes: HDV-5 (17.6%), HDV-7 (2.9%), HDV-6 (1.8%) and HDV-8 (1.6%). At referral, 312 patients (28.2%) had cirrhosis, half having experienced at least 1 episode of hepatic decompensation. Cirrhosis was significantly less frequent in African than in European patients regardless of HDV genotype. At the end of follow-up (median 3.0 [0.8-7.2] years), 48.8% of the patients had developed cirrhosis, 24.2% had ≥1 episode(s) of decompensation and 9.2% had hepatocellular carcinoma. European HDV-1 and African HDV-5 patients were more at risk of developing cirrhosis. Persistent replicative HDV infection was associated with decompensation, hepatocellular carcinoma and death. African patients displayed better response to interferon therapy than non-African patients (46.4% vs. 29.1%, p <0.001). HDV viral load at baseline was significantly lower in responders than in non-responders.
Place of birth, HDV genotype and persistent viremia constitute the main determinants of liver involvement and response to treatment in chronic HDV-infected patients.
Chronic liver infection by hepatitis delta virus (HDV) is the most severe form of chronic viral hepatitis. Despite the fact that at least 15-20 million people are chronically infected by HDV worldwide, factors determining the severity of liver involvement are largely unknown. By investigating a large cohort of 1,112 HDV-infected patients followed-up in France, but coming from different areas of the world, we were able to determine that HDV genotype, place of birth (reflecting both viral and host-related factors) and persistent viremia constitute the main determinants of liver involvement and response to treatment.
HDV 感染可导致乙型肝炎病毒（HBV）感染者发生严重的慢性肝脏疾病。然而，与预后不良相关的因素在很大程度上尚不清楚。因此，我们旨在确定 HDV 感染患者的预后因素。
法国 HDV 国家参考中心对 1112 例 HDV 感染患者进行了一项全国范围的回顾性研究，从初次就诊到最后一次记录的随访中收集了流行病学、临床、病毒学和组织学数据。
本队列的中位年龄为 36.5 岁（29.9-43.2），68.6%为男性。大多数已知出生地的患者是来自撒哈拉以南非洲（52.5%）、南欧和东欧（21.3%）、北非和中东（6.2%）、亚洲（5.9%）和南美洲（0.3%）的移民。仅有 150 例（13.8%）患者为法国本地人。在 748 例接受检测的患者中，有 659 例（88.1%）的 HDV 载量为阳性。HDV-1 占主导地位（75.9%），其次是非撒哈拉基因型：HDV-5（17.6%）、HDV-7（2.9%）、HDV-6（1.8%）和 HDV-8（1.6%）。就诊时，312 例（28.2%）患者患有肝硬化，其中一半曾经历过至少 1 次肝失代偿。无论 HDV 基因型如何，非洲患者的肝硬化发生率明显低于欧洲患者。在随访结束时（中位随访时间为 3.0 年[0.8-7.2]），48.8%的患者发展为肝硬化，24.2%的患者发生≥1 次失代偿，9.2%的患者发生肝细胞癌。欧洲的 HDV-1 和非洲的 HDV-5 患者发生肝硬化的风险更高。持续复制的 HDV 感染与失代偿、肝细胞癌和死亡相关。非洲患者对干扰素治疗的反应优于非非洲患者（46.4% vs. 29.1%，p<0.001）。在有反应者中，基线时的 HDV 病毒载量明显低于无反应者。
出生地、HDV 基因型和持续病毒血症是慢性 HDV 感染患者肝脏受累和治疗反应的主要决定因素。
乙型肝炎病毒（HBV）导致的慢性肝脏感染是慢性病毒性肝炎最严重的形式。尽管全世界至少有 1500 万至 2000 万人受到 HDV 的慢性感染，但决定肝脏受累严重程度的因素在很大程度上尚不清楚。通过对在法国接受随访的 1112 例 HDV 感染患者进行研究，但这些患者来自世界不同地区，我们能够确定 HDV 基因型、出生地（反映病毒和宿主相关因素）和持续病毒血症是决定肝脏受累和治疗反应的主要因素。
