起源，HDV基因型和持续病毒血症决定了慢性肝炎三角洲患者

StephenW

Origin, HDV genotype and persistent viremia determine outcome and treatment response in patients with chronic hepatitis delta

    Dominique Roulot †
    Ségolène Brichler †
    Richard Layese
    Françoise Roudot-Thoraval ‡
    Emmanuel Gordien ‡
    theDeltavir study group
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Published:July 03, 2020DOI:https://doi.org/10.1016/j.jhep.2020.06.038

Highlights

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    Determinants of hepatitis delta severity were studied in a large French cohort.
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    Some HDV genotypes were associated with a higher risk of developing cirrhosis.
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    African immigrants displayed better response to treatment than non-African patients.
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    Persistent replicative HDV infection was associated with poor prognosis.

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.
Methods
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.
Results
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.
Conclusion
Place of birth, HDV genotype and persistent viremia constitute the main determinants of liver involvement and response to treatment in chronic HDV-infected patients.
Lay summary
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.

StephenW

起源，HDV基因型和持续病毒血症决定了慢性肝炎三角洲患者的结局和治疗反应

    多米尼克·罗洛（Dominique Roulot）†
    塞戈琳·布里希勒†
    理查德·莱塞斯
    FrançoiseRoudot-Thoraval‡
    伊曼纽尔（Emmanuel Gordien）‡
    Deltavir研究小组
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发布时间：2020年7月3日DOI：https：//doi.org/10.1016/j.jhep.2020.06.038

强调

    •
    在一个大型法国队列中研究了肝炎三角洲严重程度的决定因素。
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    一些HDV基因型与发生肝硬化的风险较高相关。
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    非洲移民显示出比非非洲患者更好的治疗反应。
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    持续的复制性HDV感染与不良预后相关。

背景与目标
HDV感染会在HBV感染者中引起严重的慢性肝病。但是，与不良预后有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。
方法
法国国家HDV参考中心对1,112例HDV感染患者进行了一项全国性回顾性研究，收集了从初次转诊到最后记录的随访的流行病学，临床，病毒学和组织学数据。
结果
我们队列的中位年龄为36.5（29.9–43.2）岁，队列中68.6％为男性。已知出生地的大多数患者是撒哈拉以南非洲地区（52.5％），南欧和东欧（21.3％），北非和中东（6.2％），亚洲（5.9％）和南美（0.3％）的移民。只有150名患者（13.8％）是法国人。 748名接受测试的患者中有659名HDV阳性（88.1％）。 HDV-1是主要的（75.9％），其次是撒哈拉以南的基因型：HDV-5（17.6％），HDV-7（2.9％），HDV-6（1.8％）和HDV-8（1.6％）。转诊时，有312位患者（28.2％）患有肝硬化，一半的患者经历了至少1次肝失代偿。无论HDV基因型如何，非洲人的肝硬化发生率均明显低于欧洲患者。随访结束时（中位3.0 [0.8-7.2]年），有48.8％的患者发展为肝硬化，24.2％的患者发生≥1代偿失调，9.2％的患者为肝细胞癌。欧洲的HDV-1和非洲的HDV-5患者更容易发生肝硬化。持续的复制性HDV感染与代偿失调，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％对29.1％，p <0.001）。应答者的基线HDV病毒载量显着低于无应答者。
结论
出生地点，HDV基因型和持续病毒血症是慢性感染HDV的患者肝脏受累和对治疗反应的主要决定因素。
放置摘要
丙型肝炎三角洲病毒（HDV）引起的慢性肝感染是慢性病毒性肝炎的最严重形式。尽管全世界至少有15–20百万人长期受到HDV感染，但很大程度上尚不清楚决定肝脏受累程度的因素。通过对法国的1,112例HDV感染患者进行大范围的随访研究，这些患者来自世界各地，我们能够确定HDV的基因型，出生地（反映病毒和宿主相关因素）和持续存在病毒血症是肝脏受累和对治疗反应的主要决定因素。