聚乙二醇干扰素α治疗慢性丁型肝炎后晚期 HDV RNA 复发。

Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta.

机构信息

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), partner site, Hannover-Braunschweig, Germany.

出版信息

Hepatology. 2014 Jul;60(1):87-97. doi: 10.1002/hep.27102.

DOI:10.1002/hep.27102

PMID:24585488

Abstract

UNLABELLED

Interferon alpha is the only treatment option for hepatitis delta virus (HDV). Trials investigating the efficacy of pegylated interferon alpha (PEG-IFNa) showed HDV RNA negativity rates of 25-30% 24 weeks after therapy. However, the clinical and virological long-term outcome of HDV-infected patients treated with PEG-IFNa is unknown. We performed a retrospective-prospective follow-up of 77 patients treated for 48 weeks with either PEG-alfa-2a and adefovir (ADV) or either drug alone in the Hep-Net-International-Delta-Hepatitis-Intervention-Study 1 (HIDIT-1) trial. Long-term follow-up data were available for 58 out of 77 patients (75%) with a median time of follow-up of 4.5 (0.5-5.5) years and a median 3 visits per patient. Patients treated with ADV alone received retreatment with PEG-IFNa (48% versus 19%; P = 0.02) more often. Hepatitis B virus surface antigen (HBsAg) became negative in six PEG-IFNa-treated patients until the end of long-term follow-up (10%). Sixteen patients tested HDV RNA-negative 6 months after PEG-IFNa treatment who were entered in the long-term follow-up study. Out of these, nine individuals tested HDV RNA-positive at least once during further long-term follow-up, with seven patients being HDV RNA-positive at the most recent visit. Clinical endpoints (liver-related death, liver transplantation, hepatic decompensation, hepatocellular carcinoma) were observed in three PEG-IFNa-treated (8%) and three ADV-treated (14%) patients during posttreatment long-term follow-up with an overall annual event rate of 2.5% (4.9% in cirrhosis). Sequencing confirmed the reappearance of pretreatment virus strains in all cases.

CONCLUSION

Late HDV RNA relapses may occur after PEG-IFNa therapy of hepatitis delta and thus the term sustained virological response should be avoided in HDV infection. The annual posttreatment rate of clinical events in hepatitis delta patients eligible for PEG-IFNa therapy is about 2.5% and 4.9% in patients with cirrhosis.

摘要

未标注

干扰素 α 是治疗乙型肝炎病毒（HDV）的唯一选择。研究聚乙二醇干扰素 α（PEG-IFNa）疗效的试验显示，治疗 24 周后，HDV RNA 阴性率为 25-30%。然而，接受 PEG-IFNa 治疗的 HDV 感染患者的临床和病毒学长期结果尚不清楚。我们对 77 例接受 PEG-alfa-2a 和阿德福韦（ADV）或单独使用这两种药物治疗 48 周的患者进行了回顾性前瞻性随访，这些患者来自 Hep-Net-International-Delta-Hepatitis-Intervention-Study 1（HIDIT-1）试验。58 例患者（75%）可获得长期随访数据，中位随访时间为 4.5（0.5-5.5）年，中位随访次数为 3 次/例。单独接受 ADV 治疗的患者更常接受 PEG-IFNa 再治疗（48%比 19%；P=0.02）。在长期随访结束时，有 6 例接受 PEG-IFNa 治疗的患者的乙型肝炎表面抗原（HBsAg）变为阴性（10%）。16 例在接受 PEG-IFNa 治疗后 6 个月 HDV RNA 阴性的患者进入长期随访研究。其中，9 例在进一步的长期随访中至少有一次检测到 HDV RNA 阳性，7 例患者在最近的随访中 HDV RNA 阳性。在治疗后长期随访期间，3 例接受 PEG-IFNa 治疗（8%）和 3 例接受 ADV 治疗（14%）的患者发生临床终点（与肝脏相关的死亡、肝移植、肝功能失代偿、肝细胞癌），总年发生率为 2.5%（肝硬化患者为 4.9%）。测序证实所有病例均出现治疗前病毒株的再次出现。