Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, New York University School of Medicine, New York, NY, USA.
Liver Int. 2021 Jul;41(7):1498-1508. doi: 10.1111/liv.14801. Epub 2021 Feb 16.
BACKGROUND & AIMS: Nucleotides with add-on interferon treatment (NUC-IFN) provide significantly higher rates of hepatitis B surface antigen (HBsAg) loss in patients with chronic hepatitis B (CHB). This study aimed to investigate the sustainability of HBsAg loss and the prevention of clinical relapse.
Patients with CHB who achieved HBsAg loss and HBV DNA levels <20 IU/ml after IFN or NUC-IFN therapy were enrolled and followed up for 96 weeks. The primary outcome was HBsAg negativity without viremia at week 96. Secondary outcomes included virological or clinical relapse and predictors of relapse.
420 patients were included in intention-to-treat analysis with 290 and 130 in the IFN and NUC-IFN groups respectively. At week 96, the intention-to-treat analysis revealed similar outcomes between groups, including HBsAg seroreversion (24.83% vs. 23.08%, P = .70), viremia (16.90% vs 13.08%, P = .32) and clinical relapse (11.38% vs 10.00%, P = .68); the per-protocol analyses also showed HBsAg seroreversion, viremia and clinical relapse in IFN group (15.50%, 6.59% and 0.39%) did not differ from those in NUC-IFN group (15.25%, 4.24% and 0.85%, P > .05). These outcomes were similar between patients who received entecavir and those who received telbivudine/lamivudine/adefovir before the combination therapy. In NUC-IFN-treated patients, fibrosis regression was observed at week 96. Baseline HBsAb negativity was independent predictors of HBsAg sero-reversion and recurrence of viremia in IFN treated group.
NUC-IFN and IFN therapies are equally effective in achieving sustained functional cure and fibrosis regression. (ClinicalTrials.gov, Number NCT02336399).
核苷(酸)类似物联合干扰素(NUC-IFN)治疗可显著提高慢性乙型肝炎(CHB)患者乙型肝炎表面抗原(HBsAg)的清除率。本研究旨在探讨 HBsAg 清除的可持续性及预防临床复发。
对接受 IFN 或 NUC-IFN 治疗后 HBsAg 清除且 HBV DNA<20 IU/ml 的 CHB 患者进行入组和 96 周随访。主要终点为第 96 周时 HBsAg 阴性且无病毒血症。次要终点包括病毒学或临床复发及复发的预测因素。
420 例患者纳入意向治疗分析,其中 IFN 组和 NUC-IFN 组分别为 290 例和 130 例。在第 96 周时,意向治疗分析显示两组间的结果相似,包括 HBsAg 血清学转换(24.83%比 23.08%,P=0.70)、病毒血症(16.90%比 13.08%,P=0.32)和临床复发(11.38%比 10.00%,P=0.68);方案分析也显示 IFN 组 HBsAg 血清学转换(15.50%、6.59%和 0.39%)、病毒血症(15.25%、4.24%和 0.85%)与 NUC-IFN 组无差异(P>0.05)。在联合治疗前接受恩替卡韦和替比夫定/拉米夫定/阿德福韦的患者中,这些结果相似。在 NUC-IFN 治疗的患者中,第 96 周时观察到纤维化消退。IFN 治疗组中,基线 HBsAb 阴性是 HBsAg 血清学转换和病毒血症复发的独立预测因素。
NUC-IFN 和 IFN 治疗在实现持续功能性治愈和纤维化消退方面同样有效。(临床试验.gov,编号 NCT02336399)。