Jia Hongyu, Yu Guodong, Yu Jiong, Zhang Xiaoli, Yang Lisha, Wang Bin, Zhang Jiming, Bai Lang, Zhang Xinxin, Wang Kai, Zhao Ping, Yang Dongliang, Zhao Yingren, Yu Yanyan, Zhang Yimin, Gu Jueqing, Ye Chanyuan, Cai Huan, Lu Yingfeng, Xiang Dairong, Yu Liang, Lian Jiangshan, Hu Jianhua, Zhang Shanyan, Jin Ciliang, Yang Yida
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China.
Department of Infectious Diseases,Branch of the First Affiliated Hospital of Zhejiang University School of Medicine, Ningbo, Zhejiang, China.
J Clin Transl Hepatol. 2023 Oct 28;11(5):1003-1010. doi: 10.14218/JCTH.2022.00413. Epub 2023 Mar 10.
A functional cure, or hepatitis B virus (HBV) surface antigen (HBsAg) loss, is difficult to achieve in patients with hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B. The HBV vaccine and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been reported to help reduce HBsAg levels and promote HBsAg loss. In this prospective randomized trial, we evaluated HBsAg loss in patients receiving pegylated interferon-α2b (PEGIFN-α2b) and tenofovir disoproxil fumarate (TDF), with and without GM-CSF and HBV vaccination.
A total of 287 patients with HBeAg positive chronic hepatitis B and seroconversion after nucleot(s)ide analog treatment were assigned randomly to three treatment groups for 48 weeks, TDF alone (control), PEGIFN-α2b + TDF, and PEGIFN-α2b + TDF + GM-CSF + HBV vaccine. The primary endpoints were the proportions of patients with HBsAg loss and seroconversion at 48 and 72 weeks.
The cumulative HBsAg loss rates in the control, PEGIFN-α2b + TDF, and PEGIFN-α2b + TDF + GM-CSF + HBV vaccine groups at week 48 were 0.0%, 28.3%, and 41.1%, respectively. The cumulative HBsAg seroconversion rates in these groups at week 48 were 0.0%, 21.7%, and 33.9%, respectively. Multivariate regression analysis showed that GM-CSF use plus HBV vaccination was significantly associated with HBsAg loss (=0.017) and seroconversion (=0.030).
In patients with HBeAg-positive chronic hepatitis B and seroconversion after nucleot(s)ide analog treatment, immunomodulatory/antiviral treatment regimens effectively improved HBsAg loss, and the regimen including GM-CSF and HBV vaccination was most effective.
对于乙肝e抗原（HBeAg）阳性的慢性乙型肝炎患者，实现功能性治愈（即乙肝病毒（HBV）表面抗原（HBsAg）消失）较为困难。据报道，乙肝疫苗和粒细胞-巨噬细胞集落刺激因子（GM-CSF）有助于降低HBsAg水平并促进HBsAg消失。在这项前瞻性随机试验中，我们评估了接受聚乙二醇化干扰素-α2b（PEGIFN-α2b）和替诺福韦酯（TDF）治疗的患者，在联合或不联合GM-CSF及乙肝疫苗的情况下，HBsAg消失的情况。
共有287例HBeAg阳性慢性乙型肝炎且在核苷（酸）类似物治疗后发生血清学转换的患者被随机分配到三个治疗组，治疗48周，分别为单纯TDF（对照组）、PEGIFN-α2b + TDF组以及PEGIFN-α2b + TDF + GM-CSF + 乙肝疫苗组。主要终点是48周和72周时HBsAg消失和血清学转换的患者比例。
在第48周时，对照组、PEGIFN-α2b + TDF组以及PEGIFN-α2b + TDF + GM-CSF + 乙肝疫苗组的累积HBsAg消失率分别为0.0%、28.3%和41.1%。这些组在第48周时的累积HBsAg血清学转换率分别为0.0%、21.7%和33.9%。多因素回归分析表明，使用GM-CSF加乙肝疫苗与HBsAg消失（P = 0.017）和血清学转换（P = 0.030）显著相关。
对于HBeAg阳性慢性乙型肝炎且在核苷（酸）类似物治疗后发生血清学转换的患者，免疫调节/抗病毒治疗方案可有效改善HBsAg消失情况，其中包括GM-CSF和乙肝疫苗的方案最为有效。
