Broquetas Teresa, Garcia-Retortillo Montserrat, Micó Miquel, Canillas Lidia, Puigvehí Marc, Cañete Nuria, Coll Susana, Viu Ana, Hernandez Juan Jose, Bessa Xavier, Carrión José A
Department of Gastroenterology, Liver Section, Hospital del Mar Medical Research Institute, Barcelona 08003, Spain.
Laboratori de Referencia de Catalunya, El Prat de Llobregat, Barcelona 08820, Spain.
World J Hepatol. 2020 Nov 27;12(11):1076-1088. doi: 10.4254/wjh.v12.i11.1076.
Hepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues (NAs) rarely achieve hepatitis B surface antigen (HBsAg) loss.
To evaluate if the addition of pegylated interferon (Peg-IFN) could decrease HBsAg and hepatitis B core-related antigen (HBcrAg) levels and increase HBsAg loss rate in patients under NAs therapy.
Prospective, non-randomized, open-label trial evaluating the combination of Peg-IFN 180 µg/week plus NAs during forty-eight weeks NAs in monotherapy. Hepatitis B e antigen-negative non-cirrhotic chronic hepatitis B patients of a tertiary hospital, under NAs therapy for at least 2 years and with undetectable viral load, were eligible. Patients with hepatitis C virus, hepatitis D virus or human immunodeficiency virus co-infection and liver transplanted patients were excluded. HBsAg and HBcrAg levels (log10 U/mL) were measured at baseline and during ninety-six weeks. HBsAg loss rate was evaluated in both groups. Adverse events were recorded in both groups. The kinetic of HBsAg for each treatment group was evaluated from baseline to weeks 24 and 48 by the slope of the HBsAg decline (log10 IU/mL/week) using a linear regression model.
Sixty-five patients were enrolled, 61% receiving tenofovir and 33% entecavir. Thirty-six (55%) were included in Peg-IFN-NA group and 29 (44%) in NA group. After matching by age and treatment duration, baseline HBsAg levels were comparable between groups (3.1 3.2) ( = 0.25). HBsAg levels at weeks 24, 48 and 96 declined in Peg-IFN-NA group (-0.26, -0.40 and -0.44) and remained stable in NA group (-0.10, -0.10 and -0.10) ( < 0.05). The slope of HBsAg decline in Peg-IFN-NA group (-0.02) was higher than in NA group (-0.00) ( = 0.015). HBcrAg levels did not change. Eight (22%) patients discontinued Peg-IFN due to adverse events. The HBsAg loss was achieved in 3 (8.3%) patients of the Peg-IFN-NA group and 0 (0%) of the NA group.
The addition of Peg-IFN to NAs caused a greater and faster decrease of HBsAg levels compared to NA therapy. Side effects of Peg-IFN can limit its use in clinical practice.
接受核苷（酸）类似物（NAs）治疗的乙肝e抗原阴性慢性乙型肝炎患者很少能实现乙肝表面抗原（HBsAg）消失。
评估聚乙二醇干扰素（Peg-IFN）的加入是否能降低接受NAs治疗患者的HBsAg和乙肝核心相关抗原（HBcrAg）水平，并提高HBsAg消失率。
一项前瞻性、非随机、开放标签试验，评估48周期间每周180μg Peg-IFN联合NAs与NAs单药治疗的效果。一家三级医院中接受NAs治疗至少2年且病毒载量不可测的乙肝e抗原阴性非肝硬化慢性乙型肝炎患者符合条件。排除丙型肝炎病毒、丁型肝炎病毒或人类免疫缺陷病毒合并感染患者以及肝移植患者。在基线和96周期间测量HBsAg和HBcrAg水平（log10 U/mL）。评估两组的HBsAg消失率。记录两组的不良事件。使用线性回归模型通过HBsAg下降斜率（log10 IU/mL/周）评估每个治疗组从基线到第24周和第48周的HBsAg动力学。
65例患者入组，61%接受替诺福韦，33%接受恩替卡韦。36例（55%）纳入Peg-IFN-NAs组，29例（44%）纳入NAs组。按年龄和治疗时间匹配后，两组基线HBsAg水平相当（3.1对3.2）（P = 0.25）。Peg-IFN-NAs组第24周、48周和96周的HBsAg水平下降（-0.26、-0.40和-0.44），NAs组保持稳定（-0.10、-0.10和-0.10）（P < 0.05）。Peg-IFN-NAs组HBsAg下降斜率（-0.02）高于NAs组（-0.00）（P = 0.015）。HBcrAg水平未变化。8例（22%）患者因不良事件停用Peg-IFN。Peg-IFN-NAs组3例（8.3%）患者实现HBsAg消失，NAs组0例（0%）。
与NAs治疗相比，NAs联合Peg-IFN可使HBsAg水平更大幅度、更快地下降。Peg-IFN的副作用可能限制其在临床实践中的应用。
