Hepatitis B surface antigen and hepatitis B core-related antigen kinetics after adding pegylated-interferon to nucleos(t)ids analogues in hepatitis B e antigen-negative patients
Teresa Broquetas 1 , Montserrat Garcia-Retortillo 1 , Miquel Micó 2 , Lidia Canillas 1 , Marc Puigvehí 1 , Nuria Cañete 1 , Susana Coll 1 , Ana Viu 1 , Juan Jose Hernandez 2 , Xavier Bessa 1 , José A Carrión 1
Affiliations
Affiliations
1
Department of Gastroenterology, Liver Section, Hospital del Mar Medical Research Institute, Barcelona 08003, Spain.
2
Laboratori de Referencia de Catalunya, El Prat de Llobregat, Barcelona 08820, Spain.
Background: Hepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues (NAs) rarely achieve hepatitis B surface antigen (HBsAg) loss.
Aim: 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.
Methods: Prospective, non-randomized, open-label trial evaluating the combination of Peg-IFN 180 µg/week plus NAs during forty-eight weeks vs 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.
Results: 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 vs 3.2) (P = 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) (P < 0.05). The slope of HBsAg decline in Peg-IFN-NA group (-0.02) was higher than in NA group (-0.00) (P = 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.
Conclusion: 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.
Keywords: Chronic hepatitis B; Hepatitis B core-related antigen; Hepatitis B e antigen-negative; Hepatitis B surface antigen; Nucleos(t)ids analogues; Pegylated-interferon.
方法：一项前瞻性，非随机，开放标签的试验，评估与单一疗法中的NAs相比，Peg-IFN 180μg/周加NA在48周内的组合。三级医院接受NAs治疗且病毒载量无法检测的乙型肝炎e抗原阴性非肝硬化慢性乙型肝炎患者合格。排除丙型肝炎病毒，丁型肝炎病毒或人免疫缺陷病毒合并感染的患者以及肝移植患者。在基线和九十六周内测量HBsAg和HBcrAg水平（log10 U / mL）。两组均评估了HBsAg丢失率。两组均记录不良事件。使用线性回归模型，通过基线至HBsAg下降的斜率（log10 IU / mL /周）评估每个治疗组的HBsAg动力学。