Patients and study design

The design of this retrospective study is shown in Fig 1. We enrolled 61 CHB patients from 2012 to 2016 in 8 hospitals (Nagoya City University Hospital, Shinshu University Hospital, Hyogo College of Medicine Hospital, Osaka City University Hospital, Chiba University Hospital, St. Marianna Medical University Hospital, Hiroshima University Hospital, and Nippon Medical School Chiba Hokusoh Hospital). All patients were chronically infected with HBV and confirmed to be HBsAg-positive for at least 6 months. Patients with a history of hepatocellular carcinoma, cirrhosis, other causes of liver disease such as autoimmune hepatitis and primary biliary cirrhosis, or co-infection with hepatitis C virus or human immunodeficiency virus were excluded from this study. HBeAg was positive in 33 patients and negative in 28.

* Virological response (VR) was defined as HBV DNA < 2,000 IU/mL. HBeAg-negative, nucleos(t)ide analogue free at the end of observation (48 weeks after the end of Peg-IFN therapy). Abbreviations: CHB, chronic hepatitis B; HBeAg, hepatitis B e antigen; Peg-IFN, pegylated interferon; EOT, end of treatment.

The Guidelines for Hepatitis B Treatment by the Japanese Society of Hepatology recommend to treat CHB patients with ALT ≥ 31 U/L and HBV DNA ≥ 2,000 IU/mL [16]. In addition, referring to several predictive factors of response to IFN therapy in CHB, such as HBeAg status, HBV DNA, and ALT levels, the attending physicians introduced Peg-IFN therapy to the subjects in this study. None of the patients received NAs within 48 weeks prior to Peg-IFN treatment. Patients were treated with Peg-IFNα-2a weekly for 48 weeks and were observed for 48 weeks after the end of treatment (EOT) with monitoring at monthly intervals. At each follow-up, data for biochemical markers, virological markers, blood counts, and clinical status were recorded. Following data collection, the patients were divided into virological response (VR) and non-VR groups. The VR was defined as ALT < 31U/L, HBV DNA < 2,000 IU/mL, HBeAg-negative, and no need for administration of NAs until the end of the observation period (48 weeks after the EOT). Serum samples were collected at baseline and 24-weeks during the treatment.

Written informed consent was obtained from all individual participants. The study protocol conformed to the ethics guidelines of the Declaration of Helsinki and was approved by the institutional ethics review committee of Nagoya City University Hospital (60-08-0024).

We collected serum from 61 patients who received Peg-IFN monotherapy for untreated CHB. Patients were treated with Peg-IFNα-2a weekly for 48 weeks and observed up to 48 weeks after therapy. Serum samples were collected at baseline and 24-weeks during the treatment. The VR was defined as ALT < 31U/L, HBV DNA < 2,000 IU/mL, HBeAg-negative, and NAs free at 48 weeks after the EOT. There were 12 VR cases and 49 non-VR cases in this study, and comparisons were made between the VR group and the non-VR group.