HBV-seropositive patients who received clinical observation at Kyoto University Hospital and Osaka Red Cross Hospital between April 2001 and March 2020 were enrolled in this study. The inclusion criteria were: consistently seropositive for HBsAg serum HBV-DNA titer higher than 4.23 LogIU/mL (105 copies/mL) for at least 2 time-points; free from antiviral medications or interferon treatment. The exclusion criteria were: under 20 years old; coinfection with HCV, HIV, or human T-lymphotropic virus; uncontrolled malignancies; liver comorbidities such as alcohol-associated liver disease, nonalcoholic steatohepatitis, autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, immunoglobulin G4-related sclerosing cholangitis, or Wilson disease. Two to 5 serum samples were sequentially collected during the observation period. All samples were surpluses of sera drawn for clinical purposes. The collected samples were stored at −80°C.
This study conformed to the provisions of the Declaration of Helsinki. The study protocol (R2594) was approved by the ethics committee of Kyoto University and the clinical samples were obtained with written informed consent or based on an opt-out method of consent from all participants.
This study conformed to the provisions of the Declaration of Helsinki. The study protocol (R2594) was approved by the ethics committee of Kyoto University and the clinical samples were obtained with written informed consent or based on an opt-out method of consent from all participants.
