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HBV Recurrence Detected by HBV-Related Serum Markers and Immune Escape Mutations in Chronic Hepatitis B Patients
Chien-Ming Chiang1, Yih-Jyh Lin2, Wen-Chun Liu3
1Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Abstract:
The posttransplantation recurrence rate of hepatitis B virus (HBV) infection in patients with chronic hepatitis B (CHB) is underestimated and linked with unfavorable outcomes. We investigated HBV recurrence by serum assays in patients with CHB following liver transplantation. We enrolled patients with CHB who underwent liver transplantation between March 2001 and July 2021 to participate in cross-sectional testing for HBV-related serum markers, including biochemical analysis for HBsAg and hepatitis B core-related antigen (HBcrAg) and real-time RT-PCR/PCR for HBV RNA and HBV DNA, in 2022. HBV recurrence in this study was defined as positive results of at least one posttransplantation HBV-related serum markers. Next-generation sequencing was performed for those with posttransplantation virological breakthroughs. Ninety-six patients with CHB who underwent liver transplantation were enrolled. Among 84 patients who received grafts negative for HBsAg, 41 (48.8%) exhibited HBV recurrence, and they tested positive for either HBsAg or HBcrAg, or both. High-risk patients, identified using a risk stratification model, had a higher likelihood of recurrence than low-risk patients (odds ratio: 2.59, 95% confidence interval: 1.06-6.35, p = 0.038). In 51 patients who tested negative for HBsAg after receiving HBsAg-negative grafts, 8 (15.7%) had positive HBcrAg, indicating occult HBV infection (OBI). We identified immune escape mutations and altered N-glycosylation patterns on the surface protein in patients experiencing virological breakthroughs following lamivudine resistance. HBsAg plus HBcrAg levels can be used to detect posttransplantation HBV recurrence. The OBI prevalence was higher in patients transplanted with HBsAg-negative liver grafts compared to blood donors, vaccinated young population, and community-based populations reported in literatures, possibly because of immune escape mutations or altered N-glycosylation patterns of surface proteins.
