Distinct Relapse Rates and Risk Predictors after Discontinuing Tenofovir and Entecavir Therapy
Journal
Journal of Infectious Diseases
Journal Volume
217
Journal Issue
8
Pages
1193-1201
Date Issued
2018
Abstract
Background We investigated the patterns and predictors for virological relapse (VR), clinical relapse (CR), and sustained clinical response (SCR) and the outcomes of retreatment after nucleos(t)ide analogue (NUC) therapy discontinuation. Methods Patients with chronic hepatitis B who were discontinuing NUC therapy were prospectively enrolled. Viral and host predictors of relapse were evaluated, including hepatitis B virus (HBV) surface antigen (HBsAg) level, anti-HBV core antibody level, and presence of single-nucleotide polymorphisms in the genes encoding the receptors NTCP (rs2296651) and CTLA4 (rs231775) and in the 3′ untranslated regions of the genes encoding HLA-DPA1 (rs3077) and HLA-DPB1 (rs9277535); posttherapy predictors of relapse were also investigated. Information about NUC retreatment and outcomes were recorded. Results Overall, 100 patients discontinuing 3-year entecavir (ETV) or tenofovir (TDF) therapy were enrolled. Patients discontinuing TDF exhibited significantly higher rates of VR (52.9% vs 6.1%; P <.001) and CR (15.2% vs. 1.5%, P =.007) at 3 months than those discontinuing ETV, but relapse rates at 12 months were comparable. The end-of-therapy HBsAg levels predicted VR (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.19-2.21), CR (HR, 1.78; 95% CI, 1.13-2.81), and SCR (OR, 0.57; 95% CI,.35-.94). The CTLA4 (rs231775) non-GG genotype predicted VR (HR, 1.74; 95% CI, 1.01-3.00) and CR (HR, 2.06; 95% CI, 1.04-4.11), while the HLA-DPA1 (rs3077) AA genotype predicted SCR (OR, 10.84; 95% CI, 1.12-105). The HBV DNA 1 month after NUC treatment cessation was an early predictor of subsequent relapse. Conclusions Discontinuation of tenofovir disoproxil fumarate treatment rather than entecavir treatment is associated with earlier relapse, and NUC-specific posttherapy monitoring is necessary. ? 2017 The Author(s).
SDGs
Other Subjects
adenine; cytotoxic T lymphocyte antigen 4; entecavir; guanine; hepatitis B core antibody; hepatitis B surface antigen; HLA antigen class 2; HLA DPA1 antigen; HLA DPB1 antigen; sodium bile acid cotransporter; tenofovir; unclassified drug; virus DNA; antivirus agent; entecavir; guanine; hepatitis B surface antigen; hepatitis B(e) antigen; tenofovir; virus DNA; 3' untranslated region; adult; Article; chronic hepatitis B; cohort analysis; controlled study; drug withdrawal; female; genotype; human; major clinical study; male; priority journal; prospective study; recurrence risk; risk assessment; single nucleotide polymorphism; analogs and derivatives; blood; chronic hepatitis B; Hepatitis B virus; middle aged; physiology; recurrent disease; risk factor; Adult; Antiviral Agents; DNA, Viral; Female; Guanine; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged; Prospective Studies; Recurrence; Risk Factors; Tenofovir
Publisher
Oxford University Press
Type
journal article