Clin Mol Hepatol.
2024 Jan;30(1):98-108. 10.3350/cmh.2023.0194.
Hepatitis B core-related antigen dynamics and risk of subsequent clinical relapses after nucleos(t)ide analog cessation
- Affiliations
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- 1Division of Gastroenterology and Hepatology, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan
- 2School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- 3Department of Public Health, National Cheng Kung University, College of Medicine, Tainan, Taiwan
- 4Division of Gastroenterology and Hepatology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- 6Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- 7Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan
- 8Division of Gastroenterology, Department of Medicine, Lotung Poh-Ai Hospital, Yilan, Taiwan
- 9Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- 10Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USA
- KMID: 2549386
- DOI: http://doi.org/10.3350/cmh.2023.0194
Abstract
- Background/Aims
Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR).
Methods
This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR.
Results
The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5–40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7–67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1–62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12–2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21–0.81).
Conclusions
Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.
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