incidence and Prediction of HBsAg Seroconversion in a Prospective Multi-ethnic HBeAg-Negative Chronic Hepatitis B Cohort
N A Terrault 1 , A S Wahed 2 , J J Feld 3 , S L Cooper 4 , M G Ghany 5 , M Lisker-Melman 6 , R Perrillo 7 , R K Sterling 8 , M Khalili 9 , R T Chung 10 , P Rosenthal 11 , R J Fontana 12 , A Sarowar 3 , Dty Lau 13 , J Wang 2 , A S Lok 14 , Hla Janssen 3
Affiliations
Affiliations
1
Gastrointestinal and Liver Diseases Division, Keck Medicine of University of Southern California.
2
Department of Biostatistics and Epidemiology Data Center, University of Pittsburgh.
3
Toronto Centre for Liver Disease, University of Toronto.
4
San Francisco Center for Liver Disease, California Pacific Medical & Research Institute.
5
Liver Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.
6
Washington University School of Medicine and John Cochran VA Medical Center, St. Louis.
7
Baylor University Medical Center.
8
Section of Hepatology, Virginia Commonwealth University.
9
Department of Medicine, University of California San Francisco.
10
Massachusetts General Hospital, Harvard Medical School.
11
Department of Pediatrics, University of California San Francisco.
12
Department of Internal Medicine, University of Michigan.
13
Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University.
14
Division of Gastroenterology and Hepatology, University of Michigan.
PMID: 34743343 DOI: 10.1002/hep.32231
Abstract
Background & aims: Achieving HBsAg loss is an important landmark in the natural history of chronic hepatitis B. A more personalized approach to prediction of HBsAg loss is relevant in couseling patients. This study sought to develop and validate a prediction model for HBsAg loss based on quantitative HBsAg levels and other baseline characteristics.
Methods: Hepatitis B Research Network (HBRN) is a prospective cohort including 1240 untreated HBeAg-negative patients (1150 adults, 90 children) with median follow-up of 5.5 years. Incidence rates of HBsAg loss and anti-HBs acquisition were determined and a predictor score of HBsAg loss using readily available variables was developed and externally validated.
Results: Crude incidence rates of HBsAg loss and anti-HBs acquisition were 1.6 and 1.1 per 100 person-years (PY); 67 achieved sustained HBsAg loss for an incidence rate of 1.2 per 100 PY. Increased HBsAg loss was significantly associated with older age, non-Asian race, HBV phenotype (inactive carrier vs others), HBV genotype A, lower HBV DNA levels and lower and greater change in quantitative HBsAg (∆qHBsAg). The HBRN-SQuARe (sex,∆quantHBsAg, age, race) score predicted HBsAg loss over time with AUROC (95% confidence intervals) at 1 and 3 years of 0.99 (95% CI: 0.987-1.00) and 0.95 (95% CI 0.91-1.00), respectively. Validation in another cohort of 1253 HBeAg-negative patients with median follow-up of 3.1 years, HBRN-SQuARe predicted HBsAg loss at 1 and 3 years with AUROC values of 0.99 [0.98-1.00] and 0.88 [0.77-0.99], respectively.
Conclusion: HBsAg loss in predominantly untreated patients with HBeAg-negative chronic hepatitis B can be accurately predicted over a 3-year horizon using a simple validated score (HBRN-SQuARe). This prognostication tool can be used to support patient care and counseling.