Incidence and prediction of HBsAg seroclearance in a prospective multi-ethnic HBeAg-negative chronic hepatitis B cohort - PubMed (original) (raw)

. 2022 Mar;75(3):709-723.

doi: 10.1002/hep.32231. Epub 2022 Jan 26.

Abdus S Wahed 2, Jordan J Feld 3, Stewart L Cooper 4, Mark G Ghany 5, Mauricio Lisker-Melman 6, Robert Perrillo 7, Richard K Sterling 8, Mandana Khalili 9, Raymond T Chung 10, Philip Rosenthal 11, Robert J Fontana 12, Arif Sarowar 3, Daryl T Y Lau 13, Junyao Wang 2, Anna S Lok 14, Harry L A Janssen 3

Affiliations

Incidence and prediction of HBsAg seroclearance in a prospective multi-ethnic HBeAg-negative chronic hepatitis B cohort

Norah A Terrault et al. Hepatology. 2022 Mar.

Abstract

Background and aims: Achieving HBsAg loss is an important landmark in the natural history of chronic hepatitis B (CHB). A more personalized approach to prediction of HBsAg loss is relevant in counseling patients. This study sought to develop and validate a prediction model for HBsAg loss based on quantitative HBsAg levels (qHBsAg) and other baseline characteristics.

Methods: The 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 hepatitis B surface antibody (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 CHB vs. others), HBV genotype A, lower HBV-DNA levels, and lower and greater change in qHBsAg. The HBRN-SQuARe (sex,∆quantHBsAg, age, race) score predicted HBsAg loss over time with area under the receiver operating characteristic curve (AUROC) (95% CIs) at 1 and 3 years of 0.99 (95% CI: 0.987-1.00) and 0.95 (95% CI 0.91-1.00), respectively. In 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 CHB 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.

© 2021 American Association for the Study of Liver Diseases.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest:

Figures

Figure 1:

Figure 1:. Evolution of HBsAg status amongst participants with HBsAg loss during study years

Each participant’s follow-up is shown as a row, with the time of follow-up on the x-axis. Each time interval is represented by a box: Pink boxes indicate HBsAg is positive, Light green boxes indicate HBsAg is negative and Grey boxes indicate missing test results. Further, the participants are grouped into 3 broad categories indicated by the colored bar on the far left: with those with sustained HBsAg loss (BLACK bar), transient HBsAg loss (BLUE bar) and insufficient follow-up (ORANGE bar). The majority of (67/92) participants had sustained HBsAg loss.

Figure 2:

Figure 2:. Crude incidence rate (per 100 person-years) for ever HBsAg loss by selected baseline characteristics

Participants with ever HBsAg loss differed by baseline characteristics. Crude incidence rates by key baseline factors are shown: Age, Sex, Race, HBV genotype, CHB phenotype, ALT, HBV DNA and HBsAg quantitation are shown.

Figure 3:

Figure 3:. ROC curves for predicting HBsAg loss using HBRN SQuAre Models.

The SQuARe model can estimate predicted probability of HBsAg loss over time (

https://abduswahed.shinyapps.io/RShiny/

).

Figure 4:

Figure 4:. Examples of predicting probability of HBsAg loss using HBRN SQuARe Model.

Predicted probability of HBsAg loss as a function of baseline quantitative HBsAg levels and change over a one-year period for selected participants of varying race, sex, and age. Upper row for a <30 year old Asian female participant and the lower panel for a non-Asian female in their 50’s.

References

    1. Cornberg M, Lok AS, Terrault NA, Zoulim F, Faculty E-AHTEC. Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference(double dagger). J Hepatol 2020;72:539–57. - PubMed
    1. Yip TC, Wong GL, Chan HL, et al. HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues. J Hepatol 2019;70:361–70. - PubMed
    1. Su YC, Lin PC, Yu HC, Wu CC. Hepatitis B virus reactivation in patients with resolved hepatitis B virus infection receiving chemotherapy or immunosuppressive therapy. Eur J Gastroenterol Hepatol 2018;30:925–9. - PubMed
    1. Zhou K, Contag C, Whitaker E, Terrault N. Spontaneous loss of surface antigen among adults living with chronic hepatitis B virus infection: a systematic review and pooled meta-analyses. Lancet Gastroenterol Hepatol 2019;4:227–38. - PMC - PubMed
    1. Yeo YH, Ho HJ, Yang HI, et al. Factors Associated With Rates of HBsAg Seroclearance in Adults With Chronic HBV Infection: A Systematic Review and Meta-analysis. Gastroenterology 2019;156:635–46 e9. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources