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. 2022 Jun 1;225(11):1967-1973.
doi: 10.1093/infdis/jiaa192.

Hepatitis B Surface Antigen Levels Can Be Used to Rule Out Cirrhosis in Hepatitis B e Antigen-Positive Chronic Hepatitis B: Results From the SONIC-B Study

Milan J Sonneveld  1 , Bettina E Hansen  2   3 , Willem P Brouwer  1 , Henry L-Y Chan  4 , Teerha Piratvisuth  5 , Ji-Dong Jia  6 , Stefan Zeuzem  7 , Rong-Nan Chien  8 , Robert J de Knegt  1 , Cynthia Wat  9 , Vedran Pavlovic  9 , Anuj Gaggar  10 , Qing Xie  11 , Maria Buti  12 , Robert A de Man  1 , Harry L A Janssen  1   2 ; SONIC-B Study Group
Affiliations

Hepatitis B Surface Antigen Levels Can Be Used to Rule Out Cirrhosis in Hepatitis B e Antigen-Positive Chronic Hepatitis B: Results From the SONIC-B Study

Milan J Sonneveld et al. J Infect Dis. .

Abstract

Background: Serum hepatitis B surface antigen (HBsAg) levels correlate with the duration of chronic hepatitis B virus (HBV) infection and may predict the extent of hepatic fibrosis.

Methods: We analyzed data from the SONIC-B database, which contains data from 8 global randomized trials and 2 large hepatology centers. Relationship between HBsAg levels and presence of significant fibrosis (Ishak 3-4) or cirrhosis (Ishak 5-6) were explored, and clinically relevant cutoffs were identified to rule out cirrhosis.

Results: The dataset included 2779 patients: 1866 hepatitis B e antigen (HBeAg)-positive; 322 with cirrhosis. Among HBeAg-positive patients, lower HBsAg levels were associated with higher rates of significant fibrosis (odds ratio [OR], 0.419; P < .001) and cirrhosis (OR, 0.435; P < .001). No relationship was observed among HBeAg-negative patients. Among HBeAg-positive patients, genotype-specific HBsAg cutoffs had excellent negative predictive values (>97%) and low misclassification rates (≤7.1%) and may therefore have utility in ruling out cirrhosis. Diagnostic performance of the HBsAg cutoffs was comparable among patients in whom cirrhosis could not be ruled out with fibrosis 4 (FIB-4).

Conclusions: Hepatitis B virus genotype-specific HBsAg cutoffs may have utility in ruling out presence of cirrhosis in HBeAg-positive patients with genotypes B, C, and D and can be an adjunct to FIB-4 to reduce the need for further testing.

Keywords: HBsAg; cirrhosis; fibrosis; hepatitis B.

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Figures

Figure 1.
Figure 1.
Relationship between hepatitis B surface antigen (HBsAg) level and liver fibrosis and/or cirrhosis among hepatitis B e antigen (HBeAg)-positive (A) or HBeAg-negative (B) patients. Liver fibrosis was graded as no significant fibrosis (Ishak 0–2), significant fibrosis (Ishak 3–4), or cirrhosis (Ishak 5–6). The HBsAg levels are given as quintiles.
Figure 2.
Figure 2.
Predicted probability of significant fibrosis (Ishak 3–6 [A]) or cirrhosis (Ishak 5–6 [B]) according to hepatitis B surface antigen (HBsAg) level and stratified by hepatitis B e antigen (HBeAg) status. Estimates were derived by logistic regression adjusted for hepatitis B virus genotype.
Figure 3.
Figure 3.
Potential application of quantitative hepatitis B surface antigen (HBsAg) to rule out cirrhosis in clinical practice. *, Genotype-specific cutoffs: genotype B >50 000 IU/mL, genotype C >18 000 IU/mL, and genotype D >75 000 IU/mL. FIB-4, fibrosis 4; qHBsAg, quantitative HBsAg.
See this image and copyright information in PMC

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