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Multicenter Study
. 2026 Feb;63(3):374-382.
doi: 10.1111/apt.70360. Epub 2025 Sep 9.

Prediction of Hepatocellular Carcinoma and Other Liver-Related Events in Chronic Hepatitis B Patients With Metabolic Dysfunction or Metabolic Dysfunction-Associated Steatotic Liver Disease

Lesley A Patmore  1 , Ivana Carey  2 , Jordan J Feld  3 , Willem P Brouwer  1 , Keyur Patel  3 , Maria Buti  4 , Pieter Honkoop  5 , Douwe F Postma  6 , Hans Blokzijl  7 , Özgur M Koc  8 , Eva van Oorschot  8 , Kosh Agarwal  2 , Marc van der Valk  9 , Faydra I Lieveld  10   11 , Mai Kilany  3 , Matthijs Kramer  8   12 , Joep de Bruijne  10 , Mark A A Claassen  13   14 , Bettina E Hansen  15 , Robert A de Man  1 , Harry L A Janssen  1   3 , R Bart Takkenberg  16 , Milan J Sonneveld  1
Affiliations
Multicenter Study

Prediction of Hepatocellular Carcinoma and Other Liver-Related Events in Chronic Hepatitis B Patients With Metabolic Dysfunction or Metabolic Dysfunction-Associated Steatotic Liver Disease

Lesley A Patmore et al. Aliment Pharmacol Ther. 2026 Feb.

Abstract

Introduction: Metabolic dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD) are associated with an increased risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to study risk factors for HCC and to assess the performance of the PAGE-B score in this population.

Methods: We included CHB patients with ≥ 1 metabolic comorbidity from nine centres. Steatosis was diagnosed by ultrasound, CAP, or histology. Risk factors were analysed by Cox regression, and the performance of the PAGE-B score was assessed in the overall population and across relevant subgroups.

Results: We included 1922 patients. 1730 (90.0%) were overweight, 434 (22.6%) had hypertension, 254 (13.2%) dyslipidemia, 230 (12.0%) diabetes and 732 (38.1%) MASLD. Presence of cirrhosis, older age, lower platelets and lower albumin were independent risk factors for HCC. The 5-year HCC risk was 0.1%/2.0%/12.4% patients with low/intermediate/high PAGE-B scores (p < 0.001). Consistent results were obtained in patients with MASLD (0/2.8/11.1% for low, intermediate and high PAGE-B scores (p < 0.001)). PAGE-B stratified risk in patients without cirrhosis (0% vs. 1.2% and 1.8%, p < 0.001). Among the subset of patients with cirrhosis, risks were 4.2% (low), 6.9% (intermediate) and 27.3% (high) (p < 0.001).

Conclusions: CHB patients with metabolic dysfunction and/or MASLD are at significant risk of HCC. The PAGE-B score can be used to stratify HCC risk in this population, with negligible 5-year HCC incidence in those without cirrhosis and low PAGE-B scores. However, caution should be exercised in patients with cirrhosis in whom HCC risk remains significant even among those with a low PAGE-B score.

Keywords: PAGE‐B; diabetes mellitus type 2; dyslipidemia; hypertension; overweight.

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Conflict of interest statement

L.A.P.: research support and consultancy fee from Gilead Sciences. I.C.: Received a research grant from Gilead. J.J.F.: has received personal fees for consulting from AbbVie, Enanta, Gilead, Janssen and Roche, and research funding from AbbVie, Abbott, Gilead and FUJIFILM Wako Chemicals. W.P.B.: received a speakers fee from Eli Lilly. Is on the advisory board of Novo Nordisk. Participated in trials from Inventive pharma, Boehringer Ingelheim and 89BIO. K.P.: DSMB for Gilead Sciences, consulting for Novo‐Nordisk, Resalis, Merck. M.B.: Received grants and Advisory Board Gilead Sciences. P.H.: none. D.F.P.: Member of DSMB of the COBRA‐trial (Very short‐course versus standard course antibiotic therapy in patients with acute ChOlangitis after adequate endoscopic BiliaRy drAinage (COBRA trial)); consultancy fees from Gilead (payed to institution). H.B.: none. O.M.K.: none. E.vO.: none. K.A.: received a research grant from Gilead, Roche and MSD. Is an advisor for Aligos, Arbutus, Assembly, Abbvie, Biotest, Bluejay, GLG, Gilead, Immunocore, Shiniogi and Vir Biotechnology Inc. M.vd.V.: Unrestricted research funding and consultancy fees from Gilead, MSD, ViiV, all paid to his institution. F.I.L.: none. M.Ki.: none. M.Kr.: received a speakers fee from Norgine. J.dB.: research support from Terumo. M.A.A.C.: none. B.E.H.: received grants from Mirum Pharma, Intercept, Cymabay, Eiger, Ipsen/Albireo, Pliant, Advanz and Calliditas. Is a consultant for Mirum Pharma, Intercept, Cymabay, Eiger, Pliant, Advanz and Calliditas. R.A.dM.: research support from Roche. H.L.A.J.: received grants from: Gilead Sciences, GlaxoSmithKline, Janssen, Roche, Vir Biotechnology. Consultant for: Aligos, Gilead Sciences, GlaxoSmithKline, Grifols, Roche, Vir Biotechnology Inc., Precision Biosciences. R.B.T.: Speakers fees from WL gore, research support Norgine, consultancy fee 89Bio. M.J.S.: Speakers fees and research support from Gilead, Roche, Fujirebio and consultancy fees from Gilead and Albireo.

Figures

FIGURE 1
FIGURE 1
Cumulative incidences of HCC (A) in the overall cohort (B) in patients with and without cirrhosis. Patients without available information on fibrosis status at baseline were excluded from the analysis in (B).
FIGURE 2
FIGURE 2
Cumulative incidences of HCC according to PAGE‐B strata.
FIGURE 3
FIGURE 3
Cumulative incidences of HCC according to PAGE‐B score in patients without (A) and in patients with (B) MASLD.
FIGURE 4
FIGURE 4
Cumulative incidences of HCC according to PAGE‐B score in patients without (A) and in patients with (B) cirrhosis.
See this image and copyright information in PMC

References

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