Predictive Factors for Hepatocellular Carcinoma in Chronic Hepatitis B Using Structural Equation Modeling: A Prospective Cohort Study
Laurent Lam 1 , Hélène Fontaine 2 , Marc Bourliere 3 , Clovis Lusivika-Nzinga 4 , Céline Dorival 4 , Dominique Thabut 5 , Fabien Zoulim 6 , François Habersetzer 7 , Tarik Asselah 8 , Jean-Charles Duclos-Vallee 9 , Jean-Pierre Bronowicki 10 , Philippe Mathurin 11 , Thomas Decaens 12 , Nathalie Ganne 13 , Dominique Guyader 14 , Vincent Leroy 15 , Isabelle Rosa 16 , Victor De Ledinghen 17 , Paul Cales 18 , Xavier Causse 19 , Dominique Larrey 20 , Olivier Chazouilleres 21 , Moana Gelu-Simeon 22 , Véronique Loustaud-Ratti 23 , Sophie Metivier 24 , Laurent Alric 25 , Ghassan Riachi 26 , Jérôme Gournay 27 , Anne Minello 28 , Albert Tran 29 , Claire Geist 30 , Armand Abergel 31 , François Raffi 32 , Louis D'alteroche 33 , Isabelle Portal 34 , Nathanaël Lapidus 1 , Stanislas Pol 35 , Fabrice Carrat 36 , ANRS AFEF Hepather study group
Affiliations
PMID: 33930591 DOI: 10.1016/j.clinre.2021.101713
Abstract
Background & aims: The factors predicting hepatocellular carcinoma (HCC) occurrence in chronic hepatitis B need to be precisely known to improve its detection. We identified pathways and individual predictive factors associated with HCC in the ANRS CO22 HEPATHER cohort.
Methods: The study analyzed HBV-infected patients recruited at 32 French expert hepatology centers from August 6, 2012, to December 31, 2015. We excluded patients with chronic HCV, HDV and a history of HCC, decompensated cirrhosis or liver transplantation. Structural equation models were developed to characterize the causal pathways leading to HCC occurrence. The association between clinical characteristics (age, gender, body-mass index, liver fibrosis, alcohol consumption, smoking status, diabetes, hypertension, dyslipidemia, alpha-fetoprotein, HBV DNA levels, antiviral therapy) and incident HCC was quantified.
Results: Among the 4,489 patients included, 33 patients reported incident HCC. The median follow-up was 45.2 months. Age (β = 0.18 by decade, 95% CI 0.14-0.23), male gender (β = 0.23, 95% CI 0.18-0.29), metabolic syndrome (β = 0.28, 95% CI 0.22-0.33), alcohol consumption (β = 0.09, 95% CI 0.05-0.14) and HBV DNA (β = 0.25, 95% CI 0.17-0.34) had a significant and direct effect on the occurrence of advanced liver fibrosis. Liver fibrosis (β = 0.71, 95% CI 0.55-0.87) predicted, in turn, the occurrence of HCC.
Conclusions: Liver fibrosis mediates the effects of age, gender, alcohol, metabolic syndrome and HBV DNA on the occurrence of HCC. Elderly men with chronic hepatitis B, risky alcohol use, advanced liver fibrosis, metabolic syndrome and high HBV DNA levels should be monitored closely to detect the development of HCC.
Keywords: Carcinoma; Epidemiology; Hepatitis B virus; Hepatocarcinogenesis; Hepatocellular; Liver Cancer.