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Risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis B virus (HBV) infection: a systematic review and meta-analysis
Cori Campbell 1 , Tingyan Wang 1 , Anna L McNaughton 1 , Eleanor Barnes 1 , Philippa C Matthews 1 2 3
Affiliations
Affiliations
1
Nuffield Department of Medicine, University of Oxford, Medawar Building, South Parks Road, Oxford, OX1 3SY, UK.
2
Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK.
3
NIHR BRC, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK.
PMID: 33305479 DOI: 10.1111/jvh.13452
Abstract
Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide and is the largest cause of death in individuals with chronic hepatitis B virus (HBV) infection. It is uncertain how the presence of other metabolic factors and comorbidities influences HCC risk in HBV. Therefore we performed a systematic literature review and meta-analysis to seek evidence for significant associations. MEDLINE, Embase and Web of Science databases were searched from 1st January 2000 to 24th June 2020 for English studies investigating associations of metabolic factors and comorbidities with HCC risk in individuals with chronic HBV infection. We extracted data for meta-analysis and generated pooled effect estimates from a fixed-effects model. Pooled estimates from a random-effects model were also generated if significant heterogeneity was present. We identified 40 observational studies reporting on associations of diabetes mellitus (DM), hypertension, dyslipidaemia and obesity with HCC risk. Only DM had a sufficient number of studies for meta-analysis. DM was associated with >25% increase in hazards of HCC (fixed effects Hazards Ratio [HR] 1.26, 95% confidence interval (CI) 1.20-1.32, random effects HR 1.36, 95% CI 1.23-1.49). This association was attenuated towards the null in a sensitivity analysis restricted to studies adjusted for metformin use. In conclusion, in adults with chronic HBV infection, DM is a significant risk factor for HCC, but further investigation of how antidiabetic drug use and glycaemic control influence this association is needed. Enhanced screening of individuals with HBV and diabetes may be warranted.
Keywords: HCC; Hepatitis B virus; comorbidities; diabetes; hepatocellular carcinoma.
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