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AbstractBackgroundHepatocellular 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 not certain how the presence of other metabolic factors and comorbidities influences HCC risk in HBV. Therefore we performed a systematic review and meta-analysis to seek evidence for significant associations.MethodsMEDLINE, 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 report pooled effect estimates from a fixed-effects model. Pooled estimates from a random-effects model were also generated if significant heterogeneity was present.ResultsWe identified 40 observational studies reporting on associations of diabetes mellitus, hypertension, dyslipiaemia and obesity with HCC risk. Meta-analysis was possible for only diabetes mellitus due to the limited number of studies. Diabetes mellitus was associated with > 25% increase in hazards of HCC (fixed effects Hazards Ratio [HR] 1.26, 95% CI 1.20–1.32, random effects HR 1.36, 95% CI 1.23–1.49). This association was attenuated towards the null in sensitivity analysis restricted to studies adjusted for metformin use.ConclusionsIn adults with chronic HBV infection, diabetes mellitus 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.

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