Abstract
Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide and is a leading 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 1 January 2000 to 24 June 2020 for studies investigating associations of metabolic factors and comorbidities with HCC risk in individuals with chronic HBV infection, written in English. 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 the influence of antidiabetic drug use and glycaemic control on this association is needed. Enhanced screening of individuals with HBV and diabetes may be warranted.
Highlights
Hepatitis B virus (HBV) is a hepatotropic virus responsible for substantial morbidity and mortality worldwide
The World Health Organization (WHO) estimated a chronic HBV (CHB) global burden of 257 million CHB-infected individuals for 2015, with 887,000 HBV-attributable deaths reported in the same year,[1] making HBV one of the leading causes of morbidity and mortality from viral infection, for which the burden has increased in recent decades.[2]
| 499 of hepatocellular carcinoma (HCC) 16% higher in diabetes mellitus (DM) participants as compared to non-DM in analysis restricted to studies adjusting for metformin use (Figure S5)
Summary
Hepatitis B virus (HBV) is a hepatotropic virus responsible for substantial morbidity and mortality worldwide. Neither EASL, the American Association of the Study of Liver Disease (AASLD)[23] nor the Asian Pacific Association for the Study of the Liver (APASL)[24] guidelines for HBV management include recommendations for enhanced screening or DM management in CHB, despite recent clinical interest in the potential utility of metformin in preventing and treating various cancers.[25,26] there are few studies investigating associations of other potentially relevant comorbidities (such as hypertension, CHD and renal disease) and their metabolic risk factors (such as obesity and dyslipidaemia) with HCC risk. We undertook a systematic review, aiming to summarize and critically appraise studies investigating associations of relevant comorbidities and metabolic factors with risk of HCC in CHB-infected individuals
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