Objective We performed a meta-analysis of observational studies to quantify the magnitude of the association between non-alcoholic fatty liver disease (NAFLD) and risk of extrahepatic cancers.
Design We systematically searched PubMed, Scopus and Web of Science databases from the inception date to 30 December 2020 using predefined keywords to identify observational cohort studies conducted in individuals, in which NAFLD was diagnosed by imaging techniques or International Classification of Diseases codes. No studies with biopsy-proven NAFLD were available for the analysis. Meta-analysis was performed using random-effects modelling.
Results We included 10 cohort studies with 182 202 middle-aged individuals (24.8% with NAFLD) and 8485 incident cases of extrahepatic cancers at different sites over a median follow-up of 5.8 years. NAFLD was significantly associated with a nearly 1.5-fold to twofold increased risk of developing GI cancers (oesophagus, stomach, pancreas or colorectal cancers). Furthermore, NAFLD was associated with an approximately 1.2-fold to 1.5-fold increased risk of developing lung, breast, gynaecological or urinary system cancers. All risks were independent of age, sex, smoking, obesity, diabetes or other potential confounders. The overall heterogeneity for most of the primary pooled analyses was relatively low. Sensitivity analyses did not alter these findings. Funnel plots did not reveal any significant publication bias.
Conclusion This large meta-analysis suggests that NAFLD is associated with a moderately increased long-term risk of developing extrahepatic cancers over a median of nearly 6 years (especially GI cancers, breast cancer and gynaecological cancers). Further research is required to decipher the complex link between NAFLD and cancer development.
- fatty liver
- nonalcoholic steatohepatitis
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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Contributors Study concept and design: AM, GT. Acquisition of data: AM, GP, GB, AC, GT. Statistical analysis of data: AM. Analysis and interpretation of data: AM, GT. Drafting of the manuscript: AM, GT. Critical revision of the manuscript for important intellectual content: HT, CDB. All authors have read and approved the final version of the manuscript.
Funding GT is supported in part by grants from the University School of Medicine of Verona, Italy. CDB is supported in part by the Southampton National Institute for Health Research (NIHR) Biomedical Research Centre. HT is supported by the excellence initiative Centre for Promoting Vascular Health in the Ageing Community (VASCage), an R&D K-Centre (Competence Centers for Excellent Technologies (COMET) programme) funded by the Austrian Ministry for Transport, Innovation and Technology, the Austrian Ministry for Digital and Economic Affairs and the federal states Tyrol, Salzburg and Vienna.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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