The Association Between Nonalcoholic Fatty Liver Disease and Risk of Cardiovascular Disease, Stroke, and Extrahepatic Cancers

Nicolette Veracruz; Bilal Hameed; Sammy Saab; Robert J Wong

doi:10.1016/j.jceh.2020.04.018

The Association Between Nonalcoholic Fatty Liver Disease and Risk of Cardiovascular Disease, Stroke, and Extrahepatic Cancers

J Clin Exp Hepatol. 2021 Jan-Feb;11(1):45-81. doi: 10.1016/j.jceh.2020.04.018. Epub 2020 May 20.

Authors

Nicolette Veracruz¹, Bilal Hameed², Sammy Saab³, Robert J Wong⁴

Affiliations

¹ College of Medicine, Central Michigan University, Mount Pleasant, MI, USA.
² Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, CA, USA.
³ Division of Gastroenterology and Hepatology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
⁴ Division of Gastroenterology and Hepatology, Alameda Health System, Highland Hospital, Oakland, CA, USA.

Abstract

Background & aims: Although primarily a disease with liver-specific complications, nonalcoholic fatty liver disease (NAFLD) is a systemic disease with extrahepatic complications. We aim to evaluate the association between NAFLD and cardiovascular disease (CVD), stroke and cerebrovascular disease, and extrahepatic cancers.

Methods: We searched MEDLINE, EMBASE, and Cochrane Systematic Review Database from January 1, 2000 to July 1, 2019 to identify peer-reviewed English language literature using predefined keywords for NAFLD, CVD, stroke and cerebrovascular disease, and extrahepatic cancers among adults. Two reviewers independently selected studies for inclusion. Measures of association between NAFLD and CVD, stroke and cerebrovascular disease, and extrahepatic cancers were extracted. Quality assessed using Newcastle-Ottawa scale and Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Results: Thirty studies were included evaluating CVD, 16 studies evaluating stroke or cerebrovascular disease, and 13 studies evaluating extrahepatic cancers. On pooled meta-analysis assessment, NAFLD was associated with increased risk of CVD (risk ratio [RR]: 1.78; 95% confidence interval [CI]: 1.52-2.08) and stroke or cerebrovascular disease (RR: 2.08, 95% CI: 1.72-2.51). Significant heterogeneity in assessing extrahepatic cancers prevented applying meta-analysis methods, but NAFLD seemed to be associated with increased risk of breast and colorectal cancers. Overall level of quality of studies were very low by GRADE.

Conclusions: NAFLD is associated with increased risks of CVD and stroke or cerebrovascular disease among adults. There appears to be increased risk of breast and colorectal cancers. Given low quality of evidence, it is premature to make any strong conclusions to modify CVD, stroke, or cancer screening policies in patients with NAFLD.

Keywords: CV, Cardiovascular disease; NAFLD, Nonalcoholic fatty liver disease; NHANES, National Health and Nutrition Examination Survey; cardiovascular disease; extrahepatic cancer; meta-analysis; nonalcoholic fatty liver disease.