Liver Enzymes, Nonalcoholic Fatty Liver Disease, and Incident Cardiovascular Disease: A Narrative Review and Clinical Perspective of Prospective Data†

Abstract

In recent years, a strong link has been established between nonalcoholic fatty liver disease (NAFLD) and the pathogenesis of type 2 diabetes mellitus. The potential role of NAFLD in cardiovascular disease (CVD) has also attracted interest. Published studies have tended to use biochemical and imaging surrogate markers of NAFLD, such as elevated gamma glutamyl transpeptidase (GGT) and alanine aminotransferase (ALT) and fatty liver on ultrasound, when investigating associations with incident CVD events. Positive associations between both baseline GGT and temporal change in GGT, as well as cardiovascular events and cardiovascular mortality independent of alcohol intake, have been reported in several prospective studies. However, adjustment for confounders is often incomplete, and there is scant evidence of improvement in cardiovascular risk prediction beyond established risk scores when incorporating such data. There also appears to be a strong and underrecognized age interaction, with associations between GGT and incident coronary heart disease (CHD) being strong in young individuals but relatively weak in the elderly. By contrast, ALT appears to be only weakly associated with incident CHD and may exhibit a U-shaped association with total mortality. Finally, although some studies have linked imaging-defined and biopsy-confirmed NAFLD with CVD risk, the evidence is inconsistent, with few incident events and/or insufficient potential confounders. Conclusion: A diagnosis of NAFLD is insufficient to consider patients as being at high risk for CVD. The presence of NAFLD should be a clear indication for diabetes screening, but cardiovascular risk screening should be performed with the use of existing risk calculators and should be guided by established cardiovascular risk factors.