Serum gamma glutamyl transferase and alanine transaminase concentrations predict endothelial dysfunction in patients with non-alcoholic steatohepatitis

Abstract

Purpose. Cardiovascular diseases are the leading cause of death in patients with non-alcoholic steatohepatitis (NASH). We aimed to investigate the presence of endothelial dysfunction and whether serum concentrations of liver enzymes may reflect the severity of such an endothelial dysfunction in patients with NASH.Methods. Fifty patients with NASH diagnosed by liver biopsies and 30 healthy controls were included. Blood samples after fasting were harvested for measurements of glucose, insulin, cholesterol, triglyceride, and liver enzymes. All patients underwent transthoracic echocardiography and brachial and carotid artery Doppler ultrasonography to evaluate flow-mediated dilatation (FMD) and carotid artery intima-media thickness (CIMT).Results. Patients with NASH had impaired FMD (4.9 ± 2.8% to 9.3 ± 4.4%, P < 0.001) and higher CIMT (0.79 ± 0.16 mm to 0.64 ± 0.11 mm, P < 0.001) when compared with healthy controls. Linear regression analyses revealed that serum concentrations of gamma glutamyl transferase (GGT) and alanine transaminase (ALT) were associated with FMD and CIMT.Conclusions. Patients with NASH have impaired FMD and increased CIMT when compared with healthy controls. In patients with NASH, serum concentrations of GGT and ALT might have a predictive value for FMD and CIMT.

The Correlation and Risk Factors between Carotid Intima-Media Thickening and Alcoholic Liver Disease Coupled with Helicobacter pylori Infection

“…Serum ALT levels have been positively associated with the risk of carotid atherosclerosis in patients with NAFLD, suggesting that serum ALT levels could be used as a surrogate marker for cardiovascular risk in a specific clinical setting 57 . In patients with non-alcoholic steatohepatitis (NASH), serum GGT and ALT concentrations might be predictors of CIMT 58 . Increased serum ALT levels (even levels at the high end of normal) are associated with markers of CVD 59 , and they may therefore have prognostic value in assessing NAFLD patients, in whom they may potentially indicate an increased risk of CVD[62].…”

Causes of changes in carotid intima-media thickness: a literature review

“…Patients with NAFLD [ 35 , 73 - 75 ] and AFLD [ 35 , 76 ] had significantly increased CIMT, and the association between NAFLD and subclinical atherosclerosis was independent of traditional risk factors [ 75 ]. ALD may also promote the premature increase in CIMT [ 76 ] via mechanisms that might include insulin resistance [ 77 ] and abnormal liver function, including ALT [ 78 , 79 ] and GGT [ 78 ], in patients with NAFLD and NASH. Age and metabolic factors are also associated with CIM thickening in patients with ALD.…”

“…However, coronary artery disease (CAD) variants were not found to be associated with CIMT and did not appear to mediate the risk of atherothrombosis through known risk factors [ 90 ]. Additionally, impaired FMD under various statuses and diseases might led to thicker CIM [ 78 , 92 , 93 ]. Their exact mechanism remains unknown and needs to be further studied.…”

Novel Invasive and Noninvasive Cardiac-Specific Biomarkers in Obesity and Cardiovascular Diseases

“…123,124 Furthermore, it has proposed that elevated circulating levels of ALT and AST are associated with endothelial dysfunction (carotid artery intima-media thickness and flow-mediated dilatation)-induced atherosclerosis and inflammation. 125 Data from the Framingham Heart Study have shown, after adjusting for confounding variables, over a 10-year follow-up period among 3744 white adults in the United States who were free from clinical HF at baseline, there was an increased risk of AF associated with increased serum, either marker ALT or AST (>40 U/L). 115,126 Thus, ALT and AST levels are independently associated with increased CVD-related mortality and serve as surrogate predictive markers in CVD progression.…”