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Association Between Elevated Liver Enzymes and C-Reactive Protein: Possible Hepatic Contribution to Systemic Inflammation in the Metabolic Syndrome

Objective— The objective of this study was to test whether the frequent association between liver enzyme elevations and various components of the metabolic syndrome is associated with higher C-reactive protein (CRP) levels. Methods and Results— Alanine aminotransferase (ALT), alkaline phosphatase (Alk-P), and high-sensitivity CRP were measured in 1740 subjects. Adjusted geometric mean CRP was calculated for subjects with normal and elevated ALT and for subjects with normal and elevated Alk-P, adjusting for age, sex, smoking, physical activity, body mass index, fasting glucose, triglycerides, the presence of hypertension and low HDL cholesterol, and use of aspirin or hormone replacement therapy. Adjusted CRP levels were higher in subjects with elevated ALT (2.21 versus 1.94 mg/L, P=0.028) or elevated Alk-P (2.58 versus 1.66 mg/L, P<0.0001). Logistic regression showed that compared with subjects with normal liver function tests, the adjusted odds for high-risk CRP (>3 mg/L) were significantly higher in subjects with elevated ALT (OR, 1.5; 95% CI, 1.2 to 1.9, P=0.002) or elevated Alk-P (OR, 2.1; 95% CI, 1.7 to 2.6, P<0.0001). Conclusions— Elevations of liver enzymes are associated with higher CRP concentrations. Hepatic inflammation secondary to liver steatosis is a potential contributor to the low-grade inflammation associated with the metabolic syndrome.