Reliability of total overnight salivary caffeine assessment (TOSCA) for liver function evaluation in compensated cirrhotic patients

Abstract

Systemic caffeine clearance is considered the gold standard for phenotyping cytochrome P450 1A2 in epidemiological studies, and has been recommended for the non-invasive assessment of liver function in chronic liver disease. Our aim was to find a valid, simple and reliable alternative to this method, and therefore focused our attention on the measurement of an unique salivary caffeine concentration, without drug exposure. Our evaluation included 36 healthy controls, 47 patients with compensated liver cirrhosis of viral origin, and 48 obese and diabetic patients with cryptogenetic (likely metabolic) cirrhosis. All shared the same caffeine consumption habits (regular daily use of caffeinated beverages, mainly coffee). The total overnight salivary caffeine assessment (TOSCA) was determined by using a single-point concentration of salivary caffeine, after an overnight period of abstinence. Daily routine caffeine intake of our population was adequate for studying the TOSCA. This single-point concentration correlated well with caffeine clearance, measured by salivary concentrations of caffeine. Mean TOSCA in cirrhotic patients was significantly higher than in controls (p<0.001; sensitivity (%) 84.2 and specificity (%) 97.2; negative likelihood ratio=0.16 and positive likelihood ratio=30.32). A cut-off set at 4.2 microg/ml (sensitivity (%) 95.8 and specificity (%) 68.1; negative likelihood ratio=0.06 and positive likelihood ratio=3.0) successfully differentiated the type of cirrhosis. Rapid (with higher metabolism of caffeine) metabolizers were more frequent in the group of patients with cirrhosis of metabolic origin (70.8%; p<0.0001), and the opposite was true for the group of patients with cirrhosis of viral origin, which comprised many poor metabolizers (85.1%; p<0.001). Serum transforming growth factor-beta 1 concentration, mirroring ongoing fibrosis, ranked high in poor metabolizers. The association between overnight assessment and homeostasis model assessment in rapid metabolizers could result from similar roles for cytochrome P450 1A2 and insulin resistance in determining metabolic liver cirrhosis. The TOSCA, although differential between the viral and metabolic etiologies, could be considered a good diagnostic use to verify the presence and eventually the type of compensated liver cirrhosis.