EVALUATION OF METABOLIC PARAMETERS OF HEPATIC DYSFUNCTION IN SUBJECTS WITH HEPATOCELLULAR CARCINOMA AND THEIR CHANGE AFTER LIVER TRANSPLANTATION: A METABOLOMIC APPROACH

Chronic liver disease (CLD) is characterized by metabolic dysregulation, and Insulin Resistance (IR). Liver transplantation (LT) is increasingly used for the treatment of (CLD). However, it is still unclear which are the metabolic parameters that improve after LT. Among metabolites,free fatty acid (FFA) and amino acid concentrations greatly reflect impaired hepatic and adipose tissue metabolism. In particular, certain classes of lipids (i.e. unsaturated to saturated FFA as PUFA/SFA) or aminoacids (e.g. Aromatic, AAAs and Branched Chain, BCAAs) seem to be involved in the derangement of hepatic metabolism. Thus, the aim of the study was to evaluate the metabolic changes, in IR indexes, lipids and AAAs and BCAAs concentrations that occurred after surgery. Methods: We evaluated 11 non-diabetic patients with HCC due to HCV infection (BMI=) that were scheduled for LT and 11 controls (CT) (BMI=). At baseline (i.e., before LT) and at 3, 6 and 12 months after the surgery we measured concentrations and composition of plasma FFA and amino acids by gas chromatography mass spectrometry. We assess AAAs and BCAAs; palmitic/linoleic ratio and PUFA/SFA). We calculate HOMA-IR index= (Glucose x Insulin)/22.5 and AT-IR= fasting FFA x insulin that are peripheral and adipose tissue IR indexes. Results: Before LT patients with HCC, when compared to CT, showed increased AT-IR (±vs. ±), HOMA-IR index (±vs ±, both p<0.01), palmitic/linoleic (±vs. ±) and decreased PUFA/SFA ratio (±vs. ±). AAAs concentration was higher in HCC than CT (±vs ±, p<) and positively correlated with AT-IR and HOMA-IR (R=and), while BCAA were not different. During the follow up, at 3, 6 and 12 months after LT, compare to baseline there was a decrease, which tends to rise at 12 months of LT in: HOMA-IR, AT-IR and AAAs, (all p<0.05 vs baseline). No change was observed in palmitic/linoleic, PUFA/SFA and BCAA during follow up. In conclusion metabolomic analysis showed an improvement in AT-IR and peripheral IR and also an improvement in AAAs after one year to LT. These results showed that there was a recovery in organ function after LT, in particular in insulin resistance and in amino acids profile