CARNITINE METABOLISM IN PATIENTS WITH CHRONIC LIVER-DISEASE

Carnitine metabolism was studied in 79 patients with chronic Liver dis ease, including 22 patients with noncirrhotic Liver disease and 57 pat ients with different types of cirrhosis (22 patients with hepatitis B- or C-associated cirrhosis, 15 patients with alcohol-induced cirrhosis , 15 patients with primary biliary cirrhosis [PBC], and 5 patients wit h cryptogenic cirrhosis), and compared with 28 control subjects, In co mparison with control subjects, patients with noncirrhotic liver disea se showed no change in the plasma carnitine pool, whereas patients wit h cirrhosis had a 29% increase in the long-chain acylcarnitine concent ration, Analysis of subgroups of patients with cirrhosis showed that p atients with alcohol-induced cirrhosis had an increase in the total pl asma carnitine concentration (67.8 +/- 29.5 vs, 55.2 +/- 9.9 mu mol/L in control subjects), resulting from increases in both the short-chain and long-chain acylcarnitine concentration, In this group of patients , the acylcarnitine concentrations showed a close correlation with the total carnitine concentration, and the total carnitine concentration with the serum bilirubin concentration, Urinary excretion of carnitine was not different between patients with noncirrhotic or cirrhotic liv er disease and control patients, However, patients with PBC showed an increased urinary excretion of total carnitine (52.5 +/- 40.0 vs, 28.0 +/- 16.7 mu mol carnitine/mmol creatinine), resulting from an increas e in the fractional excretion of both free carnitine and short-chain a cylcarnitine, The current studies show that patients with cirrhosis ar e normally not carnitine deficient, Patients with alcohol-induced cirr hosis have increased plasma carnitine concentrations, which may result hom increased carnitine biosynthesis because of increased skeletal mu scle protein turnover, The increase in the fractional carnitine excret ion in patients with primary biliary cirrhosis may result from competi tion of bile acids and/or bilirubin with tubular carnitine reabsorptio n and or from a reduced activity of the carnitine transporter located in the proximal tubule.