with consequent organ dysfunction. Carnitine metabolism Carnitine metabolism was studied in 79 patients with could be disturbed by a variety of mechanisms in patients chronic liver disease, including 22 patients with noncirwith chronic liver disease. Dietary intake of carnitine could rhotic liver disease and 57 patients with different types be reduced, in particular in alcoholics, who consume a considof cirrhosis (22 patients with hepatitis B-or C-associated erable amount of their calories as alcohol. 5 On the other hand, cirrhosis, 15 patients with alcohol-induced cirrhosis, 15 carnitine biosynthesis could be increased because of accelerpatients with primary biliary cirrhosis [PBC], and 5 paated skeletal muscle turnover in patients with cirrhosis. 6,7 tients with cryptogenic cirrhosis), and compared with 28
Carnitine biosynthesis could also be decreased, however, control subjects. In comparison with control subjects, pasince the last step of carnitine biosynthesis, hydroxylation of tients with noncirrhotic liver disease showed no change butyrobetaine, is located almost exclusively in the liver. 4,8 in the plasma carnitine pool, whereas patients with cir-
The studies assessing carnitine metabolism in patients and rhosis had a 29% increase in the long-chain acylcarnitine experimental animals with chronic liver disease so far pubconcentration. Analysis of subgroups of patients with cirlished provide conflicting results. Rudman et al. described rhosis showed that patients with alcohol-induced cirrhoreduced carnitine plasma and tissue concentrations in pasis had an increase in the total plasma carnitine concentients with alcohol-induced cirrhosis. 9 In contrast, Fuller and tration (67.8 { 29.5 vs. 55.2 { 9.9 mmol/L in control Hoppel found increased acylcarnitine and total carnitine consubjects), resulting from increases in both the short-chain centrations in the plasma of alcoholics with or without cirrhoand long-chain acylcarnitine concentration. In this group sis. 10,11 De Sousa et al. described unchanged plasma carnitine of patients, the acylcarnitine concentrations showed a and liver concentrations but increased carnitine concentraclose correlation with the total carnitine concentration, tions in skeletal muscle in alcoholics with fatty liver, 12 and the total carnitine concentration with the serum biliwhereas Harper et al. found increased hepatic carnitine conrubin concentration. Urinary excretion of carnitine was centrations in noncirrhotic alcoholics only after a period of not different between patients with noncirrhotic or cirabstinence. 13 In contrast to patients with alcoholic liver disrhotic liver disease and control patients. However, paease, less information about carnitine metabolism is availtients with PBC showed an increased urinary excretion able in patients with liver disease of other causes. Palombo of total carnitine (52.5 { 40.0 vs. 28.0 { 16.7 mmol carnitine/ et al. described increased plasma carnitine concentrations in mmol creatinine), resulting from an increase in the fracpatients with end-stage liver disease of different causes. 14 tional excretion of both free carnitine and short-chain However, in this study, no information about the carnitine acylcarnitine. The current studies show that patients status in subgroups of patients according to the cause of liver with cirrhosis are normally not carnitine deficient. Padisease was provided. Similarly, Amodio et al. more recently tients with alcohol-induced cirrhosis have increased described increased carnitine concentrations in patients with plasma carnitine concentrations, which may result from cirrhosis of different causes. 15 No change in the plasma or increased carnitine biosynthesis because of increased liver carnitine pools was found in rats with carbon tetrachloskeletal muscle protein turnover. The increase in the ride-induced cirrhosis, 16 but an increase was found in the fractional carnitine excretion in patients with primary hepatic carnitine content in rats with secondary biliary cirbiliary cirrhosis may result from competition of bile acids rhosis. 17 Taken together, the currently available studies sugand/or bilirubin with tubular carnitine reabsorption and/ gest that the plasma and tissue carnitine pools can be altered or from a reduced activity of the carnitine transporter in patients or experimental animals with chronic liver dislocated in the proximal tubule. (HEPATOLOGY 1996;25:148ease, depending on both the cause and the progression of 153.) liver damage.
To study the influence of cause and progression of liver Patients with cirrhosis use preferentially fatty acids as a disease on carnitine metabolism in more detail, we assessed fuel, even in the nonfasted state. 1,2 Because mitochondrial the carnitine plasma concentrations and urinary excretion of oxidation of long-chain fatty acids depends on the availability carnitine in well characterized patients with different types of carnitine, 3,4 alterations in carnitine metabolism could imof cirrhosis and compared it with control subjects and papair mitochondrial fatty acid oxidation and, in particular in tients with noncirrhotic liver disease. patients with cirrhosis, lead to a decrease in energy supply
PATIENTS AND METHODS
Materials.