Reduced hepatic glycogen stores in patients with liver cirrhosis

Abstract: Background: Patients with alcoholic liver cirrhosis have reduced hepatic glycogen stores but the mechanisms leading to this finding are not clear. Methods: We therefore determined the hepatic glycogen content in patients with alcoholic (n = 9) or biliary cirrhosis (n = 8), and in control patients undergoing liver surgery (n = 14). All patients were in the postabsorptive state. In addition, we performed a morphometric analysis of the livers, and measured activities and mRNA expression of several enzymes involved in glycogen metabolism. Cirrhotic and control patients were similar regarding age and body weight. Results: Cirrhotic patients had a reduced glycogen content per gram liver wet weight (17 ± 11 versus 45 ± 17 mg/g, P < 0.05), per milliliter hepatocytes (28 ± 16 versus 52 ± 21 mg/ml, P < 0.05) and per liver (28 ± 17 versus 64 ± 22 g, P < 0.05), the reduction being observed in both patients with alcoholic or biliary cirrhosis. Liver histology confirmed these findings and revealed that the decrease in liver glycogen in cirrhotic patients was not homogenous across cirrhotic lobules. Activities of glycogen synthase and phosphorylase (total activity and active form) were not different between cirrhotic and control patients, whereas hepatic mRNA expression was decreased in cirrhotics by approximately 50%. The activity of glucokinase was decreased in cirrhotic as compared in control patients (0.06 ± 0.30 versus 0.42 ± 0.21 U/ml hepatocytes, P < 0.05), the reduction being observed in both patients with alcoholic or biliary cirrhosis. Conclusions: We conclude that patients with alcoholic or biliary cirrhosis have decreased hepatic glycogen stores per volume of hepatocytes and per liver. Decreased activity of glucokinase may represent an important mechanism leading to this finding.