Levels of two types of lectin-reactive alpha-fetoprotein (AFP), designated AFP-L3 and AFP-P4+P5, were analyzed with Lens culinaris agglutinin A and AFP-P4+P5 with erythroagglutinating phytohemagglutinin, respectively, in an attempt to determine the utility and significance of these macromolecules as early indicators of hepatocellular carcinoma during the periodic follow-up of cirrhotic patients. The subjects were 51 of 190 consecutive cirrhotic patients in whom hepatocellular carcinoma developed during a 6-year follow-up period and 21 cirrhotic patients without hepatocellular carcinoma. Serum AFP levels were of limited value to diagnose and predict hepatocellular carcinoma. The relative levels of AFP-L3 and AFP-P4+P5 in patients with hepatocellular carcinoma at the time of tumor detection were significantly higher than those in patients with cirrhosis. The sensitivity was 61%, and the specificity was 90%. Fourteen patients (48%) of 29 patients with small hepatocellular carcinomas less than 2 cm in diameter showed elevated percentage of lectin-reactive AFP. Retrospective examination of 21 patients who were positive for lectin-reactive AFP at diagnosis of hepatocellular carcinoma showed that 41% of them had already expressed lectin-reactive AFP 12 months before the direct detection of hepatocellular carcinoma by diagnostic imaging. These results lead us to conclude that the level of lectin-reactive AFP is a suitable predictive marker for the early recognition of hepatocellular carcinoma in the follow-up of patients with cirrhosis, and that measurements of the level of lectin-reactive AFP should be added to the screening methods that are now in use.

Bone mineral density (BMD) of the lumber vertebrae and factors related to bone metabolism were determined in patients with chronic viral hepatitis and patients with liver cirrhosis to clarify correlations between hepatic dysfunction, considered to be one of the causes of hepatic osteodystrophy, and decrease in bone mass. BMD of the second to fourth lumbar vertebrae was determined with a Lunar (Madison, WI, USA) DPX, a dual-energy X-ray absorptiometry diagnostic system. BMD was significantly lowest in patients with liver cirrhosis, followed by patients with chronic hepatitis, and healthy subjects, in this order. There was a significantly positive but weak correlation between albumin and BMD. Levels of 25(OH)D and 1,25(OH)2D were significantly lower in patients with liver cirrhosis than in those with chronic hepatitis. BMD and vitamin D were decreased in all patients whose cholinesterase (ChE) was below 0.3 delta pH. Urinary pyridinoline (Upyr) was significantly higher in the patients with liver cirrhosis, in whom bone mass was decreased, than in the patients with chronic hepatitis, whereas serum osteocalcin levels were distributed in the upper normal range in patients with chronic hepatitis and those with liver cirrhosis. There was a positive correlation between 25(OH)D and serum osteocalcin levels in patients with liver cirrhosis. These results indicate that osteogenesis is decreased and suggest that the decrease in BMD which occurs in viral liver cirrhosis, probably related to decreased, bone formation and slight promotion of bone resorption, reflects deranged hepatic function. This is the first report of Upyr and urinary deoxypyridinoline (UDpyr) determination in patients with liver cirrhosis and patients with chronic hepatitis. The negative correlation of Upyr and UDpyr with ChE is a novel finding.

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