Physico-chemical factors predisposing to pigment gallstone formation in liver cirrhosis

Abstract

Liver cirrhosis is associated with a high prevalence of pigmentary cholelithiasis. The major compound of pigment gallstones is unconjugated bilirubin (UCB) in the form of calcium bilirubinate salts or a black pigment polymer. Most of UCB in bile derives from enzymic or non-enzymic hydrolysis of mono- or diconjugated bilirubin. Changes in the relative ratios between these two bilirubin species have been associated with pigment gallstones. It has also been shown that UCB solubilization in bile depends on its interaction with bile salts. In order to clarify the factors predisposing cirrhotic patients to pigment stone formation, we measured UCB, monoconjugated bilirubin (MCB) and diconjugated bilirubin (DCB) in duodenal bile of 15 patients with cirrhosis, ten patients with chronic active hepatitis (CAH) and ten normal subjects, we also analyzed their relationships with lipids. In cirrhotic patients, the MCB concentration in bile was significantly ( p < 0.05) higher than in normal subjects and was correlated with the severity of the disease. Bile salts and lecithin concentrations were significantly lower in cirrhosis ( p < 0.005 vs. CAH or normals). Cirrhotic patients have a bile salts/UCB molar ratio which is one third that of CAH patients or normal subjects ( p < 0.01). No differences were found between CAH patients and controls in each of the parameters tested. In conclusion, we propose that the very low BS UCB molar ratio and the very high biliary content in MCB represent two independent physico-chemical factors predisposing cirrhotic patients to pigmentary cholelithiasis.