Jaundice in non-cirrhotic primary biliary cirrhosis: the premature ductopenic variant

The clinical and pathological findings of four females with primary biliary cirrhosis (PBC) with an unusual and hitherto not well recognised course ar e reported. Patients suffered severe pruritus and weight loss with progress ive icteric cholestasis which did not respond to such treatments as ursodeo xycholic acid and immunosuppressives. In all cases liver histology revealed marked bile duct loss without however significant fibrosis or cirrhosis. F urther diagnostic studies and repeat biopsies confirmed the absence of live r cirrhosis as well as other potential causes of hyperbilirubinaemia. Compa rison of the fibrosis-ductopenia relationship for our cases with that for a group of 101 noncirrhotic FBC patients indicated that in the former the se verity of bile duct loss relative to the amount of fibrosis was significant ly higher. The proportion of portal triads containing an interlobular bile duct was 3%, 4%, 6%, and 10% compared with 45% (median; range 8.3-100%) for controls (p <0.001). Three patients received a liver transplant 6-7 years after the first manifestation of PBC because of progressive cholestasis, re fractory pruritus, and weight loss, while the fourth patient is considering this option. In one case cirrhosis had developed at the time of transplant ation while the others still had non-cirrhotic disease. These cases suggest that cholestatic jaundice in non-cirrhotic PBC may be secondary to extensi ve "premature" or accelerated intrahepatic bile duct loss. Although the ext ent of fibrosis may be limited initially, progression to cirrhosis appears to be inevitable in the long run. Despite intact protein synthesis and abse nce of cirrhotic complications, liver transplantation in the pre-cirrhotic stage for preventing malnutrition and to improve quality of life should be considered for these patients.