Severe intrahepatic cholestasis in primary amyloidosis: a report of four cases and a review of the literature.

Liver involvement occurs frequently in patients with systemic amyloidosis, but jaundice is rare. The clinical and histopathologic features are described in four of 78 patients (5.3 per cent) with primary amyloidosis in whom severe intrahepatic cholestasis developed. The data on an additional eight patients recorded in the literature were reviewed. Criteria for inclusion were a tissue diagnosis of amyloidosis, a serum bilirubin level greater than 5 mg/100 ml, histopathologic evidence for cholestasis and no extrahepatic biliary obstruction. Hepatomegaly was present in 12 patients (100 per cent), ascites in nine (75 per cent) and pruritus in eight (67 per cent). The serum bilirubin ranged from 9 to 44 mg/100 ml, the serum alkaline phosphatase was markedly increased in 10 patients (83 per cent) and hypercholesterolemia occurred in seven (58 per cent). Microscopic examination of the liver revealed diffuse amyloid deposition and compression atrophy in 12 patients (100 per cent). The amyloid was prominent in the periportal regions, and some sparing of the centrilobular areas was observed. Bile thrombi and bilirubin staining of hepatocytes were predominantly in the centrilobular zones. Liver cell necrosis, fibrosis or nodularity was uncommon.The pathogenesis of intrahepatic cholestasis in these patients is probably related to the deposition of amyloid in a manner that interferes with the passage of bile from the canaliculi and/or the small intrahepatic bile ducts to the septal bile ducts. Obstructive jaundice carries a poor prognosis. Nine of 12 patients (75 per cent) died of renal failure three weeks to two months after the onset of jaundice. Amyloidosis should be considered in the patient with unexplained intrahepatic cholestasis, and liver tissue should be stained with Congo red and viewed under polarized microscopy.