Cholestatic jaundice associated with D-penicillamine therapy

Cholestatic jaundice is a rare complication of penicillamine therapy. We report here a 35-year-old patient who developed fever, a rash and cholestatic jaundice 16 days after commencing treatment with penicillamine for cystinuria. The jaundice subsided slowly after discontinuation of the drug and with prolonged therapy with prednisone. The literature on penicillamine-induced liver injury is reviewed.     

Cholestatic jaundice caused by D-penicillamine.

D-penicillamine is not generally considered to cause hepatic damage. Cholestatic jaundice developed in a patient with rheumatoid arthritis 4 weeks after penicillamine was added to his regimen, and he died in acute renal failure. The probability that penicillamine caused the cholestasis is discussed.     

Cholestatic liver disease associated with diphenylhydantoin therapy

Summary A ten-year-old boy presented with a prolonged cholestatic liver disease 5 weeks after starting diphenylhydantoin therapy. The initial phase of his illness was characterized by hepatocellular damage with swollen liver cells and centrilobular cholestasis. Severe hyperlipoproteinemia with eruptive xanthomata developed within 3 weeks of his initial jaundice. The second phase of his illness was characterized by portal tract inflammation with bile ductular proliferation and chronic cholestasis gradually resolving over a period of 15 months.It is postulated that diphenylhydantoin sensitivity produced swollen hepatocytes with hypertrophy of the smooth endoplasmic reticulum, reducing hepatic sinusoidal blood flow and the clearance of secondary bile salts. A fall in clearance of lipoproteins, including the cholesterol precursor of primary bile acid synthesis, may have been responsible for a reduction in serum bile acid concentration. High levels of serum lithocholic acid, largely unsulfated presumably due to decreased hepatic uptake, may have produced the prolonged second phase of this illness when histological changes resembled that seen in experimental animals following lithocholic acid administration.     

Cholestatic jaundice in two patients with primary amyloidosis: ultrastructural findings of the liver

Two patients with primary amyloidosis (amyloid light chain case) and severe cholestatic jaundice are described. Liver biopsy in the preterminal stage demonstrated amyloid deposits in the perisinusoidal space and in portal tracts, and hepatocytes were atrophic because of compression by amyloid fibrils. Ultrastructural findings showed amyloid fibrils not only in Disse's space but also in the sinusoids, and the hepatocyte microvilli facing the amyloid fibrils were spicular. There were aggregates of lysosomal granules in the vicinity of bile canaliculi and some bile canaliculi were dilated with loss of microvilli. Amyloid fibrils in the portal tract compressed bile ductules, causing wide intercellular space and separated basement membranes from their epitheliums. These findings suggested disturbance in transporting not only of essential materials from sinusoids to hepatocytes but also of secretory vesicles into bile canaliculi and leakage of bile juice from small bile ductules in preterminal stage of primary amyloidosis.     

Cholestatic jaundice in the haemolytic-uraemic syndrome: a case report.

The haemolytic-uraemic syndrome is the term used to describe the symptom complex of acute oliguric renal failure, haemolysis, and thrombocytopaenia. The pathogenesis of the syndrome is unknown though several factors have been postulated as important. Gastrointestinal disease is now recognised as a regular feature of the syndrome but hepatic involvement is uncommon and limited to occasional jaundice, hepatosplenomegaly and rises in serum transaminase values. A patient is described in whom cholestatic jaundice occurred during the prodromal illness. Its presence is unexplained but might indicate infection with an unrecognised hepatotropic agent or else lack of enteral nutrition during the prodromal phase.     

Cholestatic jaundice as a paraneoplastic manifestation of prostate adenocarcinoma.

Malignancies may cause cholestatic jaundice through well-recognized mechanisms (e.g., bile duct obstruction or widespread hepatic infiltration). Paraneoplastic syndromes associated with malignancy, particularly with renal cell carcinoma (Stauffer's syndrome) and malignant lymphoproliferative diseases, can induce a reversible form of cholestasis through an unclear pathogenetic mechanism. Prostate cancer presenting initially with cholestatic jaundice without any obvious cause (i.e., obstruction or infiltration) has been reported in 2 cases in the medical literature. We report a patient who presented with pruritus and cholestatic jaundice. During the diagnostic work-up, prostate cancer was diagnosed. Conjugated bilirubin and alkaline phosphatase levels were increased markedly with modest increases of gamma-glutamyltranspeptidase and transaminase levels. The results of appropriate investigations performed during the patient's hospitalizations indicated no evidence of hepatic metastases or extrahepatic biliary obstruction. After treatment with flutamide and leuprolide, the patient's symptoms and the laboratory abnormalities reversed rapidly. We regard the cholestatic jaundice of this patient as part of a paraneoplastic syndrome; the cause of cholestasis remains an enigma. Patients with unexplained cholestasis should be investigated for malignancies, including prostate cancer.     

Cholestatic and hepatocellular injury associated with erythromycin esters

A combined cholestatic and hepatocellular injury occurred in nine patients, following therapy with erythromycin estolate (EE) or other erythromycin derivatives. Eight of the nine patients developed jaundice within three weeks after initiation of treatment; pain was one of the main symptoms in five patients while fever and itching were noted in four patients. Symptoms and signs subsided and abnormal tests of liver function returned to normal after withdrawal of the drug. The major histologic finding was cholestasis, but the majority of cases also had evidence of hepatocellular injury of variable severity; one biopsy specimen showed centrilobular necrosis. Ultrastructural findings in one case included changes related to cholestasis as well as hepatocellular injury with striking mitochondrial abnormalities. Our data are compared with those of the literature, with special reference to morphologic features.     

Cholestatic jaundice and constitutional syndrome as early manifestations of primary systemic amyloidosis

We present the case of a 70-year-old woman who had been suffering from constitutional syndrome for several months, abdominal distension, and yellowish coloration of the skin for the previous few days with a rapidly fatal course. Examination revealed hepatomegaly and ascites. Laboratory investigations revealed hyperbilirubinemia with cholestasis. The remaining investigations (abdominal ultrasound, barium transit evaluation, bone marrow study, analysis of ascitic fluid and laparoscopy) did not establish the diagnosis. This was established by liver and subcutaneous fatty tissue biopsies, which revealed type AL amyloid deposits. Autopsy confirmed that the patient had primary systemic amyloidosis. This infrequent form of presentation of systemic amyloidosis and its poor prognosis are discussed.     

Severe hepatotoxicity with jaundice associated with paroxetine

Hepatotoxicity due to paroxetine, a selective serotonin reuptake inhibitor, is very rare, and to the best of our knowledge, only five cases of liver injury in association with paroxetine have previously been reported in the medical literature. We describe the clinical, biochemical, and pathological findings in a patient with paroxetine hepatotoxicity, which was reversed after withdrawal of the drug. The present case and the others previously reported suggest that hepatotoxicity should be taken into account as a rare complication, sometimes severe, that may occur with paroxetine.