Cholestasis patient case

Herbal remedies that have been reported to be he-patotoxic include chaparral (Larrea tridentata), germander (Teucrium chamaedrys), and life root (Senecio aureus) [18]. Cases reported patients developing jaundice, fatigue, pruritus, markedly elevated serum liver enzyme levels, severe cholestasis, hepatitis, and hepatocellular injury or necrosis documented by serial liver biopsies [19-21]. Signs and symptoms may occur as early as 3 weeks to as late as 7 months following ingestion [20,21]. 

As CHCs and POCs are metabohsed by the liver their use may adversely affect this patient, who has severely compromised liver function. CHC or POC methods should not be advocated in this case. This patient s synthetic and metabohc function is significantly impaired and therefore the metabohsm of CHCs could be affected, precipitating adverse drug reactions such as jaundice, hepatitis and cholestasis. 

Arkenau, H.T., Widjaja, A. An unusual case of cholestasis and makro-hematuria in a 52-year-old patient. Med. Klin. 2002 97 480 -483... 

Cholestasis The values of y-GT, AP and LAP are elevated (with non-response of AP in 2-4% of cases). Hyperbilirubinaemia is verifiable in about half the patients at the time of initial diagnosis. Copper values in serum and urine are elevated. (299, 345) A slight rise in transaminases is likewise observed. The first diagnostic step in determining cholestasis is sonography. 

The use of cisapride and its benefit to harm balance in children has been reviewed (25). Overall it is well tolerated. The most common adverse effects are diarrhea, abdominal cramps, borborygmi, and colic. Serious adverse events are rare and include isolated cases of extrapyramidal reactions, seizures in epileptic patients, cholestasis, QT interval prolongation and ventricular dysrhythmias, anorexia, and enuresis. Interactions of cisapride with other drugs are similar to those reported in adults. Co-administration of drugs that inhibit CYP3A4, such as imidazoles, macrolide antibiotics, the antidepressant nefazodone, and protease inhibitors such as ritonavir, are contraindicated. Furthermore, co-administration of anticholinergic drugs can compromise the beneficial effects of cisapride. 

The authors noted that two other patients in the Australian adverse reactions database also appeared to have had hepatotoxicity related to entacapone. In response, representatives of the manufacturers (Novartis) strongly contested the conclusion that any of the three reported cases demonstrated entacapone-induced hepatotoxicity, and concluded that two of the three patients had cholestasis, which is unlikely to be related to entacapone, while the third had no real evidence of hepatic dysfunction (10). These arguments were in turn rebutted by the original authors, and the possible hepatotoxicity of entacapone remains a matter of debate, although there can be no doubt that it is safer than tolcapone. 

In 20 cases of kebuzone-induced liver damage, biopsy showed hepatocellular damage with or without cholestasis, reactive hepatitis, or cholangiolitis (3). There was hepatitis with central lobular necrosis in one case. In five patients, a lymphocyte proliferation test was positive. 

Six cases of acute hepatitis occurred in four patients during the first 10 weeks of treatment, and in two after 15 weeks of therapy (3). They were represented by jaundice (n = 5), itching (n = 2), weakness (n = 3), and anorexia, nausea, and vomiting (n = 2). Increases in liver enzymes varied from 1.5 to over 30 times the upper limit of the reference range. Liver biopsy showed centrilobular or panlobular bridging necrosis in the four women and intra-hepatic cholestasis in the two men. Complete recovery of normal liver function tests ensued at follow-up after interruption of nimesulide therapy. 

Ten cases of acute hepatitis induced by formulations of greater celandine were observed over 2 years in a German University hospital (6). Perhaps ironically, this product is popular in Germany for gastric and gall-bladder problems. In five cases there was marked cholestasis but no Uver failure. After withdrawal of the product, the symptoms subsided and the Uver enzymes normalized within 2-6 months. Unintentional rechallenge led to a further episode of acute hepatitis in one patient. 

Intestinal transplantation is combined with liver transplantation in 46% of cases, because of terminal liver failure (93). Of 78 patients who had received parenteral nutrition for more than 2 years n — 66) and/ or had short bowel syndrome and could not be weaned from parenteral nutrition (n = 12), 58 developed chronic cholestasis and 37 developed one or more severe liver complication (serum bilirubin concentration 60 pmol/l, factor V (proaccelerin) 50%, portal hypertension, encephalopathy, ascites, bleeding from the gastrointestinal tract, or histological findings consisting of extensive fibrosis and cirrhosis) after 6 (3-132) months and 17 (2-155) months respectively. Liver disease was responsible for deaths in 6.5% of the patients (22% of deaths). 

In four patients with cholestatic hepatitis associated with terbinafine, all presented with jaundice and direct hyperbilirubinemia, various other clinical signs of hepatitis, and mild to moderate rises in alkahne phosphatase and hepatic transaminase activities (34,39). Biopsies in two patients showed cellular infiltrates in the portal tracts and hepatocellular and canalicular cholestasis (n — 1) and hepatocyte degeneration (n — 1). In the two cases with long-term follow-up, hepatitis was reversible after withdrawal of terbinafine and liver tests normalized within 6 months. 

In 1980, Kibe et al. found considerable amounts of bile alcohol sulfates in the bile of a patient with cholestasis [81]. Solvolysis of the bile salts gave 3 different bile alcohols which were identified as 24-nor-5/3-cholestane-3a,7a,12 ,25-tetrol, 26,27-di-nor-5 -cholestane-3a,7a,12a,24,25-pentol, and 3a,7a,12a-trihydroxy-26,27-dinor-5 -cholestan-24-one, by comparison with synthetic standards [81]. Nothing is known about the biosynthesis of these C25 and 2 bile alcohols. Since the accumulation of bile alcohols has not been found in other cases with cholestasis, it seems unlikely that cholestasis is the primary cause of the formation of bile alcohols with unusual side chains. 

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