Hepatotoxicity hepatic cholestasis

Cholestasis from other causes can increase the accumulation of ciclosporin or its metabolites, which in turn worsens hepatic cholestasis. This mechanism has been suggested in patients with bowel diseases who experienced an aggravation of hyperbilirubinemia or an increased incidence of hepatotoxicity from the combination of total parenteral nutrition and ciclosporin (SEDA-19, 348) (288). 

Yellow phosphorus was the first identified liver toxin. It causes accumulation of lipids in the liver. Several liver toxins such as chloroform, carbon tetrachloride, and bromobenzene have since been identified. I he forms of acute liver toxicity are accumulation of lipids in the liver, hepartxiellular necrosis, iii-trahepatic cholestasis, and a disease state that resembles viral hepatitis. The types of chrome hepatotoxicity are cirrhosis and liver cancer. 

Oral testosterone-replacement regimens can cause hepatotoxicity, ranging from mildly elevated hepatic transaminases to serious liver diseases (e.g., peliosis hepatitis, hepatocellular and intrahepatic cholestasis, and benign or malignant tumors). 

Hepatotoxicity Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis, have been reported rarely in postmarketing data in patients receiving infliximab. Autoimmune hepatitis has been diagnosed in some of... 

Cunningham and Matthews (1991) treated male Fischer 344 rats with 0.5, 1 or 2 mmol/kg bw 2-nitropropane daily for 10 days by gavage. At the higher dose levels, but not at 0.5 mmol/kg bw, increased hepatic DNA synthesis was found, together with moderate signs of cholestasis and hepatotoxicity. 

Herbal medicines are becoming more and more popular, and indeed some herbal products may be considered to benefit people with liver disease, e.g. Silybum marianum (milk thistle), Picrorhiza kurroa, Phyllanthus, etc. Herbal hepatotoxicity is increasingly being recognised, for example, with kava kava, black cohosh, and many traditional Chinese remedies. The range of liver injury includes minor transaminase elevations, acute and chronic hepatitis, steatosis, cholestasis, zonal or diffuse hepatic necrosis, veno-occlusive disease and acute liver failure. In addition to the potential for hepatotoxicity, herb-drug interactions may affect the safety and efficacy of concurrent medical therapy [15]. 

Kava extracts can, if overdosed (>60-120 mg kavapyr-ones/day) and/or taken over a longer period (>3 months), cause hepatotoxicity in the form of hepatic reactions and liver cell necrosis in rare cases, they may even cause cholestasis and acute liver failure (possibly leading to liver transplantation). Risk factors include the concomitant intake of medicaments and alcohol as well as a genetically based deficiency of cytochrome P450 2D6. (99, 116)... 

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. 

Fatal cholestatic hver failure occurred in a 45-year-old woman with metastatic breast cancer who was given gemcitabine and carboplatin and pre-existing liver damage. After four courses of gemcitabine -I- carboplatin she developed severe decompensated cholestatic hepatitis (9). Liver biopsy showed marked cholestasis and hepatocellular injury consistent with drug-induced hepatotoxicity. 

There have been several reports of hepatotoxicity of iodipamide, variously characterized by epigastric pain, nausea and vomiting, jaundice, pyrexia, and tenderness over the liver, with abnormal liver function tests. Biopsy has shown centrilobular necrosis (154). The incidence of abnormal liver function tests may be as high as 18% after a dose of 40 ml, and the quantity given should be as small as possible. Prior administration of glucocorticoids or sulfonylureas impairs hepatic excretion of ioglycamide. Both iodoxamate and iotroxate can affect liver function tests in a small series of cases, the degree of intrahepatic cholestasis appeared to be relatively more marked after iodoxamate than after iotroxate (SED-12, 1168) (155). 

FlncloxacUUn is the most important cause of antimicrobial dmg-indnced hepatotoxicity in varions countries (69-71). The risk has been estimated in some countries to be in the range of 1 in 10000 to 1 in 30000 prescriptions (72-74). The hepatic injnry is often severe and deaths have occnrred (73). The course can be prolonged. Cholestasis is the most freqnent and prominent feature and the so-called vanishing bile dnct syndrome can develop. Female sex, increasing age, and dnration of therapy are risk factors (75). High daily doses increase the risk (74). 

The clinical utility of thiabendazole in adults is compromised by its toxicity, which has diminished its clinical use. Frequent side effects include GI upset, fatigue, drowsiness, and headache. Occasional fever, rash, erythema multiforme, hallucinations, and sensory disturbances have been reported. Angioedema, shock, tinnitus, convulsions, and intrahepatic cholestasis, and crystalluria are rare complications. Transient leukopenia has been noted. Thiabendazole is hepatotoxic and should be used with caution in patients with hepatic disease. The effects of thiabendazole in pregnant women have not been studied adequately, so it should be used in pregnancy only when the potential benefit justifies the risk. 

All triazoles have been associated with some degree of hepatotoxicity, ranging from mild hepatitis to cholestasis and, rarely, fulminant hepatic failure." Although not entirely clear, it seems that liver... 

Liver Severe acute hepatitis with symptomatic cholestasis has again been attributed to atorvastatin. This is a rare adverse effect, which cause mixed hepatotoxicity and canalicular cholestasis [43 ]. In another case, that of a 68-year-old man who was taking... 

Liver There are a small number of reported cases of ajmaline-induced hepatitis or cholestasis associated witii chronic use of the drug. In all reports, patients had a similar clinical picture and recovered after conservative therapy. However, there are no other reports of hepatotoxicity occurring after the administration of low doses in diagnostic challenges. The mechanism of this side effect may be related to polymorphism of CYP 2D6 which is the main enzyme responsible for ajmaline metabolism. Routine liver function testing is recommended before an ajmaline challenge [10]. 

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