Cholestatic liver damage

Allergic reactions to drugs produce foci of necrosis that are scattered throughout the liver. Other agents cause severe (chlorpromazine) or mild (estrogens) cholestatic liver damage, including cholestasis and inflammation of the portal triad and hepatocellular necrosis. 

Among the more severe adverse reactions, Stevens-Johnson epidermal necrolysis syndrome, thrombocytopenia, agranulocytosis, and nephrotic syndrome have all been observed. Like diclofenac, sulindac may have some propensity to cause elevation of serum aminotransferases it is also sometimes associated with cholestatic liver damage, which disappears when the drug is stopped. 

A 67-year-old woman developed acute hepatocellular and cholestatic liver damage after taking celecoxib 100 mg/ day for 1 week (6). Celecoxib was withdrawn and the liver function tests normalized within 2 weeks. 

Of three patients, two women aged 62 and 57 and a man aged 75 years, who developed symptomatic hepatic injury 5-6 weeks after starting to take itraconazole, two had the biochemical pattern of cholestatic liver damage (38). 

Cholestatic liver damage due to ranitidine has been reported (13). 

Essex, in England. The bread made from the contaminated flour caused cholestatic liver damage. In all, there were 84 cases of jaundice and hepatocellular necrosis, subsequently referred to as Epping Jaundice . The hepatoxic response was investigated by Kopelman and coworkers155 156, and by Schoental, who confirmed that the cause was contamination of flour with 41157.158. 

Hepatic Effects. Stewart and Andrews (1966) reported a case in which a man survived drinking 1 ounce (600 mg/kg) of 1, 1, 1-trichloroethane. Serum transaminase levels remained within normal limits, but serum bilirubin levels became slightly elevated after 48 hours. Increased serum bilirubin levels may result from reduced biliary excretion (i.e., cholestatic liver damage). Alternatively, hyperbilirubinemia may result from diminished hepatic conjugative metabolism of bilirubin. 

Which hepatic structure is most closely associated with cholestatic liver damage ... 

PXR has been demonstrated to act as an LCA sensor and plays an essential role in detoxification of cholestatic bile acids [11,61]. Studies in different animal models showed that activation of PXR protected against severe liver damage induced by LCA. Pretreatment of wild-type mice, but not the PXR-null mice, with PCN reduced the toxic effects of LCA. Moreover, genetic activation of PXR by expressing the activated... 

The incidence of drug-induced liver injury with rosiglitazone has been calculated at 0.02% for alanine transaminase activity 10 times the upper end of the reference range and 0.001% for jaundice (120). The above case report is unusual because, although liver damage is rare, hepatic necrosis occurs more commonly than cholestatic hepatitis. 

High doses are used, with risk of liver damage (cholestatic, tumours) especially if the drug is taken long-term, which is certainly insufficient to deter sportsmen. They may be more inclined to take more seriously the fact that anabolic steroids suppress pituitary gonadotrophin, and so testosterone production. 

Chronic liver damage with amiodarone is much more common than acute hepatitis, but cholestatic jaundice is one of the relatively rare presentations (SEDA-19, 193) (178,179). 

These data suggest that bosentan causes cholestatic liver injury due to inhibition of bile-salt efflux and damage due to intracellular accumulation of bile salts. 

When B. officinalis was mistaken for a similar plant, Securinega suffruticosa, and was cooked in a soup used for muscle aches, lumbago, or as a tonic by 19 patients, 14 developed diarrhea, 10 had nausea and felt cold, nine had sensations of abdominal fullness, and seven vomited (3). Liver enzymes rose and the median times to median peak activities were 3 days for alanine transaminase, 2 days for aspartate transaminase, 5 days for alkaline phosphatase, and 12 days for gamma glutamyltranspeptidase. The liver damage was hepatocellular liver injury rather than cholestatic and marked jaundice did not develop. 

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. 

Erythromycin can cause two different types of liver damage (36,37), benign increases in serum transaminases, which may or may not recur on rechallenge, and cholestatic hepatitis. Reports of intrahepatic cholestasis with azithromycin (38), clarithromycin (39,40), and josamycin (41) suggest that the newer macrolides are not free of this adverse effect, although the relative risks compared with erythromycin are unclear. Similar involvement of the liver has been seen with the ester of triacetyloleandomycin, but not with the unesterified antibiotic. 

Liver damage has been described after treatment with most benzimidazoles, but it is usually cholestatic. The liver damage described in this case was granulomatous. Liver damage after mebendazole in the low dose used in this case is rare, probably because of its poor absorption. 

Cholestatic and hepatocellular liver damage occurred in a previously healthy 20-year-old woman after she took roxithromycin 150 mg bd for 4 days (8). 

There have been several reports of hepatotoxicity attributed to herbal medicines containing L. tridentata leaves (1,2). Of 18 reports of illnesses associated with the ingestion of chaparral, there was evidence of hepatotoxicity in 13 cases (3). The presentation was characterized by jaundice with a marked increase in serum hver enzymes at 3-52 weeks after ingestion, and it resolved 1-17 weeks after withdrawal. The predominant pattern of liver damage was cholestatic in four cases there was progression to cirrhosis and in two there was acute fulminant liver failure that required liver transplantation. 

A number of case reports of hepatotoxicity in association with kava use have been reported in the medical literature and to pharmacovigilance centers. Reports include cases of fulminant liver failure, severe liver damage, necrotizing hepatitis, cholestatic hepatitis, liver cell impairment, and an increase in liver enzymes (Brauer et al. 2001,2003 Bujanda et al. 2002 Campo et al. 2002 Gow et al. 2003 Humberston... 

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