Cholestatic damage

This is a chronic lesion resulting from repeated injury and subsequent repair. It may result from either hepatocyte damage or cholestatic damage, each giving rise to a different kind of cirrhosis. Thus, carbon tetrachloride will cause liver cirrhosis after repeated exposure, but also compounds, which do not cause acute necrosis, such as ethionine and alcohol may cause cirrhosis after chronic exposure. 

The liver shows the following types of toxic response steatosis (fatty liver), cytotoxic damage, cholestatic damage, cirrhosis, vascular lesions, liver tumors, and proliferation of peroxisomes. 

Which group of three serum components provides the best irrdication of cholestatic damage ... 

The term cholestatic jaundice is used to include all cases of extrahepatic obstructive jaundice. It also covers those cases of jaundice that exhibit conjugated hyperbilirubinemia due to micro-obstruction of intrahepatic biliary ductules by swollen, damaged hepatocytes (eg, as may occur in infectious hepatitis). 

Diagnosing viral hepatitis may be difficult because most infected individuals are asymptomatic. Because symptoms cannot identify the specific type of hepatitis, laboratory serologies must be obtained (Table 21-2). In addition, liver function tests may be obtained to assess the extent of cholestatic and hepatocellular injury. However, the definitive test to determine the amount of damage and inflammation of hepatic cells is a liver biopsy. 

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... 

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. 

Allergic reactions (e.g., rashes, urticaria, and eosino-philia) have been observed. These drugs have occasionally been associated with cholestatic jaundice, blood dyscrasias, hemolytic anemia, hypoglycemia, and nephrotoxicity. Recently the use of ciprofloxacin for prophylaxis protection against anthrax infection has been associated with damage to muscle ligaments. 

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. 

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. 

HRT (oral and transdermal) should not be initiated or continued in patients with decompensated cirrhosis. The hepatocyte damage is irreversible and can only worsen over time. The significant reduction in metabolic capacity and reduction in hepatic blood flow will lead to drug accumulation, with consequent increased risk of hepatotoxicity. There is also the potential to worsen the cholestatic picture in this patient, who is already profoundly jaundiced. 

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. 

Intracellular transport of bile acids mainly takes place through the cytoskeleton and intracellular structures (Golgi apparatus, endoplasmic reticulum). Here, too, cholestatic factors can prove to be damaging. Microfilaments are contractile elements not only is the intracellular transport of the bile acids disturbed, but the peristaltic activity of the canaliculi (so-called paralytic cholestasis within the lolsules) is also reduced if the functional capacity of those microfilaments becomes diminished. 

Monohydroxy bile acids (such as lithocholic acid produced in the intestine) are deemed to be cholestatic factors. They can, however, also be generated in the liver as a result of damage to the smooth endoplasmic reticulmn, with a decrease in activity of cytochrome P 450-dependent 7a-hydroxylase in cases of cholestasis, 3p-hydroxy-5S-cholic add is formed from cholesterol and converted into lithocholic acid and aUo-lithocholic acid (so-called foetal metabolic pathway of bile acids). (10)... 

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. 

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. 

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. 

---