Cholestatic hepatitis

Hepatic reactions Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely. 

Hepatic Cholestatic jaundice, chronic active hepatitis, hepatic necrosis, hepatic reactions, hepatitis (rare). 

Thromlaotic thrombocytopenic purpura, agranulocytosis, hepatitis, cholestatic jaundice, and tinnitus occur rarely... 

Adverse reactions include arthralgia, myopathy, vertigo, tremor, memory loss, alteration of taste, peripheral neuropathy, anxiety, insomnia, depression, hepatitis cholestatic jaundice, abdominal pain, alopecia, blurred vision etc. 

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... 

Liver and Gallbladder. High dosages of oral estrogens have been reported to increase the risk for jaundice, cholestatic hepatitis, gallstones, and hepatic vein blood clots. Estrogens promote the development of hepatic neoplasms associated with increased hepatic cell regenerative activity (186,187). 

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. 

Alderman S, Kailas S, Goldfarb S, et al. Cholestatic hepatitis after ingestion of chaparral leaf confirmation by endoscopic retrograde cholangiopancreatography and liver biopsy. J Clin Gastro 19(3) 242-247, 1994. 

Bohan, A., Boyer, J. L., Mechanism of hepatic transport of drugs implications for cholestatic drug reactions, Semin. Liv. Dis. 2002, 22, 123-136. 

Cholestatic hepatitis has been reported with risperidone, and liver function test abnormalities (mostly transient) have been reported with olanzapine and clozapine. 

When the real problems with benoxaprofen emerged, however, they were more serious It was apparently killing elderly patients with hepatic disorders, inducing massive photosensitivity, and causing oncholysis (separation of the nail plate from the bed) in about 15% of patients. It seems probable that at least 70 elderly patients died, and many more people suf-fered. ° Shortly after its well-publicized entry into the U.S. market, the manufacturer of benoxaprofen voluntarily withdrew its product as it caused fatal cholestatic hepatitis. " This action immediately followed news of suspension of the license to sell benoxaprofen in the United Kingdom. ... 

Hepatic Nicotinic acid hepatotoxicity (including cholestatic jaundice) has occurred. Cases of severe hepatic toxicity, including fulminant hepatic necrosis, have occurred in patients who have substituted sustained-release nicotinic acid products for immediate-release nicotinic acid at equivalent doses. Monitor ALT prior to treatment, every 6 to 12 weeks during the first year, and periodically thereafter (approximately 6-month intervals). 

Hepatotoxicity Prolonged use of high doses of androgens has been associated with the development of potentially life-threatening peliosis hepatis, hepatic neoplasms, and hepatocellular carcinoma. Cholestatic hepatitis and jaundice occur with fluoxymesterone and methyltestosterone at relatively low doses. Drug-induced jaundice is reversible when the medication is discontinued. 

Long-term experience Long-term experience with danazol is limited. Long-term therapy with other steroids alkylated at the 17 position has been associated with serious toxicity (cholestatic jaundice, peliosis hepatitis). Similar toxicity may develop after long-term danazol. 

Hepatic function impairment Fenofibrate is associated with significant increases in serum transaminases (AST or ALT). Increases to more than 3 times the upper limit of normal (ULN) occurred. Hepatocellular, chronic active and cholestatic hepatitis associated with fenofibrate therapy have been reported after exposures of weeks to several years. 

Adverse reactions may include acneiform eruptions allergic dermatitis arthropathy multiple cases of cholestatic and fulminant hepatitis drowsiness fatigue headache hepatotoxicity resembling viral or alcoholic hepatitis impotence metallic or garlic-like aftertaste peripheral neuropathy polyneuritis optic or retrobulbar neuritis restlessness occasional skin eruptions. 

Hepatotoxicity- Erythromycin administration has been associated with the infrequent occurrence of cholestatic hepatitis. This effect is most common with erythromycin estolate. 

Severe, life-threatening, and, in some cases, fatal hepatotoxicity, including fulminant and cholestatic hepatitis, hepatic necrosis, and hepatic failure, has been reported in patients treated with nevirapine (see Warnings). 

Drug-induced hepatotoxicity can present in variable manifestations, such as cell death (necrosis, apoptosis), infiammation, degeneration (steatosis), fibrosis/cirrho-sis and the development of tumors. The manifestations of drug toxicity may not be mutually exclusive and may occur sequentially, or in combination. ALT and ALP can be used to generally classify the pattern of liver injury as either hepatocellular (ALT >3x ULN), cholestatic (ALP >2x ULN, ALT/ALP <2) or mixed (elevated ALP and ALT). The successful monitoring of hepatotoxicity would identify cases before irreversible injury occurs. The activity levels of ALT, AST and ALP only increase after hepatic or cholestatic injury has occurred. Waiting for activity levels to exceed the established thresholds may be too late [3]. New biomarkers are needed to monitor/predict the specific sequence of events for different classes of hepatotoxic compounds. 

Cholestatic hepatitis Phenothiazines Oral hypoglycaemics Erythromycin estolate... 

Adverse effects occur in 3-12% in the form of rash, fever, urticaria, vasculitis, arthralgia, a lupuslike reaction, cholestatic jaundice, hepatitis, lym-phadenopathy and polyserositis but the most dangerous adverse effect is agranulocytosis (it occurs only in 0.3-0.6%). The reaction is readily reversible when the drug is discontinued. Cross-sensitivity between propylthiouracil and methimazole is about 50%, therefore switching drugs in patients with severe reactions is not recommended. 

Adverse effects that are not unequivocally related to inhibition of prostaglandin synthesis include hepatic effects (hepatitis, hepatic necrosis, cholestatic jaundice, increased serum aminotransferases), dermal effects (photosensitivities, Stevens-Johnson syndrome, toxic epidermal necrolysis, onycholysis), central nervous system (CNS) effects (headaches, dizziness, tinnitus, deafness, drowsiness, confusion, nervousness, increased sweating, aseptic meningitis), ocular effects (toxic amblyopia, retinal disturbances), and certain renal effects (acute interstitial nephritis, acute papillary necrosis). 

Cholestatic hepatitis may occur when drug therapy lasts longer than 10 days or repeated courses are prescribed. The hepatitis is characterized by fever, enlarged and tender liver, hyperbilirubinemia, dark urine, eosinophilia, elevated serum bilirubin, and elevated transaminase levels. Hepatitis has been associated with the estolate salt of erythromycin but not with other formulations. Although the hepatitis usually occurs 10 to 20 days after the initiation of therapy, it can occur within hours in a patient who has had such a reaction in the past. The hepatitis is believed to be the result of both a hepatotoxic effect and a hypersensitivity reaction this latter effect is reversible on withdrawal of the drug. Erythromycin and derivatives induce hepatic microsomal enzymes and interfere with the actions of various drugs, including theophylline and carbamazepine. 

Cholestatic. Pertaining to or characterized by suppression or stopping of the flow of bile (cholestasis), having intrahepatic or extra-hepatic causes. 

GI hemorrhage, cholestatic hepatic jaundice, leukopenia, thrombocytopenia, pan cytopenia, agranulocytosis, and aplastic or hemolytic anemia occur rarely. 

Hepatobiliary dysfunction (including cholestatic hepatitis), serious skin reactions, and severe neutropenia occur rarely. 

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