Acute hepatic necrosis

Priest RJ, Horn RC. 1965. Trichloroethylene intoxication A case of acute hepatic necrosis possibly due to this agent. Arch Environ Health 11 361-365. 

Acute hepatic necrosis (e.g., chronic or acute hepatitis B or C)... 

Bumell JM, Dennis MB Jr, Clayson KJ, et al. 1976. Evaluation of dogs of cross-circulation in the treatment of acute hepatic necrosis induced by yellow phosphoms. Gastroenterology 71 827-831. 

The thionamide drugs are all liable to cause minor and major adverse effects. Minor are rash, urticaria, arthralgia, fever, anorexia, nausea, abnormalities of taste and smell. Major are agranulocytosis, thrombocytopenia, acute hepatic necrosis, cholestatic hepatitis, lupus-like syndrome, vasculitis. 

O Neil MG, Perdun CS, Wilson MB, McGown ST, Patel S. Felbamate-associated fatal acute hepatic necrosis. Neurology 1996 46(5) 1457-9. 

Liver toxicity from lamotrigine is extremely rare. Acute hepatic necrosis occurred in the context of a hypersensitivity reaction that also involved the skin (SEDA-20, 64). 

Hepatotoxicity due to methyidopa is most often an acute hepatitis, which resolves when the drug is withdrawn. It can start at any time after the start of therapy, but it usually occurs within the first few weeks and ranges in severity from a minor disturbance of liver function tests to acute hepatic necrosis. 

Liver disease is the most important cause of increased transaminase activity in serum. In most types of liver disease, ALT activity is higher than that of AST exceptions may be seen in alcoholic hepatitis, hepatic cirrhosis, and liver neoplasia. In viral hepatitis and other forms of liver disease associated with acute hepatic necrosis, serum AST and ALT... 

Disorders of fibrinogen also occur in the liver. For example, dysfibrinogenemia may be seen in both acute and chronic liver disease and leads to prolongation of the partial thromboplastin time, Disseminated intravascular coagulation occurs with acute hepatic necrosis, presumably as a result of the release of tissue thromboplastin and defective clearance of inhibitors such as antithrombin and protein C. Thrombocytopenia may contribute to ineffective intravascular coagulation. Although commonly attributed to splenic sequestration (hypersplenism), there is evidence of antibody-mediated platelet destruction, as occurs in... 

Dizziness headache vomiting diarrhea yellow staining of skin toxic psychosis insomnia bizarre dreams blood dyscrasias urticaria blue and black nail pigmentation psoriasis-like rash acute hepatic necrosis convulsions severe exfoliative dermatitis ocular effects similar to those caused by chloroquine Quinine Dihydrochloride and Sulfate... 

Fleckenstein JL. IfyquU and acute hepatic necrosis. NEnglJMed( 9Z5) 313,48. 

Paracetamol is a remarkably safe drug and serious toxicity is almost unheard of following therapeutic doses. However, acute hepatic necrosis is a serious complication of overdosage. 

An MRL of 1 mg/kg/day has been calculated for acute oral exposure to hexachloroethane based on a NOAEL of 100 mg/kg/day from a study in male rabbits (Weeks et al. 1979). Hepatic necrosis and degeneration were observed in the treated animals at doses of 320 and 1,000 mg/kg/day. 

Only one report of human death attributed to 1,4-dichlorobenzene exposure has been located in the literature. A 60-year-old man and his wife died within months of each other due to acute yellow atrophy of the liver (also known as massive hepatic necrosis or fulminant hepatitis) (Cotter 1953). Their home had been "saturated" with 1,4-dichlorobenzene mothball vapor for a period of about 3-4 months, but no air measurements were available. Clinical symptoms included severe headache, diarrhea, numbness, clumsiness, slurred speech, weight loss (50 pounds in 3 months in the case of the husband), and jaundice. The wife died within a year of the initial exposure however, it was not clear if 1,4-dichlorobenzene was the primary cause of death. This case study did not address whether these individuals consumed excessive amounts of alcohol or had previous medical problems, such as a chronic liver infection. 

Cresols are rapidly absorbed through the skin, producing systemic effects. About 20ml of a 90% cresol solution accidentally poured over an infant s head caused chemical burns, cyanosis, unconsciousness, and death within 4 hours. Histopathologic examination showed hepatic necrosis, cerebral edema, acute tubular necrosis of the kidneys, and hemorrhagic effusions from the peritoneum, pleura, and pericardium. The blood contained 12 mg cresol/lOOdl. 

Acute exposure of experimental animals resulted in adverse effects similar to those described for humans. Rats did not survive when exposed to the vapor for longer than 6 minutes at 3 000 ppm minimum lethal concentration for an 8-hour exposure was 200ppm these exposures caused hepatic necrosis, pulmonary edema, and cloudy swelling of renal tubules. Depression of the central nervous system (CNS) was observed in rats exposed at higher concentrations, and deaths occurred within 24 hours from respiratory or cardiac... 

Patients should be warned that rifampicin colors urine, tears and other body fluids reddish-orange. Adverse effects further include rashes and pruritus and gastrointestinal complaints like nausea, anorexia and diarrhoea. With intermittent therapy a probably allergic hypersensitivity reaction can occur which mostly manifests itself as a flu-like syndrome with fever but can also result in nephritis and acute tubular necrosis. Elevation of serum transaminase levels occur frequently but clinical hepatitis is rare. Fatal outcome has been reported however. 

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). 

Colchicine often causes diarrhea and may occasionally cause nausea, vomiting, and abdominal pain. Hepatic necrosis, acute renal failure, disseminated intravascular coagulation, and seizures have also been observed. Colchicine may rarely cause hair loss and bone marrow depression as well as peripheral neuritis, myopathy, and in some cases death. The more severe adverse events have been associated with the intravenous administration of colchicine. 

A 50-year-old obese woman taking glipizide 5 mg/day who had been drinking a bottle of rum daily for 2 months developed an acute hepatitis and died (115). The viral hepatitis profile was negative. At autopsy the liver weighed 1800 g and there was focal necrosis without evidence of autoimmune or alcoholic hepatitis. There was no brain edema. 

A 62-year-old woman with normal hver function tests took troghtazone 400 mg/day in combination with gli-clazide 80 mg/day and pravastatin (125). After 9 months her transaminases were slightly above normal, but the HbAic was 7.0% and treatment was continued. Her hver enzymes were measured monthly and after 19 months rose abruptly. Troghtazone was withdrawn immediately and she received insulin. Her hver enzymes improved rapidly. A biopsy showed hepatic necrosis round the central vein and a mild inflammatory infiltrate and fibrosis in the portal area compatible with protracted acute hepatitis. A lymphocyte stimulation test and a skin test were negative for troghtazone. 

Qualitative biomarkers of acute oral exposure that are shared with other toxic compounds include a variety of electrocardiogram alterations. Postmortem biomarkers include fatty hepatic degeneration, pulmonary edema and/or congestion, widespread internal hemorrhaging, widespread intracellular fatty deposits, various myocardial damage, hepatic necrosis, hepatic fibrosis, and increased liver weight (see Section 2.2 for more detail). 

Baerg, R.D. Kimberg, D.V. Centrilobular hepatic necrosis and acute renal failure in "solvent sniffers." Ann Int Med, 1970 73 713-720... 

Liver. In humans, chronic Cd exposure does not typically result in hepatotoxicity. In laboratory animals, the liver accumulates the largest concentrations of Cd after acute or chronic exposures. In chronically exposed rats, liver injury occurs prior to renal dysfunction. Chronic Cd effects in the liver include increased plasma activities of alanine and aspartate aminotransferases, structural irregularities in hepatocytes, and decreased microsomal mixed function oxidase and CYP450 activities. Acute exposures in rats result in hepatic necrosis, particularly in parenchymal cells. Additionally, rough endoplasmic reticulum deteriorates, while smooth endoplasmic reticulum proliferates. Mitochondria are also degraded. As is the case with chronic exposure, microsomal mixed function oxidases and CYP450s are inhibited. 

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