Drug associated hepatic reactions in New Zealand: 21 years experience.

Aims: To review spontaneous reports of drug-associated adverse hepatic reactions.

Methods: Reports of drug-associated adverse hepatic reactions received by the New Zealand Centre for Adverse Reactions Monitoring over the 21 year period January 1974 to December 1994 were reviewed. Subdivision into three 7 year periods was undertaken to compare patterns.

Halothane hepatotoxicity and hepatic free radical metabolism in guinea pigs; the effects of vitamin E.

Purpose: The aim of this study was to investigate the relation between halothane hepatotoxicity and hepatic free radical metabolism and to establish a possible protective role of vitamin E against halothane hepatotoxicity.

Methods: Twenty-eight guinea pigs were used in the experiments. Halothane (1.

Halothane-induced liver injury in guinea-pigs: importance of cytochrome P450 enzyme activity and hepatic blood flow.

The basis for susceptibility to halothane-induced liver necrosis in guinea-pigs was examined. In hepatic microsomes, the following were similar in susceptible and resistant animals: total cytochrome (CYP) P450 (P450), phenobarbital-inducible pathways of mixed function oxidation (androstenedione 6 beta- and 16 beta-hydroxylase activities) and the CyP2E1-catalysed pathway of N-nitrosodimethylamine N-demethylase activity. Similarly, immunohistochemical staining of CYP2E1 protein was equivalent in livers from susceptible and resistant guinea-pigs.

Biotransformation and hepatotoxicity of HCFC-123 in the guinea pig: potentiation of hepatic injury by prior glutathione depletion.

The chlorofluorocarbon substitute 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123) is a structural analog of halothane. Both are oxidatively metabolized by CYP2EI, producing a reactive trifluoroacyl acid chloride intermediate and have been shown to cause acute liver necrosis in the guinea pig. With halothane, liver injury has been associated with the degree of reactive intermediate binding to hepatic protein.

Molecular mimicry in halothane hepatitis: biochemical and structural characterization of lipoylated autoantigens.

Exposure of human individuals to halothane causes, in about 20% of all cases, a mild transient form of hepatotoxicity. A small subset of exposed individuals, however, develops a potentially severe and life-threatening form of hepatic damage, coined halothane hepatitis. Halothane hepatitis is thought to have an immunological basis.

Novel mechanisms in chemically induced hepatotoxicity.

This review focuses on cellular events that modulate hepatotoxicity subsequent to initial liver insult. Cellular events that determine the nature and extent of hepatotoxic injury and the ultimate outcome of that injury are also discussed. The roles of cell types other than hepatocytes, hepatocyte organelle-specific processes, and regeneration in progression or recovery from liver injury are emphasized.

Hepatotoxicity in guinea pigs following acute inhalation exposure to 1,1-dichloro-2,2,2-trifluoroethane.

Groups of 10 male Hartley guinea pigs were exposed to 3.0, 2.0, 1.

[Hepatotoxicity of halogenated inhalational anesthetics studied in rats hepatocytes].

Effects of 2% halothane, 1.5% sevoflurane, 1.5% enflurane, and 1.

Possible role of HLA in hepatotoxicity. An exploratory study in 71 patients with drug-induced idiosyncratic hepatitis.

Possible associations between particular human leucocyte antigen molecules and immunoallergic hepatitis have been suggested previously (HLA-A11 in halothane hepatitis, HLA-DR6 and DR2 in nitrofurantoin hepatitis, HLA-B8 in clometacin hepatitis). In this study the HLA haplotype was determined in 71 patients with idiosyncratic hepatitis due to different drugs. The prevalence of HLA-A11 was twice as high in the 71 patients in the study (23%) as in controls (12%), but p-values were not significant when corrections were made for the large number of comparisons (n = 39).

Non-A, non-B fulminant hepatitis is also non-E and non-C.

Objectives: to define the roles of the hepatitis C and E viruses (HCV and HEV) in non-A, non-B (NANB) fulminant hepatitis.

Methods: we utilized the polymerase chain reaction to amplify HCV and HEV RNA sequences and assays to detect antibodies to HCV and HEV in the acute phase sera of eight presumed viral NANB and seven nonviral NANB fulminant hepatic failure (FHF) patients.

Results: none of the 15 patients had detectable HCV or HEV RNA or elevated HCV and IgM-HEV antibody titers in their acute phase sera.

Effect of halothane on hypoxic toxicity and glutathione status in cultured rat hepatocytes.

Background: In hypoxic rats, halothane causes hepatotoxicity at oxygen levels that would cause minimal hepatotoxicity in the absence of halothane. Using a model that excludes systemic and extrahepatic effects of halothane, the authors tested the hypothesis that halothane hepatotoxicity in the whole-rat model is caused by a direct hepatotoxic effect of halothane, which is mediated by halothane-derived free radicals.

Methods: Rat hepatocyte monolayer cultures were exposed to defined gas phases for 2 h.

Hepatic dysfunction after repeated isoflurane administration.

Isoflurane, a halogenated volatile anesthetic, has not been associated with a distinct hepatic injury syndrome, as has halothane. Previous cases of suspected isoflurane-induced hepatotoxicity have been reported but questioned. We report the case of a patient without previous liver disease who developed repeated episodes of hepatitis after repeated exposures to isoflurane.

[Halothane hepatitis].

The greatest disadvantage of the halothane, widely used in the anaesthesiology is its ability to cause liver damage. After halothane anaesthesia mild liver enzyme elevation in the one fifth of the patients was detected. The incidence of fatal halothane hepatitis is rare.

Liver damage due to free radicals.

The involvement of free radical reactions in the pathogenesis of liver injury has been investigated for many years in a few defined experimental systems using carbon tetrachloride, excess iron or ethanol as prooxidant agents. More recently, the hepatotoxicity of several other free radical-generating compounds has been characterised mainly in the rat hepatocyte model. In particular, the mechanisms by which drugs like paracetamol, halothane, paraquat or conditions such as ischemia-reperfusion exert their damaging activity to the liver have mostly been clarified.

[Evaluation of hepatic damage in personnel in the anesthesiology- resuscitation department in relation to halothane exposure].

In a simple uncontrolled toxicological study 27 workers of an anesthesiology-resuscitation department of a hospital type III were examined. Besides detailed clinical examination, determination of basic hematological and biochemical parameters as well as ultrasonography, also selected parameters of proteosynthetic function of the liver, some so-called proteins of the acute phase and the biological half-life of antipyrine were established in the workers under study. The occurrence of pathological findings in the picture of the examinations performed was related to long-term professional exposure to halothane over the period of one year before the examination.