vitamin-k-semiquinone-radical and Chemical-and-Drug-Induced-Liver-Injury

Except for bleeding complications, vitamin K antagonists (VKAs) are known to have few undesirable side effects. Herein is presented the case of a 45-year-old woman in whom liver damage was induced by fluindione and warfarin after mitral valve replacement. Hepatotoxicity is a rare complication of VKAs, both in the French National and Drug Safety registry and the medical literature. A diagnosis of VKA-induced drug damage was confirmed by the absence of other etiologies, the chronological sequence, recurrence after re-exposure to VKA, and rapid improvements after discontinuation of the drug. Despite possible cross-reactions between VKAs, the re-introduction of acenocoumarol was successfully achieved, with no recurrence of biological disturbances.

Topics: Anticoagulants; Chemical and Drug Induced Liver Injury; Drug Substitution; Female; Fibrinolytic Agents; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Heparin, Low-Molecular-Weight; Humans; Liver Function Tests; Middle Aged; Mitral Valve; Phenindione; Risk Factors; Treatment Outcome; Vitamin K; Warfarin

Acute liver injury and acute liver failure are syndromes characterized by a rapid loss of functional hepatocytes in a patient with no evidence of pre-existing liver disease. A variety of inciting causes have been identified, including toxic, infectious, neoplastic, and drug-induced causes. This article reviews the pathophysiology and clinical approach to the acute liver injury/acute liver failure patient, with a particular emphasis on the diagnostic evaluation and care in the acute setting.

Topics: Animals; Cat Diseases; Cats; Chemical and Drug Induced Liver Injury; Diet Therapy; Dog Diseases; Dogs; Liver Failure, Acute; Prognosis; Vitamin K

Nonvalvular atrial fibrillation (AF) is an independent risk factor for stroke that becomes increasingly prevalent as populations age. More than half a dozen clinical trials have demonstrated that anticoagulation with the vitamin K antagonist warfarin is the most effective therapy for stroke prophylaxis in AF. The narrow therapeutic index of warfarin requires that the intensity of anticoagulation be maintained within the international normalized ratio (INR) range of 2.0 to 3.0 to optimize efficacy while minimizing bleeding risk. The pharmacokinetics of warfarin are subject to variability due to interactions with multiple drugs and foods, making maintenance of the INR within this range difficult to achieve in clinical practice without close coagulation monitoring and frequent dose adjustments. Current guidelines recommend oral anticoagulation for high-risk individuals with AF but these inherent limitations lead to substantial underprescribing, particularly in elderly patients at greatest risk. This has stimulated the development of new agents with improved benefit-risk profiles, such as ximelagatran, the first of the oral direct thrombin inhibitors, which has a wider therapeutic margin and low potential for drug interactions, allowing fixed dosing without anticoagulation monitoring. Ximelagatran has been evaluated for stroke prevention in AF in the Stroke Prevention using an Oral Direct Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) program, the largest clinical trials of antithrombotic therapy for stroke prevention in AF to date. The phase III trials of ximelagatran in AF, SPORTIF III and V, found a fixed oral dose of ximelagatran (36 mg twice daily) comparable to dose-adjusted warfarin (INR 2.0 to 3.0) in preventing stroke and systemic thromboembolic complications among high-risk patients with AF. Results from the population of over 7000 patients in SPORTIF III and V demonstrate noninferiority of ximelagatran compared with warfarin. Data from SPORTIF III show an absolute reduction in stroke and systemic embolic events with ximelagatran compared with warfarin of 1.6% per year versus 2.3% per year, respectively ( P = 0.10). SPORTIF V further supports noninferiority between the two agents with an absolute risk reduction of 0.45%, well within the predefined noninferiority margin (95% confidence interval -0.13, 1.03; P = 0.13). Although event rates for major bleeding did not differ significantly with ximelagatran versus warfarin in either study, combined

Topics: Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Chemical and Drug Induced Liver Injury; Hemorrhage; Humans; Risk Assessment; Stroke; Thrombin; Vitamin K; Warfarin

Topics: Aflatoxins; Animals; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Tests; Cats; Cattle; Cattle Diseases; Chemical and Drug Induced Liver Injury; Chickens; Coumarins; Cricetinae; Dogs; Ducks; Goats; Guinea Pigs; Haplorhini; Humans; Mice; Poultry Diseases; Rabbits; Rats; Species Specificity; Vitamin K

A randomised clinical trial was undertaken to compare the value of a factor II, IX, and X concentrate (Prothromplex) with intravenous vitamin K1 (2-5 mg) in reversing an overdose of oral anticoagulants. Rapid partial correction of the prothrombin time, partial thromboplastin time, and the clotting factor assays were observed with the concentrate, but these changes were not always sustained. In contrast vitamin K1 did not show any great effect at two hours but at 24 hours there was always over-correction despite the conservative dosage, prothrombin times being shorter than the therapeutic range. The prothrombin complex concentrate provides a quicker, more controlled but less sustained method of reversing the coumarin defect than vitamin K1. But there remains a significant risk of hepatitis even with a preparation for which strenuous efforts have been made to minimise this risk by screening for hepatitis B virus. The risk should be carefully considered before such concentrates are infused in non-urgent conditions.

Topics: Anticoagulants; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Drug Combinations; Factor IX; Factor X; Humans; Poisoning; Prothrombin; Prothrombin Time; Thromboplastin; Time Factors; Vitamin K

Humans are daily exposed to 7,12-dimethylbenz(a)anthracene (DMBA), a well known polycyclic aromatic hydrocarbons (PAH). This study investigated the role of dietary intake of Vitamin K (VK), a polyphenolic compound, with potential antioxidative properties, against DMBA-induced hepatotoxicity. Sixty experimental animals (120-150 g) were divided into six groups (A-F): Control, DMBA (80 mg/kg bw) only, VK (0.00 g/10 kg) diet only, VK (7.5 g/10 kg) diet only, DMBA + VK (0.0 g/10 kg) diet and DMBA + VK (7.5 g/10 kg) diet. Single oral administration of DMBA (80 mg/kg body weight) to Wistar rats resulted in hepatic damage after 16 weeks. DMBA significantly (P < .05) decreased the activities of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione peroxidase (GPx). Levels of reduced glutathione (GSH) and Vitamin C were significantly decreased with increase in malondialdehyde (MDA) and nitric oxide (NO) levels in serum and liver. Aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities were significantly (P < .05) elevated in the serum but reduced in the liver of DMBA-administered group. Ingestion of 7.5 g/10 kg VK diet prevented the up regulations in inflammatory biomarkers (granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin 17A (IL-17A)) which elicited liver damaged in the DMBA-treated group. DMBA induced hepatic alterations in DMBA-treated group but was restored to near normal in VK (7.5 g/10 kg) diet group. These findings suggest the protective potential of increased dietary intake of vitamin K against DMBA-induced hepatic dysfunction.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anthracenes; Antioxidants; Ascorbic Acid; Catalase; Chemical and Drug Induced Liver Injury; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Liver; Male; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) are relatively new drugs used for stroke prevention in nonvalvular atrial fibrillation (NVAF). However, there are concerns that their use may be associated with hepatotoxic effects.. The purpose of this study was to determine whether the use of NOACs is associated with an increased risk of serious liver injury compared with the use of vitamin K antagonists (VKAs) in NVAF patients with and without prior liver disease.. Using the administrative databases of the Canadian province of Quebec's health insurances, the authors conducted a cohort study among patients newly diagnosed with NVAF between January 2011 and December 2014. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of serious liver injury (defined as either a hospitalization or related death) were estimated using time-dependent Cox proportional hazards models, comparing current use of NOACs to current use of VKAs separately among patients with or without prior liver disease.. The cohort comprised 51,887 patients, including 3,778 with prior liver disease. During 68,739 person-years of follow-up, 585 patients experienced a serious liver injury. Compared with current use of VKAs, current use of NOACs was not associated with an increased risk of serious liver injury in patients without or with prior liver disease (adjusted HR: 0.99; 95% CI: 0.68 to 1.45; and adjusted HR: 0.68; 95% CI: 0.33 to 1.37, respectively).. Compared with VKAs, NOACs were not associated with an increased risk of serious liver injury irrespective of baseline liver status. Overall, these results provide reassurance regarding the hepatic safety of NOACs.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Canada; Chemical and Drug Induced Liver Injury; Cohort Studies; Databases, Factual; Factor Xa Inhibitors; Female; Humans; Liver; Liver Function Tests; Male; Middle Aged; Risk Adjustment; Stroke; Vitamin K

The human bile salt export pump (BSEP) is a membrane protein expressed on the canalicular plasma membrane domain of hepatocytes, which mediates active transport of unconjugated and conjugated bile salts from liver cells into bile. BSEP activity therefore plays an important role in bile flow. In humans, genetically inherited defects in BSEP expression or activity cause cholestatic liver injury, and many drugs that cause cholestatic drug-induced liver injury (DILI) in humans have been shown to inhibit BSEP activity in vitro and in vivo. These findings suggest that inhibition of BSEP activity by drugs could be one of the mechanisms that initiate human DILI. To gain insight into the chemical features responsible for BSEP inhibition, we have used a recently described in vitro membrane vesicle BSEP inhibition assay to quantify transporter inhibition for a set of 624 compounds. The relationship between BSEP inhibition and molecular physicochemical properties was investigated, and our results show that lipophilicity and molecular size are significantly correlated with BSEP inhibition. This data set was further used to build predictive BSEP classification models through multiple quantitative structure-activity relationship modeling approaches. The highest level of predictive accuracy was provided by a support vector machine model (accuracy = 0.87, κ = 0.74). These analyses highlight the potential value that can be gained by combining computational methods with experimental efforts in early stages of drug discovery projects to minimize the propensity of drug candidates to inhibit BSEP.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters; Bile Acids and Salts; Cell Line; Chemical and Drug Induced Liver Injury; Humans; Quantitative Structure-Activity Relationship

Vitamin K antagonists are often used as oral anticoagulants for primary and secondary prevention of thromboembolic events. Vitamin K antagonists induce an anticoagulant effect by interfering with the vitamin K metabolism in the liver. Well-known complications are bleeding events and skin necrosis. Recent data indicate increasing numbers of cases with hepatic complications due to vitamin K antagonists ranging from mild hepatopathy to acute liver failure with high mortality. Hepatotoxicity is usually developed after a few months of latency, which is associated with unspecific symptoms, jaundice, elevated transaminase levels as well as cholestatic enzymes. Hepatotoxicity due to vitamin K antagonists is seldom; however, it should be considered in cases of elevated liver enzymes. In this case coumarin therapy should be discontinued. Caution is needed when changing to another coumarin derivative because cross-reactivity has been described.

Topics: Administration, Oral; Anticoagulants; Chemical and Drug Induced Liver Injury; Humans; Thromboembolism; Vitamin K

We report the case of a 71-year-old male patient who presented at the emergency room with episodes of epistaxis and jaundice. The patient was on therapy with phenprocoumon, atorvastatin and perindopril. Findings on admission included prominent elevation of transaminases and bilirubin and a high INR due to impaired liver function and oral anticoagulation. After exclusion of other causes like viral or autoimmune hepatitis and after having obtained a liver biopsy, a diagnosis of drug induced liver damage (DILI) was made. Epidemiology, pathophysiology and clinical signs of DILI are discussed with a special focus on coumarines, statins and ACE-inhibitors.

Topics: Administration, Oral; Aged; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Atorvastatin; Biopsy; Chemical and Drug Induced Liver Injury; Drug Interactions; Drug Therapy, Combination; Hematuria; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver; Liver Function Tests; Male; Perindopril; Phenprocoumon; Pyrroles; Vitamin K

Topics: Acute Disease; Aged; Chemical and Drug Induced Liver Injury; Cholangiopancreatography, Endoscopic Retrograde; Cholestyramine Resin; Conscious Sedation; Drug Therapy, Combination; Follow-Up Studies; Humans; Hypnotics and Sedatives; Male; Propofol; Risk Assessment; Severity of Illness Index; Treatment Outcome; Vitamin K

Topics: Androstanols; Anesthesia, General; Anesthetics, Inhalation; Anesthetics, Intravenous; Antifibrinolytic Agents; Blood Transfusion; Chemical and Drug Induced Liver Injury; Desflurane; Diagnosis, Differential; Fentanyl; Fundoplication; Gastrointestinal Hemorrhage; Humans; Infant; Isoflurane; Liver; Liver Function Tests; Male; Mobius Syndrome; Neuromuscular Nondepolarizing Agents; Piperidines; Propofol; Remifentanil; Rocuronium; Vitamin K

Topics: Anticoagulants; Azetidines; Benzylamines; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Humans; Myocardial Infarction; Thrombin; Thrombosis; Vitamin K; Warfarin

We investigated the existence of an NADH-dependent paraquat (PQ) reduction system in rat liver mitochondria (Mt) in respect to the cytotoxic mechanisms of PQ. The outer membrane fractions, free from the contamination of inner membranes but with a few microsomes, catalyzed rotenone-insensitive NADH, but not NADPH, oxidation by menadione or PQ. Anti-NADH-cytochrome b5 reductase antibody and its inhibitor p-hydroxymercuribenzonate did not inhibit the NADH-PQ reduction activity. Therefore, the respiratory systems of the inner membranes and microsomal cytochrome P450 systems could not have been responsible for the reaction. Dicoumarol, an inhibitor of NAD(P)H-quinone oxidoreductase (NQO), dose dependently suppressed the NADH oxidation in the outer membrane via PQ as well as menadione, with I50 values of 190 (for menadione) and 150 microM (for PQ). Because of a lower sensitivity to NADPH and the higher doses of dicoumarol required for its inhibition, the activity in the outer membrane may be an "NADH-quinone oxidoreductase" which partly differs from the NQO previously reported. This outer membrane enzyme produced superoxide anions in the presence of both NADH and PQ and was too tightly membrane-bound to be extracted by Triton X-100 and deoxycholate. From these results, we concluded that the free radical-producing mitochondrial NADH-quinone oxidoreductase is a novel oxidation-reduction system participating in PQ toxicity. This is in good agreement with our previous results showing that PQ selectively damaged Mt in vivo and in vitro, resulting in cell death (K.-I. Hirai et al., 1992, Toxicology 72, 1-16).

Topics: Animals; Chemical and Drug Induced Liver Injury; Dicumarol; Enzyme Inhibitors; Hydroxymercuribenzoates; Intracellular Membranes; Male; Mitochondria, Liver; NAD; NADH Dehydrogenase; Nitroblue Tetrazolium; Oxidation-Reduction; Paraquat; Quinone Reductases; Rats; Rats, Wistar; Vitamin K

The effects of induction of metallothionein (MT) on the toxicity of menadione were investigated in rat liver slices. The protective role of hepatic glutathione (GSH) was also studied and compared to that of MT. A 3-h incubation of rat liver slices with menadione (100-300 microM) containing medium (37 degrees C, pH 7.4, 95%O2:5%CO2) resulted in cellular toxicity, as shown by changes in cytosolic K, Ca and GSH concentrations and lactate dehydrogenase (LDH) leakage. A dose-dependent decrease in cytosolic K and GSH was observed concomitant with an increase in cytosolic Ca and LDH leakage after incubation with menadione. Pretreatment of rats with zinc sulphate (ZnSO4) (30 mg/kg body wt.) increased MT levels in liver slices and suppressed the toxicity of menadione. Intracellular GSH concentrations in liver slices were either depleted or increased by injection of rats with buthionine sulfoximine (BSO), (4 mmol/kg body wt.) and N-acetyl-L-cysteine (NAC) (1.6 g/kg body wt.), respectively. Intracellular GSH was found to be crucial in protection against menadione toxicity. Menadione toxicity was increased when the rats were injected with sodium phenobarbital (PB) (4 x 80 mg/kg body wt.). Pretreatment with Zn provided partial protection against menadione toxicity in liver slices from both BSO- and PB-injected rats. These findings suggest that induction of MT synthesis does protect against quinone-induced toxicity, but the role may be secondary to that of GSH. The mechanisms by which MT protect against menadione toxicity are still unclear but may involve protection of both redox cycling and sulphydryl arylation.

Topics: Acetylcysteine; Animals; Buthionine Sulfoximine; Calcium; Chemical and Drug Induced Liver Injury; Cytosol; Glutathione; In Vitro Techniques; L-Lactate Dehydrogenase; Liver; Male; Metallothionein; Methionine Sulfoximine; Phenobarbital; Potassium; Rats; Rats, Sprague-Dawley; Sulfates; Vitamin K; Zinc; Zinc Sulfate

Kupffer cells play an important role in liver function and phagocytosis of foreign particles in the hepatic portal tract. Therefore, the purpose of this study was to investigate the influence of several hepatotoxic chemicals (allyl alcohol, ethylhexanol, and menadione) and hypoxia on phagocytic activity of Kupffer cells in perfused rat liver. A recently developed optical method was used to determine rates of phagocytosis of carbon particles by Kupffer cells in periportal and pericentral regions of the liver lobule based on changes in reflected light from the liver surface (te Koppele, J.M., and Thurman, R.G. 1990. Am. J. Physiol. 259, G814-G821). With all chemicals studied, a rapid (10-30 min) decline in the rate of phagocytosis preceded parenchymal cell death as assessed from release of lactate dehydrogenase. These chemicals impaired parenchymal cell energy status as indicated by inhibition of O2 uptake and bile flow prior to cell death. Livers swell when they are damaged, a process which increases perfusion pressure and could theoretically damage the endothelium and lead to nonspecific uptake of carbon. In perfusions with a hepatotoxic concentration of allyl alcohol (350 microM), carbon particles accumulated in swollen livers after 70 min of perfusion. Histological studies revealed that carbon particles were localized predominantly in periportal regions of the liver lobule in perfusions with all hepatotoxicants studied. When perfusion pressure was elevated to 20 cm H2O in the absence of hepatotoxicants, carbon particles detected optically accumulated in upstream regions of the liver lobule (periportal or pericentral regions in perfusions in the anterograde or retrograde directions, respectively). In scanning electron microscopy of nonswollen livers, the endothelium remained intact. In swollen livers, however, the endothelium was disrupted and carbon was detected bound nonspecifically to parenchymal cells. Fifteen minutes after addition of allyl alcohol, bile canaliculi were dilated and endothelial fenestrations were enlarged. After 2 hr of perfusion with allyl alcohol, hepatic ultrastructure was severely disrupted. Thus, it is concluded that perfusion with hepatotoxic chemicals or hypoxia results in a rapid decrease of particle phagocytosis by Kupffer cells followed by changes in endothelial cell ultrastructure.

Topics: 1-Propanol; Animals; Carbon; Chemical and Drug Induced Liver Injury; Endothelium; Female; Hypoxia; Kupffer Cells; Liver; Perfusion; Phagocytosis; Propanols; Rats; Rats, Inbred Strains; Vitamin K

The alterations of mitochondrial membrane potential during the development of irreversible cell damage were investigated by measuring rhodamine-123 uptake and distribution in primary cultures as well as in suspensions of rat hepatocytes exposed to different toxic agents. Direct and indirect mechanisms of mitochondrial damage have been identified and a role for Ca2+ in the development of this type of injury by selected compounds was assessed by using extracellular as well as intracellular Ca2+ chelators. In addition, mitochondrial uncoupling by carbonylcyanide-m-chloro-phenylhydrazone (CCCP) resulted in a marked depletion of cellular ATP that was followed by an increase in cytosolic Ca2+ concentration, immediately preceding cell death. These results support the existence of a close relationship linking, in a sort of reverberating circuit, the occurrence of mitochondrial dysfunction and the alterations in cellular Ca2+ homeostasis during hepatocyte injury.

Topics: Adenosine Triphosphate; Animals; Calcium; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Cells, Cultured; Chemical and Drug Induced Liver Injury; Fluorescent Dyes; Ionomycin; Kinetics; Liver Diseases; Membrane Potentials; Mitochondria, Liver; Rats; Rats, Inbred Strains; Rhodamine 123; Rhodamines; Vitamin K

The effect of vitamin K on carbon tetrachloride-induced cellular damage of primary cultured hepatocytes was investigated by estimating prothrombin activity as a parameter of cellular function. Prothrombin activity was evaluated in primary cultured rat hepatocytes using synthetic fluorogenic peptide substrates (Boc-Val-Pro-Arg-MCA). Prothrombin activity significantly increased with the addition of vitamin K and decreased by the addition of warfarin (P less than 0.05). Carbon tetrachloride caused a significant decrease of prothrombin activity and cytotoxicity in a dose dependent manner. Prothrombin activity increased after addition of vitamin K when cells were previously exposed to carbon tetrachloride for a short period, but there was no change in cells treated for a long period. Carbon tetrachloride caused a modest increase of malondialdehyde formation after a short period of exposure and a significant increase following a long period of exposure. These results suggest that: 1) prothrombin activity is a good parameter for protein synthesis in cultured hepatocytes, 2) carbon tetrachloride-induced cytotoxicity results from different mechanisms in the early phase and the late phase of exposure, and 3) vitamin K has the ability to protect hepatocytes against the carbon tetrachloride-induced cellular damage in the early phase.

Topics: Animals; Carbon Tetrachloride Poisoning; Cells, Cultured; Chemical and Drug Induced Liver Injury; Liver; Male; Prothrombin; Rats; Vitamin K

Menadione and diquat cause toxicity in isolated hepatocytes. The toxicities of both menadione and diquat are primarily due to redox cycling and consequent oxidative stress. Menadione toxicity, however, has another component as the compound also possesses alkylating and oxidating properties allowing it to interact directly with cellular nucleophiles. Sulfite afforded considerable protection of isolated rat hepatocytes against the toxicity of menadione. This protective effect of sulfite may have several components. Sulfite effectively competed with glutathione (GSH) for conjugation with menadione, sparing intracellular GSH which may continue to detoxify reactive oxygen species formed through menadione redox cycling. The menadione sulfite conjugate undergoes much slower redox cycling than both menadione and the menadione glutathione conjugate. Sulfite also showed some degree of protection of hepatocytes from the toxicity of diquat. Diquat is a "pure" redox cycling agent and the protective effect of sulfite may involve the liberation of GSH from GSSG by sulfitolysis. This would again bolster intracellular GSH levels allowing further GSH-dependent detoxification of reactive oxygen species through cellular GSH peroxidases. In conclusion, our data illustrate the potential of inorganic sulfite to support the intracellular detoxification function of GSH, both against reactive electrophilic metabolites and against agents undergoing redox cycling.

Topics: Animals; Chemical and Drug Induced Liver Injury; Diquat; Glutathione; In Vitro Techniques; Inactivation, Metabolic; Liver; Male; Microsomes, Liver; Oxygen Consumption; Proteins; Pyridinium Compounds; Rats; Rats, Inbred Strains; Sulfites; Vitamin K

The course of haemostasis defects was investigated in dimethylnitrosamine (DMNA) acute liver necrosis. Before 18 hr there was no evidence of disseminated intravascular coagulation (DIC) nor of abnormal fibrinolysis. At 12 hr the level of the vitamin-K-dependent factors (factors II, VII, IX and X) was reduced to 25-63% of control. Factors V and VIII:C levels decreased to about 10 and 20% by 12 hr. Factor V was the only molecule which decreased significantly by 6 hr. The rapid decrease of these proteins might be related to an early parenchymal functional impairment attested by early structural lesions observed in the endoplasmic reticulum and nucleus. The isolated decrease of factor V in the absence of any significant change in serum transaminase (SGOT and SGPT) levels is proposed, at least in the rat, as an early criterion of hepatic failure.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Chemical and Drug Induced Liver Injury; Dimethylnitrosamine; Liver Diseases; Platelet Count; Rats; Time Factors; Vitamin K

An analysis of 28 cases of amanita phalloides poisoning serves as basis for a discussion of the clinical features and therapeutic problems involved. A critical review of recent experimental investigations in animals points to new possibilities in the treatment of amanita phalloides poisoning.

Topics: Adult; Amanita; Amanitins; Austria; Chemical and Drug Induced Liver Injury; Child; Exchange Transfusion, Whole Blood; Female; Humans; Male; Mushroom Poisoning; Phalloidine; Prothrombin; Renal Dialysis; Vitamin K

Topics: Acute Disease; Adolescent; Adult; Aged; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; Blood Coagulation Tests; Chemical and Drug Induced Liver Injury; Child; Cholesterol; Fatty Liver; Female; gamma-Globulins; Halothane; Hepatitis A; Humans; Indicators and Reagents; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Male; Methods; Middle Aged; Serum Albumin; Vitamin K

Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Autopsy; Chemical and Drug Induced Liver Injury; Female; Humans; Isoniazid; Necrosis; Tuberculin Test; Tuberculosis; Vitamin K

Topics: Acenocoumarol; Acute Disease; Blood Coagulation Disorders; Chemical and Drug Induced Liver Injury; Child, Preschool; Factor VII; Factor VIII; Factor X; Hemorrhage; Humans; Kidney Diseases; Kidney Function Tests; Liver Function Tests; Male; Medication Errors; Prothrombin; Prothrombin Time; Vitamin K

Topics: Alanine Transaminase; Anti-Bacterial Agents; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Cortisone; Coumarins; Humans; Kidney Diseases; Liver Diseases; Liver Function Tests; Middle Aged; Vitamin K; Water-Electrolyte Balance

Topics: Aflatoxins; Animal Feed; Animals; Anti-Bacterial Agents; Aspergillosis; Chemical and Drug Induced Liver Injury; Female; Male; Vitamin A; Vitamin E; Vitamin K

Topics: Blood Coagulation Disorders; Blood Transfusion; Chemical and Drug Induced Liver Injury; Hemorrhage; Hepatitis; Hepatitis A; Humans; Jaundice; Liver; Liver Diseases; Prothrombin Time; Surgical Procedures, Operative; Transplantation; Vitamin K

Topics: Chemical and Drug Induced Liver Injury; Cholesterol; Chromatography; Fatty Acids; Fatty Acids, Essential; Fatty Liver; Geriatrics; Hepatitis; Hypervitaminosis A; Linoleic Acid; Lipid Metabolism; Lipids; Liver; Oleic Acid; Palmitic Acid; Phospholipids; Toxicology; Vitamin K

Topics: Analgesics; Analgesics, Non-Narcotic; Anti-Bacterial Agents; Antipyretics; Brucellosis; Chemical and Drug Induced Liver Injury; Diet; Diet Therapy; gamma-Globulins; Hepatitis; Hepatitis A; Hepatitis Viruses; Humans; Hypnotics and Sedatives; Infant; Liver Function Tests; Pregnancy; Prognosis; Steroids; Syphilis; Therapeutics; Vitamin K; Vitamins; Weil Disease

Topics: Antineoplastic Agents; Chemical and Drug Induced Liver Injury; Diagnosis; Diet; Diet Therapy; Female; gamma-Globulins; Hepatitis; Hepatitis A; Hepatitis B virus; Hyperemesis Gravidarum; Liver Function Tests; Lupus Erythematosus, Systemic; Methyltestosterone; Norethindrone; Pneumonia; Prednisone; Pregnancy; Pregnancy Complications, Infectious; Pyelonephritis; Thioguanine; Toxicology; Vitamin K

Topics: Chemical and Drug Induced Liver Injury; Humans; Liver; Vitamin A; Vitamin K; Vitamins