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[Enalapril (Reniten)-associated toxic hepatitis].

A 52-year-old female was hospitalized with malaise, pruritus, jaundice, abdominal discomfort and vomiting. For 20 weeks she had been taking enalapril (Reniten) for hypertension. Serum aminotransferases and bilirubin were highly elevated with prolonged thromboplastin time. There was no evidence for extrahepatic cholestasis in ultrasonography. Serological investigations for a viral etiology of the liver failure were negative and the patient had no risk factors for viral hepatitis or exposure to hepatotoxic substances. Liver puncture revealed hepatitis of the fulminant viral hepatitis type, a picture that can be seen in a drug-induced hepatitis. The complete recovery of liver function after cessation of enalapril administration suggests acute toxic hepatitis due to enalapril. A metabolically mediated idiosyncratic reaction is the most plausible. Potential mechanisms of enalapril-induced hepatotoxicity are discussed and the current literature is surveyed.

Bilirubin↗

Nonsteroidal anti-inflammatory drugs and hepatic toxicity: a systematic review of randomized controlled trials in arthritis patients.

BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) might cause hepatic side effects, but the frequency of these laboratory and clinical side effects is uncertain. METHODS: Searches of bibliographic databases MEDLINE and EMBASE and of public archives of the Food and Drug Administration were conducted to identify randomized controlled trials of diclofenac, naproxen, ibuprofen, celecoxib, rofecoxib, valdecoxib, or meloxicam in adults with osteoarthritis or rheumatoid arthritis that provided information on aminotransferase elevations >3 x upper limit of normal, liver-related discontinuations, hepatic serious adverse events, liver-related hospitalizations, or liver-related deaths. The proportion of patients with each of the hepatic toxicity outcomes was calculated separately by using sample size weighted pooling for each NSAID. RESULTS: Sixty-seven articles from the bibliographic database and 65 studies from the Food and Drug Administration archives met inclusion criteria. Diclofenac (3.55%; 95% confidence interval [CI], 3.12%-4.03%) and rofecoxib (1.80%; 95% CI, 1.52%-2.13%) had higher rates of aminotransferase >3 x upper limit of normal than placebo (0.29; 95% CI, 0.17-0.51) and the other NSAIDs (all < or = 0.43%). The 95% CIs for liver-related discontinuations of all NSAIDs except diclofenac (2.17%; 95% CI, 1.78%-2.64%) overlapped with placebo. Only 1 liver-related hospitalization (among 37,671 patients) and 1 liver-related death (among 51,942 patients) occurred, with naproxen. CONCLUSIONS: Diclofenac and rofecoxib had higher rates of aminotransferase elevations than placebo and other NSAIDs studied. No NSAID studied had increased rates of liver-related serious adverse events, hospitalizations, or deaths.

Alanine Transaminase↗

Toxic hepatitis due to femoxetine.

A 51-year old woman treated with femoxetine--a new serotonin reuptake inhibitor with antidepressive effect--developed toxic hepatitis during the treatment. In spite of that, the elimination half-life of femoxetine in plasma was within normal limits.

Antidepressive Agents↗

[Middle molecule fraction in the serum of rats with toxic hepatitis].

An increase in the amount of the middle molecular peptide (MM) fraction in the blood serum of rats with experimental toxic hepatitis and normalization of the MM pool after the administration of the amino acid mixture Alvesin "Novy" are shown. The chromatographic spectra of the MM fraction in normal and experimental animals are compared.

Amino Acids↗

Hepatic toxicity of vitamin A and synthetic retinoids.

Vitamin A and synthetic retinoids have recently been used increasingly in a variety of health related concerns. Hepatic toxicity is an uncommon but serious side-effect of several Vitamin A derivatives which may lead to cirrhosis. This review will focus on the clinical and pathologic findings of hepatic involvement in chronic hypervitaminosis A and on the evidence concerning the potential hepatotoxicity of currently available synthetic retinoids.

Chemical and Drug Induced Liver Injury↗

[Hepatic toxicity of nitrofurantoin. Cases reported to the Center for Monitoring Adverse Drug Reactions 1968-1998].

Forty-four cases of nitrofurantoin-associated hepatic injury were reported to the Danish Center for Monitoring of Adverse Drug reactions from 1968 to 1998. Forty-one were women with a median age of 69 years. They had been treated with nitrofurantoin for median one year (two days-seven years), and all had biochemical and clinical signs of hepatitis. In five cases the injury had been provoked by a rechallenge. Twenty-seven liver biopsies showed an equal amount of acute and chronic histopathological changes. Cirrhosis was diagnosed in seven cases. Four died in liver failure; the others apparently recovered without long-term symptoms. In rare cases, nitrofurantoin can cause toxic hepatitis. Apparently elderly women in long-term treatment are more sensitive to develop this adverse reaction. The drug should be withdrawn if the patient shows any signs of hepatitis during treatment and the patient should be informed about the possible relationship to nitrofurantoin exposure. Rechallenge should not be performed.

Adult↗

[Hepatoprotective properties of balm Herbamarin and hydrolysates from marine invertebrates in toxic hepatitis and ethanol intoxication].

Protective properties of a syrup balm "Herbamarin" and food hydrolysates of scallop, octopus and crab were investigated using experimental toxic hepatitis and ethanol intoxication. Preventive administration of the balm and hydrolysates to animals subjected to an intoxications by 40% alcohol and CCl4 normalized clinical-diagnostic parameters of liver and blood plasma of experimental animals.

Alcoholic Intoxication↗

[Protective effect of phosphatidylcholine liposomes in experimental toxic hepatitis].

Level of fructose-1-monophosphate aldolase was decreased in blood serum after administration of phosphatidyl choline-containing liposomes into male rats with experimental toxic hepatitis caused by treatment with hepatotropic poison CCl4 at a dose of 0.25 ml/100 g of body mass. The rate of the aldolase level normalization depends on composition of liposomes as well as on the pathway of their administration.

Animals↗

Hepatic toxicity in South Indian patients during treatment of tuberculosis with short-course regimens containing isoniazid, rifampicin and pyrazinamide.

Results are presented of the incidence of hepatitis, nearly always with jaundice, among 1686 patients in clinical trials of the treatment of spinal tuberculosis, of tuberculosis meningitis and of pulmonary tuberculosis with short-course regimens containing rifampicin, isoniazid, streptomycin and pyrazinamide. The incidence was high in patients treated with daily regimens of isoniazid and rifampicin: 16-39% in children with tuberculous meningitis, 10% in patients with spinal tuberculosis (non-surgical cases), and 2-8% in those with pulmonary tuberculosis. Hepatitis, in those receiving rifampicin occurred more often in slow than in rapid acetylators of isoniazid, the proportions amongst those whose acetylator phenotype had been determined being 11% of 317 slow acetylators and 1% of 244 rapid acetylators. In children with tuberculous meningitis, the risk of hepatitis with isoniazid 20 mg/kg (39%) was higher than that with 12 mg/kg (16%), and appreciably lower in patients given rifampicin twice-weekly (5%) rather than daily (21%). There was no indication that pyrazinamide contributed to the hepatic toxicity.

Adolescent↗

Effect of Sargassum polycystum (Phaeophyceae)-sulphated polysaccharide extract against acetaminophen-induced hyperlipidemia during toxic hepatitis in experimental rats.

The effect of Sargassum polycystum crude extract on lipid metabolism was examined against acetaminophen-induced (800 mg/kg body wt., intraperitoneally) hyperlipidemia during toxic hepatitis in experimental rats. The animals intoxicated with acetaminophen showed significant elevation in the levels of cholesterol, triglycerides and free fatty acid in both serum and liver tissue. The levels of tissue total lipids and serum LDL-cholesterol were also elevated with depleted levels of serum HDL-cholesterol and tissue phospholipid. The acetaminophen-induced animals showed significant alterations in the activities of lipid metabolizing enzymes serum lecithin cholesterol acyl transferase (LCAT) and hepatic triglyceride lipase (HTGL). The levels of liver tissue fatty acids (saturated, mono and polyunsaturated) such as palmitic acid, stearic acid, oleic acid, linoleic acid, arachidonic acid and linolenic acid monitored by gas chromatography were considerably altered in acetaminophen intoxicated animals when compared with control animals. The prior oral administration of Sargassum polycystum (200 mg/kg body wt./day for a period of 15 days) crude extract showed considerable prevention in the severe disturbances of lipid profile and metabolizing enzymes triggered by acetaminophen during hepatic injury. Liver histology also showed convincing supportive evidence regarding their protective nature against fatty changes induced during acetaminophen intoxication. Thus the present study indicates that the protective nature of Sargassum polycystum extract may be due to the presence of active compounds possessing antilipemic property against acetaminophen challenge.

Acetaminophen↗

Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy.

PURPOSE: To identify the dose-volumetric parameters associated with the risk of radiation-induced hepatic toxicity (RIHT) in hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy. METHODS AND MATERIALS: A total of 105 hepatocellular carcinoma patients underwent three-dimensional conformal radiotherapy (total dose range, 44-58.5 Gy; median, 54). RIHT was scored within 4 months of completing three-dimensional conformal radiotherapy. The dose-volume parameters analyzed were the gross tumor volume; normal liver volume; total liver volume; radiation dose; mean dose to the normal liver; percentage of the normal liver volume receiving > or =20, > or =25, > or =30, > or =35, and > or =40 Gy; percentage of the total liver volume receiving > or =20, > or =25, > or =30, > or =35, and > or =40 Gy; and the normal tissue complication probability. RESULTS: Of the 105 patients, Grade 1 RIHT was observed in 21 (20.0%), Grade 2 in 7 (6.7%), Grade 3 in 5 (4.8%), and Grade 4 in 1 (1.0%) patient. No fatal Grade 5 RIHT developed. On multivariate analysis for predicting Grade 2 or worse RIHT, the total liver volume receiving > or =30 Gy was the only significant parameter (p < 0.001). Grade 2 or worse RIHT was observed in only 2 (2.4%) of 85 patients with a total liver volume receiving 30 Gy of < or =60% and in 11 (55.0%) of 20 patients with >60% (p < 0.001). CONCLUSION: The total liver volume receiving > or =30 Gy appears to be a useful dose-volumetric parameter for predicting the risk of RIHT. This volume should be limited to < or =60% whenever possible to minimize the risk of Grade 2 or worse RIHT.

Adult↗

An investigation on LD50 and subacute hepatic toxicity of Nigella sativa seed extracts in mice.

Nigella sativa seeds (blackseed) have been used in traditional medicine for the treatment of a variety of diseases including diarrhea and asthma, and have been shown to have various useful pharmacological effects. In this study, acute and subacute toxicity of the aqueous, methanol and chloroform extracts of the seeds have been investigated. To determine their LD50, the aqueous, methanol and chloroform extracts were administered orally, in 4 different doses, 6, 9, 14 and 21 g/kg. Mortality rate and weight changes have also been measured in all groups for 3 and 7 days, respectively. No mortality has been observed in all groups and with all doses. Methanol extracts in all doses and chloroform extract in the dose of 21 g/kg significantly decreased animals weight. Hepatic toxicity of the extracts was also investigated in the dose of 6 g/kg/day orally for 14 consecutive days by measuring ALP, SGOT and SGPT activity in blood and hepatic histological study. Degenerative changes in hepatic cells have been observed only with aqueous extract of the seeds. In conclusion, Nigella sativa extracts are relatively nontoxic in the acute toxicity test, but the possibility of hepatic damage with its aqueous extract should be considered.

Alkaline Phosphatase↗

Glutathione system and activity of NADPH-generating enzymes in the liver of intact rats and animals with toxic hepatitis receiving melatonin.

Melatonin administered to intact animals increased glutathione concentration and activities of glutathione peroxidase, glutathione reductase, NADP-isocitrate dehydrogenase, and glucose-6-phosphate dehydrogenase in the liver. In animals with toxic hepatitis melatonin treatment decreased glutathione concentration and enzyme activities, which was probably associated with inhibition of free radical oxidation under the influence of this hormone.

Animals↗

Hepatic toxicity possibly associated with kava-containing products--United States, Germany, and Switzerland, 1999-2002.

Since 1999, health-care professionals in Germany, Switzerland, and the United States have reported the occurrence of severe hepatic toxicity possibly associated with the consumption of products containing kava (i.e., kava kava or Piper methysticum). A total of 11 patients who used kava products had liver failure and underwent subsequent liver transplantation. On March 25, 2002, in response to five such case reports (four in Europe and one in the United States), the Food and Drug Administration (FDA) issued a consumer advisory and subsequently completed an investigation already underway of a similar U.S. case. This report presents the investigation of the two U.S. cases of liver failure associated with kava-containing dietary supplement products and summarizes the European cases. FDA continues to advise consumers and health-care providers about the potential risk associated with the use of kava-containing products.

Adolescent↗

[Correction of immune and hematopoietic system disorders in experimental toxic hepatitis with Lacto Flor].

Reduction in cells quantity of thymus, lymphatic nodes, bone marrow and rosette formation cells, decrease in erythrocytes and leucocytes number, suppression of antibody production are seen in experimentally developed acute toxic hepatitis (ATH). Lacto Flor preparation was established to have potential properties to restore different immune and hematological systems disorders observed in mice with ATH.

Adjuvants, Immunologic↗

[Toxic hepatitis and acute renal failure after inhalation of chloride solvents: report of one case (author's transl)].

Due to a combination of ingested ethanol and inhaled trichloroethylene (Tri) a 28 year old man developed toxic hepatitis and acute oliguric renal failure, both of which had a favorable evolution. Tri has been described as a cause of hepatic disfunction and acute renal failure due to acute tubular necrosis, although some of the cases described are controversial, because Tri was either contaminated by other dissolvents or could not be proven pure, with the exception of one case. In many there was ethanol ingestion. The Tri inhaled by our patient was found to contain less than 1% of carbon tetrachloride (C-Tchl). This would suggest the C-Tchl to be responsible for the clinical picture although the combination Tri/ethanol cannot be discarded as the causal agent, due to the small amount of contaminant present.

Acute Kidney Injury↗

[Acute renal failure, intravascular hemolysis and toxic hepatitis caused by repeated use of rifampicin (case report)].

We report the case of a 57-year-old man treated with interrupted rifampicin therapy for urinary tract tuberculosis who experienced acute renal failure, intravascular hemolysis and toxic hepatitis. This combined adverse reactions are rare. Supportive treatment with dialysis and withdrawal of rifampicin result with complete recovery. Interrupted and intermittent therapy with rifampicin should be avoided and noncompliant patients should be given alternative treatment when possible.

Acute Kidney Injury↗