Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatotoxicity has been noted by several investigators during parenteral use of clindamycin, and some have reported that drug half-life is prolonged in the presence of liver disease. We administered 300 mg of clindamycin intravenously at 12-h intervals for 2 days to patients with acute and chronic hepatitis, cirrhosis, and controls to determine whether clindamycin will exacerbate preexisting hepatic dysfunction or whether drug excretion will be delayed in patients with liver disease as compared with controls. Exacerbation of hepatotoxicity was not found in this study. There was a small, but significant, delay in drug elimination between cirrhotics and controls, even after the first dose of clindamycin (P < 0.05); however, half-lives in all categories were in the range usually considered normal. We conclude that clindamycin can be used in liver disease in some circumstances, if proper precautions are exercised.
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PMID:Use of clindamycin in patients with liver disease. 125 4

Hepatotoxicity secondary to the administration of thiabendazole has been rare since this drug was produced in 1964. In 14 of 15 patients reported previously in the literature, severe intrahepatic cholestasis resolved within seven months of the onset of illness. A recent report documented the progression to cirrhosis in a 15th patient. We report the second case of a patient with intrahepatic cholestasis that developed after treatment with thiabendazole and progressed to severe micronodular cirrhosis.
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PMID:Micronodular cirrhosis after thiabendazole. 272 25

Many compounds, including established drugs, cause liver damage through biotransformation to reactive cytotoxic metabolites which bind covalently to hepatic macromolecules. The forms of expression of such injury include acute necrosis, chronic hepatitis, cirrhosis and neoplasia. Hepatotoxicity depends on the balance between metabolic activation and inactivation and reduced glutathione protects against the toxicity of some agents by trapping their reactive electrophilic metabolites. Toxicity is usually increased by induction and decreased by inhibition of hepatic microsomal enzymes.
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PMID:Reactive metabolites as a cause of hepatotoxicity. 638 40

Hepatotoxicity may complicate therapy with methotrexate in patients with rheumatoid arthritis. Prevention of cirrhosis may depend upon early identification of liver damage, usually accomplished by serial biopsy. To determine the adequacy of noninvasive methods for identifying hepatotoxicity, 22 sets of data were obtained in patients undergoing therapy with methotrexate for rheumatoid arthritis. Comparisons were made between liver biopsy, hepatocellular enzymes and two noninvasive radioisotopic methods that have been shown to be abnormal in hepatocellular disease: the rate constant of excretion of the 14C-aminopyrine and the time from injection to peak hepatic activity of 99mTc-diisopropylimidodiacetic acid. The hepatocellular enzymes and the time-to-peak-activity of diisopropylimidodiacetic acid were not useful predictors of methotrexate-induced hepatotoxicity. The aminopyrine breath test was abnormal in approximately half the patients with hepatotoxicity but showed poor specificity. Noninvasive methods remain inferior to biopsy for the detection of mild to moderate methotrexate-induced hepatotoxicity in patients with rheumatoid arthritis.
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PMID:Comparison of methods for identifying early methotrexate-induced hepatotoxicity in patients with rheumatoid arthritis. 822 32

Alcohol causes primary malnutrition by displacing nutrients in the diet and secondary malnutrition via malabsorption and cellular injury through direct cytotoxicity. Hepatotoxicity results from metabolic disturbances associated with the oxidation of ethanol via liver alcohol dehydrogenase (ADH) and the redox changes produced by the generated NADH (the reduced form of nicotinamide adenine dinucleotide), which in turn affects the metabolism of lipids, carbohydrates, proteins, and purines. Ethanol is also oxidized in liver microsomes by an ethanol-inducible cytochrome P450, which contributes to the alcoholic's tolerance and his increased vulnerability to the toxicity of industrial solvents, anesthetics, commonly prescribed drugs, over-the-counter analgesics, chemical carcinogens, and retinoids. Increased acetaldehyde generation, with formation of protein adducts, results in antibody production, enzyme inactivation, decreased DNA repair, impaired utilization of oxygen, glutathione depletion, free radical-mediated toxicity, lipid peroxidation, and increased collagen synthesis. Therapy may eventually improve with the use of supernutrients such as S-adenosyl-L-methionine, which replenishes glutathione, restores methylation, and attenuates liver injury, as well as dilinoleoylphosphatidylcholine, which prevents cirrhosis.
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PMID:Herman Award Lecture, 1993: a personal perspective on alcohol, nutrition, and the liver. 823 56

The therapeutic effect of most immunosuppressive agents is unspecific and therefore often limited by an increased risk of infection by viral, bacterial or fungal organisms as well as by an increased incidence of malignant neoplasms. This short review includes the most commonly used immunosuppressants such as corticosteroids, azathioprine, methotrexate, cyclophosphamide and cyclosporine. The most common risks of long-term corticosteroid treatment are Cushing-like changes, decreased glucose tolerance and the usually benign steroid diabetes. Also clinically important is osteoporosis, since it can be prevented by physical training, calcium supplementation and treatment with vitamin D if necessary. Although there is still no proof of a significantly increased risk of peptic ulcer during steroid therapy, patients may develop gastrointestinal hemorrhage and even perforation without producing pain while being treated with corticosteroids. Mineralocorticoid effects, such as salt and water retention, are seen only with hydrocortisone and prednisone, whereas with synthetic steroids such as dexamethasone, sodium retention is absent despite their strong antiphlogistic activity. The most important side effect of the cytotoxic agents azathioprine, methotrexate and cyclophosphamide is marrow suppression. Due to the high turnover of neutrophils, patients most frequently suffer neutropenia rather than thrombocytopenia or anemia. Neutropenia, as well as impaired humoral and cellular immune mechanisms, are responsible for increased susceptibility to bacterial, viral or parasitic diseases during immunosuppressive therapy. Hepatotoxicity has been reported among patients receiving azathioprine (cholestatic hepatitis) and methotrexate (elevated AST levels and, rarely, liver fibrosis or cirrhosis). Cyclophosphamide causes hemorrhagic cystitis in a substantial proportion of patients, as well as an increased incidence of urothelial neoplasms. Both these side effects may be prevented by Mesna. The most important side effects of cyclosporine are acute and chronic nephrotoxicity usually associated with significantly elevated plasma levels of the drug. It must be borne in mind that severe nephrotoxicity may occur in patients receiving cyclosporine and ketoconazole together, since the latter may inappropriately increase the plasma cyclosporine level.
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PMID:[Immunosuppression--a tightrope walk between iatrogenic harm and therapy]. 892 65

Hepatotoxicity by antituberculous drugs is well known. Nonetheless, severe liver involvement is infrequent. Several series of fulminant hepatitis by antituberculous drugs have recently been reported with a much greater frequency than previously reported. The present study describes the authors' experience which, similar to other groups, has shown a marked increase with respect to previous experience. During 1994 5 patients with acute severe hepatitis associated to antituberculous drugs were admitted to the authors' unit. The mean age of the patients was 43 years (range: 25-62). Two patients were healthy HBsAg carriers, one undergoing enzymatic inducer treatment and was anti-HIV positive. Another patient presented compensated liver cirrhosis by HCV. The 5 cases received combined isoniazid and rifampicin and four had also received pyrazinamide. Four patients presented hepatic encephalopathy. Of these cases, three could not undergo emergency liver transplantation because of contraindications and died due to complications of acute severe liver failure. Another patient evolved favorably following emergency liver transplantation. The only patient who presented good evolution with conservative treatment and who did not present hepatic encephalopathy had discontinued isoniazid because of the finding of slight hypertransaminasemia during a routine analytical control. Several risk factors have been reported for the appearance of hepatotoxicity by antituberculous drugs. The factor of greatest clinical importance for the development of severe hepatotoxicity is probably continuation of the treatment once hepatic dysfunction has initiated. The important increase in cases of severe toxicity urges the need for strict analytical monitoring following initiation of treatment.
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PMID:[Severe hepatotoxicity of tuberculostatic agents. Increase in the incidence]. 899 67

The prevalence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection ranges from nearly 30% to over 50%, depending on the population. Shared modes of transmission and the success of current antiretroviral regimens have contributed to the emergence of HCV as a significant pathogen in the HIV-positive population. HIV coinfection appears to worsen HCV infection, with studies showing more severe fibrosis, a higher frequency of cirrhosis, and increased deaths from liver disease. HIV coinfection may also increase the rate of maternal-fetal transmission of HCV. Similarly, studies suggest a more rapid progression to AIDS or death for HCV genotypes 1a and 1b than for other genotypes in HIV-infected patients with hemophilia. Highly active antiretroviral therapy (HAART), such as HIV protease inhibitors, has no effect on HCV infection and may transiently increase ALT, AST, and hepatitis C viral load. Hepatotoxicity associated with HAART may or may not be related to the presence of HCV and may depend on the specific agents used. Data suggest that treating chronic hepatitis C in HIV-co-infected patients can decrease fibrosis, increase T-cell responsiveness to HCV antigens, and decrease the rate of fatal hepatomas. Interferon alpha may provide sustained biochemical or virologic responses in HIV/HCV-coinfected patients. The combination of interferon-alpha and ribavirin may also be a treatment option but is more complex, and additional research is needed. Treating HCV infection in HIV/HCV-coinfected individuals may help lower the hepatitis C viral load and permit treatment with protease inhibitors.
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PMID:Hepatitis C virus and human immunodeficiency virus: clinical issues in coinfection. 1065 64

In clinical trials, all lipid-lowering agents have been associated with mild, asymptomatic elevations of alanine aminotransferase (ALT) and asparate aminotransferase enzymes. This, along with the fact that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are hepatotoxic in some animals, led the US Food and Drug Administration (FDA) to recommend monitoring of liver enzymes for all lipid-lowering agents, except the bile acid sequestrants. Because the drugs act by different mechanisms, ALT elevations may be a pharmacodynamic effect related to lipid lowering, rather than a direct effect of the drug. Animal studies support this assumption. ALT elevations of 3 times the upper limit of normal occur in <3% of patients in clinical trials of lipid-lowering drugs. The elevations are transient and often dose-related, and they usually revert to normal while continuing therapy and have never been associated with hepatotoxicity. Confounding factors include alcohol, acetaminophen, and pre-existing liver disease, such as chronic hepatitis C and type II diabetes with fatty liver, which are both associated with mild, intermittent elevations of ALT. The more important issue is whether or not lipid-lowering agents are hepatotoxic. There are case reports of hepatotoxicity (cholestasis, jaundice, hepatitis, chronic active hepatitis, fatty liver, cirrhosis and acute liver failure) with all of the drugs, except cholestyramine. To date there are just 5 cases of documented liver failure linked to lovastatin. There is no evidence that monitoring reduces the rate of hepatotoxicity. Mild elevations of ALT that occur with many drugs, including HMG-CoA reductase inhibitors, do not predict hepatotoxicity. Liver enzyme elevations appear to be a class characteristic of lipid-lowering agents. Hepatotoxicity is a rare idiosyncratic reaction, occurring only with sustained released nicotinic acid.
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PMID:Defining patient risks from expanded preventive therapies. 1085 89

Herbal drugs are widely used and often contain highly active pharmacological compounds. Recently, reports have mounted about hepatotoxicity of herbal remedies which ranges from mild liver enzyme alterations to chronic liver disease and liver failure. Hepatotoxicity of Chinese herbs has been recognized, e.g. during treatment of patients with atopic eczema. However, the toxic compounds remain to be determined. Hepatic veno-occlusive disease may result from pyrrolizidine alkaloids which are contained in numerous plants worldwide. Teucrium chamaedrys, commonly referred to as germander, may cause hepatitis and even liver cirrhosis. Significant hepatotoxicity has also been observed after the ingestion of chaparral. Recently, greater celandine, which is widely used for biliary disorders and dyspepsia, was identified as a cause of cholestatic hepatitis. Hepatotoxic reactions have also been observed after the ingestion of Atractylis gummifera, Callilepsis laureola, Senna, Kavapyrone and Pulegium. The aim of this review is to summarize potentially hepatotoxic herbal remedies, to further elucidate their mechanisms of toxicity and thereby underline the likelihood of plants to be the cause of liver damage.
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PMID:[Liver toxicity of drugs of plant origin]. 1132 40


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