Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatotoxicity of cyamamezine, a phenothiazine structurally related to chlorpromazine, has been rarely documented. We report here a case of acute symptomatic hepatitis following a unique massive intake of cyamamezine in a suicide attempt and discuss the mechanisms of such injury.
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PMID:Cyamamezine-induced acute hepatitis after unique massive intake: a case report. 1032 65

The incidence of tuberculosis in Japan, 33.7 per 100,000 in 1997, is very high compared with USA or Western European countries. The decrease in the incidence has slowed down from the early 1980s, and the average annual rate of decrease has been 3.8% in the last 5 years. About 9 percent of tuberculosis patients defaulted from the nine-month regimen (6HRS or E/3HR) in urban areas. Regimens shorter than nine-month are needed to achieve high effectiveness of tuberculous chemotherapy. Out of 1128 new pulmonary tuberculosis patients, six-hundred twenty started treatment with six-month (2HRZS or E/4HRE) in Fukujuji Hospital, JATA, in Tokyo from January 1991 to December 1996. Out of 620, four-hundred twenty eight were both smear and culture positive, 136 were smear negative and culture positive and 56 were bacilli negative. Out of 564 bacilli positive cases, 530 were susceptible to INH and RFP. Out of 530 drug susceptible cases three hundred ninety-three patients completed the regimen. Ninety-three percent of these patients had converted to negative at two months of chemotherapy and all of them at five months. Out of 450, two-hundred ninety five completed 6-month regimen, one-hundred fifty-five were changed their regimen or prolonged duration of chemotherapy. Out of 295, nine patients (3.1%) relapsed after the completion of 6-month chemotherapy. Mean follow-up period was 17.2 months and the median was 15.5 months. The relapse rate was 2.2 per 100 person-years. Six of the relapsed cases were complicated with Diabetes Mellitus. Relapse rate was higher in patients with Diabetes Mellitus than in patients without (6/54, 7.9 per 100 person-years vs 3/237, 0.8 per 100 person-years) (p < 0.001). Drug-induced hepatotoxicity was defined as elevated serum transaminase level with clinical symptoms of hepatitis or elevated serum transaminase level more than 5 times of upper limit of normal range with or without symptoms. Drug-induced hepatotoxicity developed in 43 (8.0%) of 535 with initial normal liver function test results, this rate was similar to that in patients treated with nine-month regimen (34/420, 8.1%). But the frequency of hepatotoxicity of more than 400 IU/ml of serum transaminase level was higher in patients treated with PZA-containing regimen than with nine-month regimen (16/536, 3.0% vs 4/420, 1.0%), but this deference was not statistically significant. Hepatotoxicity developed in 13/85 (15.3%) of patients treated with PZA-containing regimen with abnormal liver function tests at the beginning of chemotherapy, and this frequency was similar to 7/65 (10.8%) in patients with nine-month regimen. The relapse rate in patients with Diabetes Mellitus was statistically higher than in without Diabetes Mellitus (7.9 vs 0.8 per 100 person-years). We concluded that the six-month regimen was highly effective, but the frequency of severe hepatotoxicity was relatively higher than in nine-month regimen and the duration of chemotherapy was not enough for patients complicated with Diabetes Mellitus. Further study is needed for sufficient chemotherapy in patients with Diabetes Mellitus.
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PMID:[Six-months chemotherapy (2HRZS or E/4HRE) of new cases of pulmonary tuberculosis--six year experiences on its effectiveness, toxicity, and acceptability]. 1035 21

This review compares the tolerability profiles of the three currently available nonsteroidal antiandrogens, flutamide, bicalutamide and nilutamide. Pharmacological effects associated with blockade of the androgen receptor are frequent with all three drugs. Gynecomastia and breast pain are seen more frequently during antiandrogen monotherapy than during combination with medical or surgical castration or castration alone, and the reverse is true for hot flashes, which are a side effect of castration. Gastrointestinal symptoms are also common to all three drugs, but diarrhea occurs more frequently in flutamide studies than in bicalutamide or nilutamide studies. Hepatotoxicity has been seen with all three antiandrogens, but acute, reversible hepatitis and fatal fulminant hepatitis have also been reported with both nilutamide and flutamide. All three drugs have been associated with asymptomatic elevations in aminotransferases and may reduce hemoglobin levels. Adverse events that have been reported with nilutamide include interstitial pneumonitis, delayed adaptation to darkness after exposure to bright light and alcohol intolerance. To date, bicalutamide appears to have some advantage over flutamide and nilutamide in terms of tolerability.
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PMID:Tolerability of Nonsteroidal Antiandrogens in the Treatment of Advanced Prostate Cancer. 1038 26

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

Hepatotoxicity due to chronic amiodarone (AD) use is well described. However, hepatitis occurring after acute administration of AD has only occasionally been reported and the pathologic findings in the liver in this condition have not been well characterized. We describe an idiosyncratic reaction, in a 40-year-old man after 6 weeks of oral AD therapy, consisting of acute hepatitis, which resolved after withdrawal of the drug. The liver biopsy showed clusters of cells with granular cytoplasm. These cells were characterized as macrophages, and phospholipid membranous inclusions were demonstrated ultrastructurally in the granular cells and in the hepatocytes. Pathologists and clinicians should be aware of this subtle histologic finding when looking for evidence to support AD hepatotoxicity.
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PMID:Granular cells as a marker of early amiodarone hepatotoxicity. 1103 6

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

To evaluate the occurrence of hepatotoxicity in patients during antiretroviral therapy (ART) that contains protease inhibitors and the role of hepatitis viruses in its development, we performed a retrospective study including 1325 HIV-infected patients treated with ART for at least 6 months. Presence or absence of hepatitis viruses, alanine aminotransferase (ALT), total bilirubin, CD4 cell count, and plasma HIV RNA levels were evaluated. Hepatotoxicity developed in a few study subjects without coinfection, whereas it was significantly higher in coinfected patients. Univariate logistic regression analysis showed that viral hepatitis coinfections are independent risk factors for hepatotoxicity. After 6 months of treatment, ritonavir was associated with higher rates of severe hepatotoxicity in the coinfected group; in fact, ritonavir seems to be the most strongly hepatotoxic agent among coinfected patients. After 12 months of therapy, hepatotoxicity occurred more frequently in patients with hepatitis C virus who did not respond to antiretroviral therapy (ART), whereas patients who did respond to ART showed decreased ALT levels. Hepatotoxicity is not exclusively an effect of drug toxicity, and the presence of hepatitis coinfection is an independent risk factor. Moreover, chronic hepatotoxicity mainly occurs in patients who did not respond to therapy. Conversely, patients who did respond to ART seemed to show improvement of chronic liver infection.
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PMID:Hepatotoxicity development during antiretroviral therapy containing protease inhibitors in patients with HIV: the role of hepatitis B and C virus infection. 1178 88

Hepatotoxicity was investigated, using plasma collected before and during treatment, in 16 human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients who responded to highly active antiretroviral therapy (HAART), during a retrospective longitudinal study. Eleven patients experienced hepatotoxicity (i.e., a >3-fold increase in alanine aminotransferase level) while receiving HAART, including 4 patients with clinical hepatitis. Control subjects were 5 patients without hepatotoxicity. Markers of HCV-specific immune responses (HCV core-specific immunoglobulin G [IgG] antibody), T cell activation (soluble [s] CD26 dipeptidyl peptidase IV [DPP IV] enzyme activity), and inflammation (nitrate/nitrite and soluble tumor necrosis factor receptor I [sTNFRI] levels) were correlated with liver damage and immune reconstitution. All patients with hepatotoxicity had increased HCV core-specific IgG antibody and sCD26 (DPP IV) activity but did not have increased nitrate/nitrite or sTNFRI levels. Hepatotoxicity without clinical hepatitis was associated with increased CD8 T cell counts. Thus, hepatotoxicity in HIV-HCV-coinfected patients who respond to HAART is associated with increased HCV-specific immune responses and T cell activation.
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PMID:Association of increased hepatitis C virus (HCV)-specific IgG and soluble CD26 dipeptidyl peptidase IV enzyme activity with hepatotoxicity after highly active antiretroviral therapy in human immunodeficiency virus-HCV-coinfected patients. 1240 69

We report 4 cases of hepatic injury in patients treated with a dextropropoxyphene-paracetamol combination in which the causal relationship with dextropropoxyphene can be suspected. These four cases show similarities with the 29 cases found in international publications. Hepatotoxicity occurs more frequently among old patients and women. Clinically, this condition can mimic a biliary tract disease with sometimes few or no symptoms. Biochemical criteria can show cholestatic, mixed or cytolytic hepatitis. Intrahepatic cholestasis may be found in liver biopsies sometimes suggesting cholangitis. Outcome is favourable on withdrawal of the drug. The mechanism of action of dextropropoxyphene is discussed.
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PMID:[Dextropropoxyphene hepatotoxicity: four cases and literature review]. 1261 Dec 1

Hepatotoxicity, predominantly cholestatic, is a rare adverse effect of gold salt therapy, which usually completely resolves within a few months. We report the case of a female patient treated for rheumatoid arthritis, who had gold salt overdose, and in whom acute cholestatic hepatitis occurred three weeks after beginning of therapy. Evolution of gold concentration was followed in plasma and urine, as well as in cutaneous and liver dry tissue. Liver biopsy showed marked inflammatory changes of interlobular bile ducts that evolved towards ductopenia, which was responsible for prolonged cholestasis still present 15 months later. In addition, sialadenitis with sicca syndrome was noted six months after onset of the disease. The mechanism of hepatotoxicity was probably immunoallergic since liver lesions were associated with hypersensitivity syndrome including dermatitis and blood and tissue eosinophilia. This is the first report of gold salt hepatotoxicity with histological demonstration of cholangitis followed by ductopenia.
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PMID:Prolonged cholestasis and ductopenia following gold salt therapy. 1265 30


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