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Topic: Hepatotoxicity

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	Risks To Your Liver (hepatotoxicity)
		Among the participants who took a non-nucleoside reverse transcriptase inhibitor (either Viramune, Sustiva, or Rescriptor) in combination with two nucleoside analogues, severe hepatotoxicity occurred in 8.2%.
		Among the participants who took a protease inhibitor in combination with two nucleoside analogues, severe hepatotoxicity occurred in 5%.
		For example, it is believed that women and people over the age of 50 are at a higher risk of developing hepatotoxicity.
	www.aidsmeds.com /LESSONS/Hepatotoxicity4.htm (346 words)

	USCAP 2003 Annual Meeting
		Nevertheless drug-induced hepatotoxicity is sufficiently common in children that it should be considered in every instance of childhood liver disease of uncertain etiology.
		The key to identifying drug hepatotoxicity in adults and children is consistently to include it in the differential diagnosis of any clinical presentation of liver disease.
		To specify the role of immune mechanisms in drug hepatotoxicity, drugs can be further categorized as "eliciting and immuno-allergic response." This may be a special type of contingent hepatotoxicity since genetic aspects of immune responsiveness may play an important role in whether an individual is likely to have an immune component with drug hepatotoxicity.
	www.uscap.org /site~/92nd/companion08h3.htm (2821 words)

	Hepatotoxicity (Site not responding. Last check: 2007-10-21)
		Hepatotoxicity (from hepatic toxicity) is chemical-driven liver damage.
		Idiosyncratic hepatotoxicity has led to the withdrawal of several drugs from market even after rigorous clinical testing as part of the FDA approval process (troglitazone, Rezulin®).
		One of the main causes of drug-induced hepatotoxicity in western countries is acetaminophen (paracetamol) poisoning, which is a symptomatic hepatotoxin.
	www.apawn.com /search.php?title=Hepatotoxicity (331 words)

	RFA-DK-02-033: HEPATOTOXICITY CLINICAL RESEARCH NETWORK
		Hepatotoxicity is the single, most common adverse drug reaction that leads to drug withdrawal and or refusal of approval by the Food and Drug Administration (FDA).
		The Hepatotoxicity Clinical Research Network investigators will be encouraged to seek out separate funding for special projects and to develop collaboration with laboratory and basic research investigators to draw upon the resources (clinical data, serum, tissue, DNA) made available by the Hepatotoxicity Clinical Research Network Database.
		The underlying concept of the Hepatotoxicity Clinical Research Network is that a core effort is essential to maintain the infrastructure required to perform screening identification and characterization of bona fide cases of drug-induced liver toxicity, possibly from several regional institutions.
	grants.nih.gov /grants/guide/rfa-files/RFA-DK-02-033.html (7358 words)

	AASLD: Severe Hepatotoxicity Rare in Patients With Elevated Liver Enzymes on Statin Therapy (Site not responding. Last check: 2007-10-21)
		But, according to new research, the risk of developing severe hepatotoxicity is the same for people with elevated liver enzymes at the start of therapy as it is for those who begin statin therapy with normal liver function tests.
		Severe hepatotoxicity was defined as development of serum bilirubin >3 mg/dL (regardless of their baseline transaminases) or elevations of AST and/or ALT >10 times the upper limit of normal in patients with normal baseline enzymes or >10-fold elevations from their baseline values of AST and/or ALT in patients with elevated liver enzymes at baseline.
		He found that mild-to-moderate hepatotoxicity occurred in 1.7% of the patients with normal enzymes compared to 4.4% of those with elevated enzymes at baseline, a difference that was statistically significant at p=0.006.
	www.pslgroup.com /dg/23d6d6.htm (719 words)

	Letters: Skin Cap Hepatotoxicity
		This case report describes a patient in whom the use of Skin Cap spray for treatment of stable plaque-type psoriasis vulgaris was associated with pustular psoriasis and hepatotoxicity.
		Alternatively, an ingredient in Skin Cap may have resulted in topical sensitization resulting in a systematized Koebner response with subsequent widespread pustular psoriasis and hepatotoxicity.
		This case serves to illustrate the importance of maintaining vigilance for the possibility of adverse events developing in over-the-counter preparations which patients may presume to be of negligible adverse risk.
	dermatology.cdlib.org /DOJvol3num2/editorials/hepatotoxicity.html (546 words)

	Acetaminophen Hepatotoxicity -- Neurotransmitter.net
		Analysis of literature data on drug-induced hepatotoxicity reveals that often upper respiratory febrile illnesses and/or inflammation states precede liver injury/diseases related to administration of drugs or hepatotoxicity associated with administration of therapeutic doses of acetaminophen in some genetically predisposed subjects.
		The study of hepatotoxicity in vitro is complicated by the difficulty of maintaining hepatocytes in culture due to a lack of understanding of the humoral and matrix requirements of these cells.
		Hepatotoxicity, resulting from the CYP2E1-mediated activation of acetaminophen, was demonstrated in the livers of CYP2E1-humanized mice by elevated serum alanine aminotransferase levels, increased hepatocyte necrosis, and decreased P450 levels.
	www.neurotransmitter.net /acetaminophen.html (16626 words)

	Hepatotoxicity associated with protease inhibitor-based antiretroviral regimens with or without concurrent ritonavir
		Hence, these data suggest that the risk of hepatotoxicity during therapy with PIs boosted by low-dose RTV is largely attributable to the primary PI, which is consistent with the observation that the plasma concentration with RTV (200 mg/day) is approximately 7% of that achieved with full-dose RTV (1200 mg/day).
		Second, we were unable to assess the risk of hepatotoxicity associated with other PI regimens, such as boosted or unboosted amprenavir, fosamprenavir, and atazanavir, or with alternative boosting strategies, such as saquinavir (1000 mg twice daily)/RTV (100 mg twice daily).
		The objective of this study was to determine the incidence of severe hepatotoxicity following the initiation of PI-based antiretroviral therapy with or without co-administration of RTV in an urban HIV clinic, and to define the role of chronic viral hepatitis in its development.
	www.natap.org /2004/HIV/120804_03.htm (2497 words)

	eMedicine - Halothane Hepatotoxicity : Article by Karl A Poterack, MD
		Type II hepatotoxicity is associated with massive centrilobular liver cell necrosis that leads to fulminant liver failure.
		The potential for volatile anesthetics to cause type II hepatotoxicity is directly related to the relative degree of their oxidative metabolism to acetylated protein adducts.
		Type I halothane hepatotoxicity is attributed to reductive (anaerobic) halothane metabolism, with reactive metabolites causing lipid peroxidation and binding to cytochrome P-450.
	www.emedicine.com /med/topic942.htm (1681 words)

	Evaluation of risk factors for antituberculosis drugs-induced hepatotoxicity (Site not responding. Last check: 2007-10-21)
		Incidence of hepatotoxicity was determined from the rate of hepatic adverse reaction cases obtained from population beginning anti-TB therapy.
		Incidence of anti-TB drugs-induced hepatotoxicity was found to be higher in younger patients, a finding that is in variance with experience of others.19,20 Majority of the patients enrolled in the study were of younger age group (Table 1).
		RMP is considered to be less hepatotoxic but is a powerful enzyme inducer, which may enhance INH hepatotoxicity.4,6,22 Formation of hydrazine, which is the key intermediate of INH metabolism and which is a potent acylating agent capable of causing liver necrosis is facilitated by RMP.
	www.priory.com /cmol/antitb.htm (3600 words)

	Characterization of Acute 4,4'-Methylene Dianiline Hepatotoxicity in the Rat
		Characterization of Acute 4,4'-Methylene Dianiline Hepatotoxicity in the Rat
		The acute hepatotoxicity of orally administered DDM was characterized in rats.
		The role of cytochrome P450 monooxygenase (MO)-mediated metabolism in DDM hepatotoxicity was evaluated using the MO inhibitors, aminobenzotriazole and SKF-525A and the MO inducers phenobarbital and ß-naphthoflavone.
	ehp.niehs.nih.gov /docs/1993/101-2/bailie.html (353 words)

	News - Less Hepatotoxicity With Isoniazid Versus Pyrazinamide/Rifampin For Latent Tuberculosis
		Severe hepatotoxicity may also occur with pyrazinamide plus rifampin, but this can be avoided by implementing intensive monitoring of liver enzymes, according to investigators.
		Hepatotoxicity was defined as a fourfold or greater increase in alanine transaminase.
		Severe hepatotoxicity was detected in 2 out of 43 pyrazinamide plus rifampin patients who received treatment before the implementation of an intensive liver enzyme monitoring program.
	docguide.com /news/content.nsf/news/8525697700573E1885256CB1000BD411 (416 words)

	Analysis of Strain Difference in Sensitivity to Cadmium-Induced Hepatotoxicity in Fischer 344 and Sprague-Dawley Rats ...
		of 3.0 and 3.5 mg Cd/kg caused hepatotoxicity in SD rats.
		Hepatotoxicity was assessed by measuring serum indices of hepatotoxicity, (A) alanine aminotransferase activity (ALT) and (B) sorbitol dehydrogenase activity (SDH).
		Stine, E. R., Gunawardhana, L., and Sipes, I. The acute hepatotoxicity of the isomers of dichlorobenzene in Fischer-344 and Sprague-Dawley rats: Isomer-specific and strain-specific differential toxicity.
	toxsci.oxfordjournals.org /cgi/content/full/67/2/329 (5052 words)

	Drug Information Journal: Hepatotoxicity in the review of clinical safety data
		It may occur as an unexpected idiosyncratic reaction to an otherwise nontoxic drug or it may be an expected consequence of the intrinsic toxicity of a drug, Laken in a sufficiently large dose to cause liver injury (1).
		Because of the importance of drug-induced hepatotoxicity in clinical medicine, researchers and regulators have vigorously pursued basic knowledge about hepatotoxicity, including types and mechanisms, the circumstances under which hepatic injury occurs, and measures to reduce the occurrence of this untoward side effect.
		Although it has been known that patients with cirrhosis and impaired liver function may have altered metabolism of certain agents and may be at added risk of liver injury, for the most part, patients with mild-to-moderate underlying chronic liver disease do not appear to be at increased risk of idiosyncratic hepatic injury from drugs (7,8,9).
	www.findarticles.com /p/articles/mi_qa3899/is_200301/ai_n9226358 (1348 words)

	Hepatotoxicity is a Common Complication of HIV Antiretroviral Therapy (Site not responding. Last check: 2007-10-21)
		The results of this analysis were presented at Digestive Disease Week and indicate that hepatotoxicity is a common complication of HIV antiretroviral therapy.
		Twenty-three percent of the patients with severe hepatotoxicity permanently discontinued therapy due to that complication, with the highest rate of discontinuation in the mono-NRTI studies (27%) and the lowest in the PI-based triple therapy studies (9.3%).
		Based upon this study, the authors conclude "there is a high rate of severe [antiretroviral] hepatotoxicity irrespective of class" and that further data are needed to identify risk factors for antiretroviral-related hepatotoxicity.
	www.hivandhepatitis.com /recent/lipo/052501.html (393 words)

	hepatotoxicity, Primary Sclerosing Cholangitis Literature
		Funk C, Ponelle C, Scheuermann G, Pantze M 2001 Cholestatic potential of troglitazone as a possible factor contributing to troglitazone-induced hepatotoxicity: in vivo and in vitro interaction at the canalicular bile salt export pump (Bsep) in the rat.
		Jaskiewicz K, Voigt H, Blakolmer K 1996 Increased matrix proteins, collagen and transforming growth factor are early markers of hepatotoxicity in patients on long-term methotrexate therapy.
		Kim SK, Kim YC 2002 Attenuation of bacterial lipopolysaccharide-induced hepatotoxicity by betaine or taurine in rats.
	www.psc-literature.org /heptox.htm (6731 words)

	Hotline - Reports of Leflunomide Hepatotoxicity in Patients with Rheumatoid Arthritis
		Serious hepatotoxicities reported included drug induced hepatitis, reactivation of viral hepatitis (especially hepatitis B), fulminant hepatic failure, jaundice, cholestasis, hepatomegaly and hepatic cirrhosis.
		If leflunomide is discontinued for reasons of hepatotoxicity and a change to another hepatotoxic DMARD is contemplated, washout and monitoring procedures should be adhered to.
		Careful attention must be given to possible contraindications, signs of hepatotoxicity and proper monitoring when considering use of leflunomide together with other potentially hepatotoxic drugs such as NSAIDs and methotrexate.
	www.rheumatology.org /publications/hotline/0801leflunomide.asp (1455 words)

	iHerb: HerbalGram The Journal of the American Botanical Council
		The purpose of the workshop was to review and discuss methods of assessing the hepatotoxicity of botanical dietary supplements with an emphasis on in vitro laboratory techniques that might be applied in screening for assessment and eventually, prediction of hepatotoxic potential.
		Unpredictable hepatotoxicity associated with either drugs or botanicals is also extremely difficult to recognize or assess because prevalence of adverse reactions ranges between 1 in 10,000 and 1 in 100,000 against a large background.
		Recognition of causality in idiosyncratic hepatotoxicity (i.e., spontaneous hepatotoxicity of no direct or demonstrable origin) is further confounded by combinations of numerous variables, including environmental conditions (underlying disease, co-medication, tissue injury), genetic factors (drug metabolism or transport differences), induction or inhibition of metabolizing enzymes, and the molecular nature of the toxicant.
	www.herbalgram.org /iherb/herbalgram/articleview.asp?a=2783&p=Y (2532 words)

	724-T. Hepatotoxicity among a Cohort of Thai HIV-Infected Patients Enrolled in HIV-NAT Antiretroviral Therapy Trials
		However, the incidence and predictors of hepatotoxicity require further examination, particularly in non-Caucasian and developing country populations.
		Severe hepatotoxicity was defined as an increase in alanine aminotransferase (ALT) level to 5 times the upper limit of normal.
		Risk of severe hepatotoxicity was highest among patients with HIV/viral hepatitis co-infection and those receiving NNRTIs.
	www.retroconference.org /2002/Abstract/12944.htm (307 words)

	Liver & GI Review Issue 10 - California Pacific Medical Center's Liver Disease Management & Transplant Program
		Cases of severe drug-induced hepatotoxicity are defined as liver enzyme elevations five or more times the normal limit.
		Often, drug-induced hepatotoxicity is only detected after a drug enters the market because animal models cannot always predict human toxicity.
		Patients with drug-induced hepatotoxicity may be asymptomatic, with liver injury diagnosed during routine blood testing, while others develop symptoms including nausea, fatigue, itching and jaundice.
	www.cpmc.org /advanced/liver/news/newsletter/newsletter-vol10.html (1972 words)

	Alternative Medicine Review: Hepatotoxicity in acute iron poisoning - Abstract
		Although hepatotoxicity is a known sequela of acute iron poisoning, the literature describing it is confined to sporadic reports.
		An understanding of the pathogenesis of the hepatotoxicity of acute iron poisoning is central to the identification of rational and effective interventions.
		From the clinical perspective, the relatively high mortality rate of iron poisoning-induced hepatotoxicity requires vigilance for its onset and earlier consideration of liver transplantation.
	www.findarticles.com /p/articles/mi_m0FDN/is_2_7/ai_85523011 (242 words)

	JAMA -- Abstract: Association of acetaminophen hepatotoxicity with fasting and ethanol use, December 21, 1994, Whitcomb ... (Site not responding. Last check: 2007-10-21)
		JAMA -- Abstract: Association of acetaminophen hepatotoxicity with fasting and ethanol use, December 21, 1994, Whitcomb and Block 272 (23): 1845
		hepatotoxicity after an overdose appears to be enhanced by fasting in
		Paracetamol hepatotoxicity and alcohol consumption in deliberate and accidental overdose
	jama.ama-assn.org /cgi/content/abstract/272/23/1845 (381 words)

	Severe hepatotoxicity uncommon with combination antiretroviral treatment (Site not responding. Last check: 2007-10-21)
		Hepatic drug toxicity occurs with all classes of antiretrovirals, the authors explain, but the factors associated with severe hepatotoxicity during ART have yet to be defined.
		According to the results, patients who developed severe hepatotoxicity were more often male; had intravenous drug use as a risk factor for HIV infection; were younger; were more often coinfected with hepatitis C, B, or D virus; and had higher baseline ALT and bilirubin levels and prolonged PT.
		All but 1 of 26 patients with severe hepatotoxicity were reactive for anti-HCV and HCV RNA, the researchers note, and 5 patients also had HBsAg or anti-HDV IgM.
	www.aidsmeds.com /news/20030404clin004.html (554 words)

	eMedicine - Isoniazid Hepatotoxicity : Article by Richard A Weisiger, MD
		Isoniazid hepatotoxicity is a common complication of antituberculosis therapy that ranges in severity from asymptomatic elevation of serum transaminases to hepatic failure requiring liver transplantation.
		While the most common presentation of isoniazid hepatotoxicity is hepatocellular damage, patients occasionally may present with true drug hypersensitivity characterized by skin rash, fever, and eosinophilia.
		Isoniazid hepatotoxicity is more common in females than males, especially the more severe forms of hepatitis leading to liver failure and death.
	www.emedicine.com /med/topic1193.htm (3207 words)

	Progress in Transplantation: Hepatotoxicity of herbal remedies: an emerging dilemma
		The purpose of this article is to review the regulation of herbal remedies, examples of drug-induced hepatotoxicity, diagnosis of herbal hepatotoxicity, and examples of hepatotoxicities related to herbal remedies, and to discuss strategies to prevent herbal hepatotoxicity from further increasing the healthcare burden.
		Although troglitazone was considered a breakthrough drug for diabetes and many diabetic patients derived benefits from it, the manufacturer of troglitazone could not justify the risk over benefit and, ultimately, the FDA stepped in to withdraw this drug from the market.
		Herbal-induced hepatotoxicity is difficult to diagnose because all other causes of liver disease must first be ruled out.
	www.findarticles.com /p/articles/mi_qa4117/is_200406/ai_n9423693 (1002 words)

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