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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The quantitative determination of hydrocarbons exhaled by animals as an in vivo index of extensive lipid peroxidation is described. Advantages and limitations of this method are discussed. Acetaminophen-induced hepatic lipid peroxidation in mice is an example of oxidative stress, the extent of which is determined in vivo by the turnover of endoplasmic reticulum monooxygenase and the cofactor, e.g. glutathione status of the liver. In microsomal suspensions, none of the assay methods for lipid peroxidation identifies acetaminophen as a prooxidant. Rather, it acts like an antioxidant. The obvious limitations of in vitro experiments are emphasized. Cytosolic metabolism of allyl alcohol also leads, in a dose-dependent manner, to extensive lipid peroxidation. Evidence is presented that release of iron from intracellular stores following overproduction of NADH may be the primary cause of this lesion. The term reductive stress is suggested for this metabolic initiation of iron redox cycling. In experimental hepatitis induced by galactosamine/endotoxin, a leukotriene-mediated pathomechanism, no signs of lipid peroxidation are detectable. This means that ethane or pentane formation are definitively not late consequences of membrane deterioration but rather early causal events in special cases of hepatotoxicity.
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PMID:Measurement of in vivo lipid peroxidation and toxicological significance. 331 1

Serious hepatotoxicity is uncommon with the proper therapeutic use of non-narcotic analgesics but experience with new non-steroidal anti-inflammatory drugs (NSAIDs) is limited. Drugs such as ibufenac, fenclofenac and benoxaprofen were withdrawn from the market because of hepatotoxicity, and liver damage has been reported on occasion with virtually all non-narcotic analgesics. However, a clear pattern of toxicity with characteristic clinical, biochemical and histopathological abnormalities has emerged with relatively few. With the exception of acute hepatic necrosis following overdosage of paracetamol, little is known of the mechanisms of liver injury induced by non-narcotic analgesics. Involvement of the liver in a generalised drug reaction does not imply specific hepatotoxicity. About 50% of patients given aspirin regularly in anti-inflammatory doses develop mild, dose-dependent reversible liver damage as shown by elevation of the plasma aminotransferase activity. Liver damage is more severe in a small minority and it may rarely be complicated by disseminated intravascular coagulation and encephalopathy with a fatal outcome. There have also been isolated reports of chronic active hepatitis associated with the use of salicylates. Salicylate hepatitis has been reported most often in young females with connective tissue diseases. Many patients with Reye's syndrome have been given aspirin during the prodromal phase, and this serious condition closely resembles subacute salicylate intoxication in children. Salicylate probably has a causal or contributory role in Reye's syndrome, but many refuse to accept this and the issue is the subject of heated debate. Paracetamol in overdosage causes acute hepatic necrosis, and liver damage has been attributed to its therapeutic use. However, most reports have involved chronic alcoholics who took excessive doses and in these patients the clinical, biochemical and pathological findings were typical of paracetamol overdosage. Many authors have failed to make the distinction between therapeutic use and a therapeutic dose. In other cases liver damage could have been caused by exposure to other agents, viral infection or naturally occurring liver disease. If these cases are excluded, there are very few reports of liver damage associated with the proper therapeutic use of paracetamol. In some cases, the picture resembled chronic active hepatitis but no causal relationship has been established between this condition and paracetamol use. Paracetamol does not cause deterioration in liver function in patients with chronic liver disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of non-narcotic analgesics on the liver. 355 80

Results concerning morphological and biochemical changes following intravenous administration of different doses of acetaminophen in dogs are reported. Acetaminophen infusion, as a parenteral solution (500 mg per kg per 90 min), produced fulminant hepatitis characterized by a good correlation between Portmann's grade of lesion and percentage of necrosis. All animals died within 76 hr after intoxication. Analysis of biochemical parameters revealed positive correlation between serum bilirubin levels and severity of the hepatic lesion. The experimental model of acetaminophen-induced hepatotoxicity is proposed as a model for evaluation of the therapeutic efficacy of new medical and surgical procedures.
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PMID:Acetaminophen-induced fulminant hepatic failure in dogs. 401 40

We report the case of a child who had deterioration of hepatic function 3 days after suffering a depressed compound skull fracture with underlying brain contusion. An abdominal enhanced CT scan revealed a wedge-shaped region of devitalised liver with associated free intraperitoneal fluid, consistent with a traumatic lesion but due to necrosis secondary to acetaminophen toxicity. Acetaminophen toxicity may occur with therapeutic doses in the presence of an ischaemic hepatitis. Any delay in the performance of CT from the time of trauma should prompt the consideration of alternative diagnoses.
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PMID:Hepatic necrosis masquerading as trauma. 899 77

We report 2 fatal cases of the acetaminophen-alcohol syndrome and review 51 reported cases in the medical literature. The MEDLINE database from January 1966 to December 1995 and bibliographies of selected articles were used to obtain the case reports. Inclusion criteria were a clear history of alcohol use, a history of acetaminophen use and/or an elevated serum acetaminophen level, peak aspartate aminotransferase (AST) greater than 800 U/L, and exclusion of other causes of hepatotoxicity by negative hepatitis serologies and/or a liver biopsy showing typical findings of acetaminophen toxicity. Demographic characteristics, clinical features, treatment, and outcome were extracted from reports meeting inclusion criteria and our own 2 cases. This syndrome affected relatively young, frequently healthy patients. Acetaminophen was invariably taken for nonsuicidal intent. The mortality rate was 32%. A typical laboratory picture was defined, characterized by an extraordinarily high AST level. Treatment with N-acetylcysteine was not effective due to delayed presentation and diagnosis. Patients who use alcohol and health care providers should be educated about this potentially fatal syndrome. Prevention is the key to reducing its occurrence.
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PMID:Enhanced hepatotoxicity of acetaminophen in the alcoholic patient. Two case reports and a review of the literature. 919 53

Little information is available on acute liver failure (ALF) in the United States. We gathered demographic data retrospectively for a 2-year period from July 1994 to June 1996 on all cases of ALF from 13 hospitals (12 liver transplant centers). Data on the patients included age, hepatic coma grade on admission, presumed cause, transplantation, and outcome. Among 295 patients, 74 (25%) survived spontaneously, 121 (41%) underwent transplantation, and 99 (34%) died without undergoing transplantation. Ninety-two of 121 patients (76%) survived 1 year after transplantation. Acetaminophen overdose was the most frequent cause (60 patients; 20%), followed by cryptogenic/non A non B non C (NANBNC; 15%), idiosyncratic drug reactions (12%), hepatitis B (10%), and hepatitis A (7%). Spontaneous survival rates were highest for patients with acetaminophen overdose (57%) and hepatitis A (40%) and lowest for those with Wilson's disease (no survivors of 18 patients). The transplantation rate was highest for Wilson's disease (17 of 18 patients; 94%) and lowest for autoimmune hepatitis (29%) and acetaminophen overdose (12%). Age did not differ between survivors and nonsurvivors, perhaps reflecting a selection bias for patients transferred to liver transplant centers. Coma grade on admission was not a significant determinant of outcome, but showed a trend toward affecting both survival and transplantation rate. These findings on retrospectively studied patients from the United States differ from those previously gathered in the United Kingdom and France, highlighting the need for further study of trends in each country.
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PMID:Etiology and outcome for 295 patients with acute liver failure in the United States. 987 98

We reported on an adolescent who suffered from cholestatic hepatitis after taking a low dose of paracetamol. It was suspected that the condition was brought about by an allergic reaction to paracetamol. Paracetamol is one of the representative intrinsic hepatotoxic drugs. There have been only a few reports on liver damage due to an allergic reaction to paracetamol. There is a need to call attention to this particular reaction.
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PMID:Acute cholestatic hepatitis caused by a probable allergic reaction to paracetamol in an adolescent. 1131 74

The causal relationship between the inhibition of antibody production and liver injury induced by single doses of acetaminophen (APAP) was investigated in mice. The liver injury and antibody production were evaluated using the serum transaminase activity and the number of antibody forming cells against sheep red blood cells (SRBC), respectively. The relevance of APAP hepatotoxicity with inhibiting antibody production was elucidated in fasted and fed mice treated with a single oral administration of APAP. In fasted mice, the oral administration of APAP produced serious liver injury, while it was not the case in the fed mice. As the antibody production was measured under these conditions, APAP significantly depressed the antibody production in fed mice as well as in fasted mice. The rate of B220 positive cells in the splenocytes was significantly decreased by APAP administration in both the fasted and fed mice. Splenocytes proliferative responses following mitogenic stimulation with concanavalin A or lipopolysaccharide were inhibited by APAP. Moreover, APAP added directly to the splenocyte culture also inhibited the in vitro antibody-producing response to SRBC. These findings indicate that the APAP-induced depression of antibody production may not be a secondary response to APAP-hepatitis, but may be a primary response to APAP.
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PMID:Inhibition of the antibody production by acetaminophen independent of liver injury in mice. 1185 66

When a patient with acetaminophen overdose arrives in the emergency room more than 14 hours after ingestion, the value of N-acetylcysteine is unproven and patient mortality is at least 10%. Anecdotal case reports have indicated benefit of extracorporeal detoxification of these late-arriving patients with acetaminophen overdose. We identified 10 patients with serious acetaminophen overdose, 8 that arrived in the emergency room 16 to 44 hours after acetaminophen overdose with plasma levels predicting severe hepatic toxicity, and 2 that arrived in the emergency room 8 to 12 hours after overdose but with exceedingly high levels. All patients developed severe hepatitis (mean peak alanine aminotransferase, 4,052; mean peak protime, 25 seconds). At 16 to 68 hours after overdose, the patients were treated for 4 to 6 hours with the Liver Dialysis System (Hemocleanse Inc, W. Lafayette, IN), a single-access hemodiabsorption system indicated for treatment of serious drug overdose and for treatment of hepatic encephalopathy. Acetaminophen levels fell an average of 73% during treatment. Treatment was repeated 24 or 48 hours later if acetaminophen was still measurable in plasma. All 10 patients recovered intrinsic liver function and general health, with liver enzymes starting to normalize 24 hours after treatment, and were discharged 3 to 7 days after overdose. No patient required liver transplant. Because market introduction of Liver Dialysis, there have been 40 more patients with acetaminophen-induced hepatotoxicity treated with Liver Dialysis. All have recovered liver function without long-term sequelae. Though most of these patients with already established hepatic toxicity from acetaminophen would recover without extracorporeal blood therapy, treatment with the Liver Dialysis System should assure recovery from acute hepatic failure, and may shorten the clinical course of the illness.
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PMID:Treatment of acetaminophen-induced hepatitis and fulminant hepatic failure with extracorporeal sorbent-based devices. 1192 6

Acetaminophen is one of the most frequently used medications in the United States. While usual dosing of acetaminophen is considered harmless, both acute and chronic overdoses can be fatal. The majority of reported cases of chronic acetaminophen toxicity in adults occur in chronic alcohol abusers, patients taking P450-inducing medications, or following massive dosing. We describe a case of toxic hepatitis free of the aforementioned risk factors associated with chronic ingestion of moderately excessive doses of acetaminophen. Our patient ingested approximately 5.0 to 6.5 g of acetaminophen daily for 6 to 8 weeks via multiple medications. The inclusion of acetaminophen in numerous medications combined with the frequency of use of acetaminophen necessitates an increased concern for not only acute but also chronic acetaminophen toxicity.
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PMID:Chronic acetaminophen toxicity: a case report and review of the literature. 1465 97


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