Evaluation of paracetamol-induced damage in liver biopsies

Lesna, M.; Watson, Alexander; Douglas, A.G.; Hamlyn, A.N.; James, Oliver

doi:10.1007/bf00445778

Cited by 27 publications

(11 citation statements)

References 12 publications

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“…The pathological investigation revealed marked microvesicular and macrovesicular fatty change as well as necrosis and hemorrhage preferentially localized in the pericentral area [19] and also showed infiltration of lymphocytes and inflammatory changes in the periportal area. From these findings, liver damage induced by toluene is considered to be the result of a direct cytotoxic effect [21]. One experimental animal study showed that exposure to toluene at concentrations of 533-800 ppm for 7 days increased liver weights, and electron microscopical examination revealed ultrastructural changes that were compatible with changes in cytochrome P-450 concentrations [22].…”

Section: Discussionmentioning

confidence: 98%

A fatal case of acute hepatitis B developed in a toluene abuser

Kato

Monma-Ohtaki

Nakamura

et al. 2008

Clin J Gastroenterol

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Liver dysfunction involving toluene intoxicity includes elevation of transaminase level and delayed complications of liver failure, but its effect on hepatitis B virus (HBV) infection is as yet unknown. Here, we report a case of fulminant hepatitis B developed in a toluene abuser. A 23-year-old female toluene abuser was admitted to a local clinic because of nausea, vomiting, and dizziness, and a mild elevation of serum transaminase level was identified. She was treated as an outpatient, but continued toluene inhalation during follow-up. Five days later, she was found in a drowsy state of consciousness and taken to the emergency unit of our institution. Laboratory findings showed an alanine aminotransferase level of 4,659 IU, a remarkably prolonged prothrombin time, and she was diagnosed with fulminant hepatitis B. Intensive care was carried out, but she died the next day. Molecular analysis revealed that the HBV isolate was classified as genotype C, and nucleotide positions that are prone to fulminant hepatitis were A at 1,762 and G at 1,764 in the core promoter region, and G at 1,896 in codon 28 in the precore region. The long-term toluene inhalation could have contributed to drastic clinical course of acute hepatitis B in this patient.

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Section: Discussionmentioning

confidence: 98%

A fatal case of acute hepatitis B developed in a toluene abuser

Kato

Monma-Ohtaki

Nakamura

et al. 2008

Clin J Gastroenterol

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“…Fourteen patients (1-14) had uninformative profiles. Three patients (15)(16)(17) showed marked elevation of free carnitine. Ten patients (18 -27) had elevated concentrations of medium-or long-chain species.…”

Section: Discussionmentioning

confidence: 99%

“…14 Microvesicular steatosis is a common although not universal finding in FAO defects, but it is distinctly uncommon in acetaminophen toxicity. 14,17,18 Interestingly, in one of the few other reported cases of steatosis in acetaminophen toxicity, the outcome was unexpectedly fatal. 18 A third alternative is that these patterns in bile are markers of a specific type of liver injury possibly related to an unknown toxin.…”

Section: Discussionmentioning

confidence: 99%

Abnormal concentrations of esterified carnitine in bile

et al. 2005

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The etiology of acute liver failure in children is unknown in a large number of cases. Defects in fatty acid oxidation have been shown to lead to severe liver injury. This retrospective analysis examined the bile acylcarnitine profiles of 27 children with acute liver failure who underwent liver transplantation or died. Results were compared with 758 postmortem samples from individuals without acute liver failure. Cumulative amounts of free carnitine, medium-or long-chain species in excess of the 95th percentile of the control group were considered abnormal. Fourteen samples had normal profiles. Three had markedly elevated concentrations of free carnitine, whereas ten showed elevations in medium-or long-chain species. The relative risk of death was 2.86 (95% confidence interval, 1.08-7.54, P ‫؍‬ .01) in the 10 children with elevated concentrations of medium-or long-chain species compared with those with normal analyses. Overall, medium-and long-chain acylcarnitines were increased in those patients who died compared with survivors, (dead vs. alive; medium-chain, 187 ؎ 74 vs. 32 ؎ 12 mol/L, P ‫؍‬ .008; long-chain, 146 ؎ 74 vs. 15 ؎ 8 mol/L, mean ؎ standard error of the mean, P ‫؍‬ .018). These studies describe biliary free and esterified carnitine profiles in children with acute liver failure. In conclusion, the findings raise the hypothesis that abnormalities in fatty acid oxidation may predispose to a worse outcome in acute liver failure. A cute liver failure (ALF) in children is a clinical syndrome consisting of biochemical evidence of severe hepatic synthetic dysfunction with or without encephalopathy. 1 In most circumstances, the etiology cannot be discerned. Well-characterized causes of ALF in children include acetaminophen toxicity, hepatitis A, hepatitis B, drug toxicity, autoimmune hepatitis, Wilson disease, and a range of rare metabolic diseases. Abnormalities in fatty acid metabolism have been associated with ALF in children.Fatty acid oxidation (FAO) plays a major role in energy production during periods of fasting. More than 25 enzymes and transporters are involved in this pathway. 2 Inherited FAO disorders represent a new and rapidly expanding class of metabolic diseases. 3,4 More than 20 FAO disorders have been described to date and present with a variety of clinical manifestations, including metabolic decompensation during fasting, hypoketotic hypoglycemia, abnormal function of fatty acid-dependent tissues, particularly liver and heart, and sudden and unexpected death. Several FAO disorders are described that present with Reye-like episodes or severe liver disease as the predominant clinical feature. Carnitine palmitoyltransferase I deficiency and medium-chain acyl-coenzyme A dehydrogenase deficiency may present with hepatomegaly, abnormal aminotransferases, steatosis, and encephalopathy. The clinical picture is not typically one of acute liver failure, although the encephalopathy is reminiscent of Reye's syndrome.

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“…Hepatocyte regeneration is seen as early as 4 days after acetaminophen overdose. 10 These cases differ from other cases of MHN because the inflammatory cell component is usually mild or nonexistent initially. 11 Inflammation increases later, with a longer overdose to tissue sampling interval as regeneration begins.…”

Section: Histopathology Of Massive Hepatic Necrosismentioning

confidence: 95%

The Histopathology of Regeneration in Massive Hepatic Necrosis

Craig

Quaglia²,

Selden³

et al. 2004

Semin Liver Dis

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Massive hepatic necrosis (MHN) is a condition that offers an opportunity to study the remarkable ability of the liver to become repopulated with hepatocytes. A maximal regenerative stimulus is expected in cases of MHN (Roskams et al. APMIS Suppl 1991;23:32-39). Sequential chronological observations, after a severe degree of liver cell loss, permit study of the human equivalent of the situation in animal models in which circulating and bone marrow-derived stem and liver progenitor cells are recruited to the hepatopoietic process. To date, the bone marrow and circulating precursors have not been identified morphologically in human material. We present data that suggest that the circulating liver progenitor could have a lymphoblastoid morphological appearance. Similar cells are seen among the cellular infiltrate of MHN. We have found that combinations of markers, such as CD117/CD133 positive CD45/tryptase negative are useful to isolate these cells using cell-sorting technology. This may facilitate their expansion in vitro and the development of their use for therapeutic purposes. In MHN, the residual portal tracts and ductular reaction with the associated lymphoid infiltrate (some of which are probably liver cell progenitors derived from the circulation) constitute the fundamental regenerative community unit in which hepatopoiesis takes place. Defining the hepatopoietic process is hindered by the lack of morphological transitional forms in the period between the progenitors within the circulation and when they assume recognizable hepatocytic form as "metaplastic" hepatocytes associated with the ductular reaction. By achieving a better comprehension of these processes of liver cell restoration, we will be better placed to accelerate liver recovery in MHN, for example by the administration of granulocyte colony stimulating factor (GCSF). Thus, more patients will be able to restore their own livers and avoid liver transplantation.

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Evaluation of paracetamol-induced damage in liver biopsies

Cited by 27 publications

References 12 publications

A fatal case of acute hepatitis B developed in a toluene abuser

A fatal case of acute hepatitis B developed in a toluene abuser

Abnormal concentrations of esterified carnitine in bile

The Histopathology of Regeneration in Massive Hepatic Necrosis

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