Hepatic iron overload in alcoholic end‐stage liver disease is associated with iron deposition in other organs in the absence of HFE‐1 hemochromatosis

Eng, Sue C.; Taylor, Scott L.; Reyes, Victoria; Raaka, Stuart; Berger, Jose; Kowdley, Kris V.

doi:10.1111/j.1478-3231.2005.01004.x

Cited by 30 publications

(15 citation statements)

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“…Mallory-Denk hyaline bodies, megamitochondria, perisinusoidal fibrosis, mild iron deposits, some degree of ductular reaction (also described as cholangiolar proliferation corresponding to proliferation of hepatic progenitors[6]), and intraparenchymal cholestasis are also described[7,8] but not required for diagnosis. Equivalent terms used for intraparenchymal cholestasis include bile pigments accumulation, bilirubinostasis, intralobular cholestasis or cholestatic alcoholic hepatitis[6,7,9].…”

Section: Introductionmentioning

confidence: 99%

Early liver biopsy, intraparenchymal cholestasis, and prognosis in patients with alcoholic steatohepatitis

et al. 2011

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BackgroundAlcoholic steatohepatitis (ASH) is a serious complication of alcoholic liver disease. The diagnosis of ASH requires the association of steatosis, evidence of hepatocellular injury with ballooning degeneration, and polynuclear neutrophil infiltration on liver biopsy. Whether these lesions, in addition to other histological features observed in liver tissue specimens, have prognostic significance is unclear.MethodsWe studied 163 patients (age 55 yrs [35-78], male/female 102/61) with recent, heavy (> 80 gr/day) alcohol intake, histologically-proven ASH (97% with underlying cirrhosis, Maddrey's score 39 [13-200], no sepsis), who had a liver biopsy performed 3 days [0-10] after hospital admission for clinical decompensation. A semi-quantitative evaluation of steatosis, hepatocellular damage, neutrophilic infiltration, periportal ductular reaction, intraparenchymal cholestasis, and iron deposits was performed by two pathologists. All patients with a Maddrey's score ≥ 32 received steroids. The outcome at 3 months was determined. Statistical analysis was performed using the Wilcoxon and Fisher's exact tests, Kaplan-Meier method, and the Cox proportional hazard model.Results43 patients died after 31 days [5-85] following biopsy. The 3-month survival rate was 74%. Mean kappa value for histological assessment by the two pathologists was excellent (0.92). Univariate analysis identified age, the Maddrey's score, the Pugh's score, the MELD score and parenchymal cholestasis, but not other histological features, as factors associated with 3-month mortality. At multivariate analysis, age (p = 0.029, OR 2.83 [1.11-7.2], intraparenchymal cholestasis (p = 0.001, OR 3.9 [1.96-7.8], and the Maddrey's score (p = 0.027, OR 3.93 [1.17-13.23] were independent predictors of outcome. Intraparenchymal cholestasis was more frequent in non survivors compared to survivors (70% versus 25%, p < 0.001). Serum bilirubin was higher in patients with severe compared to those with no or mild intraparenchymal cholestasis (238 [27-636] versus 69 [22-640] umol/l, p < 0.001).ConclusionsIn this large cohort of patients with histologically documented ASH early after admission and no sepsis, liver biopsy identified marked intraparenchymal cholestasis as an independent predictor of poor short term outcome together with age and the Maddrey's score. It may be hypothesized that incorporation of this particular variable into existing disease severity scores for ASH would improve their performance.

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Section: Introductionmentioning

confidence: 99%

Early liver biopsy, intraparenchymal cholestasis, and prognosis in patients with alcoholic steatohepatitis

et al. 2011

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“…The gradual accumulation of iron can severely affect most of body's organs, but especially the liver, pancreas and heart (Eng, Taylor, Reyes, Raaka, Berger, & Kowdley, 2005). The excess of iron in the liver can cause an enlarged liver, liver failure, liver cancer, or cirrhosis.…”

Section: The Studied Diseasesmentioning

confidence: 99%

Motivation to perform presymptomatic testing in portuguese subjects at-risk for late-onset genetic diseases

Leite¹,

Denis²,

Sequeiros³

et al. 2017

Interd

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resUMenEl papel del psicólogo clínico en el contexto del consejo genético incluye brindar apoyo a los sujetos en riesgo en el proceso de toma de decisiones, independientemente de la decisión adoptada por el sujeto (conociendo o no el resultado de las pruebas genéticas).El estudio que se informa aborda la motivación para realizar las pruebas pre-sintomáticas (PPS) de sujetos en situación de riesgo para tres enfermedades: polineuropatía amiloide familiar (PAF), la enfermedad de Huntington (EH) y la enfermedad de Machado-Joseph (EMJ) y comparar con la motivación para realizar las PPS para hemocromatosis (HH).La muestra consistió en 213 sujetos portugueses que tenían riesgo genético para contraer las tres enfermedades y 31 sujetos en situación de ries go genético para contraer hemocromatosis. Ellos fueron evaluados con una entrevista para ob tener datos sociodemográficos y debían responder a una pregunta sobre la motivación para llevar a cabo las pruebas pre-sintomáticas.Se obtuvieron siete categorías principales y las las siguientes son las más significativas para PAF, EH y EMJ: razones relacionadas con el futuro, razones relacionadas con los demás y razones relacionadas con la curiosidad y la necesidad de conocer. Para hemocromatosis, las más importantes resultaron ser razones relacionadas con los demás y las relacionadas con las características de la enfermedad.La motivación para realizar el test pre-sintomático (PST) de la PAF, EH y EMJ es externa y sin relación con la enfermedad, mientras que la motivación de los sujetos en situación de riesgo para la HH está relacionada con la enfermedad. Las razones relacionadas con los demás es una motivación común en ambos grupos. A los sujetos también les preocupa la posibilidad de transmitir la enfermedad a sus hijos.Palabras clave: Pruebas pre-sintomáticas (PPS); Enfermedad genética; Sujetos en situación de riesgo; Polineuropatía amiloide familiar (PAF) TTR V30M; Enfermedad de Huntington (EH); Enfermedad de Machado-Joseph (EMJ). aBstraCtThe role of the clinical psychologist in the context of genetic counseling includes support for the process of decision-making for subjects at-risk, regardless of the decision that was made. For this,

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“…However, one report suggests that iron overload secondary to end-stage liver disease may result in the deposition of iron in other organs including the central nervous system, and this in the absence of hemochromatosis (Eng et al 2005). Clearly, further studies of the possible role of iron in the pathogenesis of neuronal injury and neurodegeneration in Wilson's Disease are warranted.…”

Section: Wilson's Diseasementioning

confidence: 96%

Metal Toxicity, Liver Disease and Neurodegeneration

Butterworth

2010

Neurotox Res

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Hepatocerebral disorders are serious neuropsychiatric conditions that result from liver failure. These disorders are characterized neuropathologically by varying degrees of neuronal cell death in basal ganglia, cerebellum, and spinal cord, and include clinical entities such as Wilson's Disease, post-shunt myelopathy, hepatic encephalopathy, and acquired non-Wilsonian hepatocerebral degeneration. Morphologic changes to astrocytes (Alzheimer type II astrocytosis) are a major feature of hepatocerebral disorders. Neurological symptoms include Parkinsonism, cognitive dysfunction, and ataxia. Pathophysiologic mechanisms responsible for cerebral dysfunction and neuronal cell death in hepatocerebral disorders include ammonia toxicity and neurotoxic effects of metals such as copper, manganese, and iron. Molecular mechanisms of neurotoxicity include oxidative/nitrosative stress, glutamate (NMDA)-receptor-mediated excitotoxicity, and neuroinflammatory mechanisms. However, neuronal cell death in hepatocerebral disorders is limited by adaptive mechanisms that may include NMDA-receptor down-regulation, the synthesis of neuroprotective steroids and hypothermia. Management and treatment of hepatocerebral disorders include chelation therapy (Wilson's Disease), the use of ammonia-lowering agents (lactulose, antibiotics, ornithine aspartate) and liver transplantation.

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Hepatic iron overload in alcoholic end‐stage liver disease is associated with iron deposition in other organs in the absence of HFE‐1 hemochromatosis

Abstract: Iron overload secondary to end-stage liver disease can be associated with iron deposition in other organs in the absence of HFE-1 HHC.

Cited by 30 publications

References 30 publications

Early liver biopsy, intraparenchymal cholestasis, and prognosis in patients with alcoholic steatohepatitis

Early liver biopsy, intraparenchymal cholestasis, and prognosis in patients with alcoholic steatohepatitis

Motivation to perform presymptomatic testing in portuguese subjects at-risk for late-onset genetic diseases

Metal Toxicity, Liver Disease and Neurodegeneration

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