Iron as a co-morbid factor in nonhemochromatotic liver disease

Bonkovsky, Herbert L.; Lambrecht, Richard W.; Shan, Ying

doi:10.1016/s0741-8329(03)00127-7

Cited by 91 publications

(68 citation statements)

References 62 publications

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“…Excess hepatic iron can act as a pathogenic factor in several liver diseases, presumably through catalyzing hydroxyl radical production. 21,42,43 NASH/NAFLD has been thought to be one of the diseases that are aggravated by excess hepatic iron. 4,7,31 Oxidative tissue injury caused by excess iron may induce and augment lipid peroxidation and consequent liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: Impact on disease progression

Ikura¹,

Ohsawa²,

Suekane³

et al. 2006

Hepatology

126

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Nonalcoholic steatohepatitis/nonalcoholic fatty liver disease is considered to be a hepatic manifestation of various metabolic disorders. However, its precise pathogenic mechanism is obscure. Oxidative stress and consequent lipid peroxidation seem to play a pivotal role in disease progression. In this study, we analyzed the localization of oxidized phosphatidylcholine (oxPC), a lipid peroxide that serves as a ligand for scavenger receptors, in livers of patients with this steatotic disorder. Specimens of nonalcoholic fatty liver disease (15 autopsy livers with simple steatosis and 32 biopsy livers with steatohepatitis) were examined via immunohistochemistry and immunoelectron microscopy using a specific antibody against oxPC. In addition, scavenger receptor expression, hepatocyte apoptosis, iron deposition, and inflammatory cell infiltration in the diseased livers were also assessed. Oxidized phosphatidylcholine was mainly localized to steatotic hepatocytes and some macrophages/Kupffer cells. A few degenerative or apoptotic hepatocytes were also positive for oxPC. Immunoelectron microscopy showed oxPC localized to cytoplasmic/intracytoplasmic membranes including lipid droplets. Steatotic livers showed enhanced expression of scavenger receptors. The number of oxPC cells was correlated with disease severity and the number of myeloperoxidasepositive neutrophils, but not with the degree of iron deposition. In conclusion, distinct localization of oxPC in liver tissues suggest that neutrophil myeloperoxidase-derived oxidative stress may be crucial in the formation of oxPC and the progression of steatotic liver disease. (HEPATOLOGY 2006;43:506-514.)

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Section: Discussionmentioning

confidence: 99%

Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: Impact on disease progression

Ikura¹,

Ohsawa²,

Suekane³

et al. 2006

Hepatology

126

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“…Iron is a source of oxidative stress and has been shown to be a cofactor for progression in some chronic liver diseases. 86 The relationship between iron and nonalcoholic fatty liver disease (NAFLD) is unclear. Many patients with insulin resistance have elevated serum ferritin, and some have mild to moderate hepatic siderosis in a mixed distribution.…”

Section: Is Steatosis a Co-factor In Other Liver Diseases?mentioning

confidence: 99%

Steatosis: Co-factor in other liver diseases

2005

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The prevalence of fatty liver is rising in association with the global increase in obesity and type 2 diabetes. In the past, simple steatosis was regarded as benign, but the presence of another liver disease may provide a synergistic combination of steatosis, cellular adaptation, and oxidative damage that aggravates liver injury. In this review, a major focus is on the role of steatosis as a co-factor in chronic hepatitis C (HCV), where the mechanisms promoting fibrosis and the effect of weight reduction in minimizing liver injury have been most widely studied. Steatosis, obesity, and associated metabolic factors may also modulate the response to alcohol-and drug-induced liver disease and may be risk factors for the development of hepatocellular cancer. The pathogenesis of injury in obesity-related fatty liver disease involves a number of pathways, which are currently under investigation. Enhanced oxidative stress, increased susceptibility to apoptosis, and a dysregulated response to cellular injury have been implicated, and other components of the metabolic syndrome such as hyperinsulinemia and hyperglycemia are likely to have a role. Fibrosis also may be increased as a by-product of altered hepatocyte regeneration and activation of bipotential hepatic progenitor cells. In conclusion, active management of obesity and a reduction in steatosis may improve liver injury and decrease the progression of fibrosis. (HEPATOLOGY 2005;42:5-13.)

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“…Alcohol may increase iron absorption and cellular iron uptake by several possible mechanisms: (1) increased absorption via a non-carrier-mediated paracellular route [3] ; (2) iron absorption is stimulated by anemia secondary to ineffective erythropoiesis due to alcohol-induced folic acid deficiency [4,5] ; and (3) alcohol consumption is associated with decrease in enterocyte turnover through mitosis inhibition [6] , which may reduce the already limited intestinal iron excretion. Recently, it has been shown that alcohol down-regulates hepcidin transcription, which leads to increased duodenal iron absorption via a divalent metal transporter-1 (with enhanced luminal import) and ferroportin protein expression (with enhanced basolateral translocation to the circulation) [7,8] .…”

Section: Introductionmentioning

confidence: 99%

Iron homeostasis and H63D mutations in alcoholics with and without liver disease

Machado¹,

Ravasco²,

Martins³

et al. 2009

WJG

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AIM:To evaluate the prevalence of HFE gene mutation and indices of disturbed iron homeostasis in alcoholics with and without liver disease. METHODS:One hundred and fifty-three heavy drinkers (defined as alcohol consumption > 80 g/d for at least 5 years) were included in the study. These comprised 78 patients with liver disease [liver disease alcoholics (LDA)] in whom the presence of liver disease was confirmed by liver biopsy or clinical evidence of hepatic decompensation, and 75 subjects with no evidence of liver disease, determined by normal liver tests on two occasions [non-liver disease alcoholics (NLDA)], were consecutively enrolled. Serum markers of iron status and HFE C282Y and H63D mutations were determined. HFE genotyping was compared with data obtained in healthy blood donors from the same geographical area. RESULTS:Gender ratio was similar in both study groups. LDA patients were older than NLDA patients (52 ± 10 years vs 48 ± 11 years, P = 0.03). One third and one fifth of the study population had serum transferrin saturation (TS) greater than 45% and 60% respectively. Serum iron levels were similar in both groups. However, LDA patients had higher TS (51 ± 27 vs 36 ± 13, P < 0.001) and ferritin levels (559 ± 607 ng/mL vs 159 ± 122 ng/mL, P < 0.001), and lower total iron binding capacity (TIBC) (241 ± 88 µg/dL vs 279 ± 40 µg/dL, P = 0.001). The odds ratio for having liver disease with TS greater than 45% was 2.20 (95% confidence interval (CI): 1.37-3.54). There was no difference in C282Y allelic frequency between the two groups. However, H63D was more frequent in LDA patients (0.25 vs 0.16, P = 0.03). LDA patients had a greater probability of carrying at least one HFE mutation than NLDA patients (49.5% vs 31.6%, P = 0.02). The odds ratio for LDA in patients with H63D mutation was 1.57 (95% CI: 1.02-2.40). CONCLUSION:The present study confirms the presence of iron overload in alcoholics, which was more severe in the subset of subjects with liver disease, in parallel with an increased frequency of H63D HFE mutation.

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Iron as a co-morbid factor in nonhemochromatotic liver disease

Cited by 91 publications

References 62 publications

Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: Impact on disease progression

Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: Impact on disease progression

Steatosis: Co-factor in other liver diseases

Iron homeostasis and H63D mutations in alcoholics with and without liver disease

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