Prevalence of the hemochromatosis gene mutation in patients with nonalcoholic steatohepatitis and correlation with degree of liver fibrosis

Zamin, Idilio; Mattos, Ângelo Alves de; Mattos, Ângelo Zambam de; Migon, Eduardo; Bica, Cláudia Giuliano; Alexandre, Cláudio Osmar Pereira

doi:10.1590/s0004-28032006000300013

Cited by 14 publications

(22 citation statements)

References 36 publications

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“…Corroborating our results, the study by Zamin et al did not establish correlation between mutation of the C282Y and H63D gene (mutation involved in the genesis of hemochromatosis), in 20 patients with NASH. This reinforces the nonparticipation of Fe deposits in the physiopathology of NASH (23) .…”

Section: Discussionsupporting

confidence: 72%

Nonalcoholic Fatty Liver Disease in Severe Obese Patients, Subjected to Bariatric Surgery

Losekann

Weston

Carli

et al. 2013

Arq. Gastroenterol.

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-Context -Nonalcoholic fatty liver disease encompasses a spectrum of histopathological changes that range from simple steatosis to nonalcoholic steatohepatitis. Works suggest that iron (Fe) deposits in the liver are involved in the physiopathology of nonalcoholic steatohepatitis. Objective -The aim of this study was to determine the prevalence of simple steatosis and nonalcoholic steatohepatitis in patients with morbid obesity, subjected to bariatric surgery and to establish a correlation of the anatomopathological findings with the presence of liver fibrosis. Methods -A total of 250 liver biopsies were conducted in the transoperation of the surgeries. were moderate, and 6 (2.4%) cases were intense. Fibrosis was referred to in 108 (43.2%) biopsies, 95 of which (38%) were mild; 2 (0.8%) were moderate; 7 (2.8%) were intense, and cirrhosis was diagnosed in 4 (1.6%) cases. There was a correlation between the degree of steatosis and the level of inflammatory activity (r s = 0.460; P<0.001) and between the degree of this activity and the degree of fibrosis (r s = 0.583; P<0.001). Only 13 (5.2%) samples showed Fe deposits. Conclusion -There is a high prevalence of nonalcoholic steatohepatitis in these patients and a positive correlation of the degrees of nonalcoholic steatohepatitis with the intensity of fibrosis. The low prevalence of Fe deposits found makes it questionable that the presence of this ion has any participation in the physiopathogeny of nonalcoholic fatty liver disease. HEADINGS -Fatty Liver. Liver cirrhosis. Morbid obesity. Bariatric surgery. Iron metabolism disorders.

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Section: Discussionsupporting

confidence: 72%

Nonalcoholic Fatty Liver Disease in Severe Obese Patients, Subjected to Bariatric Surgery

Losekann

Weston

Carli

et al. 2013

Arq. Gastroenterol.

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“…We excluded 153 studies due to lack of data on the HFE genotypes in NAFLD participants; whose liver disease was not defined as NAFLD; or whose participants were reported included in separate reports. A total of 16 case-control studies [20, 21, 35–49] (Table 1) and 14 ‘case-only’ studies [50–63] (Table 2), or 2,610 cases and 7,298 controls were included for the current review.…”

Section: Resultsmentioning

confidence: 99%

“…Overall, twenty-two studies were originated in Europe, North America, or Australia [20, 21, 35, 37–40, 42–45, 47, 48, 50, 51, 54–60, 63], two studies in Brazil [49, 52] and Japan [61, 62], respectively and, one study each in Korea [36], Taiwan [41], India[53] and Turkey [46]. The quality of the reporting varied across the papers.…”

Section: Resultsmentioning

confidence: 99%

Hemochromatosis gene and nonalcoholic fatty liver disease: A systematic review and meta-analysis

Hernáez

Yeung

Clark

et al. 2011

Journal of Hepatology

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Background and aims Previous studies examining the relationship between the C282Y and H63D HFE mutations and presence of nonalcoholic fatty liver disease (NAFLD) have yielded conflicting results. The goal of this study was to systematically evaluate and summarize data on the association between these two variants and the presence of NAFLD. Methods The authors searched EMBASE and PUBMED from August 1, 1996 to August 12, 2010. Two investigators independently conducted data abstraction. Ethnic specific weighted prevalence was calculated, and pooled odds ratios were estimated using random effects model. Results From 2,542 references, the authors included 16 case-control studies and 14 case-only studies, or 2,610 cases and 7,298 controls. The majority of the studies came from Caucasian populations (2,287 cases and 4,275 controls). The weighted prevalence of HFE mutations in cases was comparable to controls. The meta-analysis was restricted to Caucasians only because the small sample size of non Caucasian participants. The pooled odds ratio for the presence of any HFE genetic variant in cases was 1.03 (95% CI: 0.90, 1.17; I2: 65.8%, 95% CI: 38.5, 81.0). The presence of other genotypes, and secondary analyses yielded similar non significant findings. Conclusion Our systematic review does not support an association between the HFE genetic variants and the presence of NAFLD.

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“…It is likely that similar differences (in either lipidomic profiles or dietary fat composition) may influence effects of iron overload in humans, and may partly explain the somewhat mixed results of clinical studies. Hemochromatosis gene mutations have been either associated with increased severity [14,15,35,36] or found to be unrelated [37,38] to NASH. Stainable liver iron or serum transferrin were associated with NASH severity in some [16,35,39] but not all [37,40,41] studies.…”

Section: Discussionmentioning

confidence: 99%

Iron Overload Causes Oxidative Stress and Impaired Insulin Signaling in AML-12 Hepatocytes

2013

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Background Iron overload is associated with increased severity of nonalcoholic fatty liver disease (NAFLD) including progression to nonalcoholic steatohepatitis and hepatocellular carcinoma. Aims To identify potential role(s) of iron in NAFLD, we measured its effects on pathways of oxidative stress and insulin signaling in AML-12 mouse hepatocytes. Methods Rapid iron overload was induced with 50 μM ferric ammonium citrate and 8-hydroxyquinoline. Insulin response was measured by western blot of phospho-protein kinase B. Lipid content was determined by staining with oil red O. Reactive oxygen species (ROS) were measured by flow cytometry using 5-( -6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate. Oxidative stress was measured by western blots for phospho-jnk and phospho-p38. Results Iron increased ROS (p<0.001) and oxidative stress (p<0.001), and decreased insulin signaling by 33% (p<0.001). Treatment with stearic or oleic acids (200 μM) increased cellular lipid content and differentially modulated effects of iron. Stearic acid potentiated iron-induced ROS levels by 2-fold (p<0.05) and further decreased insulin response 59% (p<0.05) vs. iron alone. In contrast, cells treated with oleic acid were protected against iron-mediated injury; ROS levels were decreased by half (p<0.01) vs. iron alone while insulin response was restored to control (untreated) levels. The anti-oxidant curcumin reduced effects of iron on insulin signaling, ROS, and oxidative stress (p<0.01). Curcumin was similarly effective in cells treated with both stearic acid and iron. Conclusions An in-vitro model of NAFLD progression is described in which iron-induced oxidative stress inhibits insulin signaling. Pathophysiological effects of iron were increased by saturated fat and decreased by curcumin.

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Prevalence of the hemochromatosis gene mutation in patients with nonalcoholic steatohepatitis and correlation with degree of liver fibrosis

Cited by 14 publications

References 36 publications

Nonalcoholic Fatty Liver Disease in Severe Obese Patients, Subjected to Bariatric Surgery

Nonalcoholic Fatty Liver Disease in Severe Obese Patients, Subjected to Bariatric Surgery

Hemochromatosis gene and nonalcoholic fatty liver disease: A systematic review and meta-analysis

Iron Overload Causes Oxidative Stress and Impaired Insulin Signaling in AML-12 Hepatocytes

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