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

Abstract

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.

Distribution and Quantitation of Skin Iron in Primary Haemochromatosis: Correlation with Total Body Iron Stores in Patients Undergoing Phlebotomy

“…Genotype may contribute to iron overload with variable penetrance and phenotypic expression may be influenced by cofactors (8,(28)(29)(30) and other additive individual factors (1,5,28). It is therefore reasonable to observe a lack of significance in the correlation between iron blood indicators and body stores, such as skin and liver over a long time-period.…”

“…It is therefore reasonable to observe a lack of significance in the correlation between iron blood indicators and body stores, such as skin and liver over a long time-period. This raises the possibility that, in some cases, there is a differential cellular iron handling, which results in variable accumulation of iron (5,6,8,15,(28)(29)(30).…”

Iron, Oxidative Stress and Health

“…Simple steatosis is usually considered benign, but the development of NASH is recognized as a precursor of more severe liver disease, and in some cases, cirrhosis and hepatocellular carcinoma (Machado et al, 2009). Machado et al, (2009) reported that pathogenesis of NASH can be explained by the "two-hit" hypothesis, (a) insulin resistance and the resultant steatosis being the "first hit". Hyperinsulinemia, increased peripheral lipolysis and reduced -oxidation lead to fat accumulation (b) the "second hit"-increased ROS/RNS.…”

Hfe Mutations and Iron Overload in Patients With Alcoholic Liver Disease

“…Moreover, serum ferritin levels are higher in ALD patients than in non-alcoholic patients with other chronic liver diseases, such as autoimmune disorders or chronic hepatitis C virus (HCV) infection. Interestingly, upon alcohol withdrawal, the increased serum ferritin levels have been shown to rapidly decrease (2,24) . Alcohol consumption has been implicated as the main cause of increased serum ferritin levels in the general population (17,24) .…”

“…Interestingly, upon alcohol withdrawal, the increased serum ferritin levels have been shown to rapidly decrease (2,24) . Alcohol consumption has been implicated as the main cause of increased serum ferritin levels in the general population (17,24) . The apparent sensitivity of this pathological process was further indicated by a study showing that even moderate alcohol ingestion can affect iron metabolism (18) .…”