Gastroenterology

Gastroenterology

Volume 116, Issue 1, January 1999, Pages 127-134
Gastroenterology

Liver, Pancreas, and Biliary Tract
The relation of iron status and hemochromatosis gene mutations in patients with chronic hepatitis C

https://doi.org/10.1016/S0016-5085(99)70236-2Get rights and content

Abstract

Background & Aims: Elevated hepatic iron concentration may affect the response to antiviral therapy in chronic hepatitis C. This study explored the contribution of genetic hemochromatosis to iron accumulation in chronic hepatitis C. Methods: HFE mutations (C282Y and H63D) were assessed in 184 patients with chronic hepatitis C virus and 487 controls. Liver biopsy specimens were available in 149 patients. Hepatic iron content was measured in 114 patients by atom-absorption spectrophotometry. Results: The C282Y and H63D allele frequencies were 7.06 and 11.6 in patients and 4.83 and 11.09 in controls, respectively. Eight patients were homozygotes (5 C282Y [2.7%] and 3 H63D [1.6%]), 2 compound heterozygotes (1%), and 49 heterozygotes (14 C282Y [7.6%] and 35 H63D [19%]). Biochemical evidence of iron overload was more common in patients with HFE mutations (28 of 47) than in those without (34 of 102; P = 0.0045). Histological iron grading and hepatic iron content overlapped among patients with or without mutations. A hepatic iron index of >1.9 was observed only in 1 of the 4 C282Y homozygotes and 1 of the 3 H63D homozygotes. Conclusions: HFE mutations contribute to but do not fully explain hepatic iron accumulation in chronic hepatitis C. Furthermore, C282Y or H63D homozygosity in chronic hepatitis C is not necessarily associated with a high hepatic iron content.

GASTROENTEROLOGY 1999;116:127-134

Section snippets

Patients

One hundred eighty-four consecutive patients with chronic HCV infection (127 men [69%] and 57 women [31%]; mean age, 48 years; age range, 20–78 years) were studied. Chronic hepatitis C was diagnosed on the basis of increased serum transaminase levels for longer than 6 months and detection of antibody to HCV (anti-HCV) and HCV RNA by polymerase chain reaction (PCR). Patients with secondary causes of iron elevation were excluded, including patients with ethanol consumption of >60 g/day. Before

Results

Table 1 shows the results of analysis for the C282Y and H63D mutations in 184 patients with chronic hepatitis C and in the control group.

. Distribution of HFE gene mutations in patients with chronic hepatitis C and in healthy controls

Mutation statusPatientsControls
C282Y/C282Y (%)5 (2.7)0
H63D/H63D (%)3 (1.6)6 (1.2)
C282Y/H63D (%)2 (1.0)8 (1.6)
C282Y/WT (%)14 (7.6)39 (8.0)
H63D/WT (%)35 (19.0)88 (18.1)
WT/WT (%)125 (67.9)346 (71.0)
Total184487

WT, wild-type.

Fifty-nine patients (32%) carried either

Discussion

The results of this study indicate that mutations of the HFE gene contribute in part to the increase of iron parameters in patients with chronic hepatitis C. About half of the patients with biochemical evidence of iron overload carried either of the two mutations associated with genetic hemochromatosis. Possible influences of HFE gene mutations in response to interferon therapy could not be evaluated because patients either did not receive treatment or are involved in ongoing therapy protocols

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    Address requests for reprints to: Peter Ferenci, M.D., Department of Internal Medicine IV, Gastroenterology and Hepatology, Währinger Gürtel 18-20, A-1090 Wien, Austria. Fax: (43) 1-40400-4735.

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