The C282Y mutation is not a significant cofactor for more severe liver disease in a cohort of irish hepatitis C patients

Abstract

Hepatic iron overload in chronic hepatitis C virus (HCV) infection is reported to be associated with increased hepatic inflammation, fibrosis and a negative response to Interferon therapy. The mechanism of iron overload in HCV is not clearly defined. Whether increases in iron occur because of HCV or whether increases in iron predate and predispose to more severe hepatitis is unclear. The involvement of even a single copy of the candidate gene for genetic Hacmochrnmatosis [Cys282Tyr (C282Y) mutation in the HLA-H gene] in the pathogenesis of liver damage in HCV has yielded conflicting results. The purpose of this study was to clarify the role of the C282Y mutation in iron accumulation and severity of liver disease in a cohort of patients with chronic HCV. Seventy six patients (F) mean age 44.1 (SD=7.19) with histologically proven chronic HCV were evaluated. The C282Y mutation was detected by PCR followed by restriction digestion with Rsal. A semiquantitative grading system (0-4) was used for histological assessment of liver iron overload on Perls' stain. Inflammatory activity (0-18, minimal-severe; Desmet, 1994) and fibrosis (0-6, Ishak; 1995) were also evaluated. The C282Y mutation was present in 13/76 (17.1%) patients including 1 homozygous (HH) and 12 heterozygous (Hn) individuals. Liver iron staining was detected in 4/76 (5.3%) patients, 1 was HH (grade III siderosis) 1 was Hn (grade I siderosis) and 2 were heterozygous normal (grade I siderosis). Inflammatory activity was minimal in 26 patients (1/26 HH and 4/26 Ha), mild in 41 (6/41 Hn) and moderate in 9 (2/9 Hn) patients. Fibrosis was absent in 24 patients (5/24 Hn), a fibrosis score of one was seen in 21 patients (1/21 HH and 4/21 Hn) and scores of greater than one were seen in 31 (3/31 Hn) patients. Condusions: Histological evidence of iron overload was seen in only 4•76 patients with the most severe (grade III) siderosis seen in a HH patient with minimal activity. There was no association between the presence of the C282Y mutation and inflammation or fibrosis in this HCV infected cohort. This result suggests that in chronic HCV patients with moderate to severe iron overload should be evaluated for genetic Haemochromatosis.