Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin

Abstract

-Context -Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. Objective -To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin. Methods -A total of 44 treatment naïve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2) and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week) and ribavirin (1.000 mg, daily) for 24 weeks. Results -Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis) and BclI (H63D mutation analysis) in 16 (37%) patients, all heterozygous (11 H63D, 2 C282Y and 3 both). Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41%) of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test). Conclusion -Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.

Hemochromatosis genes and HCV in Egyptian patients; is there a relationship?

“…On the other hand the results of this study are similar to the study of Coelho-Borges et.al that included Brazilian patients with HCV genotypes other than genotype-1 who mentioned the negative effect of H63D mutation on the sustained virological response to IFN & Ribavirin treatment and furthermore they concluded that the finding of HFE polymorphism is a durable predictor of non-response in his study. 31 The results of our study also showed that Carriers of S65C mutations specifically the T allele (HFE 193 A>T) gene polymorphism have 9.2 times risk for not responding to interferon than non-carriers which can be considered a predictor of response to Interferon based therapy. In 2012 Ishizu et.al studied the effect of HFE mutations in Japanese patients with HCV; their study included 251 CHCV patients.…”

Association between inherited monogenic liver disorders and chronic hepatitis C

“…Some studies have proposed that ferritin, being an acutephase reactant, behaves as a marker of more active and advanced liver disease. Patients with chronic HCV infection and high serum ferritin levels reportedly have significantly more severe liver inflammation and fibrosis than do patients with normal serum ferritin levels [7,33] . In our study, patients with viral persistence had slightly elevated ferritin levels.…”

“…Finally, Gilbert's syndrome is characterized by benign unconjugated hyperbilirubinemia with a frequency of 5.0% to 14.8% in Europe [6] . Most reports on the coexistence of monogenic liver diseases and HCV infection have focused primarily on hereditary hemochromatosis [7] because elevated iron levels are necessary for viral replication [8,9] . Although the associations of HCV infection with alpha-1 antitrypsin deficiency [10,11] and Gilbert's syndrome [12][13][14] have been investigated, the association of HCV infection with Wilson's disease remains unclear.…”

Human Leukocyte Antigen (HLA) and Immune Regulation: How Do Classical and Non-Classical HLA Alleles Modulate Immune Response to Human Immunodeficiency Virus and Hepatitis C Virus Infections?

“…However, another study reported no correlation between HFE polymorphisms and HCV in Majorcan patients treated with pegylated-interferon plus ribavirin (321). By contrast, heterozygosity for H63D and/or C282Y HFE gene mutation has been shown to be associated with the lack of SVR to pegylated-IFN and ribavirin combination therapy in patients with chronic HCV (322). Taken together, the MHC-Ib protein HLA-H/HFE is strongly expressed by a variety of cells such as Kupffer cells, circulating monocytes/macrophages and intestinal crypt cells.…”