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. HEADINGS – Polymorphysm, genetic. Hepatitis C, chronic. Ferritins. Interferons. All authors had access to the data, were actively involved in its analysis and interpretation, and approved the final manuscript