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 na？ve 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.