The effect of HFE gene mutation and iron overload on sustained virological response in Egyptian chronic hepatitis C patients treated with daclatasvir and sofosbuvir.

BACKGROUND/AIMS: This matched case-control study investigated the impact of HFE gene mutations on sustained virological response (SVR) in Egyptian patients with chronic hepatitis C (CHC) treated with daclatasvir and sofosbuvir.

METHODS: A total of 150 CHC patients were enrolled (75 responders and 75 non-responders) based on HCV RNA levels 12 weeks post-treatment. HFE gene mutations (C282Y, H63D, S65C) were detected by PCR-restriction fragment length polymorphism. Liver function and iron parameters were assessed.

RESULTS: Among responders, 86.67% had wild-type HFE alleles, compared to 72.00% of non-responders (p = 0.027). Heterozygous mutant alleles were more common in non-responders (28.00%) than in responders (13.33%). Wild-type carriers had 2.59 times higher odds of achieving SVR (OR, 2.59; 95% CI, 1.10-5.83). HFE mutations were significantly associated with elevated serum iron (p = 0.031) and ferritin (p = 0.044) levels, the with C282Y mutation linked to increased iron. However, after multivariate adjustment using principal component analysis, only iron overload remained a significant predictor of non-response (p < 0.001), while the association with HFE mutations was no longer significant (p = 0.647).

CONCLUSION: HFE mutations are associated with lower SVR rates and iron overload, but their impact appears mediated through disrupted iron metabolism. Iron overload emerged as the key independent predictor of treatment failure. These findings underscore the importance of evaluating iron status in conjunction with genetic factors to more accurately predict treatment outcomes in CHC patients receiving direct-acting antivirals.