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

Kodsi, Emad M.; Ismail, Hisham; Issa, Randa; Elshaarawy, Ahmed; Sakr, Moustafa A.; Shehata, Eman L.; Issak, Emad R

doi:2026.41.2.265

Korean J Intern Med > Volume 41(2); 2026 > Article

ORIGINAL ARTICLE

Gastroenterology

Korean J Intern Med. 2026;41(2):265-276. doi: https://doi.org/10.3904/kjim.2025.156

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

Emad M. Kodsi¹, Hisham Ismail², Randa Issa³, Ahmed Elshaarawy⁴, Moustafa A. Sakr⁵, Eman L. Shehata¹, and Emad R Issak⁶

¹Department of Clinical Pathology, National Liver Institute, Menoufia University, Menoufia, Eygpt
²Department of Clinical Pathology and Molecular Diagnosis, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City (USC), Sadat City, Eygpt
³Department of Medical Microbiology and Immunology, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City (USC), Sadat City, Eygpt
⁴Department of Clinical Pathology, National Liver Institute, Menoufia University, Menoufia, Eygpt
⁵Department of Genetics and Molecular Diagnosis, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City (USC), Sadat City, Eygpt
⁶Department of Interal Medicine, Internal Medicine Department, Ain Shams Univeristy, Cairo, Eygpt

Corresponding Author: Emad R Issak , Tel: +20-1272228989, Fax: +20-1066208065, Email: dr.emad.r.h.issak@gmail.com

Received: May 20, 2025; Revised: July 17, 2025; Accepted: September 11, 2025.

Abstract

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).
Conclusions: 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.

Keywords: Hemochromatosis gene polymorphism ; Iron overload ; Sustain virological response ; Daclatasvir ; Sofosbuvir