The role of iron related gene variants in liver disease severity and iron metabolism parameters in chronic hepatitis C patients treated with direct-acting antivirals

Ferreira, Joana; Bicho, Manuel; Serejo, Fátima; Faustino, Paula

http://hdl.handle.net/10400.18/6732

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Chronic hepatitis C (CHC) is usually associated with iron overload, which may modulate the severity of liver disease. Direct-acting antivirals (DAAs) have made HCV treatment faster and more efficient. However, little is known about their effect on liver disease severity and iron metabolism disruption. This study aimed to evaluate the role of iron related gene variants in liver disease severity and iron status associated parameters in CHC patients treated with DAAs. A group of 118 out of 255 CHC patients (49±12 years) was treated with DAAs and clinical evaluation was performed after 3 to 6 months. Liver fibrosis stage was assessed by FibroScan and the following iron status parameters were evaluated: serum iron (Fe), ferritin (FT), transferrin (TF), transferrin saturation (TFS) and haptoglobin (Hp). HFE common variants (H63D and C282Y) were analysed by PCR-RFLP and the TF_rs3811647 by Sanger sequencing. Statistical analysis was performed using SPSS 23.0. Before DAAs treatment, patients with higher fibrosis stage (F3/4) showed significantly higher Fe, FT and TF, and lower Hp (p=0.030; p=0.026; p=0.025; p=0.048). We found higher Fe, TFS and FT in patients HFE_CY or YY (p=0.008; p=0.003; p=0.002) and higher TF in patients TF_rs3811647_GA or AA (p=0.029). After DAAs treatment, patients presented: i) an improvement of liver fibrosis showed by a higher frequency of patients with lower fibrosis stage (F1/2) (p<0.001); and ii) an improvement of iron status revealed by lower Fe, TFS and FT (p=0.007; p=0.048; p<0.001) and higher Hp (p=0.001). We observed that only in patients HFE_CC and HFE_HD or DD, TF decreased after treatment (p=0.028; p=0.012). In these same patients and in those TF_rs3811647_GG or GA, Hp increased (p=0.003; p=0.006) after antiviral treatment. Specific genetic variants in iron related genes may have a relevant role in the predisposition for severe liver disease in CHC patients before DAAs treatment, and in the improvement of iron status after HCV clearance.