Male-specific Association between Iron and Lipid Metabolism Changes and Erythroferrone after Hepatitis C Virus Eradication

OBJECTIVE: Hepatitis C virus (HCV) eradication is associated with decreased serum ferritin and increased serum low-density lipoprotein-cholesterol (LDL-C) levels, although the mechanisms underlying these changes remain unclear. This study aimed to identify the mechanisms underlying the changes in iron and lipid metabolism after HCV eradication. METHODS: We retrospectively investigated iron and lipid metabolism changes in 22 patients with chronic hepatitis or compensated liver cirrhosis with HCV genotype 1b infection after HCV eradication. We measured the serum erythroferrone (ERFE) levels to assess the association with these metabolic changes. Patients were administered ledipasvir 90 mg and sofosbuvir 400 mg once daily for 12 weeks and were observed for 12 more weeks to evaluate the sustained virological response. RESULTS: Half of the patients were men. At baseline, the serum ferritin and ERFE levels were elevated, while the serum LDL-C levels were within the normal range. All patients achieved a sustained virological response at 24 weeks; furthermore, the serum ferritin and ERFE levels were significantly decreased, and the serum LDL-C levels were significantly increased at 24 weeks from baseline (p＜0.001, all). In men, a decrease in serum ERFE levels was correlated with changes in the serum ferritin and LDL-C levels (r=0.78, p＜0.01; r=-0.76, p＜0.01, respectively). In addition, a decrease in the serum ferritin levels was correlated with an increase in the serum LDL-C levels (r=-0.89, p＜0.001). These correlations were not observed in women. CONCLUSION: Our results suggest a possible association between iron and lipid metabolism changes and the involvement of ERFE after HCV eradication in men as well as potential sex-related differences.