Direct-Acting Antivirals Reduce Iron Parameters in Patients with HCV, Hyperferritinemia

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Statistically significant reductions in serum ferritin, transferrin saturation index, and iron levels were observed after treatment, with hyperferritinemia eradicated in nearly all patients treated with DAAs achieving SVR.

Findings from a single-center retrospective study are shining light on the impact of viral eradication with direct-acting antivirals (DAAs) on serum ferritin, transferrin saturation index, and iron levels in patients with chronic hepatitis C virus (HCV) and hyperferritinemia.

A comparison of pre- and post-treatment measurements showed statistically significant reductions across all 3 determinations, with hyperferritinemia eradicated in 97% of participants who achieved sustained virologic response (SVR), suggesting hyperferritinemia associated with HCV is unlikely to persist after treatment and therefore is not clinically relevant.1

“Numerous studies were carried out in the interferon era to determine whether the decrease in iron, through bleeding, was associated with better therapeutic results, less fibrosis progression, and a decrease in the risk of hepatocarcinoma, with disparate results,” wrote investigators.1

Ferritin serves as an indirect marker for iron levels and is frequently observed in high amounts upon acute phase reactions and as a result of ferritin being released from damaged cells in liver disease. Iron is essential for life, but both severe iron deficiency and iron overload can pose significant health risks and increase hepatic injury, especially in combination with other hepatotoxic factors. Iron has been speculated to modulate the course of HCV infection, although its clinical significance has not been confirmed thus far.2

To assess the effect of viral eradication with DAAs in patients with chronic HCV and hyperferritinemia, Agustin Castiella, MD, PhD, staff physician in the department of gastroenterology at Donostia University Hospital in Spain, and colleagues retrospectively examined pre- and post-treatment data for patients with HCV and hyperferritinemia treated with DAAs between January 2018 and December 2020. For inclusion, patients were required to have pre-treatment hyperferritinemia >400 ng/mL, be HCV-RNA detectable for more than 24 weeks by polymerase chain reaction (PCR), and achieve SVR defined as HCV-RNA not detectable by PCR 12 weeks after the end of treatment.1

Out of 621 patients treated with DAAs for HCV during the study period, 77 (12.40%) presented hyperferritinemia. Investigators excluded 3 patients, including 1 who refused treatment and 2 who lacked post-treatment ferritin measurements.1

In total, 74 patients met the inclusion criteria and were enrolled in the study. Among the cohort, 59 (79.73%) participants were male and the mean age at initiation of treatment was 58.33 (Standard deviation [SD], 8.68) years.1

Prior to treatment, the mean ferritin level among the cohort was 893.20 (SD, 1037.09), the mean transferrin saturation index was 40.96 (SD, 15.71), and the mean serum iron was 152.32 (SD, 62.07). Mean post-treatment levels were as follows: 264.17 (SD, 161.33) for ferritin, 29.82 (SD, 11.17) for transferrin saturation index, and 109.32 (SD, 39.49) for serum iron.1

Investigators pointed out significant statistical differences for pre- and post-treatment ferritin (P < .00001), transferrin saturation (P < .00001), and iron (P = .0002) determinations. Due to their lack of normal distribution, investigators used Wilcoxon signed-rank test to affirm the statistical significance of all 3 variables (ferritin P < .00001; transferrin saturation index P < .00001; iron P < .00001).1

SVR was 100% among the cohort and hyperferritinemia disappeared in 72 patients, persisting in 2 where ferritin did not normalize after treatment. Investigators noted both patients had pathologies that justified chronic hyperferritinemia: one patient was a bone marrow transplant recipient after lymphoma, and the other had high alcohol consumption after SVR.1

“[Hyperferritinemia] associated with HCV has no clinical relevance in our study. [Hyperferritinemia] in patients with HCV chronic hepatitis rarely persists after treatment and SVR and only in these cases further study would be justified,” investigators concluded.1


  1. Castiella A, Sanchez-Iturri MJ, Urreta I, et al. Effect of viral eradication with direct-acting antiviral agents on iron parameters in patients with chronic hepatitis c and hyperferritinemia. Canadian Liver Journal.
  2. Sandnes M, Ulvik RJ, Vorland M, Reikvam H. Hyperferritinemia-A Clinical Overview. J Clin Med. 2021;10(9):2008. doi:10.3390/jcm10092008