贫血是含干扰素的丙型肝炎治疗的并发症。我们表征了基于干扰素的治疗对铁调素和促红细胞生成素(EPO)产生的影响,铁代谢,溶血,和造血。标准造血[网织红细胞血红蛋白(Hb),网织红细胞生产指数(RPI),游离Hb,和触珠蛋白],铁生物化学,铁调素,在12周内测量了10名受试者的EPO水平。治疗期间Hb迅速下降,治疗前(t=0周)的平均Hb在第4周为158.6至125.2g/L(P=0.003),在第12周为122.8g/L(P=0.005)。矛盾的是,开始丙型肝炎病毒治疗后,RPI(衡量骨髓对EPO反应性的指标)从0.78%下降至0.53%(P=0.04).尽管贫血恶化,EPO水平没有显著增加。铁调素水平在3名受试者中从5.8至27.5nM(P=0.009)增加至>20nM,而其余受试者为9.6至12.3nM(P=0.5)。铁调素水平在第1周达到峰值,然后在第4周回到基线水平。以血清铁调素水平升高至>20nM的受试者的Hb下降明显更大(27.2g/L,P=0.008)和网织红细胞Hb(-1.4g/L,P=0.013)与铁调素产生没有任何变化的受试者相比。总之,用干扰素治疗的受试者的30%表现出血清铁调素水平的显著短暂增加,这与更极端的贫血和铁利用率降低相关,网织红细胞Hb降低证明了这一点。此外,对贫血和溶血的反应未能上调EPO产量(https://clinicaltrials.gov试验NCT01726400).
Anemia is a complication of interferon-containing hepatitis C treatments. We characterized effects of interferon-based therapy on hepcidin and erythropoietin (EPO) production, iron metabolism, hemolysis, and hematopoiesis. Standard hemopoiesis [reticulocyte hemoglobin (Hb), reticulocyte production index (RPI), free Hb, and haptoglobin], iron biochemistry, hepcidin, and EPO levels were measured in 10 subjects over 12 weeks. There was a rapid decline in Hb during treatment, from a mean pretreatment (t = 0 weeks) Hb of 158.6 to 125.2 g/L at week 4 (P = 0.003) and 122.8 g/L at week 12 (P = 0.005). Paradoxically, the RPI (a measure of bone marrow responsiveness to EPO) decreased on initiation of hepatitis C virus treatment from 0.78% to 0.53% (P = 0.04). Despite worsening anemia, there was no significant increase in EPO levels. Hepcidin levels increased to >20 nM in 3 subjects from 5.8 to 27.5 nM (P = 0.009) compared with 9.6 to 12.3 nM (P = 0.5) for the remainder of subjects. Hepcidin levels peaked at week 1 before returning to baseline levels at week 4. Subjects who responded with a rise in serum hepcidin levels to >20 nM had a significantly greater drop in Hb (27.2 g/L, P = 0.008) and reticulocyte Hb (-1.4 g/L, P = 0.013) compared with the subjects who did not exhibit any change in hepcidin production. In conclusion, 30% of subjects treated with interferon exhibited significant transient increase in serum hepcidin levels, which was associated with more extreme anemia and decreased iron availability as evidenced by decreased reticulocyte Hb. In addition, there was a failure to upregulate EPO production in response to anemia and hemolysis ( https://clinicaltrials.gov trial NCT01726400).