Hemolytic anemia induced by ribavirin therapy in patients with chronic hepatitis C virus infection: Role of membrane oxidative damage
Hemolytic anemia induced by ribavirin therapy in patients with chronic hepatitis C virus infection: Role of membrane oxidative damage
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DOI：
10.1053/he.2000.5789
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发表时间：
2000-04-01
期刊：
影响因子：
13.5
通讯作者：
Corrocher, R
中科院分区：
文献类型：
--
作者：
De Franceschi, L;Fattovich, G;Corrocher, R
抗病毒药物利巴韦林（RBV）被广泛用于与干扰素（IFN）联合治疗慢性丙型肝炎病毒（HCV）感染。REV的主要副作用是可逆性溶血性贫血。我们在体外研究了REV对红细胞三磷酸腺苷（ATP）含量和磷酸己糖分流（HMS）的影响。在REV存在下，ATP水平显著降低，HMS增加，表明红细胞对氧化敏感性的存在。我们研究了11例慢性丙型肝炎患者单独使用REV或与IFN联合使用的血液学效果：6例用REV（1，000 ~ 1，200 mg/d）治疗，5例用REV和IFN联合治疗（500万U，每周3次）。从治疗第0天到第60天，每半个月对患者进行一次研究。两种治疗均与血红蛋白水平（第45天的稳态水平）显著降低和网织红细胞绝对计数显著增加相关。红细胞钠钾泵活性显着减少，而钾-氯共转运及其二硫曲糖醇敏感的馏分，丙二醛和高铁血红蛋白水平显着增加。REV治疗的患者显示聚集带3的增加，这与自体抗体和补体C3片段的结合显著增加相关，表明网状内皮系统的红细胞吞噬作用。
The antiviral drug ribavirin (RBV) is widely used in combination with interferon (IFN) in the treatment of chronic hepatitis C virus (HCV) infection. A major side effect of REV is a reversible hemolytic anemia. We have evaluated the in vitro effects of REV on erythrocyte adenosine triphosphate (ATP) content and on hexosemonophosphate shunt (HMS), The ATP levels were significantly decreased in the presence of REV and the HMS was increased, suggesting the presence of red cell susceptibility to oxidation, In vivo, we have studied the hematologic effects of treatment with REV alone or in combination with IFN in 11 patients with chronic hepatitis C: 6 were treated with REV (1,000-1,200 mg/d) and 5 were treated with a combination of REV and IFN (5 million U thrice weekly). Patients were studied at semi-monthly intervals from 0 to day 60 of therapy. Both treatments were associated with a significant reduction in hemoglobin levels (steady state level at day 45) and a marked increase in absolute reticulocyte counts. Erythrocyte Na-K pump activity was significantly diminished, whereas K-Cl cotransport and its dithiotreitol-sensitive fraction, malondialdehyde and methemoglobin levels were significantly increased. REV-treated patients showed an increase in aggregated band 3, which was associated with a significantly increased binding of autologous antibodies and complement C3 fragments indicating an erithrophagocytic removal by reticuloendothelial system.