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丙型肝炎抗病毒治疗期间贫血的临床和基础问题。

Clinical and basal aspects of anemia during antiviral therapy for hepatitis C.

机构信息

Depts. of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.

出版信息

Ann Hepatol. 2009 Oct-Dec;8(4):316-24.

PMID:20009130
Abstract

BACKGROUND AND RATIONALE

Anemia is a major side effect of combination therapy for chronic hepatitis C. In this study, severity, potential risk factors for and potential underlying mechanisms of anemia were evaluated.

PATIENTS AND METHODS

44 chronic hepatitis C patients on interferon-ribavirin treatment were included. Anemia-related parameters were measured before and during treatment. Potential changes in membrane phospholipids composition of erythrocytes of patients on anti-viral treatment and potentially increased erythrocyte susceptibility to osmotic or bile salt induced stress were explored.

RESULTS

Anemia was almost universal during treatment, with evidence of hemolysis. Decrease of Hb after six months of therapy was 2.1 +/- 0.1 mmol/L (range -0.6-4.1). Higher pre-treatment Hb, highest ribavirin dose (15-17.5 mg/kg) and lower pre-treatment platelet level were independent risk factors for decrease of Hb. Serum erythropoietin levels increased during treatment with negative correlation to Hb levels at week 12 (r = -0.70, p = 0.002) and 24 (r = -0.72, p = 0.002). Erythrocyte membrane phospholipid composition did not differ between anemic patients and healthy controls. Also, resistance to osmotic or bile salt induced stress was normal in anemic patients. Phosphatidylserine exposure at the outer membrane leaflet did not change upon 24 hrs ex vivo incubation with pharmacological ribavirin concentration.

CONCLUSIONS

Anemia is almost universal during anti-HCV treatment. The extent of anemia correlates with pre-treatment levels of thrombocytes and Hb and with high ribavirin dosing. Although we found hemolysis as contributing factor, our data do not indicate that altered membrane phospholipids composition is an important factor in pathogenesis of anemia.

摘要

背景与理由

贫血是慢性丙型肝炎联合治疗的主要副作用。在这项研究中,评估了贫血的严重程度、潜在危险因素和潜在发病机制。

患者和方法

44 例接受干扰素-利巴韦林治疗的慢性丙型肝炎患者被纳入本研究。在治疗前后测量了与贫血相关的参数。探索了抗病毒治疗患者红细胞膜磷脂组成的潜在变化以及潜在增加红细胞对渗透或胆汁盐诱导的应激的敏感性。

结果

治疗期间贫血几乎普遍存在,并伴有溶血的证据。治疗 6 个月后 Hb 下降 2.1 +/- 0.1 mmol/L(范围-0.6-4.1)。治疗前 Hb 较高、利巴韦林最高剂量(15-17.5mg/kg)和治疗前血小板水平较低是 Hb 下降的独立危险因素。治疗期间血清促红细胞生成素水平升高,与第 12 周(r = -0.70,p = 0.002)和第 24 周(r = -0.72,p = 0.002)Hb 水平呈负相关。贫血患者与健康对照组的红细胞膜磷脂组成无差异。此外,贫血患者的渗透或胆汁盐诱导应激的抗性正常。在体外 24 小时用药理学利巴韦林浓度孵育后,外膜小叶的磷脂酰丝氨酸暴露没有变化。

结论

在抗 HCV 治疗期间,贫血几乎普遍存在。贫血的严重程度与治疗前血小板和 Hb 水平以及高利巴韦林剂量相关。尽管我们发现溶血是一个促成因素,但我们的数据并不表明改变的膜磷脂组成是贫血发病机制的一个重要因素。

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