Melia Michael T, Bräu Norbert, Poordad Fred, Lawitz Eric J, Shiffman Mitchell L, McHutchison John G, Muir Andrew J, Galler Greg W, Nyberg Lisa M, Lee William M, Schiff Eugene, Long Jianmin, Noviello Stephanie, Brass Clifford A, Pedicone Lisa D, Sulkowski Mark S
Johns Hopkins University School of Medicine, Baltimore, Maryland.
Clin Infect Dis. 2014 Apr;58(7):960-9. doi: 10.1093/cid/ciu009. Epub 2014 Jan 6.
Myelosuppression due to pegylated interferon (peg-IFN) is common during treatment for hepatitis C virus. The relationship between infection risk and decreases in leukocyte lines, however, is not well established. The objective of this analysis was to determine the incidence of and risk factors for infections during peg-IFN/ribavirin (RBV) therapy.
A total of 3070 treatment-naive, chronic hepatitis C genotype 1-infected patients were treated for up to 48 weeks with peg-IFN alfa-2b 1.5 µg/kg/week or 1 µg/kg/week, or peg-IFN alfa-2a 180 µg/week plus RBV. On-treatment leukocyte counts were obtained every 2-6 weeks. Dose reduction was required for a neutrophil count <0.75 × 10(9) cells/L, and treatment discontinuation was required for a neutrophil count <0.5 × 10(9) cells/L. Granulocyte colony-stimulating factor was prohibited. Data on infections were captured at each study visit and categorized according to MedDRA version 13.0.
A total of 581 (19%) patients experienced moderate, severe, or life-threatening infections as assessed by the investigator; 648 (21%) patients had at least 1 neutrophil count <0.75 × 10(9) cells/L, but only 242 (8%) sustained an infection and had a neutrophil count <0.75 × 10(9) cells/L at any time while on treatment. Twelve patients had severe or life-threatening infection and grade 3/4 neutropenia, but only 4 had temporally related infections. In a multivariate logistic regression model, nadir lymphocyte count, history of depression, and female sex, but not nadir neutrophil count, were associated with moderate, severe, or life-threatening infection.
Nadir lymphocyte count, not nadir neutrophil count, was independently associated with moderate, severe, or life-threatening infections in the IDEAL study. Clinicians should be aware of their patients' absolute lymphocyte counts during peg-IFN/RBV therapy; peg-IFN dose reductions may be a consideration in patients with significant lymphocytopenia (<0.5 × 10(9) cells/L).
聚乙二醇化干扰素（peg-IFN）所致的骨髓抑制在丙型肝炎病毒治疗期间很常见。然而，感染风险与白细胞系减少之间的关系尚未完全明确。本分析的目的是确定peg-IFN/利巴韦林（RBV）治疗期间感染的发生率及危险因素。
共有3070例初治的慢性丙型肝炎基因1型感染患者接受了长达48周的治疗，治疗方案为每周1.5μg/kg的聚乙二醇化干扰素α-2b、每周1μg/kg的聚乙二醇化干扰素α-2b或每周180μg的聚乙二醇化干扰素α-2a加RBV。每2 - 6周进行一次治疗期间白细胞计数。当中性粒细胞计数<0.75×10⁹个细胞/L时需要减少剂量，当中性粒细胞计数<0.5×10⁹个细胞/L时需要停止治疗。禁止使用粒细胞集落刺激因子。每次研究访视时收集感染数据，并根据MedDRA第13.0版进行分类。
根据研究者评估，共有581例（19%）患者发生中度、重度或危及生命的感染；648例（21%）患者至少有一次中性粒细胞计数< 0.75×10⁹个细胞/L，但只有242例（8%）在治疗期间的任何时候发生感染且中性粒细胞计数<0.75×10⁹个细胞/L。12例患者发生严重或危及生命的感染以及3/4级中性粒细胞减少，但只有4例感染与时间相关。在多因素逻辑回归模型中，淋巴细胞最低计数、抑郁症病史和女性性别（而非中性粒细胞最低计数）与中度、重度或危及生命的感染相关。
在IDEAL研究中，淋巴细胞最低计数而非中性粒细胞最低计数与中度、重度或危及生命的感染独立相关。临床医生在peg-IFN/RBV治疗期间应关注患者的绝对淋巴细胞计数；对于淋巴细胞显著减少（<0.5×10⁹个细胞/L）的患者，可能需要考虑减少peg-IFN剂量。
