Ramos-Casals Manuel, García-Carrasco Mario, López-Medrano Francisco, Trejo Olga, Forns Xavier, López-Guillermo Armando, Muñoz Carles, Ingelmo Miguel, Font Josep
Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, School of Medicine, University of Barcelona, Spain.
Medicine (Baltimore). 2003 Mar;82(2):87-96. doi: 10.1097/00005792-200303000-00003.
To determine the clinical characteristics and outcome of patients with chronic hepatitis C virus (HCV) infection presenting severe autoimmune cytopenia unrelated to interferon alpha therapy, we analyzed characteristics and outcomes of 35 patients with HCV (16 from our departments and 19 from the literature). We considered active autoimmune hemolytic anemia (AHA) as a decrease of at least 2 g/dL in hemoglobin levels, an increase of at least 0.6 mg/dL in the serum unconjugated bilirubin level, a reticulocyte count >5%, and a positive direct Coombs test. Severe neutropenia was defined as a neutrophil count <0.5 x 10(9)/L, and severe thrombocytopenia as a platelet count <30 x 10(9)/L. We identified the following cytopenias: AHA (17 cases), severe thrombocytopenia (16 cases), aplastic anemia (2 cases), severe neutropenia (1 case), refractory sideroblastic anemia (1 case), and pure red cell aplasia (1 case). Three patients simultaneously presented 2 types of severe cytopenias. Twenty-seven patients (77%) were female and 8 (23%) male, with a mean age at diagnosis of cytopenia of 51.7 years (range, 18-84 yr). Immunologic markers were detected in 19 (68%) of 28 patients, the most frequent being hypocomplementemia in 16 (57%), cryoglobulins in 15 (54%), antinuclear antibodies in 12 (43%), and rheumatoid factor in 5 (18%). Other associated processes were autoimmune diseases in 14 (50%) of 28 and human immunodeficiency virus (HIV) coinfection in 3 (9%) of 32. We found clinical and immunologic differences between HCV patients with AHA and those with severe thrombocytopenia. Patients with HCV-related AHA showed a higher prevalence of associated autoimmune diseases (71%), cryoglobulins (67%), and cirrhosis (59%). All had a good response to corticosteroids, but a poor prognosis (47% mortality). In contrast, patients with HCV-related severe thrombocytopenia had a lower prevalence of associated autoimmune diseases (11%), a poorer response to corticosteroids (55%), and lower mortality (6%), with HIV/HBV coinfections in some patients. The 35 cases presented demonstrate that different types of immune-mediated cytopenias may be severe and clinically significant in patients with HCV infection. Hemolytic anemia and severe thrombocytopenia were the most frequent cytopenias observed. Most patients responded well to corticosteroids, although a higher rate of mortality was observed in those with liver cirrhosis.
为了确定慢性丙型肝炎病毒（HCV）感染患者出现与干扰素α治疗无关的严重自身免疫性血细胞减少的临床特征和结局，我们分析了35例HCV患者的特征和结局（16例来自我们科室，19例来自文献）。我们将活动性自身免疫性溶血性贫血（AHA）定义为血红蛋白水平至少降低2 g/dL、血清非结合胆红素水平至少升高0.6 mg/dL、网织红细胞计数>5%以及直接抗人球蛋白试验阳性。严重中性粒细胞减少症定义为中性粒细胞计数<0.5×10⁹/L，严重血小板减少症定义为血小板计数<30×10⁹/L。我们确定了以下血细胞减少症：AHA（17例）、严重血小板减少症（16例）、再生障碍性贫血（2例）、严重中性粒细胞减少症（1例）、难治性铁粒幼细胞贫血（1例）和纯红细胞再生障碍（1例）。3例患者同时出现2种严重血细胞减少症。27例患者（77%）为女性，8例（23%）为男性，血细胞减少症诊断时的平均年龄为51.7岁（范围18 - 84岁）。28例患者中的19例（68%）检测到免疫标志物，最常见的是低补体血症16例（57%）、冷球蛋白15例（54%）、抗核抗体12例（43%）和类风湿因子5例（18%）。其他相关疾病为28例中的14例（50%）患有自身免疫性疾病，32例中的3例（9%）合并人类免疫缺陷病毒（HIV）感染。我们发现HCV相关AHA患者和严重血小板减少症患者在临床和免疫方面存在差异。HCV相关AHA患者中合并自身免疫性疾病（71%）、冷球蛋白（67%）和肝硬化（59%）的患病率更高。所有患者对皮质类固醇反应良好，但预后较差（死亡率47%）。相比之下，HCV相关严重血小板减少症患者合并自身免疫性疾病的患病率较低（11%），对皮质类固醇的反应较差（55%），死亡率较低（6%），部分患者合并HIV/HBV感染。所呈现的35例病例表明，不同类型的免疫介导的血细胞减少症在HCV感染患者中可能很严重且具有临床意义。溶血性贫血和严重血小板减少症是观察到的最常见的血细胞减少症。大多数患者对皮质类固醇反应良好，尽管肝硬化患者的死亡率较高。
