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Abstract：
Twenty-nine patients with HCV infection (HCV+) and mixed cryoglobulinemia (MC+) were retrospectively selected and matched for age and sex with 31 HCV+ MC- patients. Biomarkers of cholestasis (direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase), HCV-RNA and genotype, and plasma cryoprecipitates were measured before and after virus eradication; liver histology and plasma cells (aggregation and distribution), observed blinded by two pathologists, were analyzed. Sixty participants (mean age: 56.5; range: 35-77, males: 50%) with HCV infection were enrolled. Cholestasis (≥2 pathologically increased cholestasis biomarkers) was significantly higher in the MC group (p = 0.02) and correlated with cryoglobulinemia (OR 6.52; p = 0.02). At liver histological assessment, plasma cells were significantly increased in the MC+ group (p = 0.004) and tended to form aggregates more than the control group (p = 0.05). At multivariate analysis with MC, age, HCV-RNA, HBV diabetes, and cirrhosis, cholestasis was only significantly correlated to MC (OR 8.30; p < 0.05). In 25% patients, MC persisted after virus eradication with new antiviral treatment. Our study identified for the first time an association between MC, cholestasis, and an increased number of intrahepatic plasma cells in chronic hepatitis C (CHC) patients before virus eradication. Future studies are required to understand how MC contributes to liver damage and how its persistence affects the patients\' follow-up after antiviral therapies.
摘要：
回顾性选择29例HCV感染（HCV）和混合型冷球蛋白血症（MC）患者，并与31例HCVMC-患者进行年龄和性别匹配。胆汁淤积的生物标志物（直接胆红素，碱性磷酸酶,和γ-谷氨酰转移酶)，HCV-RNA和基因型，和血浆冷沉淀物在病毒根除之前和之后进行测量;肝脏组织学和浆细胞（聚集和分布），观察到两名病理学家失明，进行了分析。纳入60名HCV感染患者（平均年龄：56.5；范围：35-77，男性：50％）。MC组胆汁淤积（≥2个病理上增加的胆汁淤积生物标志物）显着升高（p=0.02），并且与冷球蛋白血症相关（OR6.52；p=0.02）。在肝脏组织学评估中，MC+组浆细胞明显增多(p=0.004),形成聚集体的趋势大于对照组(p=0.05)。在MC的多变量分析中，年龄,HCV-RNA,HBV糖尿病，和肝硬化，胆汁淤积仅与MC显著相关(OR8.30;p<0.05)。在25%的患者中，通过新的抗病毒治疗根除病毒后，MC持续存在。我们的研究首次确定了MC之间的关联，胆汁淤积,在病毒根除前，慢性丙型肝炎（CHC）患者的肝内浆细胞数量增加。未来的研究需要了解MC如何导致肝损伤，以及它的持久性如何影响患者的抗病毒治疗后的随访。
