Martín-Portugués Mario, Esteban-Sampedro Jorge, de Mendoza Carmen, Ruiz-Irastorza Guillermo, Royuela Ana, Puente Alfonso Ortega-de la, de la Cruz-Echeandía Marina, Blanco-Valencia Xiomara Patricia, Soriano Vicente, Moreno-Torres Víctor
Internal Medicine Department, Health Research Institute Puerta de Hierro-Segovia de Arana (IDIPHIM), Hospital Universitario Puerta de Hierro, Madrid, Spain.
Biobizkaia Health Research Institute, Hospital Universitario Cruces, Barakaldo, Spain.
Liver Int. 2025 Jul;45(7):e70195. doi: 10.1111/liv.70195.
The epidemiology of cryoglobulinemia in Spain has likely changed following the widespread adoption of direct-acting antivirals (DAAs) since 2015 for the treatment of hepatitis C virus (HCV) infection, the principal cause of mixed cryoglobulinemia (MC).
All hospital admissions of patients with cryoglobulinemic disease at the National Registry of Hospital Discharges were retrospectively examined in Spain from 1997 to 2022. The following primary conditions associated with cryoglobulinemia were considered: chronic viral infections, haematological diseases (HD), and autoimmune diseases (AD).
A total of 16 929 admissions for patients with cryoglobulinemic disease were recorded during the study period. Hospitalisation rates for patients with cryoglobulinemia steadily increased from 1997 to 2015 (from 10.8 to 17.9 admissions per 1 million habitants, APC = +2.1), and decreased from 2018 to 2022 (from 15.7 to 11 admissions per 1 million habitants, APC = -7) (p < 0.001 for all). The drastic changes in HCV prevalence rates determined this shift (26.3% in 1997, 52.7% in 2016 and 27.9% in 2022, p < 0.001). The proportion of patients with cryoglobulinemia associated with hepatitis B virus (HBV), paraproteinemias, non-Hodgkin lymphoma, systemic lupus erythematosus, primary Sjögren syndrome and rheumatoid arthritis steadily increased during the study period as cause of hospitalisation in patients with cryoglobulinemia (from 1997 to 2022, p < 0.001), while human immunodeficiency virus infection remained fairly stable since 2005.
The introduction of DAA as treatment for HCV has resulted in a significant reduction in hospitalisations due to cryoglobulinemia in Spain. As a result, cases due to HBV, hematologic and autoimmune diseases have emerged as conditions of growing importance associated with cryoglobulinemia hospitalisations.
自2015年广泛采用直接抗病毒药物（DAA）治疗丙型肝炎病毒（HCV）感染（混合性冷球蛋白血症（MC）的主要病因）以来，西班牙冷球蛋白血症的流行病学可能已发生变化。
对西班牙1997年至2022年国家医院出院登记处所有冷球蛋白血症疾病患者的住院情况进行回顾性检查。考虑了以下与冷球蛋白血症相关的主要病症：慢性病毒感染、血液系统疾病（HD）和自身免疫性疾病（AD）。
在研究期间，共记录了16929例冷球蛋白血症疾病患者的住院情况。冷球蛋白血症患者的住院率从1997年到2015年稳步上升（从每百万居民10.8例住院升至17.9例，年平均变化百分比（APC）=+2.1），从2018年到2022年下降（从每百万居民15.7例降至11例，APC=-7）（所有p<0.001）。HCV患病率的急剧变化决定了这种转变（1997年为26.3%，2016年为52.7%，2022年为27.9%，p<0.001）。在研究期间，作为冷球蛋白血症患者住院原因，与乙型肝炎病毒（HBV）、副蛋白血症、非霍奇金淋巴瘤、系统性红斑狼疮、原发性干燥综合征和类风湿关节炎相关的冷球蛋白血症患者比例稳步上升（1997年至2022年，p<0.001），而自2005年以来，人类免疫缺陷病毒感染保持相当稳定。
引入DAA治疗HCV已导致西班牙因冷球蛋白血症住院的人数显著减少。因此，由HBV、血液系统和自身免疫性疾病引起的病例已成为与冷球蛋白血症住院相关的日益重要的病症。
