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. 2025 Jul;45(7):e70195.
doi: 10.1111/liv.70195.

Hospitalisations With Cryoglobulin-Related Diseases in Spain Over 25 Years

Mario Martín-Portugués  1 , Jorge Esteban-Sampedro  1 , Carmen de Mendoza  1 , Guillermo Ruiz-Irastorza  2   3 , Ana Royuela  4   5 , Alfonso Ortega-de la Puente  6 , Marina de la Cruz-Echeandía  6 , Xiomara Patricia Blanco-Valencia  6 , Vicente Soriano  7 , Víctor Moreno-Torres  1   7
Affiliations

Hospitalisations With Cryoglobulin-Related Diseases in Spain Over 25 Years

Mario Martín-Portugués et al. Liver Int. 2025 Jul.

Abstract

Background: 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).

Methods: 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).

Results: 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.

Conclusions: 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.

Keywords: autoimmune diseases; cryoglobulinemia; direct‐acting antivirals; haematological conditions; hepatitis B virus; hepatitis C virus.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Trends for hospitalisations with cryoglobulinemia in Spain (1997–2022).
FIGURE 2
FIGURE 2
Trends in cryoglobulinemia etiologies in patients admitted between 1997 and 2022 in Spain.
FIGURE 3
FIGURE 3
Major conditions related to cryoglobulinemia admissions between 1997 and 2022 in Spain.
FIGURE 4
FIGURE 4
Epidemiology of HCV and non‐HCV‐related cryoglobulinemia admissions between 1997 and 2022 in Spain.
FIGURE 5
FIGURE 5
More frequent conditions associated with cryoglobulinemia in patients hospitalised in Spain during the last 25 years.
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