Abstract
PURPOSE: We aimed to describe porto-sinusoidal vascular disease (PSVD) in a large cohort of predominantly antibody deficiency (PAD) patients and sought to identify contributing factors for PSVD development by comparing CVID patients with and without PSVD. METHOD: Patients were retrospectively identified from a national database. RESULTS: Sixty-eight of 386 PAD patients, including 63 of 267 CVID patients were diagnosed with PSVD. Median time from PAD to PSVD diagnosis was 9.2 years (interquartile range, 4.6–14.5). CVID patients with late onset combined immunodeficiency and non-infectious complications were overrepresented among PSVD patients (37.5% and 87.3%, respectively). Nodular regenerative hyperplasia (NRH) was the most common finding on liver biopsy (79%), alongside with intra-sinusoidal CD8(+) T-cell infiltration (65.7%). In an adjusted multivariate model, gastro-intestinal (GI) complications (adjusted odds ratio, 4.94; 95% CI, 1.91–12.79; p = 0.001) and low naive CD4(+) T-cell count (p = 0.001) were strongly associated with the occurrence of PSVD in CVID patients, together with low serum IgA level (p = 0.018) and lymphoproliferation (p = 0.027). GI complications were observed in 90.5% of PSVD patients, preceding PSVD diagnosis in 84% of them by a median duration of 10.7 years. The 20-year probability to develop PSVD after CVID diagnosis was estimated at 38.7% (95% CI, 30.1–48.7) and 11.7% (95% CI, 5.0–26.0) in patients with or without GI complications, respectively (p < 0.001). The median overall survival from onset of PSVD was 8.4 years. CONCLUSION: Our data suggest that impaired intestinal barrier in a context of T-cell defect may play a key role in the development of PSVD in CVID patients. Whether complete control of GI complications would prevent the occurrence of PSVD remains to be evaluated. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10875-026-01985-4.