Common variable immunodeficiency disorder (CVID)-related liver disease: assessment of the main histological aspects using novel semiquantitative scoring systems, image analysis and correlation with clinical parameters of liver stiffness and portal hypertension.

Abstract

Aims: We aimed to investigate the relationship between T-cell-mediated sinusoidal injury, nodular regenerative hyperplasia like changes (NRH-LC) and fibrosis, clinical measures of fibrosis and portal hypertension, and progression rate in common variable immunodeficiency disorder (CVID)-related liver disease.

Methods: This is a retrospective single-centre study. Liver biopsies from CVID patients with liver disease were reviewed to assess for NRH-LC, fibrosis and elastosis, including collagen and elastin proportionate areas. CD3 positive T-cells infiltration and sinusoidal endothelial changes by CD34 expression were quantified by image analysis and a semiquantitative method, respectively. These findings were correlated with liver stiffness measurements (LSM) and hepatic venous pressure gradient (HVPG).

Results: NRH-LC and pericellular elastosis were present in most biopsies (32/40 and 38/40, respectively). All biopsies showed fibrosis, which was limited to pericellular in 21/40 (52.5%) and included bridging fibrous septa in 19/40 (47.5%). 28/40 liver biopsies showed enhanced sinusoidal expression of CD34. There were more CD3 positive cells in biopsies with NRH-LC compared with those without. There was no significant correlation between LSM, HVPG and fibrosis/elastosis scores. Five of seven patients with at least two biopsies showed progression in fibrosis stage.

Conclusions: NRH-LC and fibrosis in CVID patients often coexist along with the presence of sinusoidal endothelial changes and sinusoidal lymphocytic infiltration. Fibrosis progresses over time, and significant fibrosis can be observed in young patients (<30 years old), potentially reflecting a more aggressive form of CVID-related liver disease. Further studies are necessary to investigate the relationship between histological findings, clinical measures of fibrosis and portal hypertension and outcome.