Common Variable Immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency in adults and is frequently complicated by non-infectious liver disease, including nodular regenerative hyperplasia and portal hypertension (PH). Early PH in CVID is under-recognized due to heterogeneous presentations and the limited sensitivity of traditional screening tools (e.g., standard ultrasound, non-specific liver enzymes). Emerging evidence suggests that combining immunologic profiling with refined biochemical markers and advanced imaging may improve early detection. Candidate markers include soluble interleukin-2 receptor (sIL-2R) as an index of immune activation, gamma-glutamyl transferase (GGT) as a hepatobiliary stress marker, and immunophenotypic features such as reduced naïve CD45RA+CD4+ T cells and B-lymphocytopenia. Imaging innovations—particularly transient elastography for liver stiffness, spleen stiffness measurement, and systematic assessment of splenomegaly—offer promise for noninvasive, scalable screening. An integrated biomarker–imaging framework could enable earlier recognition, refine risk stratification, and guide timely intervention to reduce morbidity and mortality in CVID-associated PH.

The central goal of this Research Topic is to identify, validate, and operationalize minimally invasive biomarker and imaging strategies for the early detection and risk stratification of portal hypertension in CVID. By uniting biochemical indices, immunologic signatures, and advanced elastography-based metrics, we aim to define sensitive, specific, and clinically actionable diagnostic pathways that can be adopted across diverse care settings and inform translational research and therapeutic trials in primary immunodeficiencies.

We welcome Original Research, Reviews, Mini-Reviews, Perspectives, and Opinion pieces addressing, but not limited to, the following themes:

• Immune-related biomarker discovery and validation

• Imaging innovations and standardization in CVID

• Integrated diagnostic algorithms for CVID and their validation

• Pathophysiology and endotypes of CVID and their complications

• Clinical translation and outcomes

Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation, for instance in an independent patient population or by PCR, are considered out of scope of this section

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Novel Biomarkers and Diagnostics for Early Portal Hypertension Detection in CVID