Liver disease accompanied by enteropathy in common variable immunodeficiency: Common pathophysiological mechanisms

Area of Science:

• Immunology
• Gastroenterology
• Hepatology

Background:

• Common variable immunodeficiency (CVID) is a primary immunodeficiency with significant clinical impact.
• Liver disease, especially nodular regenerative hyperplasia (NRH), is a serious complication in CVID patients, increasing morbidity and mortality.
• The exact cause of liver disease in CVID remains unclear, and effective treatments are lacking.

Purpose of the Study:

• To compare clinical characteristics of CVID patients with and without liver-spleen axis abnormalities.
• To analyze liver and duodenal biopsies in CVID patients with portal hypertension (PH) to understand liver injury pathophysiology.
• To investigate the association between CVID, liver disease, and duodenal abnormalities.

Main Methods:

• Patients were categorized into three groups: liver disease/PH, isolated splenomegaly, and no liver-spleen abnormalities.
• Clinical and biochemical data were collected and analyzed.
• Liver and duodenal biopsies were examined, including electron microscopy, and correlated with PH and clinical findings.

Main Results:

• 32.6% of 141 CVID patients had liver disease/PH, and 19.1% had isolated splenomegaly.
• CVID patients with PH exhibited splenomegaly, thrombocytopenia, and esophageal varices, irrespective of biochemical changes.
• Duodenal celiac pattern and lymphocytic infiltration correlated with PH; NRH was found in all PH patients. Lymphocyte-mediated cytotoxicity is implicated.

Conclusions:

• Liver disease and PH are common in CVID, necessitating regular imaging surveillance.
• CVID patients with PH show a distinct immunological profile, including lymphadenopathy and altered lymphocyte counts.
• Lymphocyte-mediated cytotoxicity against hepatocytes and enterocytes is a probable mechanism underlying liver and duodenal injury in CVID.