Clinical Reviews in Allergy & Immunology

, Volume 55, Issue 3, pp 340–351 | Cite as

Common Variable Immunodeficiency and Liver Involvement

  • Junmin Song
  • Ana Lleo
  • Guo Xiang Yang
  • Weici Zhang
  • Christopher L. Bowlus
  • M. Eric Gershwin
  • Patrick S. C. LeungEmail author


Common variable immunodeficiency (CVID) is a primary B-cell immunodeficiency disorder, characterized by remarkable hypogammaglobulinemia. The disease can develop at any age without gender predominance. The prevalence of CVID varies widely worldwide. The underlying causes of CVID remain largely unknown; primary B-cell dysfunctions, defects in T cells and antigen-presenting cells are involved. Although some monogenetic defects have been identified in some CVID patients, it is likely that CVID is polygenic. Patients with CVID develop recurrent and chronic infections (e.g., bacterial infections of the respiratory or gastrointestinal tract), autoimmune diseases, lymphoproliferation, malignancies, and granulomatous lesions. Interestingly, autoimmunity can be the only clinical manifestation of CVID at the time of diagnosis and may even develop prior to hypogammaglobulinemia. The diagnosis of CVID is largely based on the criteria established by European Society for Immunodeficiencies and Pan-American Group for Immunodeficiency (ESID/PAGID) and with some recent modifications. The disease can affect multiple organs, including the liver. Clinical features of CVID patients with liver involvement include abnormal liver biochemistries, primarily elevation of alkaline phosphatase (ALP), nodular regenerative hyperplasia (NRH), or liver cirrhosis and its complications. Replacement therapy with immunoglobulin (Ig) and anti-infection therapy are the primary treatment regimen for CVID patients. No specific therapy for liver involvement of CVID is currently available, and liver transplantation is an option only in select cases. The prognosis of CVID varies widely. Further understanding in the etiology and pathophysiology will facilitate early diagnosis and treatments to improve prognosis.


Common variable immunodeficiency CVID Primary immunodeficiency B cell Hypogammaglobulinemia Infection Autoimmunity Granuloma Liver involvement Nodular regenerative hyperplasia Alkaline phosphatase 



Autoimmune enteropathy


Autoimmune hemolytic anemia


Alkaline phosphatase


Combined immunodeficiency


Common variable immunodeficiency


Granulomatous and lymphocytic interstitial lung disease


inflammatory bowel disease


International Consensus Document






Idiopathic thrombocytopenia


Intravenous immunoglobulin


Nodular regenerative hyperplasia


Primary biliary cholangitis


Primary sclerosing cholangitis


Gamma glutamyl transpeptidase


Subcutaneous immunoglobulin


Selective Immunoglobulin A deficiency


Toll-like receptor

Treg cell

Regulatory T cell


X-linked agammaglobulinemia


Compliance with Ethical Standards

This article does not contain any studies with human participants or animals performed by any of the authors.

The authors declare that they have no potential conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC 2017
corrected publication [March/2018]

Authors and Affiliations

  • Junmin Song
    • 1
    • 2
  • Ana Lleo
    • 3
  • Guo Xiang Yang
    • 1
  • Weici Zhang
    • 1
  • Christopher L. Bowlus
    • 4
  • M. Eric Gershwin
    • 1
  • Patrick S. C. Leung
    • 1
    Email author
  1. 1.Division of Rheumatology/Allergy and Clinical ImmunologyUniversity of California at Davis School of MedicineDavisUSA
  2. 2.Department of GastroenterologyShengjing Hospital of China Medical UniversityShenyangPeople’s Republic of China
  3. 3.Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research CenterMilanItaly
  4. 4.Division of Gastroenterology and HepatologyUniversity of CaliforniaDavisUSA

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