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Common Variable Immunodeficiency and Liver Involvement

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Abstract

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.

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Abbreviations

AIE:

Autoimmune enteropathy

AIHA:

Autoimmune hemolytic anemia

ALP:

Alkaline phosphatase

CID:

Combined immunodeficiency

CVID:

Common variable immunodeficiency

GLILD:

Granulomatous and lymphocytic interstitial lung disease

IBD:

inflammatory bowel disease

ICON:

International Consensus Document

Ig:

Immunoglobulin

IL:

Interleukin

ITP:

Idiopathic thrombocytopenia

IVIG:

Intravenous immunoglobulin

NRH:

Nodular regenerative hyperplasia

PBC:

Primary biliary cholangitis

PSC:

Primary sclerosing cholangitis

r-GT:

Gamma glutamyl transpeptidase

SCIG:

Subcutaneous immunoglobulin

SIgAD:

Selective Immunoglobulin A deficiency

TLR:

Toll-like receptor

Treg cell:

Regulatory T cell

XLA:

X-linked agammaglobulinemia

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Authors and Affiliations

  1. Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis School of Medicine, 451 Health Sciences Drive, Davis, CA, 95616, USA

    Junmin Song, Guo Xiang Yang, Weici Zhang, M. Eric Gershwin & Patrick S. C. Leung

  2. Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China

    Junmin Song

  3. Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano, Milan, Italy

    Ana Lleo

  4. Division of Gastroenterology and Hepatology, University of California, Davis, CA, 95616, USA

    Christopher L. Bowlus

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  1. Junmin Song
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  2. Ana Lleo
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  3. Guo Xiang Yang
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Correspondence to Patrick S. C. Leung.

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Song, J., Lleo, A., Yang, G.X. et al. Common Variable Immunodeficiency and Liver Involvement. Clinic Rev Allerg Immunol 55, 340–351 (2018). https://doi.org/10.1007/s12016-017-8638-z

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