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Nodular Regenerative Hyperplasia in Common Variable Immunodeficiency

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Abstract

Purpose

Patients with Common Variable Immunodeficiency (CVID) are subject to the development of a liver disease syndrome known as nodular regenerative hyperplasia (NRH). The purpose of this study was to define the characteristics and course of this complication of CVID.

Methods

CVID patients were evaluated by retrospective and prospective clinical course review. Liver biopsy specimens were evaluated for evidence of NRH and studied via RT-PCR for cytokine analysis.

Results

NRH in our CVID patient population occurred in approximately 5 % of the 261 patients in our total CVID study group, initially presenting in most cases with an elevated alkaline phosphatase level. While in some patients the disease remained static, in a larger proportion a more severe disease developed characterized by portal hypertension, the latter leading to hypersplenism with neutropenia and thrombocytopenia and, in some cases, to ascites. In addition, a substantial proportion of patients either developed or presented initially with an autoimmune hepatitis-like (AIH-like) liver disease that resulted in severe liver dysfunction and, in most cases to death due to infections. The liver histologic findings in these AIH-like patients were characterized by underlying NRH pattern with superimposed interface hepatitis, lymphocytic infiltration and fibrosis. Immunologic studies of biopsies of NRH patients demonstrated the presence of infiltrating T cells producing IFN-γ, suggesting that the NRH is due to an autoimmune process.

Conclusion

Overall, these studies provide evidence that NRH may not be benign but, can be a severe and potentially fatal disease complication of CVID that merits close monitoring and intervention.

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Acknowledgments

Lubna Hooda was funded in whole or in part by the Frederick National Laboratory under Contract No. HHSN261200800001E. The contents of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products or organizations imply endorsement by the US government.

Sources of funding

Funding is from the intramural program of the NIAID, NCI, National Institutes of Health. None of the authors has any financial relationships with industries that have an interest in the subject matter or materials discussed in the manuscript.

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Author notes

  1. Julia Friend

    Present address: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

Authors and Affiliations

  1. Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Ivan J. Fuss, Julia Friend, Zhiqiong Yang, Lubna Hooda & Warren Strober

  2. Clinical Research Directorate/CMRP, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA

    Lubna Hooda

  3. Mucosal Immunobiology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Jian Ping He

  4. Division of Digestive Diseases, Yale University, Bethesda, MD, USA

    James Boyer

  5. Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Liqiang Xi, Mark Raffeld & David E. Kleiner

  6. Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Theo Heller

  7. Mucosal Immunity Section, Laboratory of Host Defenses, CRC Building Rm. 5W-3864, Bethesda, MD, 20892, USA

    Ivan J. Fuss

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  1. Ivan J. Fuss
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Corresponding author

Correspondence to Ivan J. Fuss.

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Fuss, I.J., Friend, J., Yang, Z. et al. Nodular Regenerative Hyperplasia in Common Variable Immunodeficiency. J Clin Immunol 33, 748–758 (2013). https://doi.org/10.1007/s10875-013-9873-6

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  • DOI: https://doi.org/10.1007/s10875-013-9873-6

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