Nodular Regenerative Hyperplasia in Common Variable Immunodeficiency
- 913 Downloads
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.
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.
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.
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.
KeywordsCVID NRH autoimmune liver hypertension cytokine
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.
- 6.Giovanetti A, Pierdominici M, Mazzetta F, Marziali M, Renzi C, Mileo AM, et al. Unravelling the complexity of T cell abnormalities in common variable immunodefiency. J Immunol. 2007;178:3932–43.Google Scholar