title: Nodular regenerative hyperplasia in common variable immunodeficiency.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ifuss@niaid.nih.gov
authors: Ivan J
authors: IJ
authors: Fuss
authors: Julia
authors: J
authors: Friend
authors: Zhiqiong
authors: Z
authors: Yang
authors: Jian Ping
authors: JP
authors: He
authors: Lubna
authors: L
authors: Hooda
authors: James
authors: J
authors: Boyer
authors: Liqiang
authors: L
authors: Xi
authors: Mark
authors: M
authors: Raffeld
authors: David E
authors: DE
authors: Kleiner
authors: Theo
authors: T
authors: Heller
authors: Warren
authors: W
authors: Strober
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D015551:Autoimmunity; D002648:Child; D017074:Common Variable Immunodeficiency / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000453:epidemiology / Q000209:etiology / Q000276:immunology*; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D007371:Interferon-gamma; D000469:Alkaline Phosphatase