Nodular Regenerative Hyperplasia in Common Variable Immunodeficiency

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.

New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin

“…Their presence requires histological confirmation. Only a minority of CVID patients will have the granulomatous variant, lymphoid interstitial pneumonitis, nodular hyperplasia of the gut or nodular regenerative hyperplasia of the liver, proved by biopsy [64][65][66][67]69]. Therefore, meeting this criterion is not required for the diagnosis, but their presence increases diagnostic certainty.…”

“…• Lymphoid interstitial pneumonitis [64] • Granulomatous disorder [65,66] • Nodular regenerative hyperplasia of the liver [67,68] • Nodular lymphoid hyperplasia of the gut [69] • Absence of plasma cells on gut biopsy [70,71] Meeting criteria in categories ABC or ABD indicates probable CVID. Patients meeting criteria ABC and ABD should be treated with intravenous immunoglobulin/subcutaneous immunoglobulin (IVIG/scIG).…”

Idiopathic Non-Cirrhotic Intrahepatic Portal Hypertension (NCIPH)—Newer Insights into Pathogenesis and Emerging Newer Treatment Options

“…Though there has been a significant change over time in the detail of disorders associated with NCIPH there remains a consistent tendency for implicated factors to be of relevance to the immune system and gut. 35,36 Earlier studies emphasized the importance of common variable immunodeficiency (CVID). 37,38 Treatment with intravenous immunoglobulin replacement has largely resolved the issue, further supporting the notion that enteropathies associated with CVID were somehow promoting the vasculopathy of terminal portal venous radicles.…”

A review on guidelines for management and treatment of common variable immunodeficiency

“…Unexplained liver disease with portal hypertension occurs in 5-10% of the patients. Autoimmunity (69.2%) and lymphocyte abnormalities (78.6%) were observed more frequently in CVID patients with hepatic dysfunctions [169][170][171][172][173].…”