title: Nodular regenerative hyperplasia: the main liver disease in patients with primary hypogammaglobulinemia and hepatic abnormalities.
abstract: OBJECTIVE
  Liver lesions associated with primary hypogammaglobulinemia have been poorly described. We aimed to assess the clinical, histological and immune features and outcome of hepatic injury in patients with primary hypogammaglobulinemia.
  
  
  METHODS
  The medical records of 51 patients (23 patients with liver biopsy) with primary hypogammaglobulinemia and liver abnormalities were retrospectively reviewed. Forty-three controls with primary hypogammaglobulinemia but with no hepatic manifestations were analyzed in parallel.
  
  
  RESULTS
  Cholestasis (65%), mainly anicteric, and portal hypertension (50%) were the main hepatic manifestations. Histological analysis revealed non-fibrosing architectural abnormalities consistent with nodular regenerative hyperplasia (NRH) in 84% of CVID patients and in all HIGM and XLA patients. Intrasinusoidal lymphocytic infiltration, abnormalities of portal vessels and epithelioid granulomas were observed in 90%, 43% and 44% of patients, respectively. NRH was associated with portal hypertension in 75% of the cases. These patients more often presented with autoimmune diseases and peripheral lymphocytic abnormalities than control patients (p < 0.05).
  
  
  CONCLUSIONS
  Liver involvement in primary hypogammaglobulinemia mainly consists of NRH leading to chronic cholestasis and portal hypertension. Association with intrasinusoidal T cell infiltration, portal vein endotheliitis, autoimmune diseases and peripheral lymphocytic abnormalities suggests an autoimmune mechanism.
authors.affiliation: Hepatology and Gastroenterology Department, Hôpital Européen Georges Pompidou, Paris, France. georgia.malamut@egp.aphp.fr
authors.forename: Georgia
authors.initials: G
authors.lastname: Malamut
authors.forename: Marianne
authors.initials: M
authors.lastname: Ziol
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.forename: Michel
authors.initials: M
authors.lastname: Beaugrand
authors.forename: Jean François
authors.initials: JF
authors.lastname: Viallard
authors.forename: Anne Sophie
authors.initials: AS
authors.lastname: Lascaux
authors.forename: Virginie
authors.initials: V
authors.lastname: Verkarre
authors.forename: Dominique
authors.initials: D
authors.lastname: Bechade
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Christophe
authors.initials: C
authors.lastname: Cellier
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000150:complications* / Q000473:pathology; D017668:Age of Onset; D000368:Aged; D001323:Autoantibodies / Q000032:analysis; D017074:Common Variable Immunodeficiency / Q000150:complications; D004798:Enzymes / Q000097:blood; D005260:Female; D006801:Humans; D053306:Hyper-IgM Immunodeficiency Syndrome / Q000150:complications; D006965:Hyperplasia; D008099:Liver / Q000002:abnormalities* / Q000473:pathology*; D008102:Liver Circulation; D008107:Liver Diseases / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D008111:Liver Function Tests; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011169:Portal Vein / Q000002:abnormalities / Q000473:pathology; D012744:Sex Ratio; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D004798:Enzymes