Nodular regenerative hyperplasia: the main liver disease in patients with primary hypogammaglobulinemia and hepatic abnormalities.
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.
Malamut
Georgia
G
Hepatology and Gastroenterology Department, Hôpital Européen Georges Pompidou, Paris, France. georgia.malamut@egp.aphp.fr
Ziol
Marianne
M
Suarez
Felipe
F
Beaugrand
Michel
M
Viallard
Jean François
JF
Lascaux
Anne Sophie
AS
Verkarre
Virginie
V
Bechade
Dominique
D
Poynard
Thierry
T
Hermine
Olivier
O
Cellier
Christophe
C
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
D001323:Autoantibodies; D004798:Enzymes