Acquired protein S deficiency leads to obliterative portal venopathy and to compensatory nodular regenerative hyperplasia in HIV-infected patients.
OBJECTIVE
To identify the mechanism of nodular regenerative hyperplasia in HIV-infected patients.


METHODS
Case-control study.


METHODS
The hepatology and the infectious disease units of two tertiary care centers in France.


METHODS
We compared 13 consecutive HIV-positive patients with unexplained nodular regenerative hyperplasia to 16 consecutive HIV-positive patients without nodular regenerative hyperplasia, to eight HIV-negative patients with nodular regenerative hyperplasia from an identified cause and to 10 anonymous healthy blood donors.


METHODS
Patients and controls were screened for diminished protein S activity and antiprotein S immunoglobulin G (IgG) antibodies. The antiprotein S activity of purified IgG from patients and controls was assessed in a functional test of activation of protein C in which protein S serves as a cofactor. A full liver CT portography was realized on the liver explant of a case patient.


RESULTS
The CT portography disclosed diffuse obliterative portal venopathy. Levels of protein S activity were lower among patients with HIV-associated nodular regenerative hyperplasia when compared with HIV-positive patients without nodular regenerative hyperplasia and when compared with HIV-negative patients with nodular regenerative hyperplasia (P < 0.005 for all comparisons). HIV-positive patients with nodular regenerative hyperplasia had significantly higher levels of antiprotein S IgG than HIV-positive patients without nodular regenerative hyperplasia and healthy controls. Purified IgG from patients with HIV-associated nodular regenerative hyperplasia specifically inhibited the protein S-dependent protein C activation.


CONCLUSIONS
Acquired autoimmune protein S paucity and secondary thrombophilia appear to be causes of obliterative portal venopathy and compensatory nodular regenerative hyperplasia in HIV-positive patients.
Mallet
Vincent O
VO
Institut Cochin, Université Paris Descartes, CNRS, UMR 8104, Inserm, U567, Paris, France. vincent.mallet@cch.aphp.fr
Varthaman
Aditi
A
Lasne
Dominique
D
Viard
Jean-Paul
JP
Gouya
Hervé
H
Borgel
Delphine
D
Lacroix-Desmazes
Sébastien
S
Pol
Stanislas
S
D000328:Adult; D001323:Autoantibodies / Q000097:blood; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D050716:Complement C4b-Binding Protein / Q000032:analysis; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D006801:Humans; D006965:Hyperplasia / Q000209:etiology; D006975:Hypertension, Portal / Q000000981:diagnostic imaging / Q000209:etiology; D007074:Immunoglobulin G / Q000097:blood; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011169:Portal Vein / Q000473:pathology*; D011172:Portography; D017293:Protein S / Q000037:antagonists & inhibitors / Q000276:immunology; D018455:Protein S Deficiency / Q000150:complications* / Q000276:immunology
D001323:Autoantibodies; D050716:Complement C4b-Binding Protein; D007074:Immunoglobulin G; D017293:Protein S