title: Risk factors for developing de novo autoimmune hepatitis associated with anti-glutathione S-transferase T1 antibodies after liver transplantation.
abstract: De novo autoimmune hepatitis (de novo AIH) is a rare form of graft dysfunction that develops after liver transplantation (LT) in patients transplanted for conditions other than autoimmune disorders. Although characterized by biochemical, serological, and histological features of AIH, de novo AIH is sometimes associated with atypical serum autoantibodies, many of which are directed against glutathione S-transferase T1 (anti-GSTT1). GSTT1 donor/recipient genotype mismatch has been suggested as a necessary condition for the appearance of autoantibodies and de novo AIH. However, clinically evident disease is not observed in all patients with anti-GSTT1 antibodies. We examined the incidence of de novo AIH and its conditioning (risk) factors in patients with anti-GSTT1 antibodies. Anti-GSTT1 autoantibodies were detected in 29 of 419 [6.9%; 95% confidence interval (CI), 4.9-9.8] consecutive adult LT recipients with donor/recipient GSTT1 mismatch. Twenty of 27 assessable patients (74%) developed de novo AIH after a median follow-up of 26 months (95% CI, 19.2-32.8). The probability of de novo AIH was 11%, 44%, and 60% 12, 24, and 36 months after LT, respectively. No relationship emerged between de novo AIH and recipient gender, donor and recipient age, rejection episodes, immunosuppressive regime, allelic GSTT1 expression, human leukocyte antigen distribution, or cytomegalovirus infection. Multivariate analysis identified male donor [hazard ratio (HR), 3.3; 95% CI, 1.18-9.26; P = 0.018], nonalcoholic etiology (HR, 4.67; 95% CI, 1.64-13.3; P = 0.002), and high anti-GSTT1 titer (HR, 2.98; 95% CI, 1.04-8.57; P = 0.035) as independent predictors of de novo AIH. Most patients with anti-GSTT1 antibodies and donor/recipient GSTT1 mismatch developed clinically evident de novo AIH after LT. The risk of developing the disease was increased by male donor gender, nonalcoholic etiology of original liver disease, and a high anti-GSTT1 titer.
authors.affiliation: Liver Transplantation Unit, Gastroenterology and Hepatology Division (CIBERHED), Madrid, Spain. msalcedo.hgugm@salud.madrid.org
authors.forename: Magdalena
authors.initials: M
authors.lastname: Salcedo
authors.forename: Margarita
authors.initials: M
authors.lastname: Rodríguez-Mahou
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodríguez-Sainz
authors.forename: Diego
authors.initials: D
authors.lastname: Rincón
authors.forename: Emilio
authors.initials: E
authors.lastname: Alvarez
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Vicario
authors.forename: Maria-Vega
authors.initials: MV
authors.lastname: Catalina
authors.forename: Ana
authors.initials: A
authors.lastname: Matilla
authors.forename: Cristina
authors.initials: C
authors.lastname: Ripoll
authors.forename: Gerardo
authors.initials: G
authors.lastname: Clemente
authors.forename: Rafael
authors.initials: R
authors.lastname: Bañares
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D005982:Glutathione Transferase / Q000276:immunology*; D019693:Hepatitis, Autoimmune / Q000201:enzymology / Q000209:etiology* / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007166:Immunosuppressive Agents; D005982:Glutathione Transferase; C495790:glutathione transferase T1-1, human