title: Low incidence of acute rejection in hepatitis B virus positive liver transplant recipients and the impact of hepatitis B immunoglobulin.
abstract: Historically, hepatitis B virus (HBV) liver transplantation (LT) recipients have less acute cellular rejection (ACR) than those without HBV. We questioned whether this has persisted in an era of decreased Hepatitis B immunoglobulin use (HBIG) given its in vitro immunoregulatory effects. We compared the incidence, risk factors and outcomes of ACR among 40,593 primary LT recipients with HBV, hepatitis C, steatohepatitis, and immune liver disease (OPTN 2000-2011). We also assessed the in vitro effect of HBIG on alloimmune lymphoproliferation and regulatory T cell generation using mixed lymphocyte reactions. In multivariate analysis, HBV status remained a strong independent predictor of freedom from ACR (OR 0.58, 95% CI: 1.5-2.1). Patient (67.7% vs 72.3%) and graft (60.8% vs 69.1%) survival were significantly lower in patients with ACR versus no ACR for all causes except HBV. HBIG use had no statistical association with ACR. In vitro, HBIG at concentrations equivalent to clinical dosing did not inhibit lymphoproliferation or promote regulatory T cell development. In summary, the incidence and impact of ACR is lower now for HBV LT and does not appear to be secondary to HBIG by our in vitro and in vivo analyses. Rather, it may be due to the innate immunosuppressive properties of chronic HBV infection.
authors.affiliation: Department of Medicine - Division of Gastroenterology and Hepatology, 251 East Huron Street Galter Suite 3-150, Chicago, IL 60611, United States.
authors.forename: Annapoorani
authors.initials: A
authors.lastname: Veerappan
authors.affiliation: Department of Medicine - Division of Gastroenterology and Hepatology, 251 East Huron Street Galter Suite 3-150, Chicago, IL 60611, United States; Department of Preventive Medicine, 680 N. Lake Shore Drive Suite 1400, Chicago, IL 60611, United States; Northwestern University Transplant Outcomes Research Collaborative (NUTORC), 676 N. St. Clair 19th Floor, Chicago, IL 60611, United States.
authors.forename: Lisa B
authors.initials: LB
authors.lastname: VanWagner
authors.affiliation: Department of Surgery, Comprehensive Transplant Center, 676 N. St. Clair 19th Floor, Chicago, IL 60611, United States; Department of Microbiology-Immunology, 303 East Chicago Ave Ward 8-296, Chicago, IL 60611, United States.
authors.forename: James M
authors.initials: JM
authors.lastname: Mathew
authors.affiliation: Department of Surgery, Comprehensive Transplant Center, 676 N. St. Clair 19th Floor, Chicago, IL 60611, United States.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Surgery, Comprehensive Transplant Center, 676 N. St. Clair 19th Floor, Chicago, IL 60611, United States.
authors.forename: Joshua
authors.initials: J
authors.lastname: Miller
authors.affiliation: Northwestern University Transplant Outcomes Research Collaborative (NUTORC), 676 N. St. Clair 19th Floor, Chicago, IL 60611, United States; Department of Surgery, Comprehensive Transplant Center, 676 N. St. Clair 19th Floor, Chicago, IL 60611, United States.
authors.forename: Brittany
authors.initials: B
authors.lastname: Lapin
authors.affiliation: Department of Medicine - Division of Gastroenterology and Hepatology, 251 East Huron Street Galter Suite 3-150, Chicago, IL 60611, United States; Northwestern University Transplant Outcomes Research Collaborative (NUTORC), 676 N. St. Clair 19th Floor, Chicago, IL 60611, United States; Department of Surgery, Comprehensive Transplant Center, 676 N. St. Clair 19th Floor, Chicago, IL 60611, United States. Electronic address: j-levitsky@northwestern.edu.
authors.forename: Josh
authors.initials: J
authors.lastname: Levitsky
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology* / Q000209:etiology*; D006509:Hepatitis B / Q000150:complications / Q000276:immunology* / Q000821:virology; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D015994:Incidence; D016031:Liver Transplantation; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012189:Retrospective Studies; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D066027:Transplant Recipients
chemical_list: D007136:Immunoglobulins
keywords: Hepatitis B immunoglobulin; Hepatitis B virus; Immunosuppression; Liver transplantation; Rejection