title: Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients.
abstract: OBJECTIVE
  Acute rejection is detrimental to most transplanted solid organs, but is considered to be less of a consequence for transplanted livers. We evaluated risk factors for and outcomes after biopsy-proven acute rejection (BPAR) based on an analysis of a more recent national sample of recipients of liver transplants from living and deceased donors.
  
  
  METHODS
  We analyzed data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) from 2003 through 2014 as the exploratory cohort and the Scientific Registry of Transplant Recipients (SRTR) from 2005 through 2013 as the validation cohort. We examined factors associated with time to first BPAR using multivariable Cox regression or discrete-survival analysis. Competing risks methods were used to compare causes of death and graft failure between recipients of living and deceased donors.
  
  
  RESULTS
  At least 1 BPAR episode occurred in 239 of 890 recipients in A2ALL (26.9%) and 7066 of 45,423 recipients in SRTR (15.6%). In each database, risk of rejection was significantly lower when livers came from biologically related living donors (A2ALL hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.43-0.76; and SRTR HR, 0.78; 95% CI, 0.66-0.91) and higher in liver transplant recipients with primary biliary cirrhosis, of younger age, or with hepatitis C. In each database, BPAR was associated with significantly higher risks of graft failure and death. The risks were highest in the 12 month post-BPAR period in patients whose first episode occurred more than 1 year after liver transplantation: HRs for graft failure were 6.79 in A2ALL (95% CI, 2.64-17.45) and 4.41 in SRTR (95% CI, 3.71-5.23); HRs for death were 8.81 in A2ALL (95% CI, 3.37-23.04) and 3.94 in SRTR (95% CI, 3.22-4.83). In analyses of cause-specific mortality, associations were observed for liver-related (graft failure) causes of death but not for other causes.
  
  
  CONCLUSIONS
  Contrary to previous data, acute rejection after liver transplant is associated with significantly increased risk of graft failure, all-cause mortality, and graft failure-related death, regardless of primary liver disease etiology. Living donor liver transplantation from a biologically related donor is associated with decreased risk of rejection.
authors: Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address: j-levitsky@northwestern.edu.
authors: Josh
authors: J
authors: Levitsky
authors: Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: David
authors: D
authors: Goldberg
authors: Arbor Research Collaborative for Health, Ann Arbor, Michigan; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
authors: Abigail R
authors: AR
authors: Smith
authors: Arbor Research Collaborative for Health, Ann Arbor, Michigan.
authors: Sarah A
authors: SA
authors: Mansfield
authors: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
authors: Brenda W
authors: BW
authors: Gillespie
authors: Arbor Research Collaborative for Health, Ann Arbor, Michigan; Section of Transplantation, University of Michigan, Ann Arbor, Michigan.
authors: Robert M
authors: RM
authors: Merion
authors: Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.
authors: Anna S F
authors: AS
authors: Lok
authors: University of Toronto, Toronto, Ontario, Canada.
authors: Gary
authors: G
authors: Levy
authors: Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Laura
authors: L
authors: Kulik
authors: Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Michael
authors: M
authors: Abecassis
authors: Division of Transplant Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Abraham
authors: A
authors: Shaked
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000150:complications*; D006801:Humans; D017093:Liver Failure / Q000401:mortality*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016019:Survival Analysis; D066027:Transplant Recipients
keywords: Database Analysis; LT; Risk Factor; Survival