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Acute rejection associated with increased risk for death

Contrary to previous research, acute rejection after liver transplant was associated with an increased risk for graft failure, graft-failure-related death and all-cause mortality, according to recent findings published in Clinical Gastroenterology and Hepatology.

“Even though most episodes of acute rejection after solid organ transplantation are treatable, such events place recipients at increased risk for progressive graft failure and death,” Josh Levitsky, MD, MS, in the division of gastroenterology and hepatology at Northwestern University Feinberg School of Medicine, and colleagues wrote. “The classic exception to this rule has been in liver transplantation, although this concept is based on nearly 20 year-old data. The current analysis directly contrasts these older data by demonstrating increased risks for graft failure and death in liver transplant recipients who experience acute rejection.

Levitsky and colleagues evaluated risk factors and outcomes for biopsy-proven acute rejection (BPAR), based on an analysis of the Adult-to-Adult Living Donor Liver Transplantation (A2ALL) cohort of 890 patients undergoing liver transplant between 2003 and 2014. The researchers validated their data using the Scientific Registry of Transplant Recipients (SRTR) cohort of patients treated between 2005 and 2013. The researchers examined factors associated with time to first BPAR using multivariate regression or discrete-survival analysis.

They found at least 1 BPAR episode occurred in 26.9% of A2ALL transplant recipients and in 15.6% of SRTR recipients. Rejection was lower when livers came from related donors (A2ALL HR = 0.57; 95% CI, 0.43-0.76 and SRTR HR = 0.78; 95% CI, 0.66-0.91) and higher in transplant recipients who had primary biliary cirrhosis, who were younger, or who had hepatitis C. BPAR was associated with increased risk for graft failure (A2ALL HR = 6.79; 95% CI, 2.64-17.45 and SRTR HR = 4.41; 95% CI, 3.71-5.23) and death (A2ALL HR = 8.81; 95% CI, 3.37-23.04 and SRTR HR = 3.94; 95% CI, 3.22-4.83). The risk was highest in patients whose first episode occurred more than 1 year after transplant.

“We demonstrate that acute rejection in liver transplant recipients should be viewed as an important clinical event associated with an increased risk for graft failure and death,” the researchers wrote. “These data represent a paradigm shift in the importance of rejection following liver transplantation that needs consideration in guiding the implementation of more optimal donor/recipient selection, immunosuppression protocols, and immune monitoring strategies.” – by Will Offit

Disclosure: The researchers report no relevant financial disclosures.