Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients
Open accessAbstract
Background & aims 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.
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Liver transplantation is an area of unmet need, and acute rejection episodes limit survival.
“One area of unmet need is organ transplantation, in particular liver transplantation (LT), where episodes of acute rejection (AR) limit survival (26).”
From The Blood Proteoform Atlas: A reference map of proteoforms in human hematopoietic cells (2022) · cites this paper as [26]
The number of AR subjects was small but reflects the approximately 20% prevalence of AR in liver transplant recipients.
“We note that the number of AR subjects is small but reflects the ~20% prevalence of AR in LTR (26, 38–40).”
From The Blood Proteoform Atlas: A reference map of proteoforms in human hematopoietic cells (2022) · cites this paper as [26]
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- Authors
- Levitsky, J., Goldberg, D., Smith, A. R., Mansfield, S. A., Gillespie, B. W., Merion, R. M., Lok, A. S. F., Levy, G., Kulik, L., Abecassis, M., & Shaked, A.
- Affiliations
- Northwestern University (US)
- University of Pennsylvania (US)
- University of Michigan (US)
- Arbor Research Collaborative for Health (US)
- University of Toronto (CA)
- Corresponding author
- Levitsky, Josh
- ORCID
- Venue
- Clinical Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 15
- Issue
- 4
- Pages
- 584-593.e2
- ISSN
- 1542-3565 (ISSN-L)
- PMC
- PMC5326609
- OpenAlex
- W2513682679
- Cited by
- 236
- References
- 34
- Citations by year
- 2026: 18 · 2025: 27 · 2024: 32 · 2023: 33 · 2022: 30 · 2021: 21 · 2020: 33 · 2019: 18 · 2018: 14 · 2017: 10
- FWCI
- 15.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Gastroenterology and Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P30CA060553)
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK062498, U01DK062444, U01DK062484, U01DK062536, U01DK062483, U01DK085587, U01DK062494, U01DK062531, U01DK062505, U01DK085563, U01DK062496, U01DK062467, U01DK085515)
- Topics
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
- Keywords
- acute rejection, liver transplantation, graft failure, post-transplant mortality, living donor liver transplantation, deceased donor liver transplantation, primary biliary cirrhosis, hepatitis C, risk factors for rejection, cause-specific mortality, competing risks, liver-related mortality
- MeSH terms
- Adult, Aged, Female, Graft Rejection, Humans, Male, Middle Aged, Risk Factors, Cohort Studies, Survival Analysis, Liver Transplantation, Liver Failure, Transplant Recipients
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