Strategies to rescue steatotic livers before transplantation in clinical and experimental studies.
The shortage of donor livers has led to an increased use of organs from expanded criteria donors. Included are livers with steatosis, a metabolic abnormality that increases the likelihood of graft complications post-transplantation. After a brief introduction on the etiology, pathophysiology, categories and experimental models of hepatic steatosis, we herein review the methods to rescue steatotic donor livers before transplantation applied in clinical and experimental studies. The methods span the spectrum of encouraging donor weight loss, employing drug therapy, heat shock preconditioning, ischemia preconditioning and selective anesthesia on donors, and the treatment on isolated grafts during preservation. These methods work at different stages of transplantation process, although share similar molecular mechanisms including lipid metabolism stimulation through enzymes or nuclear receptor e.g., peroxisomal proliferator-activated receptor, or anti-inflammation through suppressing cytokines e.g., tumor necrosis factor-α, or antioxidant therapies to alleviate oxidative stress. This similarity of molecular mechanisms implies possible future attempts to reinforce each approach by repeating the same treatment approach at several stages of procurement and preservation, as well as utilizing these alternative approaches in tandem.
Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and Shriners Burns Hospital, Boston, MA 02114, United States.
Qiang
Q
Liu
Maria-Louisa
ML
Izamis
Hongzhi
H
Xu
Tim
T
Berendsen
Martin
M
Yarmush
Korkut
K
Uygun
D000818:Animals; D004195:Disease Models, Animal; D046148:Donor Selection; D005234:Fatty Liver / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D012307:Risk Factors; D014019:Tissue Donors / Q000600:supply & distribution*; D016896:Treatment Outcome
Clinical; Donor liver; Experimental; Liver transplantation; Steatosis