Effect of Donor Hepatic Steatosis on Ischemia Reperfusion Injury in Liver Transplant Recipient

Abstract

Introduction: Ischemia reperfusion injury (IRI) is an important complication of liver transplant (LT). The donor risk index, which does not incorporate steatosis, includes several variables known to impact on allograft survival. The purpose of this study was to report on donor liver allograft steatosis and its association with severity of IRI.

Aim: The aim of this study was to determine the effect of type and grade of donor liver steatosis on the occurrence and severity of IRI in LT recipients.

Methods: This was an observational study conducted at a single center over a period of 37 months from July 2013 to August 2016. Liver biopsy was performed twice, initially at the time of procurement before graft perfusion for steatosis assessment. Steatosis was classified as microsteatosis (MiS) or macrosteatosis (MaS) with mild, moderate, or severe grade. Second biopsy for IRI assessment was taken before skin closure in death donor LT (DDLT) and at the time of transaminitis in postoperative period (<72 hrs) in living donor LT (LDLT). IRI was graded as per neutrophil infiltrate, apoptosis, and hepatocyte cell dropout. Prevalence of IRI and association steatosis was studied along with other factors.

Results: Among 53 subjects, 35 were DDLTs and 18 were LDLTs. All live donor grafts were restricted to <15% MaS and the deceased liver grafts had different type and degree of steatosis. In DDLTs, the association between occurrence of IRI and MaS was not statistically significant (P = 0.201). In DDLTs, the mild steatosis was not significantly associated with IRI. Death donor and ischemic time were significantly associated with IRI. Child's stage and MELD scores, gender, and age were not associated with risk of IRI. Severity of IRI is significantly associated with 3-month mortality (P = 0.001).

Conclusion: In patients with mild steatosis, IRI does not correlate with steatosis. However, more patients with moderate and severe steatosis are needed to define the relationship of the two in this group of patients.

Keywords: ALT, alanine transferase; AST, aspartate transferase; CIT, cold ischemia time; DDLT, death donor liver transplant; DRI, donor risk index; ECD, extended criteria donor; EHBA, extrahepatic biliary atresia; H&E, haematoxilin & eosin; HBV, hepatitis B virus; HCV, hepatitis C virus; HPE, histopathological examination; IRI, ischemia reperfusion injury; LAI, liver attenuation index; LDLT, living donor liver transplant; LT, liver transplant; MELD, model for end-stage liver disease; MaS, macrosteatosis; MiS, microsteatosis; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; PNF, primary nonfunction (graft); WIT, warm ischemia time; cold ischemic time; ischemia reperfusion injury; macrosteatosis; microsteatosis; warm ischemic time.

Figure 1

Allograft assessment. MaS, macrosteatosis; HPE, histopathological examination; BMI, body mass index; CT, computerized tomography; LFT, liver function test.

Figure 2

Post-transplant assessment. MELD, model for end-stage liver disease; CIT, cold ischemia time; WIT, warm ischemia time; ALT, alanine transferase; AST, aspartate transferase. ICH, intra cerebral haemorrhage; ALF, acute liver failure.

Figure 3

Incidence of IRI in both DDLT and LDLT (χ² = 24.047 P < 0.001). DDLT, death donor liver transplant.