Expansion of hepatic progenitor cell in fatty liver graft after living donor liver transplantation

Abstract

Although it is known that steatotic livers have a reduced ability to regenerate, most individuals with steatosis show generally benign prognosis. We hypothesized that a proliferative blockade in steatotic hepatocytes results in the compensatory expansion of hepatic progenitor cells (HPC) during fatty liver regeneration. Fifty-four cases of living donor liver transplantation (LDLT) with a liver biopsy performed at the postoperative 10th day were examined. HPC were counted by immunofluorescence histochemical dual-staining technique using cytokeratin 7 and Ki-67, and the replicative arrest of hepatocytes was assessed by p21 immunohistochemistry. The degree of ductular proliferation during regeneration 10 days after LDLT correlated both with the degree of steatosis and the number of HPC (P < 0.001). There was no difference in the average number of HPC and the replicative arrest index between donors with or without steatosis before LDLT (P = 0.111 and P = 0.062). However, degree of steatosis correlated with both the expansion of HPC and the replicative arrest index during liver regeneration 10 days after LDLT (P < 0.001 and P < 0.001, respectively). Moreover, increased replicative arrest was strongly associated with HPC expansion (P < 0.001). In conclusion, the compensatory expansion of HPC as a result of impaired hepatocyte replication occurred during steatotic liver regeneration after LDLT.