C-terminal peptide of anaphylatoxin C3a enhances hepatic function after steatotic liver transplantation: a study in a rat model.

Abstract Background C3a, a complement component stimulates hepatocyte proliferation. In this study, we investigated whether a functional peptide from its C terminal, YAAALGLAR (C3aP), enhanced liver function after steatotic liver transplantation in a rat model. Methods Livers of Sprague-Dawley (SD) rats fed a high-fat diet for 2 months were used as donors. Their liver parenchyma displayed over 60% macrovesicular steatosis upon histopathologic examination. Weight and age-matched isogeneic SD rats were used as recipients of orthotopic liver transplantations (OLTs). Before OLT, the donor livers were perfused with University of Wisconsin solution supplemented with 10 mg/L C3aP. Postoperatively, 0.1 mL of 100 μg/mL C3aP was administered daily intraperitoneally to the experimental group. Recipients without C3aP intraperitoneal administration were the control group. We examined the survival rates, histopathologic changes, and hepatic functions of recipients. Results Six of the 10 control recipients died within 3 days posttransplantation; however, among the experimental group, 8 of 10 recipients survived beyond 7 days. Histopathologic examination showed that at day 3 posttransplantation, hepatocyte steatosis was notably reversed in the experimental group with cells undergoing active mitosis. In contrast, massive parenchymal necrosis was observed among the control group without notable hepatocyte proliferation. Furthermore, serum enzyme levels among the experimental group were significantly lower than those of the control group at day 3 postoperatively. Conclusion C3aP stimulated hepatocyte proliferation and reversed fatty degradation of hepatocytes, thus enhancing hepatic function and prolonging the survival of recipients of steatotic liver transplantations.