Anti-transforming growth factor-β1 antibody improves survival rate following partial hepatectomy in cirrhotic rats

Abstract

In a cirrhotic liver, regenerative ability is so impaired that massive resection easily complicates postoperative liver dysfunction, which frequently leads to life-threatening multiple-organ failure. Transforming growth factor-β1 (TGF-β1) is considered to be a key cytokine regulating both hepatocyte proliferation and matrix expression in fibrosis. Therefore, we investigated the effect of TGF-β1 inhibitors by using a neutralizing antibody on 70% partial hepatectomy (PHx) in cirrhotic rats. Cirrhosis was induced by intraperitoneal injections of dimethylnitrosamine (DMN) three times per week for 3 weeks. Since the cirrhotic rats died within 48 h after PHx, anti-TGF-β1 antibody or phosphate buffered saline (PBS) was administered to the rats from subcutaneously implanted osmotic pump preoperatively. Twenty-four hours after PHx, the rats were sacrificed. The anti-TGF-β1 antibodies suppressed the elevation of TGF-β1 mRNA, and increased both relative liver weight ratio and the hepatocellular DNA synthesis. The blood chemical analysis indicated that the anti-TGF-β1 antibodies significantly suppressed postoperative hyperbilirubinemia. As a result, it improved the survival rate of the rats after PHx. In the present study, we firstly demonstrated that preoperative continuous administration of anti-TGF-β1 antibodies significantly accelerates liver regeneration after PHx in DMN-treated cirrhotic rats.