Fibrotic liver regeneration after hepatectomy. How far can we perform hepatectomy for HCC patients with fibrosis?

Failure of fibrotic liver to regenerate after hepatectomy limits therapeutic options and increases demand for liver transplantation, representing a significant clinical problem. The mechanism underlying regenerative failure in fibrosis is poorly understood. We have previously proved that failure of hepatocyte-mediated regeneration in fibrotic mice triggers activation of the progenitor cell compartment and severe fibrogenic response. Focused on the fibrosis stage, we retrospectively analyzed 210 consecutive HCC patients who underwent curative hepatectomy at our facility from 2005 to 2010. Multivariate analysis revealed that extent of resection (p>0.001), intraoperative blood loss (p=0.002), and fibrosis stage (p=0.04) were independent risk factors for developing posthepatectomy liver failure defined by ISGLS. To expand the indication of hepatectomy for HCC patients with fibrosis, we searched for the effect of preoperative methylprednisolone on fibrotic mice. Preoperative steroid administration inhibited the increase of serum TNF-alpha level and hepatocyte apoptosis without suppressing the liver regeneration and improved survival rate after hepatectomy in fibrotic mice. Our basic study implied the beneficial effect and clinical relevance of preoperative steroid treatment for HCC patients, especially with fibrosis.