Pentoxifylline, but not ursodeoxycholic acid or tauroursodeoxycholic acid inhibits the proliferative effect of sera samples from primary biliary cirrhosis patients

Abstract

Abstract Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by progressive hepatic fibrosis. Fibroproliferation is one of two major events occurring in hepatic fibrosis. In this study we evaluated PBC patients sera samples ( n = 27) and our results demonstrate that the sera of PBC patients has fibroproliferative activity. Our results further demonstrate that this effect is partially mediated by platelet derived growth factor (PDGF). We then tested the effect of potential antifibrotic drugs in vitro for their ability to inhibit patient sera-stimulated proliferation. The two drugs tested were pentoxifylline and ursodeoxycholic acid (UDCA). Both pentoxifylline and UDCA have been reported to inhibit PDGF stimulated proliferation of fibroblasts. Pentoxifylline has been reported to block experimental liver fibrosis and inhibit fibroproliferation in this experimental model. UDCA has been used in clinical trials in patients with PBC. Our results indicate that pentoxifylline when added in vitro, reduced the fibroproliferative activity of PBC patient sera. UDCA and taurour-sodeoxycholic acid (TUDCA) did not reduce fibroproliferative activity of PBC patient sera. This group of PBC patients were then started on UDCA and preliminary results following 1 year of UDCA treatment indicate that there is no decrease but rather an increase in the fibroproliferative activity of PBC patient sera. These results suggest that PBC patient sera samples stimulate proliferation of fibroblasts and that this effect is due at least in part to PDGF. The results also indicate that pentoxifylline reduces the fibroproliferative activity of PBC patient sera while UDCA and TUDCA did not reduce fibroproliferation. Results obtained from PBC patients following 1 year of UDCA treatment together with results obtained from an experimental model of hepatic fibrosis following successful treatment with pentoxifylline suggest that this test may prove to be predictive of a beneficial response to potential antifibrotic drugs.