Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

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The aim of the present study was to observe the effects of Fuzheng Huayu capsule combined with Pegasys (peginterferon α-2a) on hepatic fibrosis in rats and in the treatment of patients with genotype 1 hepatitis C and hepatic cirrhosis. A dimethylnitrosamine (DMN)-induced rat model of liver injury was established. Fuzheng Huayu capsule combined with Pegasys was administered to the rats and the DMN-induced hepatocyte apoptosis was observed. In addition, a total of 100 patients with genotype 1 hepatitis C and hepatic cirrhosis were treated by oral administration of Fuzheng Huayu capsule combined with Pegasys or with Pegasys alone. The therapeutic effect of Fuzheng Huayu capsule combined with Pegasys was analyzed. Following the oral administration of Fuzheng Huayu capsule combined with Pegasys to the DMN model rats, the expression of α-smooth muscle actin was found to be significantly reduced, hemopoietic stem cell apoptosis was increased and liver cell apoptosis was reduced. These indices were significantly different compared with those in the model group (P<0.05). Liver function and liver fibrosis were markedly recovered in hepatitis C patients with hepatic cirrhosis following treatment with the combination treatment compared with those in the patients treated with Pegasys alone (P<0.05). In conclusion, the combination of Fuzheng Huayu capsule with Pegasys inhibited liver fibrosis and cell apoptosis, and may be a novel therapeutic strategy for the treatment of patients with compensated cirrhosis due to hepatitis C. This study provides a method for the optimization of existing treatment strategies and for the establishment of potentially effective combination therapies.