Primary biliary cirrhosis（PBC）is a chronic autoimmune liver disease characterized by progressive non-suppurative destruction of intrahepatic small bile ducts, leading to cirrhosis and liver failure. The pathogenesis of PBC has not been fully elucidated, and standardized diagnosis and treatment algorithms have yet to be established. Because of these unmet clinical needs, the research team which led by Pro.Zhang Fengchun ( Department of Rheumatology and immunology PUMC) has launched a series of studies on PBC, focusing on the exploration of standardized algorithms for diagnosis, treatment and prognosis assessment along with its pathogenesis. The main results are as follows:
1. Ursodeoxycholic acid (UDCA) is the first-line therapy in PBC, which could significantly improves biochemical tests (bilirubin, alkaline phosphatase and IgM et al) and delays the progression in liver histology. However, a consensus of specific UDCA regimen has not been reached, and the effects of tapering or discontinuing of UDCA on PBC patients are still unknown. Moreover, UDCA could not correct the underlining immunological dysfunction, and as a result, there are over 30% of PBC patients who fail to achieve good response to UDCA. These refractory patients progress to cirrhosis faster and has poorer prognosis. Considering the clinical needs, our team carried out a systematic clinical follow-up study on PBC last for 14 years. The results, which were published in the leading journal in liver disease, Hepatology, proved the importance of UDCA in the treatment of PBC. In this study, we advocated the early marker of long-term good response to UDCA, which makes early therapy adjustment available for refractory patients. This early marker, designated as ‘Beijing Criteria’ of early UDCA response, was accepted worldwide, providing clinical evidence for tapering or discontinuing of UDCA.
2. Successful allogeneic bone marrow mesenchymal stem cell transplantations offered new therapy for standardized PBC treatment.
3. We have prospectively analyzed the clinical and laboratory characteristics of three groups of patients, including patients with positive anti-mitochondrial antibody (AMA), patients with negative AMA, and patients complicated with connective tissue diseases. These results provide important evidence for the diagnosis and treatment of those patients.
4. We have studied autoantibodies in PBC concerning around diagnosis, differential diagnosis and treatment. (1) Using high-throughput protein chips, we screened PBC patient’s sera for new autoantibodies and found six new PBC-related markers. (2) There is no international consensus regarding the importance of anti-centromere antibody (ACA), anti-gp210 antibody and anti-sp100 antibody in the monitoring of PBC disease activity and the prediction of prognosis. Therefore, based on our earlier PBC clinical cohort study, our team analyzed the differences in these antibodies between Chinese population and other ethnic groups, providing new data for PBC researches among different ethic backgrounds.
5. Using both peripheral blood and the animal model, we have confirmed the contribution of CXCR3 and TGF-β1 signaling pathways in the pathogenesis of PBC sequentially. With clinical interventions aiming these potential therapeutic targets, we might be able to delay the development and progression of cirrhosis in PBC patients and improve long-term prognosis.
Our research team has published 71 articles on PBC, including 20 in SCI journals. Our representative works were published in the journals of Hepatology (2013 Jul;58(1):264-72. IF:11.19) and Molecular & Cellular Proteomics (2012 Sep;11(9):669-80. IF:7.25).