The Efficacy And Safety Of Fenofibrate In Combination With Ursodeoxycholic Acid In Primary Biliary Cholangitis

【Background】Primary biliary cholangitis(PBC)is an immune-mediated chronic cholestatic liver disease characterised by non-suppurative destruction of small intrahepatic bile ducts,progressing to fibrosis,biliary cirrhosis and even liver failure if left untreated.Ursodeoxycholic acid(UDCA)is currently the only drug approved by the US Food and Drug Administration for the treatment of PBC.About 60%~70% of PBC patients after receiving UDCA treatment have a complete response,unfortunately,about 30%~40% of patients have a suboptimal response to UDCA,and these patients have a more rapid progression and a worse prognosis of disease.How to implement effective treatment for the patients with incomplete response to UDCA remains to be solved.Fibrates are a class of synthesized ligands of peroxisome proliferator-activated receptors(PPARs),clinically used in the treatment of primary hypertriglyceridemia or mixed hyperlipidemia.In recent years,increasing evidence have shown that fibrates may have anticholestatic,anti-inflammatory,and antifibrotic effects,which could be used as an additional therapy for PBC with incomplete response to UDCA.However,related research based on Chinese population in PBC is rarely reported.Threrfore,the case-control study aimed to evaluate the efficacy and safety of fenofibrate in combination with UDCA in PBC with incomplete response to UDCA.【Objectives】1.To observe whether UDCA in combination with fenofibrate can improve the biochemical profiles,response rate and prognostic risk of PBC with incomplete response to UDCA;2.To investigate the influential factors associated with biochemical response;3.To evaluate the safety of UDCA in combination with fenofibrate treatment.【Methods】This was a retrospective case-control study.A total of 107 PBC patients between January 2004 and October 2015 were enrolled in this study.They were divided into the combination therapy group and UDCA therapy group depending on that if added fenofibrate(200 mg/day)on UDCA after judged to be incomplete response to UDCA monotherapy.Clinical data of all patients were collected from medical records before and after treatment at 3,6,12 months,respectively.SPSS software 17.0 was used for subsequent analysis,including biochemical profiles,response rate and GLOBE Score and so on.Two-tailed p values <0.05 were considered statistically significant.【Results】1.The serum alkaline phosphatase(ALP)levels in the combination therapy group were significantly lower than those in the UDCA therapy group at 3,6,12 months after the beginning of study(P<0.05);2.The biochemical response rate in the combination therapy group was significantly higher than that in the UDCA therapy group at 12 months after the beginning of study(P<0.05);3.The serum triglycerides(TG)and IgM levels in the combination therapy group decreased more conspicuously than those in the UDCA therapy group(P<0.05);4.The GLOBE Risk Score in the combination therapy group were significantly lower than that in the UDCA therapy group at 12 months after the beginning of study (P<0.05);5.The use of fenofibrate was independently associated with biochemical response;6.The serum urea nitrogen and creatinine levels were not significantly different between the two groups(P>0.05).【Conclusions】1.Combination therapy significantly improved the biochemical response rate,and the use of fenofibrate was independently associated with biochemical response;2.Combination therapy significantly improved the serum ALP levels,and this decrease occurred relatively early,as early as 3 months after the beginning of study;3.Combination therapy decreased the serum triglycerides(TG)and IgM levels more dramatically than UDCA therapy;4.Combination therapy significantly lowered the GLOBE Risk Score;5.In the present study,combination therapy did not significantly increase the serum urea nitrogen and creatinine levels,but the safety of long-term combination therapy deserves further evaluation.