Meta-analysis Of The Efficacy And Safety Of Fenofibrate Combined With Ursodeoxycholic Acid In The Treatment Of Primary Biliary Cholangitis

Objective: Ursodeoxycholic acid(UDCA)is currently the preferred drug for the treatment of primary biliary cholangitis(PBC),but there are still some patients with poor response.Previous studies have shown that the combination of fenofibrate can improve liver function and immunological indicators in such kind of patients,but there are different reports on adverse reactions and survival rates after fenofibrate treatment.In this paper,the efficacy and safety of fenofibrate combined with UDCA in the treatment of patients with PBC who responded poorly to UDCA were evaluated by meta-analysis to guide the clinical use of PBC.Methods: With "fenofibrate","Primary biliary cirrhosis","Primary biliary cholangitis" for key words in English;"fenofibrate","primary biliary cholangitis","primary biliary cirrhosis" are Chinese search terms.Embase,PubMed,The Cochrane Library,Wanfang,VIP,China National Knowledge Infrastructure(CNKI),and China Biology Medicine disc(CBMdisc)were searched by computer for PBC related literatures with poor response to ursodeoxycholic acid in fenofibrate treatment before December 2018.Two researchers screened and extracted data from the retrieved literatures,in which the clinical efficacy indicators were symptoms,biochemical indicators,survival rate,etc.,and then the literature quality was evaluated using the Cochrane evaluation manual.For the included studies,RevMan 5.3 software was used for statistical processing,the heterogeneity test was performed first,and different effect models were selected according to the heterogeneity,Mean difference(MD)was used to represent the continuity variable,and Odds ratio(OR)was used to represent the dichotomy variable.Both types of data were calculated with 95% confidence interval(95% confidence interval,95% CI),and the forest figure was made,and the results are analyzed.Results: Finally,10 articles were included,totaling 534 patients,of which 294 were treated with UDCA monotherapy,and 240 with UDCA combined with fenofibrate.The results of the meta-analysis were as follows:(1)Pruritus: UDCA combined with fenofibrate treatment was superior to UDCA monotherapy in improving pruritus(OR=11.84,95%CI(2.69,52.14),P=0.001).(2)ALP: UDCA combined with fenofibrate could reduce the level of ALP more effectively than UDCA monotherapy(MD=-124.08U/L;95% CI(-145.55,-102.61);P<0.00001).(3)?-GT:UDCA combined with fenofibrate was more effective than UDCA in reducing ?-GT(MD=-137.75U/L;95% CI(-222.25,-53.25);P=0.001).(4)ALT:UDCA combined with fenofibrate treatment had an advantage in reducing the level of ALT compared with UDCA monotherapy(MD=-19.91U/L,95%CI(-30.88,-8.95);P=0.0004).(5)AST: UDCA combined with fenofibrate treatment was significantly better than UDCA monotherapy in reducing AST level(MD=-12.11U/L;95% CI(-17.70,-6.53);P<0.0001).(6)IgM: UDCA combined with fenofibrate significantly reduced IgM levels compared with UDCA monotherapy(MD=-78.65g/L;95% CI(-91.50,-65.80);P<0.00001).(7)TBil: Compared with UDCA monotherapy,combining fenofibrate treatment could not effectively reduce serum TBil levels in patients(MD=-5.56umol/L;95%CI:(-12.21,1.09);P=0.10).(8)ALB: UDCA combined with fenofibrate could significantly increase the ALB level(MD= 1.41g/L;95%CI(0.06,2.76);P=0.04).(9)TC:Compared with UDCA monotherapy,combining with fenofibrate treatment was more effective in reducing TC(MD=-0.62mmol/L;95%CI(-1.10,-0.13);P=0.01).(10)TG: UDCA combined with fenofibrate showed significant advantages in lipid-lowering effect(MD=-0.43mmol/L;95%CI(-0.61,-0.25);P<0.00001)(11)Cr:The treament of UDCA combined with fenofibrate significantly increased the level of Cr,comparing with UDCA monotherapy(MD= 6.09umol/L;95%CI(0.56,11.61);P=0.03).(12)Response rate: The response rate was higher with combination of fenofibrate than with UDCA monotherapy(OR=3.50;95%CI(2.06,5.97);P < 0.00001).(13)GLOBE score:UDCA combined with fenofibrate could effectively reduce GLOBE score(MD=-0.35;95% CI(-0.60,-0.10);P=0.006),and improve the predicted survival rate of non-liver transplantation,including 5-year survival rate(MD=0.10;95% CI(0.03,0.03;P=0.004),10-year survival rate(MD=0.14;95%CI(0.11,0.17);P<0.00001),and the 15-year survival rate(MD=0.12;95%CI(0.07,0.17);P<0.00001).(14)Adverse reactions:UDCA combined with fenofibrate treatment may cause more adverse reactions than UDCA monotherapy(OR=12.54,95%CI(3.40,46.22);P=0.0001)Conclusions:UDCA combined with fenofibrate treatment can improve the symptoms,biochemical indicators,immune function and prognosis of patients with poor UDCA response,but it is also more likely to have adverse reactions,and whether it can improve histology remains to be further studied.