Systematic review and meta-analysis: bezafibrate in patients with primary biliary cirrhosis

Abstract

Background and aim: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cirrhosis (PBC), but not all cases respond well. Evidence has shown that combination therapy of UDCA with bezafibrate significantly improved liver function. A meta-analysis was performed to assess the efficacy and safety of UDCA and bezafibrate combination therapy in the treatment of PBC.

Results: Nine trials, with a total of 269 patients, were included in the analysis. The bias risk of these trials was high. Compared with UDCA alone, the combination with bezafibrate improved the Mayo risk score (mean difference [MD], 0.60; 95% confidence interval [CI], 0.25-0.95; P=0.0008) and liver biochemistry: alkaline phosphatase (MD, -238.21 IU/L; 95% CI, -280.83 to -195.60; P<0.00001); gamma-glutamyltransferase (MD, -38.23 IU/L; 95% CI, -50.16 to -25.85; P<0.00001); immunoglobulin M (MD, -128.63 IU/L; 95% CI, -151.55 to -105.71; P<0.00001); bilirubin (MD, -0.20 mg/dL; 95% CI, -0.33 to -0.07; P=0.002); triglycerides (MD, -26.84 mg/dL; 95% CI, -36.51 to -17.17; P<0.0001); total cholesterol (MD, -21.58 mg/dL; 95% CI, -30.81 to -12.34; P<0.0001), and serum alanine aminotransferase (MD, -10.24 IU/L; 95% CI, -12.65 to -78.5; P<0.00001). However, combination therapy showed no significant differences in the incidence of all-cause mortality or pruritus, and may have resulted in more adverse events (risk ratio [RR], 0.22; 95% CI, 0.07-0.67; P=0.008).

Conclusion: Combination therapy improved liver biochemistry and the prognosis of PBC, but did not improve clinical symptoms or incidence of death. Attention should be paid to adverse events when using bezafibrate.

Keywords: bezafibrate; meta-analysis; primary biliary cirrhosis; ursodeoxycholic acid.

Figure 1

Risk of bias in included studies. Notes: +, indicates an increase, −, indicates a decrease and ?, indicates this is unclear.

Figure 2

Risk of bias graph: review of authors’ judgments regarding each risk of bias item presented as percentages across all included studies.

Figure 3

Flow diagram of trial selection.

Figure 4

Mortality in primary biliary cirrhosis patients treated with monotherapy versus combination therapy. Abbreviations: CI, confidence interval; COM, combination therapy; df, degrees of freedom; SD, standard deviation; M–H, Mantel–Haenszel; UDCA, ursodeoxycholic acid monotherapy.

Figure 5

Effects of monotherapy versus combination therapy on pruritus in patients with primary biliary cirrhosis. Abbreviations: CI, confidence interval; COM, combination therapy; df, degrees of freedom; M–H, Mantel–Haenszel; UDCA, ursodeoxycholic acid monotherapy.

Figure 6

Adverse events in primary biliary cirrhosis patients treated with monotherapy versus combination therapy. Abbreviations: CI, confidence interval; COM, combination therapy; df, degrees of freedom; SD, standard deviation; M–H, Mantel–Haenszel; UDCA, ursodeoxycholic acid monotherapy.

Figure 7

Mayo risk score in primary biliary cirrhosis patients treated with monotherapy versus combination therapy. Abbreviations: CI, confidence interval; COM, combination therapy; df, degrees of freedom; SD, standard deviation; UDCA, ursodeoxycholic acid monotherapy; IV, inverse-variance.

Figure 8

Alkaline phosphatase levels in primary biliary cirrhosis patients treated with monotherapy versus combination therapy. Abbreviations: CI, confidence interval; COM, combination therapy; df, degrees of freedom; SD, standard deviation; UDCA, ursodeoxycholic acid monotherapy; IV, inverse-variance.

Figure 9

Gamma-glutamyltransferase levels in primary biliary cirrhosis patients treated with monotherapy versus combination therapy. Abbreviations: CI, confidence interval; COM, combination therapy; df, degrees of freedom; SD, standard deviation; UDCA, ursodeoxycholic acid monotherapy; IV, inverse-variance.

Figure 10

Alanine aminotransferase levels in primary biliary cirrhosis patients treated with monotherapy versus combination therapy. Abbreviations: CI, confidence interval; COM, combination therapy; df, degrees of freedom; SD, standard deviation; UDCA, ursodeoxycholic acid monotherapy; IV, inverse-variance.

Figure 11

Immunoglobulin M levels in primary biliary cirrhosis patients treated with monotherapy versus combination therapy. Abbreviations: CI, confidence interval; COM, combination therapy; df, degrees of freedom; SD, standard deviation; UDCA, ursodeoxycholic acid monotherapy; IV, inverse-variance.

Figure 12

Triglycerides levels in primary biliary cirrhosis patients treated with monotherapy versus combination therapy. Abbreviations: CI, confidence interval; COM, combination therapy; df, degrees of freedom; SD, standard deviation; UDCA, ursodeoxycholic acid monotherapy; IV, inverse-variance.

Figure 13

Total cholesterol levels in primary biliary cirrhosis patients treated with monotherapy versus combination therapy. Abbreviations: CI, confidence interval; COM, combination therapy; df, degrees of freedom; SD, standard deviation; UDCA, ursodeoxycholic acid monotherapy; IV, inverse-variance.

Figure 14

Serum bilirubin levels in primary biliary cirrhosis patients treated with monotherapy versus combination therapy. Abbreviations: CI, confidence interval; COM, combination therapy; df, degrees of freedom; SD, standard deviation; UDCA, ursodeoxycholic acid monotherapy; IV, inverse-variance.

Figure 15

Albumin levels in primary biliary cirrhosis patients treated with monotherapy versus combination therapy. Abbreviations: CI, confidence interval; COM, combination therapy; df, degrees of freedom; SD, standard deviation; UDCA, ursodeoxycholic acid monotherapy; IV, inverse-variance.

Figure 16

AST levels in primary biliary cirrhosis patients treated with monotherapy versus combination therapy. Abbreviations: AST, aspartate aminotransferase; CI, confidence interval; COM, combination therapy; df, degrees of freedom; SD, standard deviation; UDCA, ursodeoxycholic acid monotherapy; IV, inverse-variance.