A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis
Open accessAbstract
Placebo-controlled trial of bezafibrate added to ursodeoxycholic acid in PBC.
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Claims the paper makes
22 of 35 cited sources checked · 13 supported · 0 flagged · accuracy not yet measured
- Premisecitation
Patients with primary biliary cholangitis who have an inadequate response to ursodeoxycholic acid are at high risk for disease progression.
“Patients with primary biliary cholangitis who have an inadequate response to therapy with ursodeoxycholic acid are at high risk for disease progression.”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [6] 6. Parés A, Caballería L, Rodés J. Excel- lent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic acid. Gastro- enterology 2006; 130: 715-20. source
- cites [7] 7. Corpechot C, Abenavoli L, Rabahi N, et al. Biochemical response to ursodeoxy- cholic acid and long-term prognosis in pri- mary biliary cirrhosis. Hepatology 2008; 48: 871-7. source
- cites [8] 8. Kumagi T, Guindi M, Fischer SE, et al. Baseline ductopenia and treatment re- sponse predict long-term histological pro- gression in primary biliary cirrhosis. Am J Gastroenterol 2010; 105: 2186-94. source
- Premisecitation
In studies of obeticholic acid, it was associated with higher rates of severe pruritus than placebo.
“In these studies, however, obeticholic acid was associated with higher rates of severe pruritus than placebo.10”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [10] 10. Nevens F, Andreone P, Mazzella G, et al. A placebo-controlled trial of obeti- cholic acid in primary biliary cholangitis. N Engl J Med 2016; 375: 631-43. source
The Discussion (p. 10) reports higher rates of pruritus with obeticholic acid than placebo (56% and 68% versus 38%). The paper also describes increased pruritus severity in earlier studies (p. 2), but the available passages do not give comparative rates specifically for severe pruritus, so that qualifier is not fully supported. (LLM, conf=0.84)
Experimental — accuracy not yet measured
- Premisecitation
The combination of obeticholic acid with ursodeoxycholic acid has been shown to decrease the levels of biochemical markers of cholestasis in patients with primary biliary cholangitis who have had an inadequate response to ursodeoxycholic acid.
“The combination of obeticholic acid, a selective agonist of the farnesoid X receptor, with ursodeoxycholic acid has recently been shown to decrease the levels of the biochemical markers of cholestasis in patients with primary biliary cholangitis who have had an inadequate response to ursodeoxycholic acid.9,10”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [9] 9. Hirschfield GM, Mason A, Luketic V, et al. Efficacy of obeticholic acid in pa- tients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Gastroenterology 2015; 148(4): 751- 61.e8. source
- cites [10] 10. Nevens F, Andreone P, Mazzella G, et al. A placebo-controlled trial of obeti- cholic acid in primary biliary cholangitis. N Engl J Med 2016; 375: 631-43. source
- Premisecitation
Ursodeoxycholic acid is currently the standard first-line therapy for primary biliary cholangitis.
“Ursodeoxycholic acid, a hydrophilic bile acid with choleretic and liver-protective properties, is currently the standard firstline therapy for primary biliary cholangitis.2,3”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [2] 2. European Association for the Study of the Liver. EASL clinical practice guide- lines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol 2017; 67: 145-72. source
- cites [3] 3. Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ. Pri- mary biliary cirrhosis. Hepatology 2009; 50: 291-308. source
- Premisecitation
Long-term survival remains limited in patients who have an incomplete biochemical response to ursodeoxycholic acid.
“However, long-term survival remains limited in patients who have an incomplete biochemical response.[6][7][8]”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [6] 6. Parés A, Caballería L, Rodés J. Excel- lent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic acid. Gastro- enterology 2006; 130: 715-20. source
- cites [7] 7. Corpechot C, Abenavoli L, Rabahi N, et al. Biochemical response to ursodeoxy- cholic acid and long-term prognosis in pri- mary biliary cirrhosis. Hepatology 2008; 48: 871-7. source
- cites [8] 8. Kumagi T, Guindi M, Fischer SE, et al. Baseline ductopenia and treatment re- sponse predict long-term histological pro- gression in primary biliary cirrhosis. Am J Gastroenterol 2010; 105: 2186-94. source
- Premisecitation
Paris 2 criteria have been recognized as relevant predictors of clinical outcomes in several independent populations of patients with primary biliary cholangitis.
“Patients were selected on the basis of Paris 2 criteria, 15 which have been recognized as relevant predictors of clinical outcomes in several independent populations of patients with primary biliary cholangitis.24,25”
Quote in the paperNot a substantial claim2 of 3 sources checked- cites [15] 15. Corpechot C, Chazouillères O, Poupon R. Early primary biliary cirrhosis: bio- chemical response to treatment and pre- diction of long-term outcome. J Hepatol 2011; 55: 1361-7. source
- cites [24] 24. Carbone M, Mells GF, Pells G, et al. Sex and age are determinants of the clini- cal phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology 2013; 144(3): 560-569.e7. source
The Results (page unavailable) state that Paris II, along with three other UDCA-response criteria, predicted outcomes in the paper’s extended-data subgroup. The paper reports this finding in one UK-PBC cohort, not in several independent patient populations; it also found Paris I discriminated prognosis best. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [25] 25. Lammers WJ, van Buuren HR, Hirschfield GM, et al. Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study. Gastroenterology 2014; 147(6): 1338-49.e5. source
The Results (p. 4) show that alkaline phosphatase and bilirubin thresholds predicted transplant-free survival in a pooled international PBC cohort. However, the paper does not establish that the Paris 2 criteria as a set predicted clinical outcomes in several independent populations; its reported analyses concern individual biochemical thresholds. (LLM, conf=0.83)
Experimental — accuracy not yet measured
- Interpretationcitation
Bezafibrate acts in part through specific anticholestatic properties such as inhibition of bile acid synthesis and consequent reduction in endogenous bile acid overload.
“Our results suggest that bezafibrate acts in part through specific anticholestatic properties such as the inhibition of bile acid synthesis and consequent reduction in endogenous bile acid overload.33”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [33] 33. Honda A, Ikegami T, Nakamuta M, et al. Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid. Hepa- tology 2013; 57: 1931-41. source
- Findingown data
Myalgia occurred in 20% of patients in the bezafibrate group and 10% in the placebo group.
“Myalgia occurred in 20% of the patients in the bezafibrate group and in 10% in the placebo group.”
Quote in the paperNot a substantial claim - Findingown data
The rate of complete biochemical response in the bezafibrate group increased progressively until month 15, when it reached a plateau of 30 to 35%.
“The rate of complete biochemical response in the bezafibrate group increased progressively until month 15, when it reached a plateau of 30 to 35% (Fig. 1).”
Quote in the paperNot a substantial claim - Findingown data
Changes with respect to fatigue were consistent with the results of the primary outcome.
“Changes in pruritus intensity were consistent with results of the primary outcome, as were changes with respect to fatigue.”
Quote in the paperNot a substantial claim - Findingnone given
Alanine aminotransferase levels in the bezafibrate group decreased progressively.
“Alanine aminotransferase levels in the bezafibrate group decreased progressively.”
Quote in the paperSubstantial claim - Findingown data
No patients died during the trial.
“No patients died.”
Quote in the paperNot a substantial claim - Findingown data
At 24 months, normal alkaline phosphatase levels were observed in 67% of patients in the bezafibrate group and 2% in the placebo group, a difference of 65 percentage points (95% CI, 47 to 79).
“Normal levels of alkaline phosphatase were observed in 67% of the patients in the bezafibrate group and in 2% in the placebo group.”
- Also stated in: § Biochemical Measures · plain
“At 24 months, 31 patients (67%) in the bezafibrate group and 1 patient (2%) in the placebo group had normal alkaline phosphatase levels (difference, 65 percentage points; 95% CI, 47 to 79).”
Quote in the paperSubstantial claim - Also stated in: § Biochemical Measures · plain
- Findingown data
Changes in levels of total bilirubin, alkaline phosphatase, γ-glutamyltransferase, alanine aminotransferase, albumin, total cholesterol, low-density lipoprotein cholesterol, and platelet count were consistent with the primary outcome.
“The specific changes in the levels of total bilirubin, alkaline phosphatase, γ-glutamyltransferase, alanine aminotransferase, albumin, total cholesterol, and low-density lipoprotein cholesterol, and in the platelet count were consistent with results for the primary outcome (Fig. 2 and Table 2).”
Quote in the paperSubstantial claim - Findingown data
Changes in pruritus intensity were consistent with the results of the primary outcome.
“Changes in pruritus intensity were consistent with results of the primary outcome, as were changes with respect to fatigue.”
Quote in the paperNot a substantial claim - Findingown data
At baseline, serum levels of total and endogenous bile acids, ursodeoxycholic acid, and C4 did not differ significantly between the groups.
“At baseline, serum levels of total and endogenous bile acids, ursodeoxycholic acid, and C4 (a marker of bile acid synthesis) did not differ significantly between the groups.”
Quote in the paperSubstantial claim - Findingown data
The conclusion remained unchanged in sensitivity analyses.
“The conclusion remained unchanged in sensitivity analyses (Table S1 in the Supplementary Appendix).”
Quote in the paperNot a substantial claim - Findingown data
A 60% median reduction from baseline in alkaline phosphatase level was observed in the bezafibrate group at 3 months.
“A 60% median reduction from baseline in alkaline phosphatase level was observed in the bezafibrate group at 3 months.”
Quote in the paperSubstantial claim - Findingown data
In the subgroup with available histologic data at both time points, changes in histologic stage, fibrosis stage, and activity grade did not differ significantly between the groups.
“In this subgroup, changes in histologic stage, fibrosis stage, and activity grade did not differ significantly between the groups.”
Quote in the paperSubstantial claim - Findingown data
Changes in Enhanced Liver Fibrosis scores were consistent with the liver stiffness result (difference, -4 percentage points; 95% CI, -8 to -1).
“Changes in Enhanced Liver Fibrosis scores were consistent with this result (difference, -4 percentage points; 95% CI, -8 to -1) (Table S10 in the Supplementary Appendix).”
Quote in the paperNot a substantial claim - Findingown data
A similar rapid reduction in γ-glutamyltransferase level was observed among patients in the bezafibrate group.
“A similar rapid reduction in γ-glutamyltransferase level was observed among patients in the bezafibrate group.”
Quote in the paperNot a substantial claim - Findingown data
No significant differences between the groups were found in quality-of-life scores.
“No significant differences between the groups were found in the quality-of-life scores (Fig. S5 and Tables S8 and S9 in the Supplementary Appendix).”
Quote in the paperNot a substantial claim - Findingnone given
Changes in C4 levels were consistent with the results of the primary outcome.
“Changes in C4 levels were consistent with the results of the primary outcome.”
Quote in the paperNot a substantial claim - Findingown data
Four patients, two in each group, had liver complications.
“Four patients, 2 in each group, had liver complications: in the bezafibrate group, 1 patient underwent a liver transplantation and 1 was placed on a waiting list for transplantation; in the placebo group, ascites developed in 1 patient, and the total bilirubin level doubled to more than 50 μmol per liter in 1 patient.”
Quote in the paperNot a substantial claim - Findingown data
The bile acid pool decreased significantly with bezafibrate.
“acid within the bile acid pool decreased significantly with bezafibrate.”
Quote in the paperNot a substantial claim - Findingown data
In a post hoc analysis, application of the GLOBE and UK-PBC risk scores at baseline, 12 months, and 24 months showed significantly lower predicted rates of liver transplantation and death at 5, 10, and 15 years in the bezafibrate group than in the placebo group.
“In a post hoc analysis of prognostic scores, the application of the GLOBE and UK-PBC risk scores at baseline, at 12 months, and at 24 months showed significantly lower predicted rates of liver transplantation and death at 5, 10, and 15 years in the bezafibrate group than in the placebo group.”
Quote in the paperNot a substantial claim- Rests on an assumption: The GLOBE and UK-PBC risk scores accurately predict liver transplantation and death in patients with primary biliary cholangitis, including this trial population.
- Findingown data
All cases of elevated aminotransferase levels in the bezafibrate group resolved within 3 months, either spontaneously (one patient) or after glucocorticoid administration (two patients).
“All cases of elevated aminotransferase levels in the bezafibrate group resolved within 3 months, either spontaneously (in one patient) or after glucocorticoid administration (two patients, in whom liver histologic features at baseline were suggestive of associated autoimmune hepatitis).”
Quote in the paperNot a substantial claim - Findingown data
A total of 39 serious adverse events (9%) were reported in 26 patients (14 in the bezafibrate group and 12 in the placebo group).
“A total of 39 serious adverse events (9%) were reported in 26 patients (14 patients in the bezafibrate group and 12 patients in the placebo group) (Table 3, and Table S14 in the Supplementary Appendix).”
Quote in the paperNot a substantial claim - Findingown data
Myalgia was reported in 20% of patients in the bezafibrate group and 10% in the placebo group.
“Myalgia was reported in 20% of the patients in the bezafibrate group and in 10% in the placebo group.”
Quote in the paperNot a substantial claim - Findingown data
These results were confirmed in longitudinal analyses.
“These results were confirmed in longitudinal analyses.”
Quote in the paperNot a substantial claim - Findingown data
Portal hypertension and a high alkaline phosphatase level at baseline were independently associated with an inadequate biochemical response to bezafibrate.
“The factors that were independently associated with an inadequate biochemical response to bezafibrate were features of portal hypertension and alkaline phosphatase level.”
- Also stated in: § Discussion · plain
“Portal hypertension and a high alkaline phosphatase level at baseline were identified as independent predictors of treatment failure.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
Parallel changes with respect to pruritus, fatigue, and noninvasive measures of liver fibrosis were consistent with the primary result.
“Parallel changes with respect to pruritus, fatigue, and noninvasive measures of liver fibrosis were consistent with this result.”
- Also stated in: § Discussion · plain
“Parallel changes in patient-reported outcomes and noninvasive measures of liver fibrosis were consistent with this effect.”
Quote in the paperNot a substantial claim - Also stated in: § Discussion · plain
- Findingown data
Overall, 424 adverse events were reported in 88 patients (49% in the bezafibrate group and 51% in the placebo group).
“Overall, 424 adverse events were reported in 88 patients (49% in the bezafibrate group and 51% in the placebo group).”
Quote in the paperNot a substantial claim - Findingreasoning
This led to permanent discontinuation of the active drug or placebo in three patients (two in the bezafibrate group and one in the placebo group).
“This led to a permanent discontinuation of the active drug or placebo in three patients (two in the bezafibrate group and one in the placebo group).”
Quote in the paperNot a substantial claim - Findingown data
Four patients had an increase in aminotransferase levels more than 5 times the upper limit of the normal range (three in the bezafibrate group and one in the placebo group).
“Four patients had an increase in aminotransferase levels that was more than 5 times the upper limit of the normal range (three patients in the bezafibrate group and one in the placebo group).”
Quote in the paperNot a substantial claim - Findingown data
No significant between-group differences were found in changes in serum levels of high-sensitivity C-reactive protein, TNF-α, or interleukin-12.
“No significant between-group differences were found with respect to changes in the serum levels of high-sensitivity C-reactive protein, TNF-α, or interleukin-12.”
Quote in the paperNot a substantial claim - Findingown data
Bezafibrate did not increase bilirubin level in patients with cirrhotic liver disease.
“Despite initial concerns, 26 we did not observe an increase in bilirubin level in patients with cirrhotic liver disease who were treated with bezafibrate.”
Quote in the paperSubstantial claim - Findingown data
The threshold of alkaline phosphatase that best predicted an inadequate biochemical response was a level more than 2.53 times the upper limit of the normal range.
“The threshold of alkaline phosphatase that best predicted an inadequate biochemical response was a level more than 2.53 times the upper limit of the normal range.”
Quote in the paperNot a substantial claim - Findingown data
Among patients with primary biliary cholangitis who had an inadequate response to ursodeoxycholic acid, add-on therapy with bezafibrate for 24 months resulted in a higher rate of complete biochemical response than ursodeoxycholic acid therapy plus placebo.
“In this randomized trial, we found that among patients with primary biliary cholangitis who had had an inadequate response to ursodeoxycholic acid, approximately one third of the patients in the bezafibrate group, as compared with no patients in the placebo group, reached the primary outcome (i.e., normal levels of the main biochemical markers of the disease at 24 months).”
- Also stated in: § Discussion · plain
“In conclusion, in patients with primary biliary cholangitis who had had an inadequate response to ursodeoxycholic acid, add-on therapy with bezafibrate for 24 months resulted in a higher rate of complete biochemical response than ursodeoxycholic acid therapy plus placebo.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Study design and conductown data
Overall, 92 patients (92%) completed the trial.
“Overall, 92 patients (92%) completed the trial.”
Quote in the paperNot a substantial claim - Interpretationown data
Among patients with primary biliary cholangitis who had an inadequate response to ursodeoxycholic acid alone, treatment with bezafibrate in addition to ursodeoxycholic acid resulted in a rate of complete biochemical response that was significantly higher than the rate with placebo and ursodeoxycholic acid therapy.
“Among patients with primary biliary cholangitis who had had an inadequate response to ursodeoxycholic acid alone, treatment with bezafibrate in addition to ursodeoxycholic acid resulted in a rate of complete biochemical response that was significantly higher than the rate with placebo and ursodeoxycholic acid therapy.”
Quote in the paperSubstantial claim- Rests on an assumption: A complete biochemical response at 24 months is a valid measure of treatment efficacy in primary biliary cholangitis.
- Rests on an assumption: The trial population is representative of patients with primary biliary cholangitis who have an inadequate response to ursodeoxycholic acid.
- Study design and conductown data
Two patients (4%) in the bezafibrate group and 6 (12%) in the placebo group withdrew from the trial.
“Two patients (4%) in the bezafibrate group and 6 (12%) in the placebo group withdrew from the trial.”
Quote in the paperNot a substantial claim - Study design and conductown data
The characteristics of the patients did not differ between the groups at baseline.
“The characteristics of the patients did not differ between the groups at baseline (Table 1).”
Quote in the paperSubstantial claim - Study design and conductreasoning
The study had 90% power at a two-sided significance level of 5% to detect the expected difference with 100 patients, assuming a 17% loss to follow-up.
“Assuming a 17% loss to follow-up, we calculated that 100 patients would need to be enrolled for the study to have 90% power, at a two-sided significance level of 5%.”
Quote in the paperSubstantial claim - Study design and conductnone given
The trial was not large enough or long enough to assess the effect of bezafibrate on hard outcomes, such as liver transplantation and death.
“The trial was not large enough or long enough to assess the effect of bezafibrate on hard outcomes, such as liver transplantation and death.”
Quote in the paperSubstantial claim - Study design and conductown data
The trial was randomized.
“In this randomized trial, we found that among patients with primary biliary cholangitis who had had an inadequate response to ursodeoxycholic acid, approximately one third of the patients in the bezafibrate group, as compared with no patients in the placebo group, reached the primary outcome (i.e., normal levels of the main biochemical markers of the disease at 24 months).”
Quote in the paperSubstantial claim - Study design and conductown data
The trial's histologic data were too limited to determine whether the changes in liver stiffness and Enhanced Liver Fibrosis score were related to an effective reduction in liver fibrosis and hepatic inflammation.
“However, our histologic data were too limited to determine whether these changes were related to an effective reduction in liver fibrosis and hepatic inflammation.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 24
- May combine two claims. 18
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
PremisecitationAlkaline phosphatase and total bilirubin are the two most important prognostic indicators in primary biliary cholangitis.
“In the current trial, bezafibrate was associated with a rapid and sustained decrease in alkaline phosphatase level and a parallel decrease in total bilirubin, the two most important prognostic indicators in primary biliary cholangitis.25”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [25] 25. Lammers WJ, van Buuren HR, Hirschfield GM, et al. Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study. Gastroenterology 2014; 147(6): 1338-49.e5. source
The Discussion (p. 11) says alkaline phosphatase and bilirubin strongly correlate with death and liver transplantation in patients with PBC, supporting their prognostic importance. The paper does not establish that they are the two most important indicators relative to other prognostic measures. The bezafibrate result is presented as the citing trial’s own finding, not as a finding attributed to this source. (LLM, conf=0.84)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationTreatment with ursodeoxycholic acid decreases the levels of biochemical markers of cholestasis and extends the time to liver transplantation.
“Treatment with ursodeoxycholic acid decreases the levels of the biochemical markers of cholestasis and extends the time to liver transplantation.4,5”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [4] 4. Poupon RE, Balkau B, Eschwège E, Poupon R. A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. N Engl J Med 1991; 324: 1548-54. source
The trial reports significant improvements in bilirubin, alkaline phosphatase, and γ-glutamyltransferase levels with ursodiol (p. 1), supporting the biochemical-marker claim in patients with primary biliary cirrhosis. The Methods (p. 1) and Treatment Failures and Withdrawals (p. 3) assess biochemical deterioration and complications, not time to liver transplantation; that part is not established by this trial. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [5] 5. Poupon RE, Lindor KD, Cauch-Dudek K, Dickson ER, Poupon R, Heathcote EJ. Combined analysis of randomized con- trolled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterol- ogy 1997; 113: 884-90. source
Classified as probably not a substantial claim. May combine two claims.
PremisecitationLiver stiffness correlates with histologic fibrosis and is a prognostic factor in primary biliary cholangitis.
“Liver stiffness was assessed with the use of vibration-controlled transient elastography (FibroScan, Echosens); liver stiffness correlates with histologic fibrosis and is a prognostic factor in primary biliary cholangitis.16”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [16] 16. Corpechot C, Carrat F, Poujol-Robert A, et al. Noninvasive elastography-based assessment of liver fibrosis progression and prognosis in primary biliary cirrho- sis. Hepatology 2012; 56: 198-208. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe Enhanced Liver Fibrosis score is a validated measure of liver fibrosis based on serum levels of hyaluronic acid, procollagen type III N-terminal peptide, and tissue inhibitor of metalloproteinase 1.
“the Enhanced Liver Fibrosis score (a validated measure of liver fibrosis that is based on the serum levels of hyaluronic acid, procollagen type III N-terminal peptide, and tissue inhibitor of metalloproteinase 1), 21”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [21] 21. Mayo MJ, Parkes J, Adams-Huet B, et al. Prediction of clinical outcomes in primary biliary cirrhosis by serum enhanced liver fibrosis assay. Hepatology 2008; 48: 1549-57. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe UK-PBC risk score is used to predict the risk of liver transplantation and death from liver-related causes.
“projected survival estimated according to the GLOBE score (which is used to predict the risk of liver transplantation and death from any cause) and the UK-PBC risk score (which is used to predict the risk of liver transplantation and death from liver-related causes) 22”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [22] 22. Carbone M, Sharp SJ, Flack S, et al. The UK-PBC risk scores: derivation and validation of a scoring system for long- term prediction of end-stage liver disease in primary biliary cholangitis. Hepatology 2016; 63: 930-50. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe GLOBE score is used to predict the risk of liver transplantation and death from any cause.
“projected survival estimated according to the GLOBE score (which is used to predict the risk of liver transplantation and death from any cause) and the UK-PBC risk score (which is used to predict the risk of liver transplantation and death from liver-related causes) 22”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [22] 22. Carbone M, Sharp SJ, Flack S, et al. The UK-PBC risk scores: derivation and validation of a scoring system for long- term prediction of end-stage liver disease in primary biliary cholangitis. Hepatology 2016; 63: 930-50. source
The Study Entry and Outcome section defines events for the UK-PBC score and censors non-liver-related deaths. A search for “GLOBE” found no passage describing that score or its predicted outcomes, so this copy cannot verify the claim about GLOBE. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPrevious findings have suggested a suppressive effect of fibrates on immune response.
“Previous findings have suggested a suppressive effect of fibrates on immune response.13,34”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [13] 13. Levy C, Peter JA, Nelson DR, et al. Pilot study: fenofibrate for patients with primary biliary cirrhosis and an incom- plete response to ursodeoxycholic acid. Aliment Pharmacol Ther 2011; 33: 235-42. source
- cites [34] 34. Dohmen K, Mizuta T, Nakamuta M, Shimohashi N, Ishibashi H, Yamamoto K. Fenofibrate for patients with asymptom- atic primary biliary cirrhosis. World J Gas- troenterol 2004; 10: 894-8. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThis is a known effect of PPAR-α agonists.
“This is a known effect of PPAR-α agonists.[27][28][29]”
Quote in the paperNot a substantial claim2 of 3 sources checked- cites [27] 27. Zhao YY, Weir MA, Manno M, et al. New fibrate use and acute renal outcomes in elderly adults: a population-based study. Ann Intern Med 2012; 156: 560-9. source
- cites [28] 28. Ting RD, Keech AC, Drury PL, et al. Benefits and safety of long-term feno- fibrate therapy in people with type 2 dia- betes and renal impairment: the FIELD Study. Diabetes Care 2012; 35: 218-25. source
The Conclusions (page unavailable) describe an early rise in plasma creatinine associated with fenofibrate and report similar elevations in other fenofibrate studies. If “this” refers to that rise, the paper supports it for fenofibrate, but the sentence does not identify the effect and the paper does not establish it as an effect of PPAR-α agonists generally. (LLM, conf=0.73)
Experimental — accuracy not yet measured - cites [29] 29. Mychaleckyj JC, Craven T, Nayak U, et al. Reversibility of fenofibrate therapy- induced renal function impairment in ACCORD type 2 diabetic participants. Diabetes Care 2012; 35: 1008-14. source
The Conclusions (page not provided) report a rise in serum creatinine with fenofibrate and similar changes with ciprofibrate. They also say that similar changes occur with some, but not all, drugs in this class; no significant change was observed with gemfibrozil. The source therefore supports a known effect of some PPAR-α agonists, not an unqualified class-wide effect. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSeladelpar, a selective PPAR-δ agonist, has recently been shown to improve measures of cholestasis in patients with primary biliary cholangitis.
“seladelpar, a selective PPAR-δ agonist, has recently been shown to improve measures of cholestasis in patients with primary biliary cholangitis.36”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [36] 36. Jones D, Boudes PF, Swain MG, et al. Seladelpar (MBX-8025), a selective PPAR-δ agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double-blind, randomised, placebo-controlled, phase 2, proof-of-concept study. Lancet Gastroen- terol Hepatol 2017; 2: 716-26. source
May combine two claims.
PremisecitationLiver stiffness and Enhanced Liver Fibrosis score are markers of liver fibrosis that are prognostic factors in primary biliary cholangitis.
“These changes in the bezafibrate group were accompanied by a decrease in liver stiffness and Enhanced Liver Fibrosis score, two markers of liver fibrosis that are prognostic factors in primary biliary cholangitis.16,21”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [16] 16. Corpechot C, Carrat F, Poujol-Robert A, et al. Noninvasive elastography-based assessment of liver fibrosis progression and prognosis in primary biliary cirrho- sis. Hepatology 2012; 56: 198-208. source
The Discussion (page unavailable) identifies liver stiffness as a surrogate marker of fibrosis in primary biliary cirrhosis and says its value and increase over time predict poor outcomes. It describes the ELF test as having acceptable diagnostic accuracy for fibrosis or cirrhosis, but does not establish ELF as a prognostic factor. The claim is therefore supported for liver stiffness, not for ELF prognosis. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [21] 21. Mayo MJ, Parkes J, Adams-Huet B, et al. Prediction of clinical outcomes in primary biliary cirrhosis by serum enhanced liver fibrosis assay. Hepatology 2008; 48: 1549-57. source
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataTwo patients in each group had complications from end-stage liver disease.
“Two patients in each group had complications from end-stage liver disease.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn the BEZURSO trial, the primary outcome (complete biochemical response at 24 months) occurred in 31% of patients assigned to bezafibrate and 0% assigned to placebo, a difference of 31 percentage points (95% CI, 10 to 50; P<0.001).
“The primary outcome occurred in 31% of the patients assigned to bezafibrate and in 0% assigned to placebo (difference, 31 percentage points; 95% confidence interval, 10 to 50; P<0.001).”
- Also stated in: § Primary Outcome · plain
“The primary outcome was reached in 31% of the patients in the bezafibrate group and in 0% in the placebo group (difference, 31 percentage points; 95% confidence interval [CI], 10 to 50; P<0.001).”
Quote in the paperSubstantial claim- Also stated in: § Primary Outcome · plain
May combine two claims.
Findingown dataThe level of total bilirubin decreased 14% from baseline in the bezafibrate group and increased 18% in the placebo group.
“The level of total bilirubin decreased 14% from baseline in the bezafibrate group and increased 18% in the placebo group.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataLiver stiffness at 24 months decreased 15% from baseline in the bezafibrate group and increased 22% in the placebo group (difference, -36 percentage points; 95% CI, -64 to -8).
“Liver stiffness at 24 months decreased 15% from baseline in the bezafibrate group and increased 22% in the placebo group (difference, -36 percentage points; 95% CI, -64 to -8) (Fig. 2D).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThree months after the end of the trial, levels of total bilirubin, alkaline phosphatase, γ-glutamyltransferase, and aminotransferases worsened in the bezafibrate group but not in the placebo group.
“Three months after the end of trial (i.e., at the end of the washout period), levels of total bilirubin, alkaline phosphatase, γ-glutamyltransferase, and aminotransferases worsened in the bezafibrate group but not in the placebo group.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe rates of adequate biochemical response according to the Barcelona, Paris 1, Paris 2, Toronto, and GLOBE criteria were significantly higher in the bezafibrate group than in the placebo group, except for the Rotterdam criteria.
“The rates of adequate biochemical response as defined according to established criteria (Barcelona, Paris 1 and Paris 2, Rotterdam, Toronto, and GLOBE score) were significantly higher in the bezafibrate group than in the placebo group, except in the case of the Rotterdam criteria, since response according to the Rotterdam criteria can be evaluated only in late-stage disease.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataThe creatinine level increased 5% from baseline in the bezafibrate group and decreased 3% in the placebo group.
“The creatinine level increased 5% from baseline in the bezafibrate group and decreased 3% in the placebo group.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataFeatures of portal hypertension developed in 19 patients, with no significant difference between the groups (20% in the bezafibrate group and 18% in the placebo group).
“Features of portal hypertension developed in 19 patients, with no significant difference between the groups (20% in the bezafibrate group and 18% in the placebo group).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe difference in creatinine change was noticeable at month 3 and remained mostly stable during the rest of the trial.
“This difference was noticeable at month 3 and remained mostly stable during the rest of the trial (Fig. S9 in the Supplementary Appendix).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataOne patient in the bezafibrate group had a decrease in estimated glomerular filtration rate to less than 60 ml per minute (stage 3 chronic kidney disease).
“One patient in the bezafibrate group (who had a history of diabetes and hypertension) had a decrease in the estimated glomerular filtration rate (eGFR) to less than 60 ml per minute (indicating stage 3 chronic kidney disease).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataChanges in the bezafibrate group were accompanied by a decrease in liver stiffness and Enhanced Liver Fibrosis score.
“These changes in the bezafibrate group were accompanied by a decrease in liver stiffness and Enhanced Liver Fibrosis score, two markers of liver fibrosis that are prognostic factors in primary biliary cholangitis.16,21”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataBezafibrate was associated with a 5% increase in serum creatinine level from baseline, while placebo decreased 3% (difference, 7 percentage points; 95% CI, -1 to 15).
“Creatinine levels increased 5% in the bezafibrate group and decreased 3% in the placebo group from baseline (difference, 7 percentage points; 95% CI, -1 to 15).”
- Also stated in: § Discussion · plain
“Bezafibrate was associated with a 5% increase in the serum creatinine level.”
Quote in the paperNot a substantial claim- Also stated in: § Discussion · plain
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataChanges in serum IgM and IgG levels did not differ significantly between the bezafibrate and placebo groups.
“In a post hoc analysis of markers of immunity and inflammation, conducted in a subgroup of patients with available data, changes in serum IgM and IgG levels did not differ significantly between the groups.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataA total of 10 patients (4 in the bezafibrate group and 6 in the placebo group) had stage 2 chronic kidney disease at 24 months.
“A total of 10 patients (4 in the bezafibrate group and 6 in the placebo group) had stage 2 chronic kidney disease (eGFR ≥60 and <90 ml per minute) at 24 months.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataBezafibrate was associated with a rapid and sustained decrease in alkaline phosphatase level and a parallel decrease in total bilirubin.
“In the current trial, bezafibrate was associated with a rapid and sustained decrease in alkaline phosphatase level and a parallel decrease in total bilirubin, the two most important prognostic indicators in primary biliary cholangitis.25”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductown dataPatients were randomly assigned in a 1:1 ratio to receive once-daily oral placebo or bezafibrate at a dose of 400 mg.
“Patients were randomly assigned, in a 1:1 ratio, to receive once-daily oral placebo or bezafibrate at a dose of 400 mg; patients in both groups received ursodeoxycholic acid therapy.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenBreakpoints in the piecewise linear function (segmented regression) were not prespecified.
“Breakpoints in the piecewise linear function (segmented regression) were not prespecified.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenThe trial was designed as a two-group, randomized, double-blind, placebo-controlled trial.
“The trial was designed as a two-group, randomized, double-blind, placebo-controlled trial.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenCentralized balanced-block randomization (blocks of 4) was computer-generated without stratification according to center.
“Centralized balanced-block randomization (blocks of 4) was computer-generated without stratification according to center.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenAnalyses were performed in the intention-to-treat population, which included all patients who underwent randomization.
“Analyses were performed at the end of the trial in the intention-to-treat population, which included all patients who underwent randomization; patients were unaware of their group assignments.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenSensitivity analyses were performed with the use of no imputation, the last-observation-carried-forward method, and the worst-case-scenario method.
“Sensitivity analyses were performed with the use of no imputation, the last-observation-carried-forward method, and the worst-case-scenario method.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe primary outcome as reported here was analyzed without multiple imputation.
“Multiple imputation was performed to replace missing data on biochemical measures that were used to assess the primary outcome; however, the primary outcome as reported here was analyzed without multiple imputation.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenPatients were unaware of their group assignments.
“Analyses were performed at the end of the trial in the intention-to-treat population, which included all patients who underwent randomization; patients were unaware of their group assignments.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationTreatment with ursodeoxycholic acid and fibrates has the potential both to improve biochemical measures and to reduce the symptoms of primary biliary cholangitis.
“Alternatively, treatment with ursodeoxycholic acid and fibrates, which are agonists of peroxisome proliferator-activated receptors (PPARs), has the potential both to improve biochemical measures and to reduce the symptoms of primary biliary cholangitis.[11][12][13][14]”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [11] 11. Nakai S, Masaki T, Kurokohchi K, De- guchi A, Nishioka M. Combination ther- apy of bezafibrate and ursodeoxycholic acid in primary biliary cirrhosis: a pre- liminary study. Am J Gastroenterol 2000; 95: 326-7. source
- cites [12] 12. Iwasaki S, Ohira H, Nishiguchi S, et al. The efficacy of ursodeoxycholic acid and bezafibrate combination therapy for pri- mary biliary cirrhosis: a prospective, multi- center study. Hepatol Res 2008; 38: 557-64. source
- cites [13] 13. Levy C, Peter JA, Nelson DR, et al. Pilot study: fenofibrate for patients with primary biliary cirrhosis and an incom- plete response to ursodeoxycholic acid. Aliment Pharmacol Ther 2011; 33: 235-42. source
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataMultiple imputation was performed to replace missing data on biochemical measures that were used to assess the primary outcome.
“Multiple imputation was performed to replace missing data on biochemical measures that were used to assess the primary outcome; however, the primary outcome as reported here was analyzed without multiple imputation.”
Quote in the paperNot a substantial claim- Rests on an assumption: Missing biochemical data used in the multiple imputation analysis are missing at random.
May combine two claims.
Study design and conductown dataTemporary or permanent discontinuation of the active drug or placebo occurred in 13 patients in the placebo group and 7 patients in the bezafibrate group; discontinuation of ursodeoxycholic acid occurred in 4 patients in the placebo group and 2 patients in the bezafibrate group.
“Temporary or permanent discontinuation of the active drug or placebo occurred in 13 patients in the placebo group and in 7 patients in the bezafibrate group; discontinuation of ursodeoxycholic acid occurred in 4 patients in the placebo group and in 2 patients in the bezafibrate group.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationcitationThe mechanism of the creatinine increase may involve renal hemodynamic changes or increased creatinine release by muscle.
“Its mechanism may involve renal hemodynamic changes or an increased creatinine release by muscle.30”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [30] 30. Sica DA. Fibrate therapy and renal function. Curr Atheroscler Rep 2009; 11: 338-42. source
Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).
InterpretationcitationSuppression of intrahepatic proinflammatory cytokines is highly plausible.
“We found no significant changes in IgM, high-sensitivity C-reactive protein, TNF-α, or interleukin-12 serum levels, but suppression of intrahepatic proinflammatory cytokines is highly plausible.35”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [35] 35. Nagasawa T, Inada Y, Nakano S, et al. Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARdelta agonist, on development of steatohepatitis in mice fed a methionine-and choline-deficient diet. Eur J Pharmacol 2006; 536: 182-91. source
The paper relies on this without support.
A complete biochemical response at 24 months is a valid measure of treatment efficacy in primary biliary cholangitis.
“The primary outcome was a complete biochemical response, which was defined as normal levels of total bilirubin, alkaline phosphatase, aminotransferases, and albumin, as well as a normal prothrombin index (a derived measure of prothrombin time), at 24 months.”
The paper relies on this without support.
Missing biochemical data used in the multiple imputation analysis are missing at random.
“Multiple imputation was performed to replace missing data on biochemical measures that were used to assess the primary outcome; however, the primary outcome as reported here was analyzed without multiple imputation.”
The paper relies on this without support.
The trial population is representative of patients with primary biliary cholangitis who have an inadequate response to ursodeoxycholic acid.
“Patients 18 years of age or older who had received a diagnosis of primary biliary cholangitis according to established criteria 2 were recruited at 21 centers throughout France.”
The paper relies on this without support.
The GLOBE and UK-PBC risk scores accurately predict liver transplantation and death in patients with primary biliary cholangitis, including this trial population.
“In a post hoc analysis of prognostic scores, the application of the GLOBE and UK-PBC risk scores at baseline, at 12 months, and at 24 months showed significantly lower predicted rates of liver transplantation and death at 5, 10, and 15 years in the bezafibrate group than in the placebo group.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the BEZURSO trial, ALP normalization occurred in 67% of the bezafibrate group compared with 2% in placebo (p < 0.001).
“ALP normalization occurred in 67% compared with 2% in placebo (p < 0.001).”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [40]
The Biochemical Measures section reports normal alkaline phosphatase levels at 24 months in 67% of the bezafibrate group versus 2% of the placebo group. It does not report P<0.001 for that comparison; the Methods section says secondary outcomes were reported with confidence intervals, without P values. The P<0.001 in the Primary Outcome section applies to a different, composite outcome. (LLM, conf=0.91)
Experimental — accuracy not yet measuredThe BEZURSO trial established bezafibrate as a highly effective adjunct to UDCA in PBC, though it remains off-label in the United States.
“This pivotal phase 3 trial established bezafibrate as a highly effective adjunct to UDCA in PBC, though it remains off-label in the United States.”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [40]
The Methods and Results (Abstract) identify BEZURSO as a phase 3 trial and report a complete biochemical response in 31% of patients receiving bezafibrate plus UDCA, versus 0% receiving placebo plus UDCA. The Discussion limits that finding to patients with an inadequate response to UDCA and says larger studies are needed to assess clinical outcomes. Our copy does not state whether bezafibrate is off-label in the United States. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn the BEZURSO trial, the primary endpoint, biochemical response at 24 months, was achieved in 31% of the bezafibrate group versus 0% of the placebo group (p < 0.001).
“The primary endpoint, biochemical response at 24 months, was achieved in 31% of the bezafibrate group versus 0% of the placebo group (p < 0.001).”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [40]
In the BEZURSO trial, differences in clinical outcomes such as liver decompensation were not statistically significant.
“However, differences in clinical outcomes such as liver decompensation were not statistically significant.”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [40]
In the BEZURSO trial, improvements were noted in pruritus, fatigue, and non-invasive fibrosis markers (liver stiffness and ELF score).
“Improvements were also noted in pruritus, fatigue, and non-invasive fibrosis markers (liver stiffness and ELF score).”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [40]
In the BEZURSO trial, adverse events included higher rates of myalgia (20% vs. 10%) and a modest increase in serum creatinine.
“Adverse events included higher rates of myalgia (20% vs. 10%) and a modest increase in serum creatinine [40].”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [40]
In 2018, a prospective, placebo-controlled, randomised controlled trial in France showed that bezafibrate improved liver biochemistries and liver stiffness in patients with incomplete responses to ursodeoxycholic acid.
“In 2018, a prospective, placebo-controlled, randomised controlled trial (RCT) in France showed that bezafibrate improved liver biochemistries and liver stiffness in patients with incomplete responses to ursodeoxycholic acid.102”
From Primary biliary cholangitis. (2024) · cites this paper as [102]
Fenofibrate and bezafibrate improve liver function tests in patients with PBC.
“Fenofibrate [109] and bezafibrate [110] were shown to improve liver function test in patients with PBC.”
From Pemafibrate, a new selective PPARα modulator: drug concept and its clinical applications for dyslipidemia and metabolic diseases (2020) · cites this paper as [110]
No major side effects of bezafibrate were observed during short-term treatment (3 weeks) in the FITCH trial, nor during the 2-year treatment of PBC in the BEZURSO trial.
“No major side effects of bezafibrate were observed during short-term treatment (3 weeks) in the FITCH trial, 219 nor during the 2-year treatment of PBC in the BEZURSO trial.220”
From EASL Clinical Practice Guidelines on sclerosing cholangitis (2022) · cites this paper as [220]
Bezafibrate in combination with UDCA exerts strong additive anticholestatic effects in PSC and PBC.
“As bezafibrate in combination with UDCA also exerts strong additive anticholestatic effects in PSC and PBC, 219,220”
From EASL Clinical Practice Guidelines on sclerosing cholangitis (2022) · cites this paper as [220]
The antipruritic effect of bezafibrate has been described as sustained under cholestatic conditions.
“and the antipruritic effect of bezafibrate has been described as sustained under cholestatic conditions, 220,221”
From EASL Clinical Practice Guidelines on sclerosing cholangitis (2022) · cites this paper as [220]
Bezafibrate in combination with ursodeoxycholic acid therapy shows anti-inflammatory, anti-fibrotic and anti-cholestatic effects in PBC patients.
“The treatment of PBC patients seems as well promising by administration of another pan-PPAR agonist (Bezafibrate -even if predominantly for PPAR-α) in combination with ursodeoxycholic acid therapy, showing anti-inflammatory, anti-fibrotic and anti-cholestatic effects.[155].”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [155]
In the BEZURSO phase 3 trial, bezafibrate 400 mg/day over 24 months resulted in complete biochemical response in 31% of patients with PBC with an incomplete response to UDCA versus 0% on placebo; 67% normalised ALP; it also improved pruritus and liver stiffness.
“Bezafibrate: BEZURSO (phase 3)70: bezafibrate 400 mg/day over 24 months resulted in complete biochemical response (defined as normalisation of hepatic serum biochemistry including ALP, aminotransferases, albumin, bilirubin and prothrombin index) in 31% of patients with PBC with an incomplete response to UDCA vs 0% on placebo; 67% normalised ALP; also improved pruritus and liver stiffness.”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [70]
Bezafibrate 400 mg/day over 24 months resulted in complete biochemical response in 31% of PBC patients with incomplete response to UDCA, and complete normalisation of ALP in 67%.
“Bezafibrate 400 mg/day over 24-month resulted in complete biochemical response in 31% of patients with PBC with an incomplete response to UDCA70 (table 1). In 67% of patients even complete normalisation of alkaline phosphatase was observed”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [70]
At least 3 months of dual and triple therapy was required because this duration was considered sufficient to assess biochemical response.
“A minimal 3 months of dual and triple therapy was required since this period of time was considered sufficient to assess biochemical response.10,14”
From Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult‐to‐treat primary biliary cholangitis (2021) · cites this paper as [14]
In the BEZURSO trial, 69% of bezafibrate-treated patients did not achieve complete biochemical response, while 70% achieved a good response by Paris-2 criteria.
“In the BEZURSO trial, 69% of the BZF-treated patients did not reach complete biochemical response, but 70% achieved a good response according to Paris-2 criteria.14”
From Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult‐to‐treat primary biliary cholangitis (2021) · cites this paper as [14]
Between 30% and 50% of UDCA poor responders do not respond adequately to second-line OCA or fibrates.
“These data suggest that 30% to 50% of UDCA poor-responders do not adequately respond to second-line therapies with OCA or fibrates.”
From Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult‐to‐treat primary biliary cholangitis (2021) · cites this paper as [14]
Fibrates have a known beneficial effect on pruritus associated with PBC.
“This result is in accordance with the known beneficial effect of fibrates on PBC-associated pruritus.14,15,22”
From Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult‐to‐treat primary biliary cholangitis (2021) · cites this paper as [14]
Bezafibrate is a broad PPAR agonist with anticholestatic, anti-inflammatory, and antifibrotic properties.
“bezafibrate, a broad peroxisome proliferator-activated receptor (PPAR) agonist with anticholestatic, 14 anti-inflammatory, 15 and antifibrotic 16 properties”
From Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial (2021) · cites this paper as [14]
Recent publications provide initial evidence that bezafibrate improves pruritus in patients with primary biliary cholangitis.
“Most recent publications provided first evidence for improved pruritus during bezafibrate treatment in PBC patients.14,18”
From Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial (2021) · cites this paper as [14]
In the BEZURSO trial, median baseline pruritus in bezafibrate-treated PBC patients was 1 of 10 on VAS, suggesting clinically nonrelevant pruritus for most included patients.
“In the BEZURSO trial on treatment with bezafibrate of PBC patients incompletely responding to UDCA, the median baseline pruritus in bezafibrate-treated patients was 1 of 10 on a VAS, suggesting a clinically nonrelevant level of pruritus for most of the included PBC patients.14”
From Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial (2021) · cites this paper as [14]
Bezafibrate appears to be a relatively safe therapeutic strategy for patients with fibrosing cholangiopathies.
“Because no serious adverse effects were observed during the present study and limited adverse effects in the recent Bezafibrate in Combination With Ursodeoxycholic Acid in Primary Biliary Cirrhosis (BEZURSO) trial in PBC, 14 bezafibrate appears to be a novel and relatively safe therapeutic strategy against severe or modest cholestasis-associated pruritus for patients with fibrosing cholangiopathie”
From Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial (2021) · cites this paper as [14]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
White-woman percentage exceeds the possible count
MinorThe table permits at most 47 white women in the bezafibrate group and 46 in the placebo group, or 93 of 100 patients. The stated 95% is therefore impossible.
“Overall, 95% of the patients were white women, and the mean (±SD) age was 53±10 years.”
“Female sex -no.(%) 49 (98) 46 (92) White race -no.(%) ‡ 47 (94) 48 (96)”
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Mechanisms and molecules: What are the treatment targets for primary biliary cholangitis?
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- Authors
- Corpechot, C., Chazouillères, O., Rousseau, A., Le Gruyer, A., Habersetzer, F., Mathurin, P., Goria, O., Potier, P., Minello, A., Silvain, C., Abergel, A., Debette-Gratien, M., Larrey, D., Roux, O., Bronowicki, J.-P., Boursier, J., de Ledinghen, V., Heurgue-Berlot, A., Nguyen-Khac, E., Zoulim, F., Ollivier-Hourmand, I., Zarski, J.-P., Nkontchou, G., Lemoinne, S., Humbert, L., Rainteau, D., Lefèvre, G., de Chaisemartin, L., Chollet-Martin, S., Gaouar, F., Admane, F.-H., Simon, T., & Poupon, R.
- Affiliations
- Inserm (FR)
- Université Paris-Sud (FR)
- From the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, Hepatology and Gastroenterology Department, Saint-Antoine University Hospital, Assistance Publique–Hôpitaux de Paris (APHP) (C.C., O.C., S.L., F.G., R.P.), INSERM Unité Mixte de Recherche (UMR) S938 (C.C., O.C., S.L., R.P.) and the Biochemistry Laboratory (L.H., D.R.), Saint-Antoine University Hospital, APHP, INSERM Unité 1157/UMR 7203, Sorbonne University, the Biochemistry Laboratory, Tenon University Hospital,...
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-06-07
- Volume
- 378
- Issue
- 23
- Pages
- 2171-2181
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2807617765
- Semantic Scholar
- 85ed62f9ab17377d94ccba2da14f863ee36a14a6
- Cited by
- 635
- References
- 36
- Citations by year
- 2026: 73 · 2025: 91 · 2024: 66 · 2023: 71 · 2022: 89 · 2021: 79 · 2020: 76 · 2019: 64 · 2018: 18 · 2016: 1
- FWCI
- 28.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (Le Centre pour la Communication Scientifique Directe) (submittedVersion)
- Funders
- Arrow Génériques, Lyon, France
- Assistance Publique – Hôpitaux de Paris, Paris, France (Programme Hospitalier de Recherche Clinique (PHRC))
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- primary biliary cirrhosis, bezafibrate, ursodeoxycholic acid, peroxisome proliferator-activated receptor agonists, biochemical response, liver fibrosis, pruritus, fatigue
- MeSH terms
- Adult, Hypolipidemic Agents, Bezafibrate, Bile Acids and Salts, Cholangitis, Double-Blind Method
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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