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Cited by 78Liver Diseases and ImmunityDrug Transport and Resistance MechanismsPediatric Hepatobiliary Diseases and Treatments

Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult‐to‐treat primary biliary cholangitis

Open access
Soret, Pierre‐Antoine, Lam, Laurent, Carrat, Fabrice, Smets, Lena, Berg, Thomas, Carbone, Marco, Invernizzi, Pietro, Leroy, Vincent +20 more·2021·Alimentary Pharmacology & Therapeutics
DOI 10.1111/apt.16336
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Abstract

Summary: Background: Obeticholic acid (OCA) and fibrates are second‐line therapies for patients with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA). Aim: To know whether OCA and fibrates, administered together in combination with UDCA, have additive beneficial effects in patients with difficult‐to‐treat PBC. Methods: PBC patients treated for ≥3 months with UDCA, OCA and fibrates (bezafibrate or fenofibrate) due to failure of either second‐line therapy were included in a multicentre, uncontrolled retrospective cohort study. Changes in biochemical liver tests and pruritus were analysed using a generalised linear mixed‐effect model. Results: Among 58 patients included, half received OCA as second‐line and fibrates as third‐line therapy (Group OCA‐Fibrate), while the other half had the inverse therapeutic sequence (Group Fibrate‐OCA). The mean duration of triple therapy was 11 months (range 3‐26). Compared to dual therapy, triple therapy was associated with a significant gain in alkaline phosphatase (ALP) reduction: 22% per first year (95% CI 12%‐31%), an effect that was stronger in OCA‐Fibrate than in Fibrate‐OCA group. Triple therapy was associated with a 3.4 (95% CI 1.4‐8.2) odds ratio (OR) of reaching normal ALP and with a significant decrease in gamma‐glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. The ORs of achieving the Paris‐2 and Toronto criteria of adequate biochemical response were 6.8 (95% CI 2.8‐16.7) and 9.2 (95% CI 3.4‐25.1) respectively. Finally, triple therapy significantly improved pruritus in OCA‐Fibrate but not in Fibrate‐OCA group. Conclusions: Triple therapy with UDCA, OCA and fibrates is able to normalise biochemical liver tests and improve pruritus in patients with difficult‐to‐treat PBC.

Integrity signals

Registry

Crossref · 10.1111/apt.16336

Cites

10 of 10 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 20 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    All patients subsequently received triple therapy with UDCA, OCA, and fibrates for at least 3 months.

    “All had subsequently been exposed to triple therapy with UDCA, OCA and fibrates for a minimal period of 3 months.”
    Quote in the paperSubstantial claim
  • Findingown data

    All patients had previously failed to respond adequately to standard UDCA and then to a second-line option with UDCA.

    “All patients had previously failed to adequately respond to standard UDCA, then to a second-line option (OCA or fibrates) in combination with UDCA.”
    Quote in the paperSubstantial claim
  • Findingown data

    After excluding AIH overlap, triple vs dual therapy was associated with a 25% greater reduction per year in ALT in the entire cohort (95% CI 12% to 36%, p<0.001).

    “ALT 25% 12% -36% < 0.001”
    Quote in the paperSubstantial claim
  • Findingown data

    After excluding AIH overlap, triple vs dual therapy was associated with a 13% greater reduction per year in bilirubin in the entire cohort (95% CI 4% to 22%, p=0.008).

    “Table S11.Reduction gain per year in secondary outcomes under triple vs. dual therapy as estimated on the entire cohort after the exclusion of patients with features of AIH overlap syndrome.Reduction gain 95% confidence interval P-value Bilirubin 13% 4% -22% 0.008”
    Quote in the paperSubstantial claim
  • Findingown data

    Triple therapy was associated with a 13% per year reduction in AST, 95% CI 3% to 21%, p<0.01.

    “AST (13% per year; 95%CI 3% to 21%; p<0.01)”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 37
  • May combine two claims. 22

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    The 11 Belgian patients previously reported in the literature took part in this study.

    “The 11 Belgian patients previously reported in the literature participated in this study.17”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The UDCA dose was 15.4 mg/kg/day.

    “The dose of UDCA was 15.4 (4.0) mg/kg/d (range 7.6 to 24.6).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The cohort comprised 29 patients in the OCA-Fibrate group and 29 in the Fibrate-OCA group.

    “They consisted of 29 patients who received OCA as second-line therapy then fibrates as third-line therapy (Group OCA-Fibrate) and 29 others who experienced the inverse therapeutic sequence, namely fibrates as second-line therapy then OCA as third-line therapy (Group Fibrate-OCA).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    All patients with PBC-AIH overlap had stable corticosteroid and immunosuppressive drug doses at inclusion.

    “All of them had stable doses of corticosteroids and immunosuppressive drugs at the time of inclusion.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Median prior UDCA therapy duration was 4.1 years.

    “The median duration of prior UDCA therapy was 4.1 years (range 1.0 to 24.8).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Median liver stiffness was 9.9 kPa and 22% of patients had proven or predicted cirrhosis.

    “The median LSM was 9.9 kPa (range 4.2 to 48.0) and 22% of patients had proven or predicted cirrhosis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The study included 58 eligible patients from 19 centers in 7 Western countries.

    “In total, 58 eligible patients from 19 centers across 7 Western countries were included in this retrospective cohort study”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Eleven patients, 19%, had features of PBC-AIH overlap syndrome.

    “Eleven (19%) patients were considered to have features of PBC-AIH overlap syndrome.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At baseline of second-line therapy, patients were mainly women around 50 years old with persistent cholestasis despite UDCA, with median ALP 2.7 xULN and pruritus in 59%.

    “As expected, patients were mainly women of 50 years old exhibiting significant persisting clinical and/or biochemical features of cholestasis despite UDCA therapy (median ALP level: 2.7 xULN; pruritus 59%).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    At baseline of dual therapy, the OCA-Fibrate and Fibrate-OCA groups differed significantly in GGT (p<0.01).

    “GGT (xULN) | 5.0 (4.5) | 8.2 (10.1) | < 0.01”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    ORs for adequate biochemical response remained highly significant in each group but were consistently higher in OCA-Fibrate than in Fibrate-OCA.

    “When assessed by group, these ORs remained highly significant in each group but were consistently higher in Group OCA-Fibrate than in Group Fibrate-OCA (Appendix, Table S12).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    After excluding AIH overlap, triple vs dual therapy was associated with an odds ratio of 2.2 per year of having no pruritus in the entire cohort (95% CI 0.7 to 7.1, p=0.187).

    “Odds ratio of no pruritus 95% confidence interval P-value Entire cohort 2.2 0.7 -7.1 0.187”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    At baseline of dual therapy, the OCA-Fibrate and Fibrate-OCA groups differed significantly in age (p<0.05).

    “Age (yrs) | 51.8 (16.6) | 46.0 (13.5) | < 0.05”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    After excluding AIH overlap, triple vs dual therapy was associated with a 36% greater reduction per year in itch intensity score in the entire cohort (95% CI -34% to 69%, p=0.234).

    “Table S13.Reduction gain per year in itch intensity score and odds ratio of having no pruritus under triple vs. dual therapy as estimated on the entire cohort and by group after the exclusion of patients with features of AIH overlap syndrome.Reduction gain in itch 95% confidence interval P-value Entire cohort 36% -34% -69% 0.234”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    In the Fibrate-OCA group, the odds ratio per year of having no pruritus under triple vs dual therapy was 0.7 (95% CI 0.1 to 4.0, p=0.714).

    “Group Fibrate-OCA 0.7 0.1 -4.0 0.714”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Total follow-up from UDCA initiation was 8.6 years.

    “Total follow-up from UDCA initiation was 8.6 (10.7) years (range 1.9 to 27.5).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Treatment groups were comparable except that the Fibrate-OCA group was younger and had higher GGT and transaminase levels than the OCA-Fibrate group.

    “Treatment groups were comparable except for a younger age and higher GGT and transaminases levels in Group Fibrate-OCA compared to Group OCA-Fibrate.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Dual therapy lasted a median of 2.8 years and triple therapy a median of 0.8 years, mean 11 months, range 3 to 26 months.

    “Total duration of dual therapy was 2.8 (4.3) years (range 0.3 to 9.8) and that of triple therapy was 0.8 (0.6) years (mean 11 months; range 3 to 26 months).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Triple therapy did not significantly change itch intensity score in the whole population, with a mean reduction of 13% per year, 95% CI -58% to 52%, p=0.7.

    “Compared to dual therapy, the mean change following triple therapy in itch intensity score was not significant when assessed on the entire population: mean gain reduction 13% per year (95%CI -58% to 52%; p=0.7).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    In the Fibrate-OCA group, triple vs dual therapy was associated with a -36% change per year in itch intensity score (95% CI -278% to 51%, p=0.553).

    “Group Fibrate-OCA -36% -278% -51% 0.553”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Myalgias were reported in 2 patients, 3%, and in both cases the symptom began before fibrates were introduced.

    “Myalgias were reported in 2 (3%) patients.In both cases, this symptom preceded fibrates introduction.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Complete follow-up and the durations of dual and triple therapy did not differ between groups.

    “Neither the complete follow-up nor the durations of dual and triple therapies differed between groups (Appendix, Table S6).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    In the Fibrate-OCA group, the odds ratio per year of having normal ALP under triple vs dual therapy was 1.7 (95% CI 0.4 to 7.9, p=0.486).

    “Group Fibrate-OCA 1.7 0.4 -7.9 0.486”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    OCA is currently the only officially approved drug for PBC patients who are resistant to or intolerant of UDCA.

    “OCA, a selective Farnesoid-X receptor (FXR) agonist, is currently the only drug officially approved in patients with resistance or intolerance to UDCA.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All statistical models were checked using residual plots.

    “All statistical models were verified based on residual plots.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    OCA improves key biochemical markers in PBC but is linked to pruritus and possible liver injury in patients with advanced disease.

    “OCA has shown efficacy on key biochemical markers of PBC, but has been associated with pruritus and potential risk of liver injury in patients with most advanced disease.[10][11][12]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10][11][12]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The model was adjusted for within-subject random effects, age, gender, and UDCA dose.

    “The model was adjusted for within-subject random effects, age, gender, and UDCA dose.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    A generalized linear mixed-effects model was used to account for clustering from repeated observations within patients.

    “Differences between triple and dual therapies in all patients and by treatment group were assessed using a generalized linear mixed-effects model (GLMM) to account for clustering due to repeated observation from the same patient, as repeated measures within a patient are correlated.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Fenofibrate, a selective PPAR-a agonist, has effects comparable to bezafibrate in high-risk PBC.

    “while fenofibrate (FNF), a selective PPAR-a agonist, has comparable effects.[13][14][15][16]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13][14][15][16]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    OCA and fibrates added to UDCA have shown additive biochemical effects in PBC, but their long-term benefit is not established.

    “Two second-line therapies, namely obeticholic acid (OCA) and fibrates, administrated in association with UDCA, have shown additive biochemical effects in PBC, though their longterm benefit has yet to be proven.9”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    All participants' data were included in the analysis because the mixed-effects model can handle unbalanced and missing data.

    “All data from all participants were included in the analysis, as GLMM allows for unbalanced and missing data.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    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”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Adjustment for OCA and fibrate doses was not possible because of collinearity with therapeutic groups and the limited number of explanatory variables allowed by the small sample.

    “Because of collinearity between therapeutic groups and doses of second-or third-line drugs, and the limited number of explanatory variables allowed due to the small size of the studied population, complementary adjustment for OCA and fibrates doses was not possible.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    A report of 11 Belgian patients who failed OCA suggests that adding bezafibrate may lower ALP and bilirubin and reduce OCA-induced pruritus.

    “A recent report of 11 Belgian patients who had failed to respond to OCA suggests that BZF add-on therapy may reduce ALP and bilirubin levels and mitigate OCA-induced pruritus.17”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17]

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Bezafibrate, a pan-PPAR agonist, improves symptoms and biochemical features in high-risk PBC patients.

    “Bezafibrate (BZF), a pan-PPAR agonist, has shown beneficial effects on both symptoms and biochemical features of high-risk PBC patients”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13][14][15][16]

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductcitation

    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”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [10] source

      Not checked in the free run.

    • cites [14] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    A sensitivity analysis excluding patients with AIH overlap features was performed for all results.

    “For all results, a sensitivity analysis excluding patients with features of AIH overlap syndrome was performed.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The results suggest that fibrates and OCA affect different mechanisms leading to PBC, including liver inflammation and cholestasis, which may explain their additive benefits.

    “These results suggest that fibrates and OCA have different impact on the mechanisms that concomitantly lead to PBC, including liver inflammation and cholestasis, and may explain their additive beneficial effects.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: OCA and fibrates act on different pharmacological targets, so their combination with UDCA may have additive or synergistic effects.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The main limitation of this retrospective study concerns evaluation of tolerance and safety.

    “The main limitation of this retrospective study concerns the evaluation of tolerance and safety.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The relative changes per year cannot reflect the actual kinetics of biochemical liver tests, which mostly vary within the first 3 to 6 months before stabilizing.

    “These rates, which were used for comparison purposes, cannot pretend to reflect the actual kinetics of biochemical liver tests, which mostly vary within the first 3 to 6 months of additional therapy before they stabilize.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Triple therapy with UDCA, OCA, and fibrates can improve and even normalize biochemical and clinical features of PBC, supporting additive or synergistic effects of FXR and PPAR agonists.

    “we showed that triple therapy with UDCA, OCA, and fibrates has the potential to improve and even normalize the biochemical and clinical features of the disease, a finding that supports additive or synergistic effects of FXR and PPAR agonists in the treatment of PBC.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: OCA and fibrates act on different pharmacological targets, so their combination with UDCA may have additive or synergistic effects.
    • The authors state this as an assumption: OCA and fibrate dose covariates had little impact on the results because few dosage changes occurred during the study.

  • May combine two claims.

    Interpretationown data

    The present data suggest that fibrates are more effective than OCA at reducing ALP, while OCA may have stronger effects on GGT and transaminases.

    “it appears from the present data that fibrates are more efficient than OCA in reducing ALP level, whereas OCA could have stronger effects than fibrates on GGT and transaminases.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Normal bilirubin and normalization of ALP should be treatment goals to improve survival in PBC.

    “It has been shown that bilirubin within the normal range and normalization of ALP should be the goals of treatment for improved survival in PBC.21”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning

    Selecting patients treated with triple therapy for at least 3 months excluded those with early intolerance and those who had discontinued one of the dual therapies.

    “By selecting patients who had been treated with triple therapy for at least 3 months, we have de facto excluded those who had experienced early intolerance to this combination, as well as those who had previously discontinued one of both dual therapies.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The baseline differences between groups may be related to a higher proportion of PBC-AIH overlap in Fibrate-OCA, 28%, than in OCA-Fibrate, 10%.

    “These differences may be related to a greater proportion of patients with PBC-AIH overlap syndrome in Group Fibrate-OCA (28%) than in Group OCA-Fibrate (10%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Triple therapy with UDCA, OCA, and fibrates can normalize biochemical liver tests and improve pruritus in patients with difficult-to-treat PBC.

    “Triple therapy with UDCA, OCA and fibrates is able to normalize biochemical liver tests and improve pruritus in patients with difficult-to-treat PBC.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: OCA and fibrates act on different pharmacological targets, so their combination with UDCA may have additive or synergistic effects.
    • The authors state this as an assumption: OCA and fibrate dose covariates had little impact on the results because few dosage changes occurred during the study.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The study did not use a matched control group; patients served as their own controls, and a linear mixed-effects model controlled for within-subject autocorrelations.

    “We did not use a matched control group for the comparison of triple therapy with dual therapy.Instead, the patients were their own controls and we applied a linear mixed-effects model to control for within-subject autocorrelations.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    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”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [14] source

      Not checked in the free run.

    • cites [15]

      Not checked in the free run.

    • cites [22] source

      Not checked in the free run.

48 of 48

  • The paper relies on this without support.

    Hard-to-treat PBC patients make up 10% to 15% of all PBC patients.

    “These hard-to-treat patients, who represent 10% to 15% of all PBC patients, are in needs for optimized treatment.”

  • The paper relies on this without support.

    OCA and fibrates act on different pharmacological targets, so their combination with UDCA may have additive or synergistic effects.

    “As OCA and fibrates have different pharmacological targets, their combination in addition to UDCA (i.e.triple therapy) may have additive or even synergistic effects.”

  • The paper relies on this without support.

    Little is known about the effects of the triple combination in PBC.

    “Little is known about the effects of this triple combination in PBC.”

  • The authors state this as an assumption.

    OCA and fibrate dose covariates had little impact on the results because few dosage changes occurred during the study.

    “However, we assume these covariates would have had only little impact on results since few changes in dosage occurred during the study.”
4 of 4

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?

  • Alkaline phosphatase was normalised in nearly half of patients receiving triple therapy of ursodeoxycholic acid, obeticholic acid, and PPAR agonist for 1-2 years, and the alkaline phosphatase-lowering effect of obeticholic acid-PPAR agonist was greater than that of PPAR agonist-obeticholic acid.

    “Alkaline phosphatase was normalised in nearly half of patients receiving the triple therapy of ursodeoxycholic acid, obeticholic acid, and PPAR agonist for 1-2 years, and the alkaline phosphatase-lowering effect of obeticholic acid-PPAR agonist was greater than that of PPAR agonist-obeticholic acid.114”

    From Primary biliary cholangitis. (2024) · cites this paper as [114]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Several currently explored drugs (eg, NR ligands) simultaneously target multiple key pathogenetic processes and may show synergistic effects when combined in management of cholestatic and fatty liver diseases, for example, combining FXR and PPAR ligands in PBC and NASH.

    “Several of the currently explored drugs (eg, NR ligands) simultaneously target multiple key pathogenetic processes and may show even synergistic effects when combined in the management of these disorders, for example, combining FXR and PPAR ligands in PBC232 233 and NASH.234”

    From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [232]

Cites

Flagged first, then by citations

Research works printed but not linked: 14

  1. 10.1111/apt.16023 · DOI
  2. 10.1111/hepr.12270 · DOI
  3. 10.1053/j.gastro.2005.12.029 · DOI · Paper page
  4. 10.1038/ajg.2010.216 · DOI · Paper page
  5. Montano‐Loza AJ, 2020, Definition and management of patients with primary biliary cholangitis and an incomplete response to therapy, Clin Gastroenterol Hepatol, 3, 30926‐5
  6. 10.1002/hep.31017 · DOI
  7. 10.1016/S1386-6346(99)00033-9 · DOI
  8. 10.1111/j.1365-2036.2010.04512.x · DOI · Paper page
  9. Smets L, 2020, Improved markers of cholestatic liver injury in patients with primary biliary cholangitis treated with obeticholic acid and bezafibrate, Hepatology, 3, 10.1002/hep.316 · DOI
  10. 10.1016/j.jhep.2011.02.031 · DOI · Paper page
  11. 10.1002/hep.510280203 · DOI · Paper page
  12. 10.14309/ajg.0000000000000557 · DOI · Paper page
  13. 10.1038/ajg.2017.287 · DOI · Paper page
  14. 10.1053/j.gastro.2012.12.005 · DOI · Paper page

Cited by

Sorted by citations

Authors
Soret, P., Lam, L., Carrat, F., Smets, L., Berg, T., Carbone, M., Invernizzi, P., Leroy, V., Trivedi, P., Cazzagon, N., Weiler‐Normann, C., Alric, L., Rosa‐Hezode, I., Heurgué, A., Cervoni, J., Dumortier, J., Potier, P., Roux, O., Silvain, C., Bureau, C., Anty, R., Larrey, D., Levy, C., Pares, A., Schramm, C., Nevens, F., Chazouillères, O., & Corpechot, C.
Affiliations
  • Assistance Publique – Hôpitaux de Paris (FR)
  • Universitair Ziekenhuis Leuven (BE)
  • Leipzig University (DE)
  • Monza Italy
  • Centre Hospitalier Universitaire de Grenoble (FR)
  • University Hospitals Birmingham NHS Foundation Trust (GB)
  • Padova Italy
  • Hamburg Germany
  • Toulouse France
  • Créteil France
  • Centre Hospitalier Universitaire de Reims (FR)
  • Besançon France
  • Lyon France
  • Orléans France
  • Clichy France
  • Poitiers France
  • Centre Hospitalier Universitaire de Nice (FR)
  • Montpellier France
  • Miami USA
  • Barcelona Spain
Corresponding author
Corpechot, Christophe
ORCID
Venue
Alimentary Pharmacology & Therapeutics
Publisher
Wiley
Published
2021-03-25
Volume
53
Issue
10
Pages
1138-1146
ISSN
  • 0269-2813 (ISSN-L)
  • 1365-2036
DOI
10.1111/apt.16336
OpenAlex
W3137256548
Cited by
78
References
10
Citations by year
2026: 5 · 2025: 20 · 2024: 18 · 2023: 11 · 2022: 15 · 2021: 9
FWCI
7.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Alimentary Pharmacology & Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • BOA (University of Milano-Bicocca) (submittedVersion)
  • Lirias (submittedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
Funders
  • GlaxoSmithKline
  • Gilead Sciences
  • Inventiva Pharma
Topics
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
Keywords
primary biliary cirrhosis, obeticholic acid, fibrates, bezafibrate, fenofibrate, ursodeoxycholic acid, triple therapy, combination therapy, alkaline phosphatase, pruritus, treatment response
MeSH terms
Chenodeoxycholic Acid, Cholagogues and Choleretics, Humans, Liver Cirrhosis, Biliary, Retrospective Studies, Ursodeoxycholic Acid, Fibric Acids

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 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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.

What counts as a claim ›How we measure confidence ›How we check this ›

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