The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Effectiveness of Fenofibrate in Treatment-Naive Patients With Primary Biliary Cholangitis: A Randomized Clinical Trial
Abstract
INTRODUCTION: Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease, and patients with inadequate response to ursodeoxycholic acid (UDCA) treatment show reduced long-term survival. Recent studies have shown that fenofibrate is an effective off-label therapy for PBC. However, prospective studies on biochemical response including the timing of fenofibrate administration are lacking. This study is aimed to evaluate the efficacy and safety of fenofibrate in UDCA treatment-naive patients with PBC. METHODS: A total of 117 treatment-naive patients with PBC were recruited from the Xijing Hospital for a 12-month randomized, parallel, and open-label clinical trial. Study participants were assigned to receive either UDCA standard dose (UDCA-only group) or fenofibrate at a daily dose of 200 mg in addition to UDCA (UDCA-Fenofibrate group). RESULTS: The primary outcome was biochemical response percentage in patients according to the Barcelona criterion at 12 months. In the UDCA-Fenofibrate group, 81.4% (69.9%–92.9%) of patients achieved the primary outcome and 64.3% (51.9%–76.8%) in the UDCA-only group achieved the primary outcome ( P = 0.048). There was no difference between the 2 groups in noninvasive measures of liver fibrosis and biochemical markers other than alkaline phosphatase at 12 months. Creatinine and transaminases levels in the UDCA-Fenofibrate group increased within the first month, then returned to normal, and remained stable thereafter until the end of the study, even in patients with cirrhosis. DISCUSSION: In this randomized clinical trial in treatment-naive patients with PBC, the combination of fenofibrate and UDCA resulted in a significantly higher biochemical response rate. Fenofibrate seemed to be well-tolerated in patients.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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 citing paper
“In a randomized trial, creatinine and transaminases levels in the UDCA-fenofibrate dual therapy group increased within the first month, then returned to normal, and remained stable thereafter until the end of the study, even in patients with cirrhosis [15].”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [15]
In the citing paper
“There is growing evidence that adding fenofibrate to UDCA in patients with UDCA-resistant PBC significantly improves biochemical markers, especially ALP.”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [15]
In the citing paper
“These effects collectively reduce cholesterol and hepatic inflammation, and it reflects by reductions in serum ALP and GGT levels [7,15,39].”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [15]
In the citing paper
“The primary outcome, biochemical response at 12 months according to the Barcelona criterion, was achieved in 46/57 patients (81.4%) in the UDCA–fenofibrate group and 36/60 patients (64.3%) in the UDCA-only group, with a statistically significant difference (p = 0.048) [15].”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [15]
In the citing paper
“However, there were no statistical differences between the UDCA–fenofibrate and UDCA-only groups in liver stiffness measured by transient elastography (p = 0.335), FIB-4 score (p = 0.692), and GGT (p = 0.605) [15].”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [15]
In the citing paper
“From a comparative perspective, OCA and fibrates both achieve ALP reduction, but fibrates often provide greater biochemical response and potential pruritus relief, whereas OCA is limited by dose-dependent pruritus and contraindications in cirrhosis [15,22,27].”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [15]
Citations
Cites
Wai, C.-T., Greenson, J. K., Fontana, R. J., Kalbfleisch, J. D., Marrero, J. A., Conjeevaram, H. S., & Lok, A. S.-F. (2003) · Hepatology · doi:10.1053/jhep.2003.50346 · Cited by 4,406
Vallet‐Pichard, A., Mallet, V. O., Nalpas, B., Verkarre, V., Nalpas, A., Dhalluin-Venier, V., Fontaine, H., & Pol, S. (2007) · Hepatology · doi:10.1002/hep.21669 · Cited by 2,085
The PPARs: From Orphan Receptors to Drug Discovery
Willson, T. M., Brown, P. J., Sternbach, D. D., & Henke, B. R. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm990554g · Cited by 1,816
A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis
Nevens, F., Andreone, P., Mazzella, G., Strasser, S. I., Bowlus, C., Invernizzi, P., Drenth, J. P. H., Pockros, P. J., Regula, J., Beuers, U., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1509840 · Cited by 1,131
Lindor, K. D., Bowlus, C. L., Boyer, J., Levy, C., & Mayo, M. (2019) · Hepatology · doi:10.1002/hep.30145 · Cited by 913 · cited 2×
“Obeticholic acid (OCA), a selective agonist of the farnesoid X receptor, has been approved as a second-line therapy for UDCA in patients with incomplete responses (3,4).”
MethodParés, A., Caballería, L., & Rodés, J. (2006) · Gastroenterology · doi:10.1053/j.gastro.2005.12.029 · Cited by 756
A Multicenter, Controlled Trial of Ursodiol for the Treatment of Primary Biliary Cirrhosis
Poupon, R. E., Balkau, B., Eschwège, E., Poupon, R., & the UDCA–PBC Study Group* (1991) · New England Journal of Medicine · doi:10.1056/nejm199105303242204 · Cited by 755
Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis
Corpechot, C., Abenavoli, L., Rabahi, N., Chrétien, Y., Andréani, T., Johanet, C., Chazouillères, O., & Poupon, R. (2008) · Hepatology · doi:10.1002/hep.22428 · Cited by 646 · cited 2×
“However, approximately 30% – 40% of patients show inadequate responses to UDCA and have impaired long-term survival (7 – 10).”
BackgroundA Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis
Corpechot, C., Chazouillères, O., Rousseau, A., Le Gruyer, A., Habersetzer, F., Mathurin, P., Goria, O., Potier, P., Minello, A., Silvain, C., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1714519 · Cited by 642
Lammers, W. J., van Buuren, H. R., Hirschfield, G. M., Janssen, H. L. A., Invernizzi, P., Mason, A. L., Ponsioen, C. Y., Floreani, A., Corpechot, C., Mayo, M. J., et al. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.08.029 · Cited by 498
Corpechot, C., Chazouillères, O., & Poupon, R. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2011.02.031 · Cited by 460
Kuiper, E. M. M., Hansen, B. E., de Vries, R. A., den Ouden–Muller, J. W., van Ditzhuijsen, T. J. M., Haagsma, E. B., Houben, M. H. M. G., Witteman, B. J. M., van Erpecum, K. J., & van Buuren, H. R. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.01.003 · Cited by 460
Lammers, W. J., Hirschfield, G. M., Corpechot, C., Nevens, F., Lindor, K. D., Janssen, H. L. A., Floreani, A., Ponsioen, C. Y., Mayo, M. J., Invernizzi, P., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.07.061 · Cited by 441
Carbone, M., Mells, G. F., Pells, G., Dawwas, M. F., Newton, J. L., Heneghan, M. A., Neuberger, J. M., Day, D. B., Ducker, S. J., Sandford, R. N., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2012.12.005 · Cited by 386
Kumagi, T., Guindi, M., Fischer, S. E., Arenovich, T., Abdalian, R., Coltescu, C., Heathcote, J. E., & Hirschfield, G. M. (2010) · American Journal of Gastroenterology · doi:10.1038/ajg.2010.216 · Cited by 372
Hirschfield, G. M., Dyson, J. K., Alexander, G. J. M., Chapman, M. H., Collier, J., Hübscher, S., Patanwala, I., Pereira, S. P., Thain, C., Thorburn, D., et al. (2018) · Gut · doi:10.1136/gutjnl-2017-315259 · Cited by 362 · cited 2×
“Obeticholic acid (OCA), a selective agonist of the farnesoid X receptor, has been approved as a second-line therapy for UDCA in patients with incomplete responses (3,4).”
MethodHarms, M. H., van Buuren, H. R., Corpechot, C., Thorburn, D., Janssen, H. L. A., Lindor, K. D., Hirschfield, G. M., Parés, A., Floreani, A., Mayo, M. J., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.04.001 · Cited by 289 · cited 1×
“Treatment with UDCA at 13 – 15 mg/kg/d can decrease the levels of cholestasis markers, ALP and g -glutamyltransferase (GGT) (5), and extend transplant-free survival (6).”
Backgroundde Vries, E., Bolier, R., Goet, J., Parés, A., Verbeek, J., de Vree, M., Drenth, J., van Erpecum, K., van Nieuwkerk, K., van der Heide, F., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.10.001 · Cited by 224
Schattenberg, J. M., Pares, A., Kowdley, K. V., Heneghan, M. A., Caldwell, S., Pratt, D., Bonder, A., Hirschfield, G. M., Levy, C., Vierling, J., et al. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.01.013 · Cited by 191
Levy, C., Peter, J. A., Nelson, D. R., Keach, J., Petz, J., Cabrera, R., Clark, V., Firpi, R. J., Morelli, G., Soldevila-Pico, C., et al. (2011) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2010.04512.x · Cited by 186
Carbone, M., Nardi, A., Flack, S., Carpino, G., Varvaropoulou, N., Gavrila, C., Spicer, A., Badrock, J., Bernuzzi, F., Cardinale, V., et al. (2018) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(18)30163-8 · Cited by 155
Cheung, A. C., Lapointe‐Shaw, L., Kowgier, M., Meza‐Cardona, J., Hirschfield, G. M., Janssen, H. L. A., & Feld, J. J. (2016) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13465 · Cited by 139
Hegade, V. S., Khanna, A., Walker, L. J., Wong, L.-L., Dyson, J. K., & Jones, D. E. J. (2016) · Digestive Diseases and Sciences · doi:10.1007/s10620-016-4250-y · Cited by 86
Bowlus, C. L., Galambos, M. R., Aspinall, R., Hirschfield, G. M., Jones, D. E. J., Dörffel, Y., Gordon, S. C., Harrison, S. A., Kremer, A. E., Mayo, M. J., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.02.033 · Cited by 84
Liver Injury in Patients With Cholestatic Liver Disease Treated With Obeticholic Acid
Eaton, J. E., Vuppalanchi, R., Reddy, K. R., Satapathy, S. K., Ali, B., & Kamath, P. S. (2019) · Hepatology · doi:10.1002/hep.31017 · Cited by 81
Vuppalanchi, R., Caldwell, S. H., Pyrsopoulos, N., deLemos, A. S., Rossi, S., Levy, C., Goldberg, D. S., Mena, E. A., Sheikh, A., Ravinuthala, R., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2021.08.025 · Cited by 79
Ghonem, N. S., Auclair, A. M., Hemme, C. L., Gallucci, G. M., de la Rosa Rodriguez, R., Boyer, J. L., & Assis, D. N. (2020) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1930 · Cited by 57
Li, C., Zheng, K., Chen, Y., He, C., Liu, S., Yang, Y., Li, M., Zeng, X., Wang, L., & Zhang, F. (2022) · Therapeutic Advances in Chronic Disease · doi:10.1177/20406223221114198 · Cited by 38
Additional fibrate treatment in UDCA‐refractory PBC patients
Chung, S. W., Lee, J., Kim, M. A., Leem, G., Kim, S. W., Chang, Y. W., Lee, H. Y., Yoon, J. S., Park, J. Y., Lee, Y. B., et al. (2019) · Liver International · doi:10.1111/liv.14165 · Cited by 34
Yang, C., Guo, G., Li, B., Zheng, L., Sun, R., Wang, X., Deng, J., Jia, G., Zhou, X., Cui, L., et al. (2022) · Hepatology International · doi:10.1007/s12072-022-10431-7 · Cited by 27
Self-citationGallucci, G. M., Trottier, J., Hemme, C., Assis, D. N., Boyer, J. L., Barbier, O., & Ghonem, N. S. (2021) · Hepatology Communications · doi:10.1002/hep4.1787 · Cited by 26
Ding, D., Guo, G., Liu, Y., Zheng, L., Jia, G., Deng, J., Sun, R., Wang, X., Guo, C., Shang, Y., et al. (2022) · Hepatology Communications · doi:10.1002/hep4.2103 · Cited by 26
Self-citationGuoyun, X., Dawei, D., Ning, L., Yinan, H., Fangfang, Y., Siyuan, T., Hao, S., Jiaqi, Y., Ang, X., Guanya, G., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.948362 · Cited by 13
Self-citation
Cited by
Sorted by citations
Lipid metabolism in homeostasis and disease
Li, Z., Deng, W., Yang, L., Tang, C., Yue, J.-M., Monteiro, O., Baptista‐Hon, D. T., & Li, T. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02357-x · Cited by 58
Primary biliary cholangitis: Personalizing second-line therapies
Levy, C., & Bowlus, C. L. (2024) · Hepatology · doi:10.1097/hep.0000000000001166 · Cited by 39
PPAR agonists for the treatment of cholestatic liver diseases: Over a decade of clinical progress
Hayes, C. M., Gallucci, G. M., Boyer, J. L., Assis, D. N., & Ghonem, N. S. (2024) · Hepatology Communications · doi:10.1097/hc9.0000000000000612 · Cited by 31
Mechanism-guided drug development and treatment for liver fibrosis: a clinical perspective
Zeng, X., Huang, D., Zhu, Z., Cai, Q., Yang, Y., Lu, H., & Chen, J. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1574385 · Cited by 33
Guo, Z., He, K., Pang, K., Yang, D., Lyu, C., Xu, H., & Wu, D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084321 · Cited by 29
Metadata
- Authors
- Liu, Y., Guo, G., Zheng, L., Sun, R., Wang, X., Deng, J., Jia, G., Yang, C., Cui, L., Guo, C., Shang, Y., & Han, Y.
- Affiliations
- National Clinical Research Center for Digestive Diseases (CN)
- Corresponding author
- Liu, Yansheng
- Guo, Guanya
- Zheng, Linhua
- Venue
- American Journal of Gastroenterology
- Published
- 2023-03-09
- Volume
- 118
- Issue
- 11
- Pages
- 1973-1979
- ISSN
- 0002-9270 (ISSN-L)
- 1572-0241
- OpenAlex
- W4323652914
- Cited by
- 55
- References
- 33
- Citations by year
- 2026: 18 · 2025: 19 · 2024: 15 · 2023: 3
- FWCI
- 9.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- primary biliary cirrhosis, fenofibrate, ursodeoxycholic acid, combination therapy, treatment-naive patients, biochemical response, liver fibrosis, drug safety, liver cirrhosis, off-label therapy
- MeSH terms
- Cholagogues and Choleretics, Drug Therapy, Combination, Humans, Liver Cirrhosis, Biliary, Fenofibrate, Prospective Studies, Ursodeoxycholic Acid, Treatment Outcome
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.
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 ›
Are you an author, or do you see a problem with this page? Request a review
