Efficacy and safety of fenofibrate add-on therapy in patients with primary biliary cholangitis refractory to ursodeoxycholic acid: A retrospective study and updated meta-analysis
Open accessAbstract
Background: Ursodeoxycholic acid (UDCA) is currently used for the treatment of primary biliary cholangitis (PBC), but some people do not respond well to UDCA. It reported that the combination of fenofibrate and UDCA can improve the clinical indices in these patients. However, more high-quality evidence is needed to improve guideline recommendations. Methods: Through an updated meta-analysis, studies included were valued by the Cochrane Evaluation Manual and Robins-I. Biochemical and clinical indicator changes in UDCA-refractory PBC patients receiving combination therapy were analyzed by Revman 5.42. Then, we explored the influence of fenofibrate dose and the effectiveness and safety of long-term application by retrospective cohort study. Results: Our meta-analysis included nine publications with a total of 389 patients, including 216 treated with UDCA alone and 173 who received combination therapy. The meta-analysis showed that combination therapy was more effective than UDCA monotherapy in decreasing biochemical parameters, such as ALP, GGT, IgM, and TG. However, the occurrence of pruritus and adverse events was slightly higher with combination therapy than with UDCA monotherapy. A total of 156 patients were included in our cohort study: 68 patients underwent UDCA monotherapy, and 88 patients underwent combination therapy. Among UDCA-refractory patients, fenofibrate add-on therapy significantly improved the ALP normalization rate. Conclusion: The combination of fenofibrate and UDCA can decrease biochemical parameters, of UDCA-refractory PBC patient. Furthermore, the efficacy and safety of long-term combination therapy were also confirmed in our cohort study.
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These effects collectively reduce cholesterol and hepatic inflammation, reflected by reductions in serum ALP and GGT levels.
“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 [39]
The Results (Meta-analysis of biochemical response and adverse events; page unavailable) report greater reductions in ALP and GGT with fenofibrate plus UDCA than with UDCA alone. The Results (Biochemical measures; page unavailable) also report a reduction in cholesterol from baseline, and the Discussion describes possible anti-inflammatory effects. The paper does not establish that reduced hepatic inflammation is reflected by the ALP and GGT reductions, so that link is not supported. (LLM, conf=0.85)
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Cites
ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions
Sterne, J. A., Hernán, M. A., Reeves, B. C., Savović, J., Berkman, N. D., Viswanathan, M., Henry, D., Altman, D. G., Ansari, M. T., Boutron, I., et al. (2016) · BMJ · doi:10.1136/bmj.i4919 · Cited by 20,329 · see citing works
Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis
Arroyo, V., Ginès, P., Gerbes, A. L., Dudley, F. J., Geñtilini, P., Laffi, G., Reynolds, T. B., Ring‐Larsen, H., & Schölmerich, J. (1996) · Hepatology · doi:10.1002/hep.510230122 · Cited by 1,697 · see citing works
Hirschfield, G. M., Beuers, U., Corpechot, C., Invernizzi, P., Jones, D., Marzioni, M., & Schramm, C. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.03.022 · Cited by 1,480 · cited 1× · see citing works
“…of fenofibrate, and there is no relevant research report on the dosage of fenofibrate (Chinese Society of Hepatology and ChineseMedical Association, 2022; European Association for the Study of the Liver, 2017; Lindor et al., 2018), the meta-analysis is still needed to provide medical evidence.”
BackgroundLindor, K. D., Bowlus, C. L., Boyer, J., Levy, C., & Mayo, M. (2019) · Hepatology · doi:10.1002/hep.30145 · Cited by 913 · cited 6× · see citing works
“However, some patients could not benefit from UDCA FIGURE 4 Risk of bias in the included studies based on Robins-I.”
BackgroundMethodInfluentialBiochemical 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 1× · see citing works
“Among those criteria, the Paris I and Paris II criteria are frequently used to evaluate biochemical responses to UDCA in patients with advanced PBC (stage IIIIV) and early PBC (stage I-II), respectively (Corpechot et al., 2008).”
MethodA 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 635 · see citing works
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 · see citing works
Corpechot, C., Chazouillères, O., & Poupon, R. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2011.02.031 · Cited by 460 · see citing works
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 · see citing works
Harms, 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 · see citing works
Lleo, A., Wang, G.-Q., Gershwin, M. E., & Hirschfield, G. M. (2020) · The Lancet · doi:10.1016/s0140-6736(20)31607-x · Cited by 253 · see citing works
Poupon, R. Y. (2012) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/s2210-7401(12)70015-3 · Cited by 224 · see citing works
Impairment of hepatic Stat-3 activation and reduction of PPARα activity in fructose-fed rats
Roglans, N., Vilà, L., Farré, M., Alegret, M., Sánchez, R. M., Vázquez‐Carrera, M., & Laguna, J. C. (2007) · Hepatology · doi:10.1002/hep.21499 · Cited by 221 · see citing works
Ros, J. E., Libbrecht, L. J., Geuken, M., Jansen, P. L. M., & Roskams, T. (2003) · The Journal of Pathology · doi:10.1002/path.1379 · Cited by 198 · see citing works
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 · see citing works
Kok, T., Bloks, V. W., Wolters, H., Havinga, R., Jansen, P. L. M., Staels, B., & Kuipers, F. (2003) · Biochemical Journal · doi:10.1042/bj20020981 · Cited by 161 · see citing works
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 · see citing works
Rosenson, R. S., Wolff, D. A., Huskin, A. L., Helenowski, I. B., & Rademaker, A. W. (2007) · Diabetes Care · doi:10.2337/dc07-0015 · Cited by 117 · see citing works
Hirschfield, G. M., Beuers, U., Kupcinskas, L., Ott, P., Bergquist, A., Färkkilä, M., Manns, M. P., Parés, A., Spengler, U., Stiess, M., et al. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2020.09.011 · Cited by 108 · see citing works
Fenofibrate for patients with asymptomatic primary biliary cirrhosis
Dohmen, K., Mizuta, T., Nakamuta, M., Shimohashi, N., Ishibashi, H., & Yamamoto, K. (2004) · World Journal of Gastroenterology · doi:10.3748/wjg.v10.i6.894 · Cited by 99 · see citing works
Ghonem, N. S., Ananthanarayanan, M., Soroka, C. J., & Boyer, J. L. (2013) · Hepatology · doi:10.1002/hep.26894 · Cited by 86 · see citing works
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 · see citing works
Fenofibrate treatment in patients with primary biliary cirrhosis
Ohira, H., Sato, Y., Ueno, T., & Sata, M. (2002) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2002.05944.x · Cited by 82 · see citing works
Fenofibrate in Primary Biliary Cirrhosis: A Pilot Study
Liberopoulos, E. N., Florentin, M., Elisaf, M., Mikhailidis, D. P., & Tsianos, E. V. (2010) · The Open Cardiovascular Medicine Journal · doi:10.2174/1874192401004010120 · Cited by 74 · see citing works
Xiao, H., Wang, Q., Liu, Y., Zheng Rui, Y. O. U., Zhao Lian, B. I. A. N., Qiu, D., & Ma, X. (2012) · Journal of Digestive Diseases · doi:10.1111/j.1751-2980.2012.00574.x · Cited by 63 · see citing works
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 · see citing works
Guo, C., Zhang, Y., He, L., Wang, F., Chen, K., Li, J., Li, S., Liu, T., Zheng, Y., Wang, J., et al. (2015) · Drug Design Development and Therapy · doi:10.2147/dddt.s79837 · Cited by 54 · see citing works
Huang, Z., Zhou, X., NICHOLSON, A. C., Gotto, A. M., Hajjar, D. P., & Han, J. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.331 · Cited by 53 · see citing works
Ólafsson, S., Gudjónsson, H., Selmi, C. F., Amano, K., Invernizzi, P., Podda, M., & Gershwin, M. E. (2004) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2004.40397.x · Cited by 49 · see citing works
Walker, L. J., Newton, J. L., Jones, D. E. J., & Bassendine, M. F. (2008) · Hepatology · doi:10.1002/hep.22670 · Cited by 43 · see citing works
Chen, K., Li, J., Wang, J., Xia, Y., Dai, W., Wang, F., Shen, M., Cheng, P., Zhang, Y., Wang, C., et al. (2014) · PPAR Research · doi:10.1155/2014/215631 · Cited by 37 · see citing works
Matsumoto, K., Ohfuji, S., Abe, M., Komori, A., Takahashi, A., Fujii, H., Kawata, K., Noritake, H., Tadokoro, T., Honda, A., et al. (2022) · Journal of Gastroenterology · doi:10.1007/s00535-021-01836-6 · Cited by 35 · see citing works
Dat, N. Q., Thủy, L. T. T., Hieu, V. N., Hai, H., Hoang, D. V., Hải, N. T. T., Thuy, T. T. V., Komiya, T., Rombouts, K., Dong, M. P., et al. (2021) · Hepatology · doi:10.1002/hep.31752 · Cited by 35 · see citing works
Duan, W., Ou, X., Wang, X., Wang, Y., Zhao, X., Wang, Q., Wu, X., Zhang, W., Ma, H., You, H., et al. (2018) · Revista Española de Enfermedades Digestivas · doi:10.17235/reed.2018.5533/2018 · Cited by 30 · see citing works
Cançado, G. G. L., Couto, C. A., Guedes, L. V., Braga, M. H., Terrabuio, D. R. B., Cançado, E. L. R., Ferraz, M. L. G., Villela‐Nogueira, C. A., Nardelli, M. J., Faria, L. C., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.818089 · Cited by 14 · see citing works
Zandanell, S., Straßer, M., Feldman, A., Strebinger, G., Aigner, G., Niederseer, D., Laimer, M., Mussnig, B., Paulweber, B., Datz, C., et al. (2021) · Postgraduate Medicine · doi:10.1080/00325481.2021.1885945 · Cited by 9 · see citing works
Chen, K., Li, J., Wang, J., Xia, Y., Dai, W., Wang, F., Shen, M., Cheng, P., Zhang, Y., Wang, C., et al. (2014) · PPAR Research · doi:10.1155/2014/864839 · Cited by 6 · see citing works
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Liu, Y., Guo, G., Zheng, L., Sun, R., Wang, X., Deng, J., Jia, G., Yang, C., Cui, L., Guo, C., et al. (2023) · American Journal of Gastroenterology · doi:10.14309/ajg.0000000000002238 · Cited by 55 · see citing works
Self-citationKanda, T., Sasaki, R., Kimura, N., Abé, H., Yoshida, T., Hayashi, K., Sakamaki, A., Yokoo, T., Kamimura, H., Tsuchiya, A., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26051883 · Cited by 14 · see citing works
Saeedian, B., Babajani, N., Bagheri, T., Shirmard, F. O., & Pourfaraji, S. M. (2025) · BMC Gastroenterology · doi:10.1186/s12876-025-03821-2 · Cited by 14 · see citing works
Sohal, A., & Kowdley, K. (2023) · Hepatic Medicine : Evidence and Research · doi:10.2147/hmer.s361077 · Cited by 6 · see citing works
Primary biliary cholangitis: current insights and novel therapies
Granito, A., Παππάς, Γ., Napoli, L., Stefanini, B., Tirotta, D., & Muratori, P. (2026) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2026.2672493 · Cited by 8 · see citing works
Ding, D., Hu, Y., Jia, G., Wang, B., Zheng, L., Deng, J., Sun, R., Wang, X., Guo, G., Cui, L., et al. (2024) · Hepatology International · doi:10.1007/s12072-024-10743-w · Cited by 6 · see citing works
Li, W., Chen, W., Niu, X., Zhao, C., Tu, P., Li, J., Liu, W., & Song, Y. (2023) · Molecules · doi:10.3390/molecules28124801 · Cited by 6 · see citing works
Jamal, F., Elshaer, A., Alatout, M. H., Odeh, N. B., Youssef, A., Abo Abdullah, H., Elmasry, S., Shahin, T., Abdul Nabi, H., Worden, A. R., et al. (2025) · Biomedicines · doi:10.3390/biomedicines13102335 · Cited by 6 · see citing works
Arroyave, E., Saldarriaga, Ó. A., Bhatti, S., Bergman, I., Graham, R. P., Tana, M. M.-S., Balitzer, D. J., Khan, K. A., Kueht, M., & Stevenson, H. L. (2025) · Modern Pathology · doi:10.1016/j.modpat.2025.100728 · Cited by 5 · see citing works
Jian, Z., Xiu, T., & Shen, Q. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1797227 · Cited by 1 · see citing works
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Rojas-Amaris, N., Marenco‐Flores, A., Barba, R., Mendoza, R., Patwardhan, V. R., & Bonder, A. (2025) · Current Hepatology Reports · doi:10.1007/s11901-025-00700-y
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Sohal, A., Alamgir, M., & Kowdley, K. V. (2026) · Hepatology International · doi:10.1007/s12072-026-11088-2
Khamis, F., Teoh, E.-S., & Chan, W. (2026) · Singapore Medical Journal · doi:10.4103/singaporemedj.smj-2025-184
- Authors
- Guoyun, X., Dawei, D., Ning, L., Yinan, H., Fangfang, Y., Siyuan, T., Hao, S., Jiaqi, Y., Ang, X., Guanya, G., Xi, C., Yulong, S., & Ying, H.
- Affiliations
- Xijing Hospital (CN)
- Corresponding author
- Yulong, Shang
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2022-08-30
- Volume
- 13
- Pages
- 948362-948362
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC9468667
- OpenAlex
- W4293548232
- Cited by
- 13
- References
- 38
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 1 · 2023: 3
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81770569, No. 81820108005, 81820108005)
- 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
- fenofibrate, ursodeoxycholic acid, primary biliary cirrhosis, adjunctive therapy, combination therapy, long-term treatment safety, pruritus, gamma-glutamyl transferase, IgM, triglycerides
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