Fibrates for the Treatment of Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid: An Exploratory Study

Cançado, Guilherme Grossi Lopes; Couto, Cláudia Alves; Guedes, Laura Vilar; Braga, Michelle Harriz; Cançado, Eduardo Luiz Rachid; Ferraz, Maria Lúcia Gomes; Villela-Nogueira, Cristiane Alves; Nardelli, Mateus Jorge; Faria, Luciana Costa; Oliveira, Elze Maria Gomes; Rotman, Vivian; Mazo, Daniel Ferraz de Campos; Borges, Valéria Ferreira de Almeida e; Mendes, Liliana Sampaio Costa; Codes, Liana; Signorelli, I; Levy, Cynthia; Bittencourt, Paulo Lisboa

doi:10.3389/fphar.2021.818089

Cited by 7 publications

(3 citation statements)

References 22 publications

(34 reference statements)

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“…Recently, it has been reported that fibrates can be clinically useful in the treatment of hypertriglyceridemia and mixed hyperlipidemia and have anti-inflammatory, antifibrotic, and cholestasis-lowering effects. Fibrates can also ameliorate the biochemical characteristics of patients with PBC ( Cancado et al, 2021 ); Rosenson et al, 2007 , but the change in pruritus symptoms was not obvious. Although many observational studies have been published ( Cheung et al, 2016 ; Corpechot et al, 2018 ; Duan et al, 2018 ; Ghonem et al, 2020 ), the mechanism by which fibrates reduce the biochemical markers of cholestasis and whether the application of fibrates can improve the survival rate of patients with these diseases remain unclear.…”

Section: Discussionmentioning

confidence: 99%

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

Xuan

Ding

Liu³

et al. 2022

Front. Pharmacol.

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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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Section: Discussionmentioning

confidence: 99%

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

Xuan

Ding

Liu³

et al. 2022

Front. Pharmacol.

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“…Thus, PFIC2 patients may benefit from this type of pharmacological treatment [ 66 ]. The use of fibrates, such as the PPAR agonists bezafibrate, fenofibrate, and elafibranor ( Table 1 ), could also be beneficial for the treatment of PBC patients who do not respond to UDCA [ 67 ].…”

Section: Current Treatmentsmentioning

confidence: 99%

Gene Therapy for Acquired and Genetic Cholestasis

Martínez-García

Molina

González‐Aseguinolaza

et al. 2022

Biomedicines

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Cholestatic diseases can be caused by the dysfunction of transporters involved in hepatobiliary circulation. Although pharmacological treatments constitute the current standard of care for these diseases, none are curative, with liver transplantation being the only long-term solution for severe cholestasis, albeit with many disadvantages. Liver-directed gene therapy has shown promising results in clinical trials for genetic diseases, and it could constitute a potential new therapeutic approach for cholestatic diseases. Many preclinical gene therapy studies have shown positive results in animal models of both acquired and genetic cholestasis. The delivery of genes that reduce apoptosis or fibrosis or improve bile flow has shown therapeutic effects in rodents in which cholestasis was induced by drugs or bile duct ligation. Most studies targeting inherited cholestasis, such as progressive familial intrahepatic cholestasis (PFIC), have focused on supplementing a correct version of a mutated gene to the liver using viral or non-viral vectors in order to achieve expression of the therapeutic protein. These strategies have generated promising results in treating PFIC3 in mouse models of the disease. However, important challenges remain in translating this therapy to the clinic, as well as in developing gene therapy strategies for other types of acquired and genetic cholestasis.

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“…2 Cancado et al showed that 50% of UDCA nonresponders treated with add-on ciprofibrate or bezafibrate had a biochemical response at one year. 66 The combination of UDCA and bezafibrate decreased mortality and improved transplant-free survival compared with patients on UDCA monotherapy. 5,66 Pruritus was also significantly improved by bezafibrate in subjects with PBC.…”

Section: Fibratesmentioning

confidence: 99%

Primary Biliary Cholangitis, Liver Transplantation, and Hepatocellular Carcinoma: A Mini-review

Rawashdeh¹,

Couillard²,

Rawshdeh³

et al. 2022

Gene Expr

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Primary biliary cholangitis (PBC) is an organ-specific chronic autoimmune disease characterized by T-lymphocyte mediated destruction of intrahepatic biliary epithelial cells due to a combination of genetic and possible environmental factors. PBC progresses to hepatic fibrosis and cirrhosis, with the potential of developing hepatocellular carcinoma (HCC) if left untreated. PBC is more common in middle-aged women. It is diagnosed in patients with elevated liver enzymes and the serological hallmark of antimitochondrial antibody (AMA). Early diagnosis and treatment are crucial in improving survival and preventing longterm complications of liver disease. Ursodeoxycholic acid (UDCA) is first-line treatment for PBC. Obeticholic acid (OCA) and fibrates, in combination with UDCA or as monotherapy, may be given to PBC patients with partial or no UDCA response. Liver transplantation has thus been indicated in patients with decompensated cirrhosis or unresectable HCC.

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Fibrates for the Treatment of Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid: An Exploratory Study

Cited by 7 publications

References 22 publications

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

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

Gene Therapy for Acquired and Genetic Cholestasis

Primary Biliary Cholangitis, Liver Transplantation, and Hepatocellular Carcinoma: A Mini-review

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