Therapeutic efficacy of decreased nitrite production by bezafibrate in patients with primary biliary cirrhosis

Akbar, Sk. Md. Fazle; Furukawa, Shinya; Nakanishi, Seiji; Abe, Masanori; Horiike, Norio; Onji, Morikazu

doi:10.1007/s00535-004-1518-3

Cited by 27 publications

(4 citation statements)

References 18 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The therapeutic efficacy of bezafibrate, a hypolipidemic drug, has been shown in patients with PBC in some pilot studies. Down-regulation of nitrite production by dendritic cells may have some relationship with the therapeutic efficacy of bezafibrate for PBC (24). In our study, we found that bezafibrate could reduce BAFF-stimulated B-cell-induced Treg cell apoptosis and promote TGF-β and IL-10 expression in Tregs.…”

Section: Discussionmentioning

confidence: 99%

BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

Zhang

et al. 2013

Braz J Med Biol Res

View full text Add to dashboard Cite

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

Zhang

et al. 2013

Braz J Med Biol Res

View full text Add to dashboard Cite

show abstract

“…A number of small clinical studies have assessed the potential efficacy of fibrates in PBC [47-72] (Table 1). Firstly, in 1999 Iwasaki et al reported a significant improvement in the biochemical profile and disease symptoms after adding bezafibrate in PBC that were non-responders to UDCA.…”

Section: Introductionmentioning

confidence: 99%

Proposed therapies in primary biliary cholangitis

Floreani

Sun

Zou

et al. 2016

Expert Review of Gastroenterology & Hepatology

View full text Add to dashboard Cite

Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is a model autoimmune disease with chronic cholestasis characterized by the hallmark of anti-mitochondrial antibodies and treated with ursodeoxycholic acid (UDCA). However, approximately 20-40% of patients incompletely respond to UDCA and have an increased risk of disease progression. Although there have been significant advances in the immunobiology of PBC, these have yet to be translated into newer therapeutic modalities. Current approaches to controlling the immune response include broad immunosuppression with corticosteroids as well as targeted therapies directed against T and B cells. In contrast, ameliorating cholestasis is the focus of other therapies in development, including obeticholic acid. In this article the authors will discuss ongoing clinical trials and, in particular, the rationale for choosing agents that may effectively target the aberrant immune response.

show abstract

“…Evidence shows that the combination therapy of UDCA and bezafibrate significantly improved liver function early in 1 month. 21 Combination therapy reduced the serum levels of gamma-glutamyltransferase, ALP, and immunoglobulin M, but there were no significant differences in the incidence of all-cause mortality, adverse events, and pruritus. 12 , 22 However, none of the studies elucidated the long-term prognosis, efficacy, and safety of combination therapy.…”

Section: Discussionmentioning

confidence: 91%

“… 24 , 25 It has been proposed that bezafibrate plays a therapeutic role by downregulation of nitrite production by dendritic cells. 21 One study evaluated changes in the serum cytokine levels in response to treatment to identify the cytokines that reflect improved clinical results. Serum interleukin-18 (IL-18) levels in the groups at two time points were measured before (baseline) assignment of either treatment and after 12 months of the assigned treatment, but no significant difference was observed between the two groups.…”

Section: Discussionmentioning

confidence: 99%

Systematic review and meta-analysis: bezafibrate in patients with primary biliary cirrhosis

Yin

Xia

et al. 2015

DDDT

View full text Add to dashboard Cite

Background and aimUrsodeoxycholic acid (UDCA) is the standard treatment for primary biliary cirrhosis (PBC), but not all cases respond well. Evidence has shown that combination therapy of UDCA with bezafibrate significantly improved liver function. A meta-analysis was performed to assess the efficacy and safety of UDCA and bezafibrate combination therapy in the treatment of PBC.ResultsNine trials, with a total of 269 patients, were included in the analysis. The bias risk of these trials was high. Compared with UDCA alone, the combination with bezafibrate improved the Mayo risk score (mean difference [MD], 0.60; 95% confidence interval [CI], 0.25–0.95; P=0.0008) and liver biochemistry: alkaline phosphatase (MD, −238.21 IU/L; 95% CI, −280.83 to −195.60; P<0.00001); gamma-glutamyltransferase (MD, −38.23 IU/L; 95% CI, −50.16 to −25.85; P<0.00001); immunoglobulin M (MD, −128.63 IU/L; 95% CI, −151.55 to −105.71; P<0.00001); bilirubin (MD, −0.20 mg/dL; 95% CI, −0.33 to −0.07; P=0.002); triglycerides (MD, −26.84 mg/dL; 95% CI, −36.51 to −17.17; P<0.0001); total cholesterol (MD, −21.58 mg/dL; 95% CI, −30.81 to −12.34; P<0.0001), and serum alanine aminotransferase (MD, −10.24 IU/L; 95% CI, −12.65 to −78.5; P<0.00001). However, combination therapy showed no significant differences in the incidence of all-cause mortality or pruritus, and may have resulted in more adverse events (risk ratio [RR], 0.22; 95% CI, 0.07–0.67; P=0.008).ConclusionCombination therapy improved liver biochemistry and the prognosis of PBC, but did not improve clinical symptoms or incidence of death. Attention should be paid to adverse events when using bezafibrate.

show abstract

Therapeutic efficacy of decreased nitrite production by bezafibrate in patients with primary biliary cirrhosis

Cited by 27 publications

References 18 publications

BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

Proposed therapies in primary biliary cholangitis

Systematic review and meta-analysis: bezafibrate in patients with primary biliary cirrhosis

Contact Info

Product

Resources

About