Biochemical and plasma lipid responses to pemafibrate in patients with primary biliary cholangitis

Abstract

Aim Fibrate addition to ursodeoxycholic acid (UDCA) therapy has been shown to improve both liver biochemistry and long‐term prognosis in primary biliary cholangitis (PBC) patients showing an incomplete biochemical response to UDCA alone. We herein describe the clinical outcome of seven cases of PBC that received the new selective peroxisome proliferator‐activated receptor α modulator, pemafibrate, in combination with UDCA therapy to investigate the biochemical and plasma lipid responses to the drug. Methods Of 124 initially enrolled PBC patients, 12 treated with UDCA alone and seven receiving UDCA plus bezafibrate showed alkaline phosphatase (ALP) levels above the upper limit of normal (330 U/L). Ultimately, seven patients with PBC and dyslipidemia who had agreed to biweekly visits at our hospital for UDCA plus pemafibrate combination therapy were retrospectively analyzed. Results In the four cases that switched from bezafibrate to pemafibrate, ALP became significantly decreased (0.031) and γ‐glutamyltransferase tended to decrease (0.063) over the 3 months following pemafibrate addition. Two patients showed a greater than 50% reduction in ALP. No remarkable differences were observed for plasma lipid levels, alanine aminotransferase, aspartate aminotransferase, or the liver fibrosis marker Mac‐2 binding protein glycosylation isomer between these time points. No adverse drug reactions were recorded. Conclusions Pemafibrate might be another option for PBC patients with an incomplete response to UDCA therapy.

Investigation of immune complexes formed by mitochondrial antigens containing a new lipoylated site in sera of primary biliary cholangitis patients

“…In general, IC formation and its deposition leads to inflammation via interactions with leukocytes or complement and the consequent inflammation and tissue damage may lead to fibrosis. M2BPGi is a liver fibrosis marker [40,41], and ALP, ALT and AST are markers of liver damage; however, no differences were observed in these levels between the two groups. These results showed that IC does not directly lead to liver fibrosis and liver injury.…”

The ursodeoxycholic acid response score predicts pathological features in primary biliary cholangitis

“…12,37 Furthermore, pemafibrate, the selective PPARα modulator, has been reported to have potential as a new second-line treatment instead of bezafibrate in combined therapy with UDCA for patients with PBC who had an inadequate response to UDCA. 38 In addition, several agents including immunomodulators, bile acid regulators and anti-inflammatory/oxidative stress suppressors are additional candidates for the treatment of patients with PBC who had an inadequate response to UDCA treatment. 12 With limited treatment options, assessing the response to UDCA treatment remains key, as it is the most crucial prognosis predictor for patients with PBC.…”

Prognostic significance of serum tyrosine concentration in patients with primary biliary cholangitis under ursodeoxycholic acid therapy

“…However, some PBC patients show early deterioration, even under UDCA administration. Recently, a combination of fibrate, an antagonist of peroxisome proliferator‐activated receptors, with UDCA was reported to improve biochemical response in PBC patients showing inadequate response to UDCA alone . However, PBC still remains one of the leading causes of end‐stage liver diseases .…”

“…Recently, a combination of fibrate, an antagonist of peroxisome proliferator-activated receptors, with UDCA was reported to improve biochemical response in PBC patients showing inadequate response to UDCA alone. 14,15 However, PBC still remains one of the leading causes of end-stage liver diseases. 4 Herein, 14.7% of the study cohort developed liver-related events during study period, with an annual incidence of liver-related Serum tyrosine and prognosis in PBC patients Hepatology Research 2020; :214-223.…”