Effects of pemafibrate on primary biliary cholangitis with dyslipidemia

Abstract

Aim The purpose of this study was to examine the effect of pemafibrate (PEM) in primary biliary cholangitis (PBC) patients with dyslipidemia. Methods Patients who were diagnosed with PBC between June 2018 and December 31, 2020 were included in the study if they also had dyslipidemia and their alkaline phosphatase (ALP) or gamma‐glutamyl transferase (GGT) levels remained above the normal range despite taking 600 mg/day ursodeoxycholic acid (UDCA) for at least 6 months. Patients who were treated with UDCA alone were administered PEM as an add‐on (PEM‐add group), and patients who were treated with UDCA and bezafibrate (BEZ) for at least 6 months were given PEM instead of BEZ (PEM‐switch group). Clinical parameters were compared in all patients, and the levels of ALP, GGT, the estimated glomerular filtration rate (eGFR), and creatinine (Cr) were compared between the PEM‐add and PEM‐switch groups. Improvement in cholangitis was also evaluated. Results In the PEM‐add group, both ALP and GGT improved in 40 of 46 patients (87.0%). In the PEM‐switch group, both ALP and GGT improved in 15 of 29 patients (51.7%). In the PEM‐switch group, however, significant improvement was seen in eGFR and Cr. Conclusions Administration of PEM is effective in PBC patients with dyslipidemia who are refractory to UDCA monotherapy. In patients using both UDCA and BEZ, there was an advantage in switching to PEM if they had renal damage; however, improvement of ALP and GGT occurred in about 50%.

Macrophage Activation Markers Predict Liver-Related Complications in Primary Biliary Cholangitis

“…Approximately 80% of asymptomatic patients have a higher risk of becoming symptomatic within ten years [ 6 ]. However, at baseline, only 20% are symptomatic [ 7 ]. The American Association for the Study of Liver Diseases Practice Guidance on PBC found no significant correlation between these symptoms and disease stage, although patients with more advanced disease stages generally have more symptoms [ 8 ] Among twenty (26.0%) out of the seventy-seven patients overall, twelve developed pruritus, two ascites, six esophageal varices, two hepatocellular carcinoma, and two jaundice, including patients who developed several symptoms.…”

“…Disturbances of the gut–liver axis are associated with various chronic liver diseases [ 10 ]. Epithelial barrier function and innate immunity both play crucial roles in the pathogenesis of PBC and its various forms of autoimmunity [ 7 ]. Having a defective epithelial barrier and increased intestinal permeability (IP) can promote an immunological response and elevate levels of circulating endotoxin [ 11 ].…”

Safety and efficacy of switching to pemafibrate from bezafibrate in patients with chronic liver disease

“…To the best of our knowledge, few reports have examined the effects of switching from conventional fibrates to pemafibrate. [13][14][15] In the package insert for bezafibrate in Japan, the incidence of adverse effects is listed as UDCA plus fibrates than with UDCA monotherapy. 16 Dohmen et al…”

Pemafibrate for primary biliary cholangitis with dyslipidemia: A proposal of a new treatment from Japan

“…In this study, Yamaguchi et al showed that PEM add-on was as effective as BEZ add-on in PBC patients with dyslipidemia refractory to UDCA monotherapy. 5 They also showed that switching from BEZ to PEM normalized serum biliary enzyme activities in about 50% of patients who were an incomplete response to the combination of UDCA+BEZ. In some cases, biliary enzymes worsened after switching from BEZ to PEM, but it may be worth trying when UDCA+BEZ is not effective enough.…”

“…Yamaguchi et al. demonstrated that effectiveness and safety of PEM for PBC 5 . However, there are several points to be clarified in the future.…”