Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases

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.

Section: Introductionmentioning

confidence: 99%

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

Joshita

Umemura

Yamashita

et al. 2019

“…However, the beneficial effects of UDCA on the clinical outcomes of patients with advanced stages of PBC remain controversial . Furthermore, the rate of histological progression (HP) varies substantially among patients with PBC . There are currently no established biological markers to identify potential end‐points to assess the HP of PBC.…”

Section: Introductionmentioning

confidence: 99%

Identification of clinical risk factors for histological progression of primary biliary cholangitis

Fujinaga

Namisaki

Moriya

et al. 2019

Aim To identify laboratory predictors of histological progression (HP) of primary biliary cholangitis (PBC). Methods Sequential biopsies were carried out on 35 (11.4%) of 308 patients with PBC treated with ursodeoxycholic acid (UDCA). Patients were divided into high γ‐glutamyl transpeptidase (GGT) (n = 18) and low GGT (n = 17) groups, based on the median value of GGT at baseline. Patients were then categorized as showing HP (progressive group, PG) or lacking HP (non‐progressive group, NPG) according to the Scheuer and Nakanuma classifications, with the latter grading liver fibrosis (fibrosis score) and bile duct loss (BDL score). Results According to the Scheuer definition, 12 patients had HP and 23 did not. According to the Nakanuma definition, 8 and 27 patients were in the PG and NPG groups, respectively. The fibrosis and BDL scores progressed in 13 and 8 patients, respectively, whereas 22 and 25 patients did not show HP, respectively. Fisher's exact probability test analysis revealed that the rate of HP using the Nakanuma fibrosis score was significantly higher in the high GGT group compared to the low GGT group (P < 0.05). However, no significant correlation was found between the HP of PBC and the biochemical response to UDCA therapy. Both univariate and multivariate logistic regression analyses indicated that the serum GGT level at baseline is an independent risk factor for an increased Nakanuma fibrosis score. Conclusions The level of serum GGT at baseline is significantly associated with liver fibrosis progression in PBC, and therefore could help to predict the HP of PBC.

“…PBC mainly affects middle‐aged women, and progresses slowly to decompensated cirrhosis, with severe jaundice, ascites, and variceal hemorrhage. Although the underlying pathogenesis of PBC remains unclear and a complete cure has not yet been developed, ursodeoxycholic acid (UDCA) has been shown, in several randomized controlled trials, to suppress PBC progression, and is currently the first‐line treatment used in clinical practice . Continuous administration of UDCA has been reported to improve the biochemical profile of PBC patients, as well as inhibit histological progression, and improve the survival rate .…”

Section: Introductionmentioning

confidence: 99%

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

Amano

Ikeda

Hayashida

et al. 2020

Aim Chronic liver insufficiency is often associated with alteration in amino acid metabolism. We evaluated the prognostic value of changes in serum amino acid concentrations in patients with primary biliary cholangitis. Methods A total of 75 primary biliary cholangitis patients who started urusodeoxycholic acid therapy were retrospectively enrolled. Baseline serum concentrations of branched‐chain amino acids and tyrosine, and branched‐chain amino acid‐to‐tyrosine ratio were determined. The hazard ratios of factors associated with liver‐related events were analyzed by Cox proportional hazard analysis. Results Of the 75 patients enrolled, 12 showed a decrease in serum branched‐chain amino acid levels, and 15 showed an increase in serum tyrosine levels. The branched‐chain amino acid‐to‐tyrosine ratio decreased in 16 patients. During a median 5.6‐year follow up, liver‐related events occurred in 11 patients. Multivariate analysis showed that high serum tyrosine levels at baseline and high alkaline phosphatase levels 48 weeks after starting urusodeoxycholic acid therapy were independent risk factors for event occurrence. From the receiver operator characteristics curve analysis, serum tyrosine concentration >110 μmol/L was identified as a cut‐off value with an adjusted hazard ratio of 20.9 (95% confidence interval 4.3–101.5, P < 0.001). Kaplan–Meier analysis showed that the 5‐year cumulative incidences of event occurrence in patients with high and low serum tyrosine concentration were 56.5% and 5.5%, respectively (P < 0.001). The 10‐year survival probabilities also showed significant differences between patients with high and low serum tyrosine concentration (44.9% vs. 92.0%, P < 0.001). Conclusion Elevation of serum tyrosine concentration indicates a high risk of liver‐related events in primary biliary cholangitis patients receiving urusodeoxycholic acid therapy.