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Prospective study of bezafibrate for post operated bilirary atresia

bezafibrate for post operated bilirary atresia

10

Four male individuals and six female individuals with a median age of 29.5 (IQR 24.0-35.0) years participated in the study. All patients had undergone portoenterostomy (Kasai or Suruga 2 modification procedure) for BA, with a median age of 67.0 (IQR 51.0-85.0) days at surgery. None of the patients had a hepatitis B or C history.

Consent was obtained from 10 patients or their surrogates. Ten patients were screened, and all were found to be eligible and enrolled. They were started on bezafibrate for 12 weeks. At 6 weeks, one patient experienced an adverse event and discontinued the medication, but the study continued. After 12 weeks of observation following the completion of bezafibrate treatment, the study was terminated for all 10 patients.

One patient developed rhabdomyolysis, which was considered an adverse event related to Bezafibrate (BZF) administration, and it was discontinued at 6 weeks. Hospitalization was not required, and symptoms resolved after discontinuing BZF administration. One patient with elevated liver enzyme levels at week 12, which were not elevated at week 6, recovered without intervention. The association between elevated liver enzyme levels and BZF administration was unclear. We observed a significant decrease in the mean hemoglobin (Hb) concentration from 13.8 to 13.1 (p=0.0035) between the 0- and 12-week periods. This decrease in the Hb level was minimal and did not require treatment. Cholangitis associated with biliary atresia was observed four times in three patients. Three of the four cholangitis episodes occurred after BZF administration. All patients with cholangitis recovered with appropriate antibiotic treatment.

The main outcome was assessed using FAS analyses. FAS analysis revealed that the mean change in the ALP levels between weeks 0 and 12 was -67 U/L (p=0.0024). The mean ALP levels at weeks -12, 0, 6, 12, and 24 were 283 U/L, 245 U/L, 150 U/L, 178 U/L, and 270 U/L, respectively. The difference from week 0 was significant for weeks 6 (p=0.0007) and 12 (p=0.013); however, it was not significant for weeks -12 (p=0.15) and 24 (p=0.34). Secondary outcomes were assessed using the FAS analysis. The gamma-GTP, level demonstrated a decrease in the mean value between weeks 12 and 0, at -49 IU/L (p=0.038). The mean gamma-GTP, level at weeks -12, 0, 6, 12, and 24 was 220 IU/L, 216 IU/L, 150 IU/L, 166 IU/L, and 248 IU/L, respectively. The difference from Week 0 was significant for Week 6 (p=0.0123). The difference from Week24 was significant for Week6 (p=0.0003) and Week 12 (p=0.0024). No significant changes were observed in the total bile acid, T-Bil, D-Bil, AST, or ALT levels. The average triglyceride levels at weeks 6 (64 mg/dL, p=0.0201) and 12 (62 mg/dL, p=0.0086) were significantly lower than those at week 0 (104 mg/dL). No significant changes existed in the LDL-Cho and T-Cho levels.

This prospective study assessed the effect of bezafibrate (BZF) use in native-liver survivors of BA. Administration of BZF decreased the levels of cholestasis markers, alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (g-GTP), in native-liver survivors of BA, indicating its potential as a new treatment alternative to delayed liver transplantation in this population.

Mar. 31, 2025

No

None

https://jrct.mhlw.go.jp/latest-detail/jRCTs031210066

Terui Keita

Chibe University Hospital

1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan

kta@chiba-u.jp

Kawaguchi Yunosuke

Chibe University Hospital

1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan

+81-43-222-7171

yunosuke.kawaguchi@chiba-u.jp

Complete

May. 06, 2021

Interventional

single arm study

open(masking not used)

no treatment control/standard of care control

single assignment

treatment purpose

1) Postoperative patients with biliary atresia
2) Patients whose serum ALP value exceeds the normal upper limit of the institutional standard at two points: from 1 year to 28 days before consent acquisition and at the time of consent acquisition
3) Patients aged 18 to 80 at the time of consent
4) Patients who have received sufficient explanation before participating in this study, and who have obtained the patient's and substitute voluntary written consent after sufficient understanding.

1) Patients whose T-Bil value is 5 times the upper limit of the normal value of the facility standard and IU / L or more
2) Patients whose ALP value is 10 times the upper limit of the normal value of the facility standard and IU / L or mor
3) Patients after liver transplantation
4) Patients who changed the drug dosage and treatment within 3 months before administration of the study drug
5) Patients with cholangitis (the criteria for moderate acute cholangitis in the Acute Cholangitis / Cholecystitis Clinical Practice Guideline 2018) in 3 months before administration of the study drug
6) Patients who used bezafibrate for 3 months before the start
7) Patients with renal dysfunction whose Creatinine clearance <60 mL / min or eGFR <60 mL / min / 1.73 m2 can be calculated using the prediction formula.
8) Patients whose CK value is at least twice the upper limit of the normal value of the facility standard
9) Patients who are pregnant, may become pregnant, within 28 days after giving birth, or breastfeeding
10) Patients with allergies to bezafibrate
11) In addition, patients who are judged by the investigator or the investigator to be inappropriate for conducting this study safely.

Both

Biliary Atresia

Bezafibrate 400 mg/day is orally administered to patients after biliary atresia in two divided doses after breakfast and dinner.

Obstructive jaundice

D001656

Amount of ALP change between Week 12 and Week 0 (baseline)

Test values and changes g-GTP, Bil, AST, ALT, total bile acid, LDL-Cho, TG, T-Cho at each time point (Week-12 , Week0 ,Week12 ,Week24 )

+81-43-226-2616

April. 16, 2021

none