Use of Probiotics to Prevent Cholangitis in Children With Biliary Atresia After the Kasai Portoenterostomy

Use of Probiotics to Prevent Cholangitis in Children With Biliary Atresia

Abstract

Biliary atresia (BA) is an idiopathic, progressive, and fatal disease if untreated. Since Kasai first introduced the operation for BA in 1959, there have been encouraging results in treating this disease. Ascending cholangitis is a frequent and often recurrent complication. It may worsen the prognosis, with an increase in mortality, secondary failure of restoration of bile flow, and possible exacerbation of portal hypertension. For patients who have had restoration of bile flow with a timely portoenterostomy, the recurrence of ascending cholangitis is the single most significant variable pertaining to long-term prognosis. Patients with multiple episodes of ascending cholangitis are more likely to require liver transplantation than those without multiple recurrences. Therefore, the prevention of cholangitis is crucial in the management of patients who have had a Kasai portoenterostomy.

Some oral antibiotics, like trimethoprim-sulfamethoxazole (TMP/SMZ) and neomycin have showed the effect to prevent against ascending cholangitis. But, we should consider the problem of drug resistance after long-term use of antibiotics. Is there any better and safer treatment? Probiotics are live microorganisms, which have beneficial effects on human health. Many studies have showed that probiotics have effects to treat or prevent intestinal infection or inflammation even for patient after liver transplantation. The aim of this study is to investigate the possibility of use of probiotics in prophylaxis of ascending cholangitis.

We want to enroll 20 BA patients aged 0 to 3 years, who had a Kasai operation. Ten patients are treated with neomycin (25 mg/kg/d, qid, 4 days a week). Another 10 patients receive Lactobacillus casei rhamnosus, Lcr 35 (8x108 CFU/day, bid) The duration of treatment is 6 months. Bacterial cultures of stool are performed before treatment and 1 month, 3 months and 6 months after treatment to evaluate the change of intestinal flora. Another 10 BA patients, from 1991 to 1996, aged 0 to 3 years, without prophylaxis after portoenterostomy, were served as the historical control group. Comparisons of the episodes of cholangitis, time to the first episode, and body weight change are made among the three groups.

Study Overview

• Status: Completed
• Conditions: Biliary Atresia
• Intervention / Treatment: Drug: Neomycin; Drug: Lactobacillus casei rhamnosus (Lcr35)

Detailed Description

Biliary atresia (BA) is an idiopathic, progressive, and fatal disease if untreated. Since Kasai first introduced the operation for BA in 1959, there have been encouraging results in treating this disease. Ascending cholangitis is a frequent and often recurrent complication. It may worsen the prognosis, with an increase in mortality, secondary failure of restoration of bile flow, and possible exacerbation of portal hypertension. For patients who have had restoration of bile flow with a timely portoenterostomy, the recurrence of ascending cholangitis is the single most significant variable pertaining to long-term prognosis. Patients with multiple episodes of ascending cholangitis are more likely to require liver transplantation than those without multiple recurrences. Therefore, the prevention of cholangitis is crucial in the management of patients who have had a Kasai portoenterostomy.

Some oral antibiotics, like trimethoprim-sulfamethoxazole (TMP/SMZ) and neomycin have showed the effect to prevent against ascending cholangitis. But, we should consider the problem of drug resistance after long-term use of antibiotics. Is there any better and safer treatment? Probiotics are live microorganisms, which have beneficial effects on human health. Many studies have showed that probiotics have effects to treat or prevent intestinal infection or inflammation even for patient after liver transplantation. The aim of this study is to investigate the possibility of use of probiotics in prophylaxis of ascending cholangitis.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Biliary atresia patients aged 0 to 3 years, who had a Kasai operation

Exclusion Criteria:

• The patients who had received liver transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neomycin prescribed; Interventions: 10 cases received Neomycin for 6 months	Drug: Neomycin
Experimental: Probiotics (Lactobacillus casei rhamnosus, Lcr35) prescribed; Interventions: 10 cases received Probiotics for 6 months	Drug: Lactobacillus casei rhamnosus (Lcr35)
No Intervention: control; 10 cases without intervention were historical control.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
episodes of cholangitis	episodes of cholangitis during 6 months of intervention	6 months after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gain of body weight	the change of z-score of body weight after 6 months of intervention	6 months after intervention

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Mei-Hwei Chang, Professor, National Taiwan University

Publications and helpful links

General Publications

• Lien TH, Bu LN, Wu JF, Chen HL, Chen AC, Lai MW, Shih HH, Lee IH, Hsu HY, Ni YH, Chang MH. Use of Lactobacillus casei rhamnosus to Prevent Cholangitis in Biliary Atresia After Kasai Operation. J Pediatr Gastroenterol Nutr. 2015 May;60(5):654-8. doi: 10.1097/MPG.0000000000000676.

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 14, 2005

Study Record Updates

• Last Update Posted (Estimate): August 21, 2013
• Last Update Submitted That Met QC Criteria: August 19, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Biliary atresia, cholangitis, probiotics, prophylaxis
• Additional Relevant MeSH Terms: Digestive System Diseases; Congenital Abnormalities; Biliary Tract Diseases; Bile Duct Diseases; Digestive System Abnormalities; Cholangitis; Biliary Atresia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Neomycin
• Other Study ID Numbers: 921201