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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Use of Probiotics to Prevent Cholangitis in Children With Biliary Atresia

Conditions
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Biliary Atresia

Intervention / Treatment
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* Drug: Lactobacillus casei rhamnosus (Lcr35)
* Drug: Neomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biliary atresia patients aged 0 to 3 years, who had a Kasai operation Exclusion Criteria: The patients who had received liver transplantation

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biliary atresia, cholangitis, probiotics, prophylaxis