Sustained biochemical response to oral antibiotics in pediatric PSC and ASC are correlated to changes in gut microbiota during therapy
(2018) The International Liver Congress EASL — Location: Dijon, France (11.April.2018)
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- Background and aim Concomitant presence of autoimmune hepatitis and primary sclerosing cholangitis (PSC) is labelled as autoimmune sclerosing cholangitis (ASC) in children. Based upon the possible implication of microbiota in the pathogenesis of PSC, oral antibiotics are increasingly being used as a novel therapeutic approach and shown to have benefit in PSC but their role in pediatric ASC is not well evaluated. We prospectively analysed the gut microflora before and after antibiotic therapy in children with ASC or PSC alone, and evaluated whether changes in gut microflora correlated with response to treatment. Methods Patients diagnosed with ASC or PSC on basis of biochemical, liver biopsy and radiology findings were included. They prospectively received metronidazole (MTZ) for 14 days as induction or rescue therapy. Antibiotics were administrated in addition to the standard treatment of UDCA for PSC patients and azathioprine, UDCA and/or steroids for ASC patients. Stool samples were collected before and after antibiotic therapy. DNA isolation, amplification and Illumina sequencing to profile the microbiota composition were performed using the bacterial 16s rRNA. The beta-diversity measured the dissimilarity between each paired stool samples. The outcome parameters to assess the efficacy of antibiotics were reduction liver enzymes and subsequently achievement of sustained biochemical remission. Results Seven children (4 ASC, 3 PSC) were included, of which 5 have a concomitant ulcerative colitis (UC). All patients showed a significant decrease in their AST (-44%, p<0.025), ALT (-56%, p<0.025) and GGT (-41%, p<0.025) under MTZ. Three children relapsed after stopping MTZ while the four others children showed a sustained biochemical remission (liver enzymes below 1.5 times upper limit of normal) after a median follow-up of 375 days. Among these four patients, three exhibited a wide different microbial composition before and after MTZ as expressed by the beta-diversity variation. On the contrary, the microbiota of patients who relapsed remained unchanged pre- and post-MTZ. Conclusions Our study suggests that oral antibiotic could be an effective treatment of ASC and PSC, especially those with a concomitant UC, and that intestinal microflora play a major role in these diseases as sustained biochemical remission is associated with wide changes in gut microbiota communities after taking antibiotics.
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sambon, Everard, A., Varma, S., Stephenne, X., Smets, F., Scheers, I., Komuta, M., Cani, P., & Sokal, E. (2018). Sustained biochemical response to oral antibiotics in pediatric PSC and ASC are correlated to changes in gut microbiota during therapy. The International Liver Congress EASL, Dijon, France.