Dataset Information

Healthy donor faecal transplant for corticosteroid non-responsive severe alcoholic hepatitis.

ABSTRACT: Patients with severe alcoholic hepatitis (SAH) have high mortality in the presence of steroid unresponsiveness in the absence of clear treatment recommendations. Liver transplantation is the curative option in such cases but is controversial in the wake of severe infections, post-transplant recidivism and long waiting on deceased donor listing. Animal and human studies have shed light on the beneficial effects of gut microbiota modulation in alcoholic liver disease. We present the first report of faecal microbiota transplantation (FMT) in a steroid non-responder in whom, clinical, biochemical and liver disease severity scores improved post-FMT and demonstrate distinct bacterial population changes pre-FMT and post-FMT. Healthy donor FMT could be safe and efficacious in SAH not responding to corticosteroid treatment, as a bridge to liver transplantation (LT) or in candidates who are unwilling or not ideal for LT for improvement in short-term transplant free survival. Larger controlled studies are required for confirmation.

SUBMITTER: Philips CA

PROVIDER: S-EPMC5695424 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Healthy donor faecal transplant for corticosteroid non-responsive severe alcoholic hepatitis.

Philips Cyriac Abby CA Phadke Nikhil N Ganesan Karthik K Augustine Philip P

BMJ case reports 20171108

Patients with severe alcoholic hepatitis (SAH) have high mortality in the presence of steroid unresponsiveness in the absence of clear treatment recommendations. Liver transplantation is the curative option in such cases but is controversial in the wake of severe infections, post-transplant recidivism and long waiting on deceased donor listing. Animal and human studies have shed light on the beneficial effects of gut microbiota modulation in alcoholic liver disease. We present the first report o ...[more]

PMID: 29122905

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Project description:Background & aimsIn patients with severe alcoholic hepatitis (SAH), little is known about the profile of peripheral blood mononuclear cells (PBMCs) at baseline and during corticosteroid therapy, among those who can be treated successfully with steroids (steroid-responders [R] and those who cannot (steroid-non-responders [NR]); 2 groups with different outcomes.MethodsWe performed RNA-seq analysis in PBMCs from 32 patients with definite SAH, at baseline and after 7 days of corticosteroids. The data were sorted into R and NR (n = 16, each group) using the Lille model and 346 blood transcription modules (BTMs) were identified. BTMs are predefined modules of highly co-expressed PBMC genes, which can determine specific immune cell types and cellular functions. The activity of each BTM was taken as the mean value of its member genes.ResultsAt baseline, 345 BTMs had higher activity (i.e. were upregulated) in NR relative to R. The 100 most upregulated BTMs in NR, included several modules related to lymphoid lineage (T, B, and natural killer [NK] cells), modules for cell division and mitochondrial respiratory electron transport chain (ETC, relating to energy production), but only a few modules of myeloid cells. Correlation studies of BTM activities found features of significantly greater activation/proliferation and differentiation for T and B cells in NR relative to R. After 7 days of corticosteroids, NR had no significant changes in BTM activities relative to baseline, whereas R had downregulation of BTMs related to innate and adaptive immunity.ConclusionsAt baseline and during corticosteroid therapy, increased activity in the PBMCs of gene modules related to activation/proliferation and differentiation of T and B cells, NK cells, and mitochondrial ETC, is a hallmark of SAH patients who are steroid-non-responders.Lay summaryPatients with severe alcoholic hepatitis receive steroid therapy as the main line of treatment; however, this treatment is ineffective in some patients. This only becomes apparent after 7 days of steroid therapy. We have developed an approach where it can be estimated if a patient is going to respond or not to steroid therapy using the gene expression information of blood cells. This method will allow clinicians to assess the response of patients to steroids earlier, and will help them in adopting alternate strategies if the treatment is found to be ineffective in a particular patient.

Dataset Information

Healthy donor faecal transplant for corticosteroid non-responsive severe alcoholic hepatitis.

Publications

Healthy donor faecal transplant for corticosteroid non-responsive severe alcoholic hepatitis.

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