Human Microbiota and Liver Transplant

Sponsor

Hospital Vall d'Hebron (Other)

Overall Status

Completed

CT.gov ID

NCT02223468

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The microbiota represents the collections of microbial communities that colonize a host. In health, the microbiota protects against pathogens and maturation of the immune system. In return, the immune system determines the composition of the microbiota. Altered microbial composition (dysbiosis) has been correlated with a number of diseases in humans. The real role of the microbiota in transplant recipients is still unknown even though we suspect that it may be affected directly or indirectly by immunosuppressive drugs and antimicrobial prophylaxis taken by transplant patients, as well as by inflammatory process secondary to ischemia/reperfusion injury.

A number of studies have investigated the impact of liver transplantation on the intestinal microbiota. In a recent analysis of stool flora (Microb Ecol 2013; 65: 781-791) in 12 liver transplant recipients, changes in the microbiota were correlated to post-transplant infections. The authors suggested that the shift to pathogenic strains of bacteria due to the use of prophylactic antibiotics may be contributing to post-transplant complications. In a larger study, Wu et al (Hepatobiliary Pancreat Dis Int 2012; 11: 40-50) demonstrated marked changes in the gut microbiota post-transplantation with an increase in Enterobacteriaceae and Enterococcus, and reduction in Eubacteria, Bifidobacterium and Lactobacillus species. These changes, however, resolved over time such that by 6 months, at times when bacterial prophylaxis ends and immunosuppression is reduced.

A better characterization of the impact of post-transplant therapy on the human microbiota has the potential to improve our understanding of the infection process and translate into development of new therapeutic strategies.

The main goal of this study is to characterize intestinal microbiota and confirm the same bacterial DNA in peripheral blood and portal lymph nodes in patients affected with end-stage chronic liver disease, and to analyze its evolution from the moment of inclusion in waiting list throughout the first year after liver transplantation. For each patient, a healthy CONTROL with a similar age (± 10 years) will be selected from the same family setting, in whom just one sample will be obtained during the enrollment phase.

The second goal is to analyze the potential associations between microbiota flora and transplant outcomes during the same period.

Condition or Disease	Intervention/Treatment	Phase
Intestinal Microbiota Complication of Transplanted Liver Acute Rejection of Liver Transplant Infection

Study Design

Study Type:

Observational

Anticipated Enrollment :

40 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Prospective Study To Characterize The Human Microbiota In Liver Transplantation And Its Impact On Early Outcome

Study Start Date :

Jan 1, 2016

Actual Primary Completion Date :

Aug 1, 2021

Actual Study Completion Date :

Aug 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
CASE-CONTROL CASE: Liver transplant recipients (n=20) CONTROL: A healthy person with a similar age (±10 years) to the control selected from the same family setting (n=20)

Outcome Measures

Primary Outcome Measures

Analyses of changes in microbiota composition before and post-transplant [Before transplant, 1st, 3rd, 7th, 14th and 28th post-transplant and 3rd, 6th, 9th and 12th months post-transplant]
Stool samples will be obtained from the liver transplant recipient following the time frame described above. A healthy CONTROL with a similar age (± 10 years) will be selected from the same family setting, in whom just one sample will be obtained during the enrollment phase

Secondary Outcome Measures

Incidence of biopsy proven acute cellular rejection [Evaluation at 3rd, 6th, 9th and 12th months post-trasplant]
If liver dysfunction is observed, percutaneous liver biopsy will be performed and histological severity will be searching following the Banff criteria
Incidence of post-transplant infection requiring antibiotherapy (oral or endovenous) [Evaluation at 3rd, 6th, 9th and 12th months post-trasplant]
Incidence of Diabetes Mellitus de novo post-transplant [12 months post-trasplant]
Incidence of Obesity (BMI≥30 kg/m2) post-transplant [12 months post-transplant]
Incidence of renal dysfunction (creatinine ≥ 1.5mg/dL and/or MDRD formula Glomerular Filtrate Rate < 60 mL/min/1.73m2) [Evaluation at 3rd, 6th, 9th and 12th months post-trasplant]
Patient and graft survival rates [Evaluation at 3rd, 6th, 9th and 12th months post-trasplant]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 68 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

First liver transplant
Patients aged 18-70 years
Able to consent and agree in participate in the current study for one year

Exclusion Criteria:

Multiorgan transplantation and/or liver transplant from cardiac arrest donor and/or with ABO incompatibility.
Uncontrolled concomitant infections (including HIV seropositivity) and/or diarrhoea, vomiting or active gastric ulcer.
Fulminant hepatic insufficiency as first indication for liver transplant
Hemodynamic instability prior to liver transplant.
Recipient presenting present or previous neoplasia, except for non-metastatic basal of squamous cutaneous carcinoma or localized hepatocarcinoma with diameter <5cm or <3known lesions with diameter <3cm.
Significant comorbidity
Breastfeeding or female patients at fertile age without negative pregnancy test and accepting the use of reliable fertility control method
Any pretransplant antibiotherapy (oral or endovenous) or enrolled in any clinical assay

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institut de Recerca Hospital Vall d´Hebron	Barcelona		Spain	08035

Sponsors and Collaborators

Hospital Vall d'Hebron

Investigators

Principal Investigator: Itxarone Bilbao, PhD/MD, Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
Study Chair: Chaysavanh Manichanh, PhD/MD, Physiology and Pathophysiology of the Digestive Tract, Institut de Recerca Vall d´Hebron, Barcelona (Spain)
Study Chair: Cristina Dopazo, PhD/MD, Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
Study Chair: Francisco Guarner, PhD/MD, Department of Gastroenterology Disease, Hospital Vall d´Hebron (Barcelona, Spain)
Study Chair: Mireia Caralt, PhD/MD, Department of HBP Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
Study Chair: Lluis Castells, PhD/MD, Department of Internal Medicine, Liver Unit, Hospital Vall d´Hebron (Barcelona, Spain)
Study Chair: Jose Luis Lazaro, MD, Department of HBP Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
Study Chair: Fernando Azpiroz, PhD/MD, Department of Gastroenterology Disease, Hospital Vall d´Hebron (Barcelona, Spain)
Study Chair: Ramón Charco, PhD/MD, Department of HBP Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)