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NCT Number: NCT02223468

Human Microbiota and Liver Transplant

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.

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Key information

Age range

18 year–68 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Institut de Recerca Hospital Vall d´Hebron

Barcelona, 08035, Spain

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  1. Analyses of changes in microbiota composition before and post-transplant

    Time frame: 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 outcomes

  1. Incidence of biopsy proven acute cellular rejection

    Time frame: 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

  2. Incidence of post-transplant infection requiring antibiotherapy (oral or endovenous)

    Time frame: Evaluation at 3rd, 6th, 9th and 12th months post-trasplant

  3. Incidence of Diabetes Mellitus de novo post-transplant

    Time frame: 12 months post-trasplant

  4. Incidence of Obesity (BMI≥30 kg/m2) post-transplant

    Time frame: 12 months post-transplant

  5. Incidence of renal dysfunction (creatinine ≥ 1.5mg/dL and/or MDRD formula Glomerular Filtrate Rate < 60 mL/min/1.73m2)

    Time frame: Evaluation at 3rd, 6th, 9th and 12th months post-trasplant

  6. Patient and graft survival rates

    Time frame: Evaluation at 3rd, 6th, 9th and 12th months post-trasplant

Sponsors and collaborators

Lead sponsor

Hospital Vall d'Hebron

Other

Registry information

Official study title

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

Important dates

Study start
2016
Primary completion
2021
Study completion
2021
First posted
Aug 22, 2014
Registry last updated
Aug 4, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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