Understanding the pathophysiological mechanisms that play a role in liver cirrhosis and its complications. For that aim, we want to study the functional and morphological intestinal epithelial barrier and microbiota of both small and large intestine…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary aim is to study differences in small and large intestinal
permeability between patients with compensated and decompensated cirrhosis by
means of a sugar permeability test.
Secondary outcome
To assess tight junction structure and proteins in biopsy specimens of small
and large intestine.
To assess intestinal microbiota in fecal samples and in biopsy specimens of
both small and large intestine using molecular methods.
To assess inflammatory, oxidative stress markers, and cytokine profile
To assess VOC by analyzing human breath samples.
To study components which may affect the intestinal integrity by using a
3-dimensional Caco-2 cell culture model.
To compare the results of the above mentioned tests between patients with
compensated and decompensated cirrhosis.
To compare the decompensated situation with the stable situation in the same
patients after three to six months.
To compare cirrhotic patients with healthy controls.
Background summary
Patients with liver cirrhosis have an increased risk to develop
life-threatening complications such as spontaneous bacterial peritonitis (SBP).
Impairment in the intestinal barrier, changes in de number and composition of
the intestinal microbiota and alterations in immune defenses have been
suggested to be involved in liver cirrhosis and its complications. Dysfunction
of the intestinal barrier for example results in the ongoing passage of toxic
substances from the gastrointestinal tract that may damage the liver, leading
to oxidative stress, inflammation and eventually liver cirrhosis. In addition,
bacterial translocation is considered a key step in the development of
spontaneous infections, mainly SBP, in patients with liver cirrhosis.
We hypothesize that patients with decompensated liver cirrhosis have a more
impaired intestinal epithelial barrier and altered intestinal microbiota than
patients with compensated liver cirrhosis.
Study objective
Understanding the pathophysiological mechanisms that play a role in liver
cirrhosis and its complications. For that aim, we want to study the functional
and morphological intestinal epithelial barrier and microbiota of both small
and large intestine in patients with compensated and decompensated cirrhosis
and in a control group of healthy individuals.
Study design
This study is an observational study.
Study burden and risks
- No side effects are expected from sampling blood, apart from the possible
occurrence of a small bruise.
- No side effects are expected from fecal sampling and breath sampling.
- No health risks are associated with the consumption of the sugars and the
subsequent collection of 24-h urine.
- The collection of duodenal biopsy specimens is generally excepted in medical
practice and is considered safe. The overall complication rate, including
mucosal biopsy, following diagnostic upper GI endoscopy is 0.13%. Perforation
related to diagnostic upper GI endoscopy is uncommon with an estimated
frequency of 0.03%. Significant bleeding is a rare complication of diagnostic
upper endoscopy. Bleeding may be more likely in individuals with
thrombocytopenia and/or coagulopathy (e.g. in patients with liver cirrhosis).
The risk of infectious complications of upper endoscopy might be increased in
patients with cirrhosis; rates of bacteremia range from 0% to 13%.
The risk of complications is not increased when taking multiple biopsy
specimens.
- The collection of sigmoid biopsy specimens is generally excepted in medical
practice and is considered safe. In patients undergoing sigmoidoscopies for
medical reasons, there is a small (0.09%) risk of bowel perforation and
bleeding at the biopsy sites. The risk of complications is not increased when
taking multiple biopsy specimens.
P.O. Box 5800
6202 AZ Maastricht
NL
P.O. Box 5800
6202 AZ Maastricht
NL
Listed location countries
Age
Inclusion criteria
Patients with liver cirrhosis:
Inclusion criteria:
- Liver cirrhosis of any cause
- A score of greater-than or equal to 5 assessed according to the Child-Pugh classification
- Age between 18 and 75 years;Healthy individuals:
Inclusion criteria:
- Normal medical history and physical examination
- Age between 18 and 75 years
- BMI between 18-30 kg/m-2
Exclusion criteria
Patients with liver cirrhosis:
Exclusion criteria:
- Known gastrointestinal diseases (such as inflammatory bowel disease and celiac disease),
chronic renal disease (i.e. a glomular filtration rate of <= 60 ml/min per 1.73 m2 estimated from
the Modification of Diet in Renal Disease (MDRD) equation) or diabetes mellitus
- Major abdominal surgery interfering with gastrointestinal function (except for uncomplicated
appendectomy, cholecystectomy and hysterectomy, other surgery upon judgement of the
principle investigator);Healthy individuals:
Exclusion criteria:
- Abnormal liver tests (i.e. ALT, AST, γ-GT) according to the reference values for normal ranges of the liver enzymes at the laboratory of clinical chemistry of the Maastricht University medical Center.
- History of gastrointestinal diseases and/or liver diseases.
- Major abdominal surgery interfering with gastrointestinal function (except for uncomplicated appendectomy, cholecystectomy and hysterectomy, other surgery upon judgement of the principle investigator)
- History of alcohol abuse or current excessive alcohol consumption (> 2 alcoholic beverages per day or > 14 alcoholic beverages per week)
- Use of medication (that may interact with intestinal permeability i.e. NSAIDs, proton pump inhibitors)
- Administration of investigational drugs in the 180 days prior to the study
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT01081236 |
| CCMO | NL31078.068.09 |
| OMON | NL-OMON28338 |