Breath Analysis Using an Electronic Nose in Non Alcoholic Fatty Liver Disease

Study Overview
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Brief Summary
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The purpose of this is to analyse human exhaled breath by means of a device called electronic nose(eNose) in patients with non-alcoholic fatty liver disease (NAFLD) as a way to non-invasive assessment of liver disease.This device is medically adapted and clinically validated in patients with lung conditions.

Detailed Description
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Human exhaled breath contains over 3000 volatile organic compounds (VOCs) that vary in relative concentration in health and disease. Metabolic disorders affecting the liver, such as NAFLD, produce disproportionate organic compounds produced as a by-product of metabolism and thus expired in exhaled breath, excreted in urine and detectable in blood. NAFLD prevalence is increasing and has reached epidemic proportions affecting 90% of obese adults and 22%-53% of obese children.Liver biopsy is the gold standard in diagnosing NAFLD, but it is unpleasant and can lead to complications. There is an unmet need to develop a non-invasive method of assessing liver disease. Comon Invent (Delft, Netherlands) together with the respiratory department at the Amsterdam Medical Centre (AMC), University of Amsterdam, have adapted the electronic nose known as SpiroNose as a prototype device for clinical use. Sensitive electronic sensors detect molecules in breath and generate signals. Complex algorithms and analytical technics allow pattern recognition of breath samples from different subjects. Well charaterised patients will be selected into clinical categories of non-alcoholic fatty liver disease with and without cirrhosis and be compared with healthy individuals. Edinburgh will be the only site conducting this study. In addition to exhaled breath analysis, blood and urine will be collected to study the end products of metabolism.Furthermore, stool and urine collected from some subjects will be analysed to understand the role of gut bacteria in fermentation, metabolic products as a result cause VOC production.

Official Title
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Breath Analysis Using an Electronic Nose in Non Alcoholic Fatty Liver Disease (BEN) Study

Conditions
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Non-alcoholic Fatty Liver Disease

Intervention / Treatment
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* Device: Breath analysis - electronic signature Breath-print


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy individuals with no known or self declared medical illness with BMI (body mass index) within normal range (18.5-25) Non alcoholic fatty liver disease without cirrhosis Compensated (no evidence of ascites, encephalopathy) NAFLD cirrhosis; assessed by scoring system - Child's Pugh Exclusion Criteria: Ongoing or recent (within last 6months) alcohol consumption more than 21 units per week for males and 14 units per week for females. BMI > 40 Chronic respiratory disease e.g. Chronic obstructive pulmonary disease (COPD), asthma, interstitial fibrosis Use of antibiotics within last 4 weeks of sample collection and inflammatory bowel disease, irritable bowel syndrome, celiac sprue, or other chronic inflammatory diseases of the intestines (for intestinal microbiome analysis) Other known liver disease e.g. Primary Biliary Cholangitis/cirrhosis (PBC), Alcoholic liver disease (ALD), Autoimmune and hepatitis Inability to provide informed consent. Participation in other clinical intervention/drug trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy<br>Healthy volunteer: self-declared healthy individual (no known illness or medications) with Normal BMI | Device: Breath analysis - electronic signature Breath-print<br>* Patients and Healthy volunteers ( as defined in 3 cohorts) will breath into disposable, once-use only bacterial filter channeled into electronic device comprising on sensors capable to reacting to organic compounds. Breathing manoeuvre will be simple, non-exertional and relaxed. 2 breathing manoeuvres will be performed and sensor responses will be captured.<br>|
| Nonalcoholic steatohepatitis<br>NAFLD without cirrhosis: Metabolic syndrome with known liver disease (NAFLD, excluding other coexisting liver condition) without cirrhosis | Device: Breath analysis - electronic signature Breath-print<br>* Patients and Healthy volunteers ( as defined in 3 cohorts) will breath into disposable, once-use only bacterial filter channeled into electronic device comprising on sensors capable to reacting to organic compounds. Breathing manoeuvre will be simple, non-exertional and relaxed. 2 breathing manoeuvres will be performed and sensor responses will be captured.<br>|
| NAFLD Cirrhosis<br>NAFLD cirrhosis: well characterised NAFLD compensated cirrhosis (Child's A-B) | Device: Breath analysis - electronic signature Breath-print<br>* Patients and Healthy volunteers ( as defined in 3 cohorts) will breath into disposable, once-use only bacterial filter channeled into electronic device comprising on sensors capable to reacting to organic compounds. Breathing manoeuvre will be simple, non-exertional and relaxed. 2 breathing manoeuvres will be performed and sensor responses will be captured.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterise the electronic signature breath-print in pre-defined cohorts | Identify disease specific electronic nose wave pattern | 12 months | 
| Characterisation of exhaled breath composition | Molecular characterisation of breath volatile organic compounds through Gas Chromatography and Mass Spectrometry | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profiling intestinal microbiome and assessing end-metabolic products in urine | Demonstrate dysbiosis in stool microbial and characterise metabolic products in urine of cohorts studied | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Electronic nose, Non invasive diagnosis of NAFLD, NAFLD, exhaled breath analysis, Volatile organic compounds