Investigating Pathological Mechanisms in Non-alcoholic Fatty Liver Disease

Study Overview
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Brief Summary
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To identify key characteristics of the tissue resident and peripherally circulating immune-phenotype in addition to blood markers, metabolic profile, faecal and oral microbiota in non-alcoholic fatty liver disease

Detailed Description
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In this study, the investigators will collect tissue, blood, stool, urine and saliva samples at the same time in order to enable a comprehensive disease phenotyping and ability to compare immunological, microbiological and metabolic features in patients with varying stages of NAFLD and healthy controls. To date there are limited published data evaluating simultaneously-obtained samples from adipose, gut and liver tissue and peripheral blood in NAFLD. The majority of participants in this study will be recruited from the bariatric surgery services enabling multiple tissue samples to be collected at time of surgery with minimal additional risk to participants.

Official Title
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Investigating Pathological Mechanisms in Non-alcoholic Fatty Liver Disease: Cross-sectional Comparative Study Between Patients and Healthy Controls

Conditions
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Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Procedure: Bariatric Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Confirmed non-alcoholic Fatty liver disease (diagnosed clinically, radiologically or histologically) If diabetic, Diagnosed with Type 2 Diabetes Mellitus OR • Healthy Control: no diagnosis of any liver condition including NAFLD o NAFLD excluded by Fibroscan Controlled Attenuation Parameter (CAP) score of <222 dB/m Exclusion Criteria: Unwilling or unable to give informed consent Type 1 Diabetes Mellitus Other form of liver disease (other than NAFLD) o Viral hepatitis, Auto-immune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, haemochromatosis, Sarcoidosis, cystic fibrosis, sickle cell disease Taking medication associated with liver dysfunction (except methotrexate) Auto-immune disease which in the investigator's opinion may confound immune profiling Concomitant immunosuppressive medications (except methotrexate, short course oral steroids or inhaled corticosteroids) Currently pregnant Any major organ transplant (excluding corneal or hair transplant) Regular alcohol intake greater than 14 units a week for female participants and 21 units a week for male participants

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Control<br>non-obese individuals without fatty liver disease | |
| Obese wihtout non-alcoholic steatohepatitis<br>Body mass index greater than 30 without liver histological evidence of non-alcoholic fatty liver disease | Procedure: Bariatric Surgery<br>* Already clinically indicated surgical procedures<br>* Other names: Upper GI surgery;|
| Obese Non-alcoholic steatohepatitis<br>Body mass index greater than 30 with liver histological evidence of non-alcoholic fatty liver disease | Procedure: Bariatric Surgery<br>* Already clinically indicated surgical procedures<br>* Other names: Upper GI surgery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of weight loss surgery upon Non-alcoholic steatohepatitis | Proportion of patients developing resolution of NASH after weight loss surgery | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of weight loss surgery upon Non-invasive measures of fibrosis | Evaluation of changes in liver transient elastography post weight loss surgery | Six months |