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

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.

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

Participants will be identified from outpatient clinics of Bariatric, Gastroenterology, and Hepatology services at Homerton and King College Hospitals in addition to Gastroenterology outpatients from the Barts Health NHS Trust. Healthy control participants will be identified from patients undergoing outpatient assessment, gastroscopy or surgery for other non-malignant gastrointestinal disorders at hospital sites.