Investigating Pathological Mechanisms in Non-alcoholic Fatty Liver Disease

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

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

Study Overview

• Status: Recruiting
• Conditions: Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Procedure: Bariatric Surgery

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 153

Contacts and Locations

• Study Contact: Name: William Alazawi, MD Phd; Phone Number: +442078822308; Email: w.alazawi@qmul.ac.uk
• Study Contact Backup: Name: James Brindley, Md Phd; Phone Number: +442078827198; Email: james.brindley@nhs.net

Study Locations

• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, E9 6SR
      • Recruiting
      • Homerton University Hospital Foundation Trust
      • Contact: Rosemary Mullett; Phone Number: +44208 510 5117; Email: rosemary.mullett@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Queen Mary University of London
• Collaborators: King's College Hospital NHS Trust; Barts & The London NHS Trust; Homerton University Hospital NHS Foundation Trust
• Investigators: Principal Investigator: William Alazawi, MD Phd, Queen Mary University of London

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2019
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: October 23, 2019
• First Submitted That Met QC Criteria: October 24, 2019
• First Posted (Actual): October 28, 2019

Study Record Updates

• Last Update Posted (Actual): June 3, 2025
• Last Update Submitted That Met QC Criteria: June 2, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 247449

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No