Digestive System Diseases

Symptoms and General Pathology

All Conditions

Neoplasms

Liver Cirrhosis

Carcinoma

Carcinoma, Hepatocellular

Liver Diseases

Fibrosis

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Hematinics

All Drugs and Chemicals

Liver Extracts

Healthy Controls with or without risk factors for Chronic Liver Disease (i.e. patients referred due to concerns re: liver disease but found to have no evidence of chronic liver disease following assessment)

Patients with evidence of Liver Fibrosis on the basis of current diagnostic techniques / expert opinion.

Patients with evidence of Compensated Cirrhosis on the basis of current diagnostic techniques / expert opinion.

Patients with evidence of Decompensated Cirrhosis on the basis of current diagnostic techniques / expert opinion.

Patients with evidence of Hepatocellular Carcinoma on the basis of current diagnostic techniques / expert opinion.

Participants will be asked to provide 500mls of exhaled breath which will be loaded on to thermal desorption tubes and analysed via Mass Spectrometry.

Breath Analysis

Michael J Hewitt, MBBS BSc

Michael J Hewitt, MBBS

George B Hanna, FRCS

This study aims to determine whether a breath test could be used for early detection of hepatic fibrosis, cirrhosis or hepatocellular carcinoma.

Patients who are attending for a planned liver outpatient services or investigations will be approached to provide a breath sample.

Multi platform mass spectrometry analysis will be performed to establish volatile biomarkers that can discriminate between fibrosis, cirrhosis and hepatocellular carcinoma.

Volatile organic compound (VOCs) emitted from the human body have been of interest to researchers for several decades. In 1971, Pauling et al reported that breath and urine contained approximately 250 and 280 VOCs respectively in normal human subjects. VOCs are traditionally measured in food industry and counter-terrorism. Routine clinical applications include the alcohol breathalyser, 13-C urea breath test for H. pylori, nitric oxide in asthma, and hydrogen/methane test for bacteria overgrowth.

Preliminary work has suggested that there is alteration in the VOC profile of patients with liver disease. It is suggested that as fibrosis increases, liver function is impaired, resulting in increased levels of certain compounds. These compounds are then present at higher levels within the blood stream and when they reach the lungs, they are exhaled. There has also been work demonstrating a change in the profile of VOCs within cancers, demonstrating specific "breath signatures" in patients with oesophageal cancer. At Imperial College London, Marker et al have developed a breath test as screening test for oesophageal cancer with comparable sensitivity and specificity to other screening methods (e.g. faecal occult blood testing). The investigators would aim to achieve similar with hepatobiliary disease via a prospective cross-sectional study aimed at determining the diagnostic accuracy of exhaled breath volatile organic compounds (VOC) for the detection of liver disease.

Patients will be recruited from outpatient clinics and hospital wards based across Imperial College Healthcare Trust. They may also be recruited from the radiology department when attending for liver biopsies or hepatocellular carcinoma surveillance ultrasound scans. When attending for their appointment, a member of the research team will discuss the research project with the patient, explain that is requires the patient to provide a breath +/- urine sample. Patients will be provided with a patient information leaflet. If the patient is to agree to this, they will be asked to sign a written consent form. If a recent PHES test has not been performed, one will be conducted otherwise no additional investigations, invasive or otherwise will be required of the patients.

For patients under regular follow up within the trust, they may be asked to consent to further breath samples being taken at future appointments to facilitate longitudinal follow up. Patients will be entitled to withdraw at any point.

Patients attending for endoscopy, fibroscan or liver biopsy will have been nil by mouth for 4-6 hours prior to the procedure as per local guidelines. For those attending outpatient appointments, if identified prior to their appointment by their clinical team, the investigators will aim to contact the patients and request that they fast. Should they not be fasted, they may be asked to perform basic oral hygiene techniques (e.g. rinsing mouth with water), prior to the breath sample being taken. A food diary of the preceding 24 hours will be taken as part of the pre-sampling questionnaire.

As part of the consent process, patients will also be asked permission to access their hospital records for the purpose of the research study only, including their blood tests, radiology and pathology results. All data will be anonymised and all hospital records shall be handled with strict confidentiality in accordance with the Data Protection Act 1998 and the General Data Protection Regulation (GDPR).

Patients will be asked to give a number of exhalations into a breath sampling device until a defined volume of breath has been sampled. This may be done via one of several techniques. The investigators preferred option is that they breathe into a custom designed nalophan bag which is attached to thermal desorption tubes and a breath sampling device. Alternatively, patient may be asked to perform normal tidal breathing whilst wearing a face mask, which takes around 2 minutes on average. Patients located at St Mary's Hospital may also be asked to breathe directly into a mass spectrometer machine (SYFT Voice200Ultra). This mass spectrometer instrument is a self-contained mobile device which can be moved between clinical areas within St Mary's Hospital. Sampling by this method will involve a single deep nasal inhalation followed by complete exhalation via their mouth into a plastic cylinder connected to a tube leading to the mass spectrometer itself. This is repeated three times within a 60 second window. The investigators expect the breath sampling process to take no longer than 5-10 minutes in total. Patients will be requested to pass urine into a standardised 60ml urine specimen vial, which will be immediately sealed. 20ml of urine will be aliquoted into a standard 60ml specimen vial.

The VOCs from the breath will be trapped onto adsorbent tubes inserted into the breath taking device. After sampling the adsorbent tube is removed from the device, capped and transported back to the laboratory at St Mary's Hospital London for analysis. Samples will be transported by courier or by a member of the research team. The sample(s) shall undergo analysis via mass spectrometry instruments, at St Mary's Hospital London.

Breath VOCs sampled on adsorbent tubes will be analysed within 48 hours of collection. The sample constituents are destroyed within the mass spectrometer for detection meaning that no clinical material will remain after analysis by the mass spectrometry instruments. Urine samples will be stored within a registered tissue bank in accordance with the Human Tissue Act and disposed of following analysis.

As part of the study, the investigators will aim to follow patients up longitudinally to ascertain if a participant's VOC profile changes with progression or regression of liver disease. At each appointment, before sample is taken, the participant's consent will be reviewed and if the participant is still willing to continue in the study, further breath and urine samples will then be collected. This would be for a maximum of 24 months.

Breath VOCs sampled on adsorbent tubes will be analysed within 48 hours of collection. The sample constituents are destroyed within the mass spectrometer for detection meaning that no clinical material will remain after analysis by the mass spectrometry instruments. Urine samples will be stored within a registered tissue bank (REC Ref no. 04/Q0403/119, custodian Prof G Hanna) in accordance with the Human Tissue Act and disposed of following analysis.

Volatile Organic Compounds for the Assessment of Liver Disease

Volatile Organic Compounds for the Assessment of Liver Disease: Assessment of Hepatobiliary Disease Through Non-Invasive Detection of Exhaled Volatile Organic Compounds

Diagnostic accuracy will be measured by calculating the sensitivity and specificity of the test for detection of fibrosis / cirrhosis / hepatocellular carcinoma. Sensitivity and specificity values are represented by a number between 0 to 1 indicating the test's ability to pick up true positive results and true negative results respectively, where a number closer to one indicates a greater detection ability.

Imperial College London

Infections

Rare Diseases

Communicable Diseases

Hepatitis A

Hepatitis

Hepatitis, Chronic

Hepatitis D

Hepatitis D, Chronic

Hepatitis, Viral, Human

Virus Diseases

RNA Virus Infections

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Anti Delta

Yaşar Bayındır, MD

Mustafa Kemal Çelen, MD

Yasar Bayındır, MD

Yeşim Taşova, MD

Çiğdem Mermutluoğlu, MD

Yakup Demir, MD

Mustafa Celen, MD

Cigdem Mermutluoglu, MD

The aim of these study to determine the prevalence of hepatitis Delta virus (HDV) infections and the prognosis of HDV patients in Turkey's southeast. The investigators intend to arrange training sessions for 250 family physicians in Diyarbakir, Batman, Mardin, and Sanliurfa in order to determine those goals. The investigators will talk about diagnosing hepatitis B virus (HBV), HDV, hepatitis C virus (HCV), and Human Immunodeficiency virus (HIV) infections during these events. To ensure that patients with simultaneous HDV infection are evaluated for HIV/HCV and to detect liver fibrosis with a non-invasive method.

Study Objectives:

The aim of these study to determine the prevalence of HDV infections and the prognosis of HDV patients in Turkey's southeast. The investigators intend to arrange training sessions for 250 family physicians in Diyarbakir, Batman, Mardin, and Sanliurfa in order to determine those goals. The investigators will talk about diagnosing HBV, HDV, HCV, and HIV infections during these events. To ensure that patients with simultaneous HDV infection are evaluated for HIV/HCV and to detect liver fibrosis with a non-invasive method.

Primary Objectives:

To reveal the status of HDV infection in Turkey within the framework of the national hepatitis elimination program by providing training to family physicians.

Second Objectives:

* To determine the frequency and type of HDV in HBV patients (HDV/HCV co-infection).
* Providing HBV, HCV, HDV and HIV awareness training to family physicians.
* To determine the virological and liver fibrosis of patients with anti-Delta positivity.
* To determine the status of patients with HBV infection who are followed by family physicians.
* To ensure that patients with HDV infection are evaluated for liver cirrhosis and liver cancer.
* To determine the HDV/HIV co-infection rate.
* To determine the HDV/HCV co-infection rate.
* Determining the vertical transmission rate in viral hepatitis and contributing to elimination by emphasizing the importance of this rate.

Study Population:

To ensure that 20,000 patients with HBsAg positivity in Diyarbakir, Mardin, Batman and Sanliurfa are evaluated for HDV infection. To investigate HDV positive patients for liver fibrosis using the fibroscan method.

Number of Volunteers to Participate in the Study:

It is planned to include a total of 20,000 patients with HBsAg positivity from four provinces in this study.

Study Design:

Hepatitis Delta Virus infection poses a greater risk of developing both cirrhosis and liver cancer than other viral hepatitis agents. The Southeastern Anatolia region where HDV infection is most common in Turkey. It is planned to include four provinces (Diyarbakir, Batman, Mardin and Sanliurfa) in this study. In this study, family physicians will be reached through the Health Directorate of each province.

All Family Physicians will be educated about the prognosis and complications of HBV and especially HDV infection. The training will be carried out by the Infectious Diseases or Gastroenterology specialists of that province. Anti-Delta will be tested in all patients applying to health institutions. At the same time, all HBsAg positive patients followed by each family physician will be evaluated for the presence of HDV infection. All patients with anti-Delta positivity will be tested for HIV and HCV to determine their HDV/HIV co-infection and HDV/HCV co-infection status. Simultaneously, the liver fibrosis of patients with Anti-Delta positivity will be evaluated by the fibroscan method. Fibrosis-4 (FIB-4) and Child Pugh scoring will be performed on all patients simultaneously.

After receiving ethics committee approval for this study, the data collection process for family physicians' training and follow-up patients will be completed between April and July 2024. In total, it is anticipated to reach 250 Family Physicians in the entire region. In addition, demographic characteristics of HDV patients will be determined by reaching the Infectious Diseases and Gastroenterology Centers in four provinces. A five-question survey would be organized for all family physicians before and after the training in order to measure their knowledge level and evaluate the contribution of the training. This survey will be applied and analyzed via Slido.

After determining the biochemical and virological status of all HDV infections detected in four provinces, fibrosis of the liver will be measured with Fibroscan and FIB-4, which are non-invasive methods. As a result of the study, it is aimed to diagnose an estimated 1000 HDV-infected patients and score their liver fibrosis. It is aimed to complete the biochemical, virological, demographic and liver fibrosis status and statistical analyzes of all HDV-infected patients by 31.12.2024. The status of all patients in need of treatment or transplantation will be determined and their follow-up and treatment will be carried out in line with the recommendations of international and national treatment guidelines. The writing phase of all analyzed data will be completed and finalized by 31.01.2025.

One of the important reasons why both hepatitis B infection (HBV) and HDV infections are common is related to the fact that until recently vertical transmission was an important risk factor.

Both the diagnostic approach and follow-up and effective treatment options for HDV infections are still limited. It is also clearly known that HDV infection carries a higher risk of hepatocellular carcinoma (HCC) and cirrhosis than HBV infection. It is known that 90% of patients with viral hepatitis origin who are transplant candidates in our country have HDV infection.

Find HDV and Determine Its Status in Turkey

Find HDV and Determine Its Status in Turkey "SITU(HD)VATION"

Study data will be shared with researchers periodically.

The primary endpoint of this study is to determine the frequency of HDV in certain regions of Southern Anatolia, and the virological and liver fibrosis status of patients with HDV infection.

To determine the rate of HIV and HCV co-infection in HDV positive patients and to determine the demographic characteristics of HDV infected cases.

SOUTHEAST NEUROLOGY AND INFECTIOUS DISEASES SOCIETY

Gilead Sciences

Deputy Chief Physician, Prof. Dr., M.D.

participants will receive the 6 months intervention immediately

participants will receive the intervention after the 6-month follow-up visit

Participants in the intervention group will receive (1) weekly telephone or videoconference coaching; (2) health education print materials and tip sheets;(3) navigation to programs and resources to help participants meet behavioral goals (e.g., fitness events, classes and webinars, etc); (4) text messages related to behavioral skills; (5) a Fitbit activity tracker and Aria scale; (6) resistance tubes and instructional video for strengthening exercise (if resistance exercise module is chosen); and (7) tools to manage portion sizes.

Intervention Group

Patients in the control arm will initially receive written education material about the risk factors for liver cancer and management options. They will be offered the intervention after they complete the 6-month assessment.

Control Group

Karen Basen-Engquist, MD

Karen Basen-Engquist

To determine the effectiveness of a behaviorally-based tailored disease management intervention in patients with fibrosis or steatosis and risk factors for cirrhosis.

Hypothesis: A technology-assisted self-management intervention that addresses diet, physical activity, alcohol use, and medication adherence can produce regression in fibrosis as measured by FIB-4 in patients with fibrosis or steatosis and risk factors for cirrhosis, including chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, alcohol use, or non-alcoholic fatty liver disease (NAFLD).

Primary objective:

To test the effect of the behavioral intervention on fibrosis in a randomized trial. We will randomize eligible HOPE Clinic patients to (i) a 6-month self-management intervention to help participants implement behavioral changes to manage their disease or (ii) a wait-list control group that will receive the intervention after their 6-month assessment.

Secondary objective:

Evaluate changes in behavioral risk factors for liver fibrosis or steatosis (body composition, physical activity, diet, medication adherence, alcohol use), metabolic syndrome, and patient activation and other behavioral determinants.

Liver Cancer Prevention Randomized Control Trial

A Randomized, Prospective Study of a Behaviorally-based Tailored Disease Management Intervention vs Control in Patients With Risk Factors for Liver Disease

Cancer Prevention Research Institute of Texas

M.D. Anderson Cancer Center

Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

Diabetes Mellitus

Diabetes Mellitus, Type 2

Fatty Liver

Non-alcoholic Fatty Liver Disease

Metabolic Diseases

Glucose Metabolism Disorders

Endocrine System Diseases

Visceral Steatosis

Luca Miele

Non-alcoholic hepatic steatosis (NAFLD) is characterised by the excessive accumulation of triglycerides in the liver and is often associated, in the absence of significant alcohol consumption, with insulin resistance and metabolic syndrome with which it shares the most frequent clinical manifestations (hypertension, dyslipidaemia, visceral adiposity, glucose intolerance). Due to the pandemic spread of obesity and diabetes and by virtue of better control of viral hepatitis, NAFLD is the most common cause of liver damage in Western countries with a prevalence of around 20-30% of the general population.

The clinical impact of NAFLD in diabetes is considerable and represents a real driver of the major clinical outcomes that impact on the health of the individual, consequently creating a real 'burden of disease' especially in those populations considered to be at higher risk of disease severity.

Individuals with diabetes are, in fact, those at greatest risk of developing the clinical sequelae of NAFLD and often do not receive adequate hepatological support and a correct hepatic pathology. In fact, it has been documented in the literature that the presence of diabetes increases the severity of liver damage, bringing the risk of NASH up to 80% and increasing the risk of significant fibrosis to 30-40% of subjects with hepatic steatosis as well as representing an independent predictor for significant fibrosis. Lastly, the increased risk of hepatocarcinoma in subjects with diabetes and NAFLD should not be overlooked, as documented by our group and confirmed in a large Italian case series.

In subjects with diabetes, moreover, the presence of NAFLD is not only associated with worse glycaemic control, but also with micro- and macro-vascular complications as well as nephrological and neuropathic complications and increased mortality.

Therefore, the possibility of applying the non-invasive fibrosis scores currently available for NAFLD on a large scale, in a population at high risk of progressive liver disease, would make it possible to characterise (a) the true epidemiology of significant fibrosis (F3 or higher); (b) allow primary prevention actions to be carried out by optimising the use of resources or by identifying subjects at greater risk of damage progression; (c) understand, in cases with a long history of disease the true prevalence of clinical outcomes; (d) understand the epidemiology of comorbidities and polypharmacy as a function of significant fibrosis.

DIAbetes and NAFLD

Prevalence and Clinical Impact of Liver Fibrosis Associated With Non-alcoholic Hepatic Steatosis (NAFLD) in Individuals With Type 2 Diabetes and Relationship With Diabetes Therapies

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Volatile Organic Compounds for the Assessment of Liver Disease	NCT04620538	Cirrhosis Cirrhosis, Live... Fibrosis, Liver Hepatocellular ... Hepatocellular ...	Breath Analysis	18 Years - 90 Years	Imperial College London
Find HDV and Determine Its Status in Turkey	NCT06248580	Chronic Hepatit... Fibrosis, Liver Hepatocellular ... Cirrhosis, Live... Transmission Ve...	Anti Delta	18 Years -	Guven Health Group
Liver Cancer Prevention Randomized Control Trial	NCT05196867	Liver Diseases Fibrosis, Liver Cirrhosis, Live...	Intervention Gr... Control Group	18 Years -	M.D. Anderson Cancer Center
Volatile Organic Compounds for the Assessment of Liver Disease	NCT04620538	Cirrhosis Cirrhosis, Live... Fibrosis, Liver Hepatocellular ... Hepatocellular ...	Breath Analysis	18 Years - 90 Years	Imperial College London
Find HDV and Determine Its Status in Turkey	NCT06248580	Chronic Hepatit... Fibrosis, Liver Hepatocellular ... Cirrhosis, Live... Transmission Ve...	Anti Delta	18 Years -	Guven Health Group
Find HDV and Determine Its Status in Turkey	NCT06248580	Chronic Hepatit... Fibrosis, Liver Hepatocellular ... Cirrhosis, Live... Transmission Ve...	Anti Delta	18 Years -	Guven Health Group
Liver Cancer Prevention Randomized Control Trial	NCT05196867	Liver Diseases Fibrosis, Liver Cirrhosis, Live...	Intervention Gr... Control Group	18 Years -	M.D. Anderson Cancer Center
DIAbetes and NAFLD	NCT06315361	NAFLD Diabetes NASH Fibrosis, Liver Cirrhosis, Live... Liver Cancer		18 Years - 80 Years	Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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