Biomarkers for the Prognosis of Decompensated Alcoholic Liver Disease

NCT ID: NCT01701687

Last Updated: 2015-08-03

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 36 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2015-07-31

Brief Summary

Fibroscan is a non invasive imaging investigation which measures liver stiffness, known to correlate well with liver scarring and cirrhosis on liver biopsy. Indocyanine green is an inert dye which is purely extracted from the blood by liver cells, and is hence an excellent marker of both liver cell function and overall liver blood flow. There is little data for either of these biomarkers regarding outcomes in alcoholic liver disease. We aim to establish the accuracy of these liver biomarkers in predicting important liver related outcomes (death, transplantation and hospital readmission with cirrhosis related consequences) in patients with severe (decompensated) alcoholic liver disease. Moreover, we will assess whether the serial measurement of biomarkers has any impact on alcohol abstinence, motivation or quality of life. Over an 18 month period, 125 consecutive hospital inpatients with decompensated alcoholic liver disease will undergo baseline biomarker measurement, routine blood and urine tests and qualitative questionnaires. These will be measured during their initial hospital admission (0 months) with subsequent repeat measurement during follow up visits at 1, 2, 4 and 6 months. Each study visit time will be in the region of 30-40 minutes to complete these investigations. The end of the study for individual patients will be patient death, liver transplantation or 6 month from study enrolment; whichever occurs first.

Detailed Description

This is a single centre longitudinal cohort feasibility pilot study of patients with decompensated alcoholic liver disease. We aim to recruit 125 consecutive patients with decompensated alcoholic liver disease over an 18 month period. This number is based upon approximately 10 admissions per month to acute liver services with decompensated alcoholic liver disease and includes a presumed 20% dropout rate during follow up, giving a total cohort of 100 patients. Patients will undergo a maximum of 6 months follow up following study recruitment.

The purposes of this study are:

1. To assess the performance of diagnostic liver biomarkers (Indocyanine Green, Fibroscan and blood and urinary biomarkers) in predicting mortality in decompensated alcoholic liver disease.

2. To compare the diagnostic and prognostic end points of these biomarkers with existing cirrhosis prognostic scoring systems (Child Pugh, MELD and UKELD).

3. To assess the performance of diagnostic biomarkers as a therapeutic aid to quality of life and alcohol abstinence.

Potentially eligible patients i.e. adults with decompensated liver disease with alcohol as a major co-factor, and acutely admitted secondary to sequelae of hepatic decompensation, will be approached by an existing member of their clinical care team (The CI & Co-Investigators form part of this team). Any patient who decides to take part in the study will have a baseline inpatient study visit either on their inpatient ward or to the NDDC Biomedical Research Unit (BRU). Subsequent follow up visits will be to the BRU.

Inclusion Criteria:

• Male or female patients 18-75 years of age
• Diagnosis of cirrhosis based upon:

• a) Histological confirmation
• b) Combination of clinical and radiological criteria
• c) Validated non invasive biomarker
• Alcohol as the primary aetiology for liver cirrhosis
• Hospital admission related to decompensated liver disease (e.g. ascites, varices, sepsis, alcoholic hepatitis)
• Active alcohol drinking prior to index hospital admission

Exclusion Criteria:

• Grade 3 or 4 hepatic encephalopathy
• Hepatocellular carcinoma
• Active non hepatic malignancy
• Known complete portal vein thrombosis
• Alcohol abstinence at time of index hospital admission
• Pregnancy
• Active cardiac devices

The research visit will require measurement of ICG clearance, Fibroscan, blood tests, urine tests and questionnaires. They will then be required to attend study visits at 1, 2, 4 and 6 months following the baseline study visit, after which study follow up will cease.

Patients will undergo study visits at the following intervals:

• Baseline visit (study visit 0)
• 1 month (study visit 1)
• 2 months (study visit 2)
• 4 months (study visit 3)
• 6 months (study visit 4)

The following data will be collected for the purposes of this research project at the baseline and subsequent study visits:

• Collection of demography, anthropometry, drug history, smoking, alcohol intake, blood pressure, full blood count, renal function, liver function, coagulation and serum samples
• Brief abdominal examination to detect presence of moderate to severe ascites (for the purposes of Child Pugh score measurement)
• ICG analysis
• Transient elastography (Fibroscan)
• Blood and urinary biomarkers (proteomics and metabonomics)
• Chronic Liver Disease Quality of Life Questionnaire
• Alcohol intake assessments (28 Day AUDIT tool)
• Alcohol STAR tool for qualitative assessment (to assess the influence of Fibroscan/ICG readings on motivation, beliefs and alcohol abstinence)

Demography and history are taken as part of normal clinical care. All patients will be offered standard follow up from both outpatient hepatology clinic and hospital alcohol liaison services throughout the period of study.

Conditions

Alcoholic Liver Diseases; Decompensated Cirrhosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Decompensated Alcoholic Cirrhosis

Recruited patients will have diagnosed liver cirrhosis (histological, radiological or accepted clinical parameters)admitted with an episode of decompensation. Patients must still be drinking hazardous alcohol quantities (\>14 units for women, \>21 units for men) at study enrollment

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Male or female patients 18-75 years of age
• Diagnosis of cirrhosis based upon:

• a) Histological confirmation
• b) Combination of clinical and radiological criteria
• c) Validated non invasive biomarker
• Alcohol as the primary aetiology for liver cirrhosis
• Hospital admission related to decompensated liver disease (e.g. ascites, varices, sepsis, alcoholic hepatitis)
• Active alcohol drinking prior to index hospital admission

Exclusion Criteria

• Grade 3 or 4 hepatic encephalopathy
• Hepatocellular carcinoma
• Active non hepatic malignancy
• Known complete portal vein thrombosis
• Alcohol abstinence at time of index hospital admission
• Pregnancy
• Active cardiac devices (e.g. cardiac pacemaker, implantable cardioverter defibrillator)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute for Health Research, United Kingdom

OTHER_GOV

Sponsor Role: collaborator

University of Nottingham

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Neil Guha, MRCP, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Nottingham

Locations

Nottingham University Hospitals NHS Trust

Nottingham, Notts, United Kingdom

Countries

United Kingdom

Other Identifiers

12050

Identifier Type: -

Identifier Source: org_study_id