Biomarkers for the Prognosis of Decompensated Alcoholic Liver Disease (BANDED)

• ClinicalTrials.gov Identifier: NCT01701687
• Recruitment Status: Completed
• First Posted: October 5, 2012
• Last Update Posted: August 3, 2015
• Sponsor: University of Nottingham
• Collaborator: National Institute for Health Research, United Kingdom
• Information provided by (Responsible Party): University of Nottingham

Study Description

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.

Condition or disease
Alcoholic Liver Diseases; Decompensated Cirrhosis

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 36 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: The Feasibility of Liver Biomarkers as Prognostic Markers in Decompensated Alcoholic Liver Disease
• Study Start Date: September 2012
• Actual Primary Completion Date: July 2015
• Actual Study Completion Date: July 2015

Groups and Cohorts

Group/Cohort
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

Outcome Measures

Primary Outcome Measures :

1. Liver Related Death [ Time Frame: 6 months ]
   The proportion of deaths up to 6 months from the baseline visit directly attributable to consequences of cirrhosis

Secondary Outcome Measures :

1. Non-Liver related death [ Time Frame: 6 months ]
   Mortality unrelated to liver disease up to 6 months from baseline study visit
2. Hospital Readmission [ Time Frame: 6 months ]
   Hospital readmission secondary to complications of cirrhosis
3. Alcohol abstinence [ Time Frame: 6 months ]
   Proportion of patients abstinent from alcohol at the 6 month timepoint

Biospecimen Retention:   Samples Without DNA

Serum, plasma and urine stored at -80 degrees centigrade under written patient consent

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Potentially eligible patients are adult patients with decompensated liver disease with alcohol as a major co-factor, and acutely admitted secondary to sequelae of hepatic decompensation. 100 patients will be recruited for baseline visit over an 30 month study enrolment period, with a 6 month follow up period for all patients.

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)

Contacts and Locations

Locations

United Kingdom

Nottingham University Hospitals NHS Trust

Nottingham, Notts, United Kingdom, NG7 2UH

Sponsors and Collaborators

University of Nottingham

National Institute for Health Research, United Kingdom

Investigators

• Principal Investigator: Neil Guha, MRCP, PhD; University of Nottingham

More Information

• Responsible Party: University of Nottingham
• ClinicalTrials.gov Identifier: NCT01701687
• Other Study ID Numbers: 12050
• First Posted: October 5, 2012
• Last Update Posted: August 3, 2015
• Last Verified: July 2015

Keywords provided by University of Nottingham:

Cirrhosis; Alcoholic liver disease; Decompensated liver cirrhosis; Hazardous alcohol

Additional relevant MeSH terms:

Liver Cirrhosis; Liver Diseases; Liver Diseases, Alcoholic; Fibrosis; Pathologic Processes; Digestive System Diseases; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders