Clinical trial NCT01701687: Biomarkers for the Prognosis of Decompensated Alcoholic Liver Disease
Official title: The Feasibility of Liver Biomarkers as Prognostic Markers in Decompensated Alcoholic Liver Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alcoholic Liver Diseases
Decompensated Cirrhosis
Keywords: Cirrhosis
Alcoholic liver disease
Decompensated liver cirrhosis
Hazardous alcohol
Lead sponsor: University of Nottingham
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2012-10-05
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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)

Primary outcomes:
measure: Liver Related Death
timeFrame: 6 months
Secondary outcomes:
measure: Non-Liver related death
timeFrame: 6 months
measure: Hospital Readmission
timeFrame: 6 months
measure: Alcohol abstinence
timeFrame: 6 months
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
state: Notts
Study officials:
affiliation: University of Nottingham
name: Neil Guha, MRCP, PhD
role: PRINCIPAL_INVESTIGATOR
References: