Biomarkers for the Prognosis of Decompensated Alcoholic Liver Disease
Condition: Alcoholic Liver Diseases; Decompensated Cirrhosis
MeSH terms: Liver Diseases; Liver Cirrhosis; Liver Diseases, Alcoholic; Fibrosis
Study type: Observational

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.
    

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.
      
Biospecimen description: 
      Serum, plasma and urine stored at -80 degrees centigrade under written patient consent
    
Keywords: Cirrhosis; Alcoholic liver disease; Decompensated liver cirrhosis; Hazardous alcohol