Dynamic Liver Tests in Liver Disease
Condition: Hepatitis B; Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis B; Hepatitis
Study type: Observational

Summary: 
      Chronic viral hepatitis often leads to liver scarring - cirrhosis. If the virus is eradicated
      from the liver, the liver scarring and liver function often recovers. In some patients the
      damage is too severe and recovery does not take place. It is not yet known which patients
      have liver disease that is too advanced to benefit from therapy nor is it known how fast the
      recovery occurs.

      Non-intrusive dynamic liver testing (DLT) may allow us to predict the functionality of the
      liver post treatment and may guide us in treatment choices - for example patients who are
      predicted not to recover may be prioritised for transplantation. Indocyanine green (ICG) is a
      dye solely excreted by the liver into bile and used to measure its dynamic function.
      Transient elastography is similar to ultrasound and measures the degree of fibrosis within
      the liver.

      The investigators hypothesise that the use of non-intrusive dynamic liver testing
      pre-treatment, will allow us to delineate patients before therapy who will have functional
      liver recovery following viral eradication.

      The investigators hypothesise that monitoring changes in liver fibrosis and liver function in
      patients with historical viral clearance will allow an assessment of the likely speed of
      recovery of liver fibrosis and function - for example if all patients 5 years after treatment
      for viral hepatitis induced cirrhosis have 'normal' fibrosis and liver function scores the
      investigators will be able to conclude that recovery is complete within 5 years.

      The investigators will perform a study pre and post-treatment assessing liver function using
      non-intrusive dynamic liver testing in addition to currently-used 'liver function' scoring
      systems, in a multivariate analysis, to determine whether or not the investigators can
      identify patients who are will have functional liver recovery post therapy.
    

Detailed description: 
      Multiple diseases affect the liver's performance, including hepatitis' B and C viruses.
      Hepatitis infects the liver; ultimately leading to cirrhosis associated with complications
      (e.g. bleeding and death), termed decompensated cirrhosis. Hepatitis induced decompensated
      liver disease is likely to improve upon eradication of the virus as will liver function.

      Recently, Hepatitis C has seen new, more efficacious therapies, allowing functional outcomes
      to be evaluated following viral clearance. It has been shown this treatment regime is
      effective in eliminating the virus in 70% of patients but functional improvement to be 40%
      with the rest stagnating or becoming worse. These patients may have benefited from liver
      transplantation initially, followed by viral eradication therapy.

      Treatment of the Hepatitis B virus is to stop more copies to be produced within cells. This
      on the most part is successful and the liver recovers. However, after 5 years of treatment
      26% of people do not recover sufficiently and the ability to identify these early is
      important to their future management.

      Non-intrusive dynamic liver testing (DLT) may allow us to predict the functionality of the
      liver post treatment and may guide us in adequate management strategies. Indocyanine green
      (ICG) is a dye solely excreted by the liver into bile and used to measure its dynamic
      function. Transient elastography is similar to ultrasound and measures the degree of fibrosis
      within the liver.

      The investigators hypothesise the use of non-intrusive dynamic liver testing pre-treatment,
      will allow us to delineate patients early, who would benefit from the most intensive
      treatments (e.g. transplant), and spare those with less severe disease the risks and
      potential side effects.

      The investigators will perform a study pre and post-treatment for DLT. These will be
      amalgamated with currently-used scoring systems, in a multivariate analysis, to ascertain the
      values and thus best-treatment option for patients.
    

Intervention name(s): Transient elastography; Indocyanine Green excretion
Intervention type(s): Device; Device
Intervention description(s): Transient elastography will be measured using a Fibroscan® machine which is manufactured by echosens®. It has a CE mark of 0459.
It is a non-invasive method to accurately measure stiffness of a patient's liver without the need for a liver biopsy. This is measured by an externally placed ultrasound probe which creates an elastic shear wave at 50Hz, and measures the velocity of the echo through the liver tissue. The liver stiffness is measured in kilopascals (kPa). It has been shown to be 99% effective in detecting cirrhosis in hepatitis C and has been shown to correlate with hepatoma production in both hepatitis C and hepatitis B. Values range from - normal < 9.6 kPa, significant fibrosis 9.6-11.4kPa, cirrhosis >11.5kPa. It cannot be used in patients with ascites.; The machine to monitor the elimination of Indocyanine green is manufactured by PULSION medical systems (Munich, Germany) and consists of the PulsioFlex monitor and LiMON module. The LiMON module is a finger probe which measure near-infrared wavelengths between 805nm and 905nm. The absorption maximum for Indocyanine green is 800nm and emission at 830nm. This is then used to produce two calculations. The first is plasma disappearance rate of indocyanine green (PDRICG). This is based on working out the constant and backward extrapolation and expressed as a percentage per minute. The other is the retention ratio after 15 minutes (ICG15).
Other intervention name(s): Fibroscan; Pulsion Limon system
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Potential patients will be seen in clinic by their clinical team and will come to an
        agreement with regard to the treatment options available to them. Those that meet the above
        criteria will then be offered the opportunity to partake in research with the understanding
        these tests will not affect their treatment in any way. They will be referred to the
        research team for informed consent to be taken.