Clinical trial NCT02782247: Dynamic Liver Tests in Liver Disease
Official title: Changes in Dynamic Liver Function Tests in Patients With Chronic Viral Hepatitis Undergoing Antiviral Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis B
Hepatitis C
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
Collaborators: name: LAPresearch UK
First posted: 2016-05-25
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
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.

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Patients attending The Royal London Hospital with cirrhosis (defined as fibroscan score \>11.5 OR aspartate aminotransferase (AST) to platelet ratio index (APRI) score \>2 OR liver biopsy or imaging report of cirrhosis) who are planning to commence antiviral therapy for either chronic hepatitis B or chronic hepatitis C.
* Patients attending The Royal London Hospital with cirrhosis (defined as above) due to chronic hepatitis C infection who have undergone successful antiviral therapy in the past.
* Patients attending The Royal London Hospital with cirrhosis (defined as above) due to chronic hepatitis B infection who are taking antiviral medication
* Age 18 or above
* Willing and able to provide Informed consent

Exclusion Criteria:

* Any inclusion criteria not met
* Pregnancy or breast feeding
* Known allergy to ICG

Primary outcomes:
measure: Change from baseline following 1 year of treatment for chronic viral hepatitis with cirrhosis using transient elastography.
timeFrame: Baseline, 4 months and 1 year
measure: Change from baseline following 1 year of treatment for chronic viral hepatitis with cirrhosis using indocyanine green excretion test using plasma disappearance rate.
timeFrame: Baseline, 4 months and 1 year
measure: Change from baseline following 1 year of treatment for chronic viral hepatitis with cirrhosis using indocyanine green excretion test using plasma retention rate at 15 minutes.
timeFrame: Baseline, 4 months and 1 year
Secondary outcomes:
measure: Percentage of participants achieving normal fibroscan and or indocyanine green excretion test results at 3 or 5 years post initiation of treatment for viral hepatitis.
timeFrame: 3 years, 5 years
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Bart's Health NHS
Study officials:
affiliation: Queen Mary University of London
name: Graham Foster, PhD, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, Washington MK, Germanidis G, Flaherty JF, Aguilar Schall R, Bornstein JD, Kitrinos KM, Subramanian GM, McHutchison JG, Heathcote EJ. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013 Feb 9;381(9865):468-75. doi: 10.1016/S0140-6736(12)61425-1. Epub 2012 Dec 10.
citation: Gupta S, Chawla Y, Kaur J, Saxena R, Duseja A, Dhiman RK, Choudhary NS. Indocyanine green clearance test (using spectrophotometry) and its correlation with model for end stage liver disease (MELD) score in Indian patients with cirrhosis of liver. Trop Gastroenterol. 2012 Apr-Jun;33(2):129-34. doi: 10.7869/tg.2012.30.
citation: Wilder J, Patel K. The clinical utility of FibroScan((R)) as a noninvasive diagnostic test for liver disease. Med Devices (Auckl). 2014 May 3;7:107-14. doi: 10.2147/MDER.S46943. eCollection 2014.
citation: Faybik P, Hetz H. Plasma disappearance rate of indocyanine green in liver dysfunction. Transplant Proc. 2006 Apr;38(3):801-2. doi: 10.1016/j.transproceed.2006.01.049.
citation: Procopet B, Berzigotti A, Abraldes JG, Turon F, Hernandez-Gea V, Garcia-Pagan JC, Bosch J. Real-time shear-wave elastography: applicability, reliability and accuracy for clinically significant portal hypertension. J Hepatol. 2015 May;62(5):1068-75. doi: 10.1016/j.jhep.2014.12.007. Epub 2014 Dec 13.
citation: Foster GR, Irving WL, Cheung MC, Walker AJ, Hudson BE, Verma S, McLauchlan J, Mutimer DJ, Brown A, Gelson WT, MacDonald DC, Agarwal K; HCV Research, UK. Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis. J Hepatol. 2016 Jun;64(6):1224-31. doi: 10.1016/j.jhep.2016.01.029. Epub 2016 Jan 30.