Dynamic Liver Tests in Liver Disease

NCT02782247 | Completed

• 1 other identifier: 011006
• Study Type: observational
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis B; Hepatitis C

Outcome Measures

Primary Outcomes (3)

• Change from baseline following 1 year of treatment for chronic viral hepatitis with cirrhosis using transient elastography.

  Patients are treated for hepatitis B or hepatitis C and tested at baseline, 4 months and 1 year. Scores range from 0 to 75kPa with cirrhosis defined as above 11.5kPa. Change in baseline is noted. (Change = 4 month or 1 year measurement - baseline).

  Baseline, 4 months and 1 year

• Change from baseline following 1 year of treatment for chronic viral hepatitis with cirrhosis using indocyanine green excretion test using plasma disappearance rate.

  Patients are treated for hepatitis B or hepatitis C and tested at baseline, 4 months and 1 year. Measurement of plasma disappearance rate of Indocyanine green (PDRicg) is measured with normal between 18-25%/min. Change in baseline is noted.

  Baseline, 4 months and 1 year

• 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.

  Patients are treated for hepatitis B or hepatitis C and tested at baseline, 4 months and 1 year. Measurement of retention rate of indocyanine green at 15 minutes is measured (ICG15) with normal being below 10%. Change in baseline is noted.

  Baseline, 4 months and 1 year

Secondary Outcomes (1)

• 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.

  3 years, 5 years

Study Arms (3)

Short term Hepatitis C patients

60 patients with chronic hepatitis C infection and cirrhosis who are planning to start antiviral therapy will be enrolled. Patients will be tested within 3 months prior to starting treatment. This will be repeated at 16 weeks (+/- 1 week) and again 1 calendar year after treatment initiation. Patients will have transient elastography and Indocyanine green excretion tests at each appointment.

Device: Transient elastography; Device: Indocyanine Green excretion

Medium term Hepatitis C patients

60 patients with chronic hepatitis C infection and cirrhosis who have been successfully treated in the past 3 or 5 years (+/- 3 months). Patients will have transient elastography and Indocyanine green excretion tests at each appointment.

Device: Transient elastography; Device: Indocyanine Green excretion

Hepatitis B Patients

60 patients with chronic hepatitis B and cirrhosis will be tested within 3 months prior to starting treatment. This will be repeated at 16 weeks (+/- 1 week) and again 1 calendar year after treatment initiation. Patients who have started treatment past 3 or 5 years (+/- 3 months) will also be tested. Patients will have transient elastography and Indocyanine green excretion tests at each appointment.

Device: Transient elastography; Device: Indocyanine Green excretion

Interventions

Transient elastography DEVICE

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.

Also known as: Fibroscan

Hepatitis B Patients; Medium term Hepatitis C patients; Short term Hepatitis C patients

Indocyanine Green excretion DEVICE

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).

Also known as: Pulsion Limon system

Hepatitis B Patients; Medium term Hepatitis C patients; Short term Hepatitis C patients

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• Pregnancy or breast feeding
• Known allergy to ICG

Sponsors & Collaborators

• Queen Mary University of London: lead
• LAPresearch UK: collaborator

Study Sites (1)

Bart's Health NHS

London, E1 2AT, United Kingdom

Location

Related Publications (6)

• 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.

  PMID: 23234725 BACKGROUND

• 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.

  PMID: 23025060 BACKGROUND

• 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.

  PMID: 24833926 BACKGROUND

• 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.

  PMID: 16647475 BACKGROUND

• 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.

  PMID: 25514554 BACKGROUND

• 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.

  PMID: 26829205 BACKGROUND

MeSH Terms

Conditions

Hepatitis B; Hepatitis C

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Flaviviridae Infections; RNA Virus Infections

Study Officials

• Graham Foster, PhD, MBBS

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2016
• First Posted: May 25, 2016
• Study Start: May 1, 2016
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: March 8, 2023

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)