Dynamic Liver Tests in Liver Disease

NCT ID: NCT02782247

Last Updated: 2023-03-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

52 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-05-31

Study Completion Date

2022-10-31

Brief Summary

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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

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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.

Conditions

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Hepatitis B Hepatitis C

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Transient elastography

Intervention Type 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.

Indocyanine Green excretion

Intervention Type 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).

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.

Transient elastography

Intervention Type 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.

Indocyanine Green excretion

Intervention Type 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).

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.

Transient elastography

Intervention Type 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.

Indocyanine Green excretion

Intervention Type 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).

Interventions

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Transient elastography

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.

Intervention Type DEVICE

Indocyanine Green excretion

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).

Intervention Type DEVICE

Other Intervention Names

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Fibroscan Pulsion Limon system

Eligibility Criteria

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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

* Pregnancy or breast feeding
* Known allergy to ICG
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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LAPresearch UK

UNKNOWN

Sponsor Role collaborator

Queen Mary University of London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Graham Foster, PhD, MBBS

Role: PRINCIPAL_INVESTIGATOR

Queen Mary University of London

Locations

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Bart's Health NHS

London, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 23234725 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23025060 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24833926 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16647475 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25514554 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26829205 (View on PubMed)

Other Identifiers

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011006

Identifier Type: -

Identifier Source: org_study_id

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