HCC Surveillance: Comparison of Abbreviated Non-contrast MRI and Ultrasound Surveillance in Cirrhotic Patients With Suboptimal Ultrasound Visualisation

Hepatocellular Carcinoma Clinical Trial

Official title:

HCC Surveillance: Comparison of Abbreviated Non-contrast MRI and Ultrasound Surveillance in Cirrhotic Patients With Suboptimal Ultrasound Visualisation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04455932
• Other study ID #: 2019/PID15472
• Status: Recruiting
• Phase: N/A
• Start date: January 2022
• Est. completion date: March 2027

Study information

• Verified date: September 2021
• Source: Concord Repatriation General Hospital
• Contact: Jessica Yang, MBBS
• Phone: +61297676495
• Email: jessica.yang1[@]health.nsw.gov.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

All international guidelines recommend 6-monthly ultrasound surveillance for patients at risk for liver cancer (hepatocellular carcinoma or HCC), such as patients with cirrhosis. The aim of surveillance is to detect HCC at an early stage when it is still potentially curable. Currently only 4 out of 10 HCCs are detected at the early stage. Ultrasound surveillance for HCC has a wide ranging sensitivity, dependent on many factors such as operator experience, patient body habitus and liver parenchymal heterogeneity due to chronic liver disease and cirrhosis. In a select group of patients, surveillance ultrasound can be suboptimal or near non-diagnostic. Currently no guideline offers an alternative surveillance tool for patients who have suboptimal surveillance ultrasounds.

Description:

The investigators plan to conduct a prospective study to examine the diagnostic performance of abbreviated non-contrast MRI (aNC-MRI) versus ultrasound, in a select group of cirrhotic patients with poor ultrasound visualisation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 476
• Est. completion date: March 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 85 Years

Eligibility

Inclusion criteria

• Patients with cirrhosis (all causes of cirrhosis, except obscure causes such as vascular or congenital fibrosis) AND reduced visualisation of their liver on ultrasound (vB and vC).
• The criteria of cirrhosis can be obtained with any of the following methods:

1. Histologically by liver biopsy

2. Past signs of decompensated liver disease such as ascites, encephalopathy, varices or bacterial peritonitis

3. Clinically suspicion of cirrhosis PLUS one of the following:

1. Radiological evidence of morphologic changes of the liver and evidence of portal hypertension on US, CT or MRI examinations, including the identification of hepatic surface nodularity, splenomegaly, portal collaterals, varices and ascites

2. Fibroscan (transient elastography) median liver stiffness >12.5 kPa, the Fibroscan must be performed by an experienced technician and interpreted by the hepatologist

3. Platelet count <100 (x10^9/L) with no alternative cause

• Absence of previous history or current suspicion of HCC - Absence of HCC is defined by liver US, multiphase CT or contrast-enhanced MRI within 6 months prior to surveillance
• Patient is able to comply with scheduled visits, evaluation plans and other study procedures in the opinion of the investigator
• Patient is willing to provide written informed consent Exclusion criteria
• Contraindications to MRI scan (defibrillator, pacemaker, metallic foreign body, severe claustrophobia etc.)
• Contraindications to gadolinium
• Age above 85 years old or younger than 20 years old
• Pregnancy or breast feeding
• Any other condition which, in the opinion of the Investigator, would make the patient unsuitable for enrolment for the trial or could interfere with the completion of the study

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• HCC
• Hepatocellular Carcinoma

Intervention

Diagnostic Test:
• Abbreviated non-contrast MRI of the liver
every 6 months
• Ultrasound surveillance
every 6 months
• Multiphase contrast-enhanced liver MRI
screening

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Gosford Hospital	Gosford	New South Wales
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
New Zealand	North Shore Hospital	Takapuna	Auckland

Sponsors (1)

Lead Sponsor	Collaborator
Concord Repatriation General Hospital

Countries where clinical trial is conducted

Australia,  New Zealand, 

References & Publications (26)

Benson AB 3rd, D'Angelica MI, Abbott DE, Abrams TA, Alberts SR, Saenz DA, Are C, Brown DB, Chang DT, Covey AM, Hawkins W, Iyer R, Jacob R, Karachristos A, Kelley RK, Kim R, Palta M, Park JO, Sahai V, Schefter T, Schmidt C, Sicklick JK, Singh G, Sohal D, S — View Citation

Besa C, Lewis S, Pandharipande PV, Chhatwal J, Kamath A, Cooper N, Knight-Greenfield A, Babb JS, Boffetta P, Padron N, Sirlin CB, Taouli B. Hepatocellular carcinoma detection: diagnostic performance of a simulated abbreviated MRI protocol combining diffus — View Citation

Burak KW, Sherman M. Hepatocellular carcinoma: Consensus, controversies and future directions. A report from the Canadian Association for the Study of the Liver Hepatocellular Carcinoma Meeting. Can J Gastroenterol Hepatol. 2015 May;29(4):178-84. — View Citation

Chan MV, McDonald SJ, Ong YY, Mastrocostas K, Ho E, Huo YR, Santhakumar C, Lee AU, Yang J. HCC screening: assessment of an abbreviated non-contrast MRI protocol. Eur Radiol Exp. 2019 Dec 18;3(1):49. doi: 10.1186/s41747-019-0126-1. — View Citation

Chernyak V, Fowler KJ, Kamaya A, Kielar AZ, Elsayes KM, Bashir MR, Kono Y, Do RK, Mitchell DG, Singal AG, Tang A, Sirlin CB. Liver Imaging Reporting and Data System (LI-RADS) Version 2018: Imaging of Hepatocellular Carcinoma in At-Risk Patients. Radiology — View Citation

Chitturi S, Wong VW, Chan WK, Wong GL, Wong SK, Sollano J, Ni YH, Liu CJ, Lin YC, Lesmana LA, Kim SU, Hashimoto E, Hamaguchi M, Goh KL, Fan J, Duseja A, Dan YY, Chawla Y, Farrell G, Chan HL. The Asia-Pacific Working Party on Non-alcoholic Fatty Liver Dise — View Citation

Colli A, Fraquelli M, Casazza G, Massironi S, Colucci A, Conte D, Duca P. Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol. 2006 Mar;101(3):51 — View Citation

D'Avola D, Labgaa I, Villanueva A. Natural history of nonalcoholic steatohepatitis/nonalcoholic fatty liver disease-hepatocellular carcinoma: Magnitude of the problem from a hepatology clinic perspective. Clin Liver Dis (Hoboken). 2016 Oct 27;8(4):100-104 — View Citation

European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018 Jul;69(1):182-236. d — View Citation

Hanna RF, Miloushev VZ, Tang A, Finklestone LA, Brejt SZ, Sandhu RS, Santillan CS, Wolfson T, Gamst A, Sirlin CB. Comparative 13-year meta-analysis of the sensitivity and positive predictive value of ultrasound, CT, and MRI for detecting hepatocellular ca — View Citation

Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero JA. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018 Jan;67(1):358-380. doi: 10.1002/hep.29086. — View Citation

Kokudo N, Hasegawa K, Akahane M, Igaki H, Izumi N, Ichida T, Uemoto S, Kaneko S, Kawasaki S, Ku Y, Kudo M, Kubo S, Takayama T, Tateishi R, Fukuda T, Matsui O, Matsuyama Y, Murakami T, Arii S, Okazaki M, Makuuchi M. Evidence-based Clinical Practice Guideli — View Citation

Korean Liver Cancer Study Group (KLCSG); National Cancer Center, Korea (NCC). 2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma. Gut Liver. 2015 May 23;9(3):267-317. doi: 10.5009/gnl14460. — View Citation

Lee JY, Huo EJ, Weinstein S, Santos C, Monto A, Corvera CU, Yee J, Hope TA. Evaluation of an abbreviated screening MRI protocol for patients at risk for hepatocellular carcinoma. Abdom Radiol (NY). 2018 Jul;43(7):1627-1633. doi: 10.1007/s00261-017-1339-5. — View Citation

Lewis S, Kamath A, Chatterji M, Patel A, Shyknevsky I, Dyvorne HA, Kuehn B, Taouli B. Diffusion-weighted imaging of the liver in patients with chronic liver disease: comparison of monopolar and bipolar diffusion gradients for image quality and lesion dete — View Citation

Marrero JA, Ahn J, Rajender Reddy K; Americal College of Gastroenterology. ACG clinical guideline: the diagnosis and management of focal liver lesions. Am J Gastroenterol. 2014 Sep;109(9):1328-47; quiz 1348. doi: 10.1038/ajg.2014.213. Epub 2014 Aug 19. — View Citation

Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, Roberts LR, Heimbach JK. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018 A — View Citation

Park SH, Kim B, Kim SY, Shim YS, Kim JH, Huh J, Kim HJ, Kim KW, Lee SS. Abbreviated MRI with optional multiphasic CT as an alternative to full-sequence MRI: LI-RADS validation in a HCC-screening cohort. Eur Radiol. 2020 Apr;30(4):2302-2311. doi: 10.1007/s — View Citation

Saunders D, Seidel D, Allison M, Lyratzopoulos G. Systematic review: the association between obesity and hepatocellular carcinoma - epidemiological evidence. Aliment Pharmacol Ther. 2010 May;31(10):1051-63. doi: 10.1111/j.1365-2036.2010.04271.x. Epub 2010 — View Citation

Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med. 2014 Apr 1;11(4):e1001624. doi: 10.1371/journal.pmed.1001624. eCollection — View Citation

Son JH, Choi SH, Kim SY, Jang HY, Byun JH, Won HJ, Lee SJ, Lim YS. Validation of US Liver Imaging Reporting and Data System Version 2017 in Patients at High Risk for Hepatocellular Carcinoma. Radiology. 2019 Aug;292(2):390-397. doi: 10.1148/radiol.2019190 — View Citation

Tillman BG, Gorman JD, Hru JM, Lee MH, King MC, Sirlin CB, Marks RM. Diagnostic per-lesion performance of a simulated gadoxetate disodium-enhanced abbreviated MRI protocol for hepatocellular carcinoma screening. Clin Radiol. 2018 May;73(5):485-493. doi: 1 — View Citation

Tzartzeva K, Obi J, Rich NE, Parikh ND, Marrero JA, Yopp A, Waljee AK, Singal AG. Surveillance Imaging and Alpha Fetoprotein for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis: A Meta-analysis. Gastroenterology. 2018 May;154(6):170 — View Citation

Wang C, Wang X, Gong G, Ben Q, Qiu W, Chen Y, Li G, Wang L. Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies. Int J Cancer. 2012 Apr 1;130(7):1639-48. doi: 10.1002/ijc.2 — View Citation

Whang S, Choi MH, Choi JI, Youn SY, Kim DH, Rha SE. Comparison of diagnostic performance of non-contrast MRI and abbreviated MRI using gadoxetic acid in initially diagnosed hepatocellular carcinoma patients: a simulation study of surveillance for hepatoce — View Citation

Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016 Jul;64(1):73-84. doi: 10.1002/hep.28431. Epub 2016 Fe — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HCC detection with US surveillance versus aNC-MRI surveillance	The detection of hepatic malignancy on the two modalities will be compared; Sensitivity, specificity, PPV and NPV of HCC detection with US surveillance vs aNC-MRI surveillance; Correlation with diagnostic imaging (multiphase CT or MRI) and/or histopathology as a reference standard; For the diagnosis of HCC we will accept; Imaging diagnosis based on the Liver Imaging Reporting and Data System (LI-RADS); Any pathological proof on biopsy or excision The HCC will then be staged based on the Barcelona clinic liver cancer (BCLC) staging system; For the diagnosis of non-HCC hepatic malignancy we will accept; Imaging diagnosis based on the Liver Imaging Reporting and Data System (LI-RADS); Any pathological proof on biopsy or excision	3 or 5 years

External Links

•   US LIRADS CORE 2017