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

Overview

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.

Detailed 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.

Interventions

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

Primary outcome measures

• HCC detection with US surveillance versus aNC-MRI surveillance [Time frame: 3 or 5 years]

Eligibility criteria

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:

• Histologically by liver biopsy
• Past signs of decompensated liver disease such as ascites, encephalopathy, varices or bacterial peritonitis
• Clinically suspicion of cirrhosis PLUS one of the following:

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Screening

Study locations

Australia · 9 centers

• Royal Prince Alfred Hospital — Camperdown
• Concord Repatriation General Hospital — Concord
• Gosford Hospital — Gosford
• Prince of Wales Hospital — Randwick
• Westmead Hospital — Westmead
• Princess Alexandra Hospital — Brisbane
• St Vincent's Hospital Melbourne — Fitzroy
• Austin Hospital — Heidelberg
• … and 1 more center

New Zealand · 1 center

• North Shore Hospital — Takapuna

Publications

• 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.2019190035. Epub 2019 Jun 18. PMID 31210614
• 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 2014 Apr. PMID 24691105
• 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):1706-1718.e1. doi: 10.1053/j.gastro.2018.01.064. Epub 2018 Feb 6. PMID 29425931
• 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 carcinoma. Abdom Radiol (NY). 2016 Jan;41(1):71-90. doi: 10.1007/s00261-015-0592-8. PMID 26830614
• 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):513-23. doi: 10.1111/j.1572-0241.2006.00467.x. PMID 16542288
• 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. 2018 Dec;289(3):816-830. doi: 10.1148/radiol.2018181494. Epub 2018 Sep 25. PMID 30251931
• European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018 Jul;69(1):182-236. doi: 10.1016/j.jhep.2018.03.019. Epub 2018 Apr 5. No abstract available. PMID 29628281
• 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. doi: 10.1002/cld.579. eCollection 2016 Oct. No abstract available. PMID 31041073

Identifiers

NCT: NCT04455932 · 2019/PID15472

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗