DALLAS – For more than a decade, the Liver Imaging Reporting and Data System (LI-RADS) has been used to standardize the interpretation and reporting of liver lesions in patients at high risk for hepatocellular carcinoma (HCC).
Yet, predicting what happens with indeterminate liver nodules (ILNs), which are frequently encountered on diagnostic imaging after positive HCC surveillance results, remains difficult, according to researchers from the University of Texas Southwestern in Dallas and colleagues, including the Michael E. DeBakey VAMC in Houston.
For the report published in the American Journal of Gastroenterology, the investigative team conducted a multicenter retrospective cohort study among patients with one or more newly detected LI-RADS 3 (LR-3) lesion larger than 1 cm or LI-RADS 4 (LR-4) lesion of any size (per LI-RADS v2018) between January 2018 and December 2019.1
Of 307 patients with ILNs, 208 had LR-3 lesions, 83 had LR-4 lesions, and 16 had both LR-3 and LR-4 lesions, the authors noted. Patients were followed with repeat imaging at each site per institutional standard of care.
Results indicated that HCC incidence rates for patients with LR-3 and LR-4 lesions were 110 (95% CI 70-150) and 420 (95% CI 310-560) per 1,000 person-year, respectively.
The researchers explained that, in multivariable analysis, incident HCC among patients with LR-3 lesions was associated with older age, thrombocytopenia (platelet count ≤150 ×10 9 /L), and elevated serum alpha-fetoprotein levels. Among those with LR-4 lesions, however, incident HCC was associated with a maximum lesion diameter >1 cm.
“Although most patients had follow-up computed tomography or magnetic resonance imaging, 13.7% had no follow-up imaging and another 14.3% had follow-up ultrasound only,” the researchers advised, adding, “ILNs have a high but variable risk of HCC, with 4-fold higher risk in patients with LR-4 lesions than those with LR-3 lesions, highlighting a need for accurate risk stratification tools and close follow-up in this population.”
Recently, an international study published in Abdominal Radiology looked at the value of Contrast-Enhanced Ultrasound (CEUS) and whether that is a clinically useful additional step when computed tomography (CT) or Magnetic resonance imaging (MRI) results are inconclusive.2
“Hepatocellular carcinoma (HCC) is a unique cancer allowing tumor diagnosis with identification of definitive patterns of enhancement on contrast-enhanced imaging, avoiding invasive biopsy. However, it is still unclear to what extent,” wrote the first authors from the University of California, San Diego and colleagues.
They described how a prospective international multicenter validation study for CEUS Liver Imaging Reporting and Data System (LI-RADS) was conducted between January 2018 and August 2021. It enrolled 646 patients at risk for HCC with focal liver lesions, and CEUS was performed using an intravenous ultrasound contrast agent within 4 weeks of CT/MRI.
Liver nodules were categorized based on LI-RADS (LR) criteria, according to the report, which added that histology or one-year follow-up CT/MRI imaging results were used as the reference standard. The researchers evaluated the diagnostic performance of CEUS for inconclusive CT/MRI scan in two scenarios for which the AASLD recommends repeat imaging or imaging follow-up: observations deemed non-characterizable (LR-NC) or with indeterminate probability of malignancy (LR-3).
The investigators advised that “75 observations on CT or MRI were categorized as LR-3 (n = 54) or LR-NC (n = 21) CEUS recategorization of such observations into a different LR category (namely, into one among LR-1, LR-2, LR-5, LR-M, or LR-TIV) resulted in management recommendation changes in 33.3% (25/75) and in all but one (96.0%, 24/25) observation, the new management recommendations were correct.”
The study concluded that CEUS LI-RADS “resulted in management recommendations change in a substantial number of liver observations with initial indeterminate CT/MRI characterization, identifying both non-malignant lesions and HCC, potentially accelerating the diagnostic process and alleviating the need for biopsy or follow-up imaging.”
Background information in the article noted that hepatocellular carcinoma (HCC) is among the most lethal cancers worldwide but has an improved survival rate when accurately diagnosed at an early, curative stage.
“Compliance with HCC surveillance programs help accomplish this goal,” the authors noted. “Unlike most solid cancers, HCC diagnosis and treatment planning can often be confidently established through noninvasive dynamic contrast imaging without the need for biopsy. Consequently, the precision of imaging diagnosis is of paramount importance.”
LI-RADs was established to ensure a standardized approach to the technique, terminology, interpretation, and reporting of liver imaging in individuals at risk for HCC, the study added. Initially developed in 2011 for computed tomography (CT) and magnetic resonance imaging (MRI), LI-RADS was expanded to include contrast-enhanced ultrasound (CEUS) in 2017.
“The current American Association for the Study of Liver Diseases (AASLD) practice guidance on the prevention, diagnosis, and treatment of HCC recommends [ultrasound] as the first-line imaging modality for HCC surveillance, and contrast-enhanced, multiphase CT and MRI for diagnosis of HCC in patients with nodules ≥ 1 cm detected by surveillance,” according to the report. “These guidelines also accept the possibility of CEUS as a second-line modality in cases where MRI and CT are inconclusive, unavailable, or contraindicated, or when tumor biopsy is not feasible.”
On the other hand, the National Comprehensive Cancer Network (NCCN) Guidelines for Hepatobiliary Cancers do not currently include CEUS in the HCC diagnosis algorithm as of this publication, but note that CEUS has comparable diagnostic accuracy as MRI.
The researchers said they believe CEUS “is capable of re-categorizing CT/MRI-indeterminate lesions with high accuracy, resulting in meaningful management recommendation changes. We therefore conduct a sub-analysis to explore the clinical impact of CEUS to further characterize focal liver nodules with LR-3 and LR-NC CT/MRI categorization.
- Singal AG, Parikh ND, Shetty K, Han SH, Xie C, Ning J, Rinaudo JA, Arvind A, Lok AS, Kanwal F; Translational Liver Cancer Investigators. Natural History of Indeterminate Liver Nodules in Patients With Advanced Liver Disease: A Multicenter Retrospective Cohort Study. Am J Gastroenterol. 2024 May 29. doi: 10.14309/ajg.0000000000002827. Epub ahead of print. PMID: 38686922.
- Kono Y, Piscaglia F, Wilson SR, Medellin A, et. Al. CEUS LI-RADS Trial Group. Clinical impact of CEUS on non-characterizable observations and observations with intermediate probability of malignancy on CT/MRI in patients at risk for HCC. Abdom Radiol (NY). 2024 Jun 11. doi: 10.1007/s00261-024-04305-9. Epub ahead of print. PMID: 38860996.
