EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma European Association for the Study of the Liver (2025). EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. Journal of hepatology, 82(2), 315–374. https://doi.org/10.1016/j.jhep.2024.08.028 Liver cancer is the sixth most prevalent cancer and the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) being responsible for 90% of cases [1]. Managing HCC is complex and requires continuous knowledge updates and a multidisciplinary approach. In February 2025, the European Association for the Study of the Liver (EASL) released new HCC guidelines, reflecting advancements in surveillance, diagnosis, and treatment since 2018 [2]. What is new in the surveillance, imaging diagnosis and staging of HCC? HCC surveillance target population remains debated. Patients with cirrhosis should undergo surveillance unless they face a high risk of death from non-HCC-related causes or if curative treatment cannot be provided. Individuals with chronic liver disease and advanced fibrosis without cirrhosis, such as metabolic dysfunction-associated liver disease, face a higher risk of HCC compared to the general population. However, surveillance is not currently recommended for these patients due to insufficient evidence. Abdominal ultrasound every six months remains the standard surveillance imaging tool due to its accessibility and cost-effectiveness. Updated guidelines support using ultrasound and alpha-fetoprotein as a valid surveillance option. Limited data support alternative imaging techniques, such as abbreviated magnetic resonance imaging (MRI) or other serum biomarkers for routine surveillance. Following a stepwise carcinogenesis model, HCC typically arises in a liver with chronic tissue damage. As liver nodules progress from benign to malignant, vascular changes become detectable via contrast-enhanced imaging, forming the basis for non-invasive HCC diagnosis. In addition to cirrhotic patients, as previously proposed, the 2025 guidelines broaden the application of non-invasive diagnostic criteria to include patients with chronic hepatitis B virus (HBV) infection or history of HCC. For patients outside these groups, biopsy is required. Non-invasive diagnosis applies only to high-risk patients since benign and malignant lesions mimic HCC in low-risk groups. For newly detected nodules, regardless of lesion size, advanced imaging methods such as contrast-enhanced ultrasound (CEUS), multiphase computed tomography (CT), and MRI should be used to assess characteristic vascular patterns in previously mentioned high-risk patients. We highlight that, in contrast to earlier guidelines that evaluated lesions primarily based on size, the updated algorithm enhances risk assessment. The 2025 guidelines now acknowledge that the CEUS diagnostic algorithm can be used in the same patients as the CT/MR algorithm, but it can only be applied to lesions visible on pre-contrast ultrasound. Nevertheless, they favour CT or MRI over CEUS because of their higher sensitivity and the need for follow-up staging with CT or MRI after CEUS. CEUS remains an option when CT or MRI are inconclusive. There is no preference between contrast-enhanced CT or MRI for non-invasive HCC diagnosis. Extracellular contrast agents (ECAs) are now preferred over hepatospecific (HBAs) in contrast-enhanced MRI. In contrast to ECAs, HBAs evaluate the hepatocellular function, with HCCs frequently showing hypointensity during the hepatobiliary phase [3]. Viewing this hypointensity as a secondary finding rather than a primary diagnostic criterion is essential. Moreover, HBAs can cause transient motion artefacts in arterial-phase imaging, potentially compromising diagnostic quality. | The 2025 guidelines emphasise standardising imaging interpretation and recommend using the Liver Imaging Reporting and Data System (LI-RADS). Both LI-RADS CT/MR and LI-RADS CEUS categorise liver lesions based on their likelihood of malignancy, facilitating consistent communication and clinical decision-making [4]. The LR-5 category in LI-RADS provides results comparable to those of the EASL 2018 algorithm for the non-invasive diagnosis of HCC. However, LI-RADS is now preferred because it introduces valuable enhancements, such as the LR-M and LR-TIV categories, which help identify nodules at malignancy risk that do not meet the LR-5 category. New guidelines specify that initial HCC staging should include contrast-enhanced chest, abdomen, and pelvis CT scans, which were not explicitly recommended in 2018. Additional imaging is generally unnecessary, though MRI may provide supplementary details when considering surgery, thermal ablation, or radiation therapy. Staging is essential for prognosis and treatment decisions. The Barcelona Clinic Liver Cancer (BCLC) classification remains the recommended system [5]. It integrates tumour burden, liver function, and overall health status (e.g. ECOG-PS), acting as a staging tool and treatment guide. In conclusion, the 2025 EASL guidelines enhance HCC management through personalised surveillance and standardised diagnostic protocols. They highlight advanced radiological techniques, better staging criteria, and LI-RADS implementation to improve diagnostic accuracy and support clinical decisions. References: [1]. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 68(6), 394–424. https://doi.org/10.3322/caac.21492 [2]. European Association for the Study of the Liver (2018). EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. Journal of hepatology, 69(1), 182–236. https://doi.org/10.1016/j.jhep.2018.03.019 [3]. Kitao, A., Matsui, O., Yoneda, N., Kozaka, K., Shinmura, R., Koda, W., Kobayashi, S., Gabata, T., Zen, Y., Yamashita, T., Kaneko, S., & Nakanuma, Y. (2011). The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid-enhanced MR imaging. European radiology, 21(10), 2056–2066. https://doi.org/10.1007/s00330-011-2165-8 [4]. Chernyak, V., Fowler, K. J., Kamaya, A., Kielar, A. Z., Elsayes, K. M., Bashir, M. R., Kono, Y., Do, R. K., Mitchell, D. G., Singal, A. G., Tang, A., & Sirlin, C. B. (2018). Liver Imaging Reporting and Data System (LI-RADS) Version 2018: Imaging of Hepatocellular Carcinoma in At-Risk Patients. Radiology, 289(3), 816–830. https://doi.org/10.1148/radiol.2018181494 [5]. Reig, M., Forner, A., Rimola, J., Ferrer-Fàbrega, J., Burrel, M., Garcia-Criado, Á., Kelley, R. K., Galle, P. R., Mazzaferro, V., Salem, R., Sangro, B., Singal, A. G., Vogel, A., Fuster, J., Ayuso, C., & Bruix, J. (2022). BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. Journal of hepatology, 76(3), 681–693. https://doi.org/10.1016/j.jhep.2021.11.018 Rita Trovisco is a second-year radiology resident at the Unidade Local de Saúde de Santo António (ULSSA) in Porto, Portugal. She finished her undergraduate medical education at the University of Porto's Faculty of Medicine and has developed a keen interest in thoracic and abdominal radiology. Comments may be sent to ritatrovisco@gmail.com |