2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.

Keywords: Diagnosis; Guidelines; Hepatocellular carcinoma; Management.

Figure 1.

Crude death rate and age-standardized death rate in South Korea in calendar years 2010 to 2020.

Figure 2.

Annual number of liver cancer deaths, liver disease deaths and liver transplantations in South Korea during calendar years 2010 to 2020.

Figure 3.

Diagnostic algorithm. HCC, hepatocellular carcinoma; CHB, chronic hepatitis B; CHC, chronic hepatitis C; CT, computed tomography. ^*The radiological hallmarks for diagnosing “definite” HCC on multiphasic contrast-enhanced CT or magnetic resonance imaging (MRI) are arterial phase hyperenhancement (APHE) with washout appearance in the portal venous, delayed, or hepatobiliary phases. These criteria should be applied only to a lesion that does not show either marked T2 hyperintensity or targetoid appearances on diffusion-weighted images or contrast-enhanced images. For a second-line imaging modality, the radiologic hallmarks of contrast-enhanced ultrasonography (blood-pool contrast agent or Kupffer cell-specific contrast agent) for a “definite” diagnosis of HCC are APHE with mild and late (≥60 seconds) washout. These criteria should be applied only to a lesion that does not show either rim or peripheral globular enhancement in the arterial phase. ^†For the diagnosis of “probable” HCC, ancillary imaging features are applied as follows: there are two categories of ancillary imaging features, including imaging features favoring malignancy in general (mild-to-moderate T2 hyperintensity, restricted diffusion, threshold growth) and those favoring HCC in particular (enhancing or non-enhancing capsule, mosaic architecture, nodule-in-nodule appearance, fat or blood products in the mass). For nodules without APHE, “probable” HCC can be assigned only when the lesion fulfills at least one item from each of the two categories of ancillary imaging features. For nodules with APHE but without washout appearance, “probable” HCC can be assigned when the lesion fulfills at least one of the aforementioned ancillary imaging features.

Figure 4.

Definite hepatocellular carcinoma (HCC) on multiphasic magnetic resonance imaging (MRI) with hepatocyte-specific contrast agent. A 1.7-cm liver nodule (arrow) is detected on surveillance ultrasound in a patient with liver cirrhosis. The lesion shows the radiological hallmarks of HCC, i.e., arterial phase hyperenhancement and washout appearance (portal venous phase, delayed phase, and hepatobiliary phase) on multiphasic MRI using hepatocyte-specific contrast agent (gadoxetic acid) but does not show marked T2 hyperintensity or targetoid appearances on diffusion-weighted images and contrast-enhanced images. Therefore, this nodule can be noninvasively diagnosed as “definite” HCC.

Figure 5.

Definite hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound. A 3.5-cm liver nodule is detected in a patient with chronic hepatitis B. On contrast-enhanced ultrasound using blood-pool contrast agent, the nodule shows arterial phase hyperenhancement and mild washout on 3 minutes delayed image. Therefore, it can be noninvasively diagnosed as “definite” HCC.

Figure 6.

Probable hepatocellular carcinoma (HCC) on dynamic contrast-enhanced computed tomography (CT). On dynamic contrast-enhanced CT in a patient with chronic hepatitis B, there is a 2-cm liver nodule (arrow) with arterial phase hyperenhancement. This nodule does not show a washout appearance in the portal venous phase or delayed phase, so it cannot be non-invasively diagnosed as “definite” HCC. However, based on the presence of enhancing capsule in the portal venous phase and delayed phase, an ancillary imaging feature of HCC, this nodule can be diagnosed as “probable” HCC.

Figure 7.

Probable hepatocellular carcinoma (HCC) on multiphasic magnetic resonance imaging (MRI) with hepatocyte-specific contrast agent. On multiphasic MRI with hepatocyte-specific contrast agent (gadoxetic acid), a 2.5-cm nodule (arrows) is found in segment VII of the liver in a patient with liver cirrhosis. This lesion is indistinguishable from surrounding liver parenchyma on precontrast T1-weighted image and arterial phase image but shows hypointensity on portal venous phase, delayed phase, and hepatobiliary phase images. Since it does not show arterial phase hyperenhancement, an imaging diagnosis of “definite” HCC cannot be made. However, it shows mild-to-moderate T2 hyperintensity and focal signal drop on the opposed phase image in comparison with an in-phase image, which suggests the presence of intra-tumoral fat. Therefore, based on MRI ancillary imaging features, this nodule can be diagnosed as a “probable” HCC.

Figure 8.

First-line treatment of 2022 Korean Liver Cancer Association-National Cancer Center Korea practice guidelines for patients with hepatocellular carcinoma, Child-Pugh class A, no portal hypertension, and Eastern Cooperative Oncology Group performance status 0–1. mUICC, modified Union for International Cancer Control; VI, vascular or bile duct invasion; RFA, radiofrequency ablation; cTACE, conventional transarterial chemoembolization; TARE, transarterial radioembolization; Other local ablation, percutaneous ethanol injection (PEI), microwave ablation (MWA), and cryoablation; EBRT, external beam radiation therapy; Vp, portal vein invasion; LT, liver transplantation; DEB-TACE, drug eluting bead-TACE; TACE, cTACE and DEB-TACE; HAIC, hepatic arterial infusion chemotherapy.

Figure 9.

Treatment algorithm of systemic therapy for hepatocellular carcinoma. AFP, alpha-fetoprotein. ^*If patients have absolute or relative contraindications for immune-checkpoint inhibitors or bevacizumab, multiple tyrosine kinase inhibitors such as sorafenib or lenvatinib should be recommended.