Journal of Liver Cancer

Volume 23(2); September 2023

Editorials

Implications of the first edition of the Korean expert consensus-based practice recommendations for transarterial chemoembolization in the management of hepatocellular carcinoma: Jin Wook Chung; J Liver Cancer. 2023;23(2):235-237. Published online July 25, 2023; DOI: https://doi.org/10.17998/jlc.2023.06.29

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Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma: strengths and shortcomings: Sung Won Lee, Min Kyu Kang, Xiang Zhang; J Liver Cancer. 2023;23(2):238-240. Published online September 20, 2023; DOI: https://doi.org/10.17998/jlc.2023.09.12

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Recommendation and Guideline

Transarterial chemoembolization for hepatocellular carcinoma: 2023 expert consensus-based practical recommendations of the Korean Liver Cancer Association: Yuri Cho, Jin Woo Choi, Hoon Kwon, Kun Yung Kim, Byung Chan Lee, Hee Ho Chu, Dong Hyeon Lee, Han Ah Lee, Gyoung Min Kim, Jung Suk Oh, Dongho Hyun, In Joon Lee, Hyunchul Rhim; J Liver Cancer. 2023;23(2):241-261. Published online July 14, 2023; DOI: https://doi.org/10.17998/jlc.2023.05.22

2,227 Views
139 Downloads
3 Citations

Abstract PDF

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

Citations

Citations to this article as recorded by

Liver resection in selective hepatocellular carcinoma with Vp3 or Vp4 portal vein tumor thrombosis improves prognosis
Manuel Lim, Jongman Kim, Jinsoo Rhu, Gyu-Seong Choi, Jae-Won Joh
Journal of Liver Cancer.2024; 24(1): 102. CrossRef
A refined prediction model for survival in hepatocellular carcinoma patients treated with transarterial chemoembolization
Hae Lim Lee, Seok Hwan Kim, Hee Yeon Kim, Sung Won Lee, Myeong Jun Song
Frontiers in Oncology.2024;[Epub] CrossRef
Implications of the first edition of the Korean expert consensus-based practice recommendations for transarterial chemoembolization in the management of hepatocellular carcinoma
Jin Wook Chung
Journal of Liver Cancer.2023; 23(2): 235. CrossRef

Review Articles

The role of lenvatinib in the era of immunotherapy of hepatocellular carcinoma: Matthew Man Pok Lee, Landon Long Chan, Stephen Lam Chan; J Liver Cancer. 2023;23(2):262-271. Published online August 17, 2023; DOI: https://doi.org/10.17998/jlc.2023.07.17

2,737 Views
253 Downloads
2 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) frequently presents as advanced stage with poor prognosis and high mortality. Systemic treatment is the treatment of choice for advanced disease. In 2007, the first multi-kinase inhibitor (MKI) sorafenib was approved and shown to modestly prolong overall survival (OS). The progress of systemic therapy has been slow afterwards until 2018 when lenvatinib, another MKI, was shown to be non-inferior to sorafenib on median OS as the first-line therapy for HCC. Since then, remarkable progress has been achieved on the treatment of advanced HCC, including the development of second-line targeted treatment, including regorafenib, cabozantinib and ramucirumab from 2017 to 2019. A growing focus has been placed on immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated protein 4. These ICIs have proven their potency in treating HCC as both initial and subsequent line of therapy. At present, both regimens of atezolizumab combined with bevacizumab, as well as the combination of tremelimumab and durvalumab, are recommended as the first-line treatments based on positive phase III clinical trials. With the advancement of ICIs, it is anticipated that the role of MKIs in the treatment of HCC will evolve. In this article, lenvatinib, one of the most commonly used MKIs in HCC, is chosen to be reviewed.

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Reduced-Dose or Discontinuation of Bevacizumab Might Be Considered after Variceal Bleeding in Patients with Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab: Case Reports
Kyeong-Min Yeom, Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
Medicina.2024; 60(1): 157. CrossRef
The Position of Multikinase Inhibitors in the Era of Immune-Checkpoint Inhibitors for Hepatocellular Carcinoma
Beom Kyung Kim
Gut and Liver.2024; 18(1): 3. CrossRef

Diagnosis of hepatocellular carcinoma using Sonazoid: a comprehensive review: Woo Kyoung Jeong; J Liver Cancer. 2023;23(2):272-283. Published online September 19, 2023; DOI: https://doi.org/10.17998/jlc.2023.08.25

1,177 Views
82 Downloads
1 Citation

Abstract PDF

Sonazoid contrast-enhanced ultrasonography (CEUS) is a promising technique for the detection and diagnosis of focal liver lesions, particularly hepatocellular carcinoma (HCC). Recently, a collaborative effort between the Korean Society of Radiology and Korean Society of Abdominal Radiology resulted in the publication of guidelines for diagnosing HCC using Sonazoid CEUS. These guidelines propose specific criteria for identifying HCC based on the imaging characteristics observed during Sonazoid CEUS. The suggested diagnostic criteria include nonrim arterial phase hyperenhancement, and the presence of late and mild washout, or Kupffer phase washout under the premise that the early or marked washout should not occur during the portal venous phase. These criteria aim to improve the accuracy of HCC diagnosis using Sonazoid CEUS. This review offers a comprehensive overview of Sonazoid CEUS in the context of HCC diagnosis. It covers the fundamental principles of Sonazoid CEUS and its clinical applications, and introduces the recently published guidelines. By providing a summary of this emerging technique, this review contributes to a better understanding of the potential role of Sonazoid CEUS for diagnosing HCC.

Citations

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Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma: strengths and shortcomings
Sung Won Lee, Min Kyu Kang, Xiang Zhang
Journal of Liver Cancer.2023; 23(2): 238. CrossRef

Imaging prognostication and tumor biology in hepatocellular carcinoma: Diana Kadi, Marilyn F. Yamamoto, Emily C. Lerner, Hanyu Jiang, Kathryn J. Fowler, Mustafa R. Bashir; J Liver Cancer. 2023;23(2):284-299. Published online September 15, 2023; DOI: https://doi.org/10.17998/jlc.2023.08.29

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110 Downloads

Abstract PDF: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, and represents a significant global health burden with rising incidence rates, despite a more thorough understanding of the etiology and biology of HCC, as well as advancements in diagnosis and treatment modalities. According to emerging evidence, imaging features related to tumor aggressiveness can offer relevant prognostic information, hence validation of imaging prognostic features may allow for better noninvasive outcomes prediction and inform the selection of tailored therapies, ultimately improving survival outcomes for patients with HCC.

Management of early-stage hepatocellular carcinoma: challenges and strategies for optimal outcomes: Jae Hyun Yoon, Sung Kyu Choi; J Liver Cancer. 2023;23(2):300-315. Published online September 21, 2023; DOI: https://doi.org/10.17998/jlc.2023.08.27

2,183 Views
145 Downloads
4 Citations

Abstract PDF

Although hepatocellular carcinoma (HCC) is associated with a poor prognosis, management of early-stage HCC is often successful with highly efficacious treatment modalities such as liver transplantation, surgical resection, and radiofrequency ablation. However, unfavorable clinical outcomes have been observed under certain circumstances, even after efficient treatment. Factors that predict unsuitable results after treatment include tumor markers, inflammatory markers, imaging findings reflecting tumor biology, specific outcome indicators for each treatment modality, liver functional reserve, and the technical feasibility of the treatment modalities. Various strategies may overcome these challenges, including the application of reinforced treatment indication criteria with predictive markers reflecting tumor biology, compensation for technical issues with up-to-date technologies, modification of treatment modalities, downstaging with locoregional therapies (such as transarterial chemotherapy or radiotherapy), and recently introduced combination immunotherapies. In this review, we discuss the challenges to achieving optimal outcomes in the management of early-stage HCC and suggest strategies to overcome these obstacles.

Citations

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Diosgenin potentiates the anticancer effect of doxorubicin and volasertib via regulating polo-like kinase 1 and triggering apoptosis in hepatocellular carcinoma cells
Eman H. Yousef, Mohamed E. El-Mesery, Maha R. Habeeb, Laila A. Eissa
Naunyn-Schmiedeberg's Archives of Pharmacology.2024;[Epub] CrossRef
Comparison of Surgical Resection and Radiofrequency Ablation in Elderly Patients with Hepatocellular Carcinoma
Jun Il Kim, Jayoun Lee, Gi Hong Choi, Min Woo Lee, Dong Ah Park, Jeong-Ju Yoo
Digestive Diseases and Sciences.2024; 69(3): 1055. CrossRef
Radiofrequency for hepatocellular carcinoma larger than 3 cm: potential for applications in daily practice
Ji Hoon Kim, Pil Soo Sung
Journal of Liver Cancer.2024; 24(1): 1. CrossRef
Efficacy of Transarterial Chemoembolization (TACE) for Early-Stage Hepatocellular Carcinoma
Moonhyung Lee, Hyun Phil Shin
Medicina.2023; 59(12): 2174. CrossRef

A multidisciplinary approach with immunotherapies for advanced hepatocellular carcinoma: Yu Rim Lee; J Liver Cancer. 2023;23(2):316-329. Published online September 22, 2023; DOI: https://doi.org/10.17998/jlc.2023.09.04

1,564 Views
102 Downloads
2 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) is a highly aggressive disease that is usually diagnosed at an advanced stage. Advanced HCC has limited treatment options and often has a poor prognosis. For the past decade, tyrosine kinase inhibitors have been the only treatments approved for advanced HCC that have shown overall survival (OS) benefits; however, but their clinical efficacy has been limited. Recent trials have demonstrated promising advancements in survival outcomes through immunotherapy-based treatments, such as combinations of immune checkpoint inhibitors (ICIs) with other ICIs, antiangiogenic drugs, and locoregional therapies. The atezolizumab-bevacizumab and durvalumab-tremelimumab (STRIDE) regimen has significantly improved survival rates as a first-line treatment and has become the new standard of care. Therefore, combined treatments for advanced HCC can result in better treatment outcomes owing to their synergistic effects, which requires a multidisciplinary approach. Ongoing studies are examining other therapeutic innovations that can improve disease control and OS rates. Despite improvements in the treatment of advanced HCC, further studies on the optimal treatment selection and sequences, biomarker identification, combination approaches with other therapies, and development of novel immunotherapy agents are required. This review presents the current treatment options and clinical data of the ICI-based combination immunotherapies for advanced HCC from a multidisciplinary perspective.

Citations

Citations to this article as recorded by

Reduced-Dose or Discontinuation of Bevacizumab Might Be Considered after Variceal Bleeding in Patients with Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab: Case Reports
Kyeong-Min Yeom, Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
Medicina.2024; 60(1): 157. CrossRef
Hepatocellular Carcinoma: Advances in Systemic Therapy
Insija Ilyas Selene, Merve Ozen, Reema A. Patel
Seminars in Interventional Radiology.2024; 41(01): 056. CrossRef

Original Articles

Feasibility of additional radiotherapy in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab: Tae Hyun Kim, Bo Hyun Kim, Yu Ri Cho, Young-Hwan Koh, Joong-Won Park; J Liver Cancer. 2023;23(2):330-340. Published online May 16, 2023; DOI: https://doi.org/10.17998/jlc.2023.04.14

1,777 Views
112 Downloads
1 Citation

Abstract PDF Supplementary Material

Background/Aim
Radiotherapy (RT) is an effective local treatment for hepatocellular carcinoma (HCC). However, whether additional RT is safe and effective in patients with advanced HCC receiving atezolizumab plus bevacizumab remains unclear. This retrospective cohort study aimed to evaluate the feasibility of additional RT in these patients.
Methods
Between March and October 2021, we retrospectively analyzed seven patients with advanced HCC who received RT during treatment with atezolizumab plus bevacizumab. The median prescribed RT dose was 35 Gy (range, 33–66). Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) after RT were analyzed.
Results
The median follow-up duration after RT was 14.2 months (range, 10.0–18.6). Of the seven patients, disease progression was noted in six (85.7%), the sites of disease progression were local in two (28.6%), intrahepatic in four (57.1%), and extrahepatic in four (57.1%). The median time of FFLP was not reached, and PFS and OS times were 4.0 (95% confidence interval [CI], 3.6–4.5) and 14.8% (95% CI, 12.5–17.2) months, respectively. The 1-year FFLP, PFS, and OS rates were 60% (95% CI, 43.8–76.2), 0%, and 85.7% (95% CI, 75.9–95.5), respectively. Grade 3 or higher hematologic adverse events (AEs) were not observed, but grade 3 nonhematologic AEs unrelated to RT were observed in one patient.
Conclusions
The addition of RT may be feasible in patients with advanced HCC treated with atezolizumab plus bevacizumab. However, further studies are required to validate these findings.

Citations

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Letter regarding “Feasibility of additional radiotherapy in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab”
Sun Hyun Bae, Hee Chul Park
Journal of Liver Cancer.2023; 23(2): 402. CrossRef

Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma: Kyoungdo Mun, Jiwon Han, Pureun Roh, Jonggeun Park, Gahee Kim, Wonhee Hur, Jeongwon Jang, Jongyoung Choi, Seungkew Yoon, Youngkyoung You, Hojoong Choi, Pilsoo Sung; J Liver Cancer. 2023;23(2):341-349. Published online June 12, 2023; DOI: https://doi.org/10.17998/jlc.2023.04.30

2,521 Views
168 Downloads
1 Citation

Abstract PDF

Background/Aim
Cancer-associated fibroblasts (CAFs) play an immunosuppressive role in the tumor microenvironment (TME) of human cancers; however, their characteristics and role in hepatocellular carcinoma (HCC) remain to be elucidated.
Methods
Nine tumor and surrounding liver tissue samples from patients with HCC who underwent surgery were used to isolate patient-derived CAFs. Cell morphology was observed using an optical microscope after culture, and cell phenotypes were evaluated using flow cytometry and immunoblotting. Cytokines secreted by CAFs into culture medium were quantified using a multiplex cytokine assay.
Results
CAFs were abundant in the TME of HCC and were adjacent to immune cells. After culture, the CAFs and non-tumor fibroblasts exhibited spindle shapes. We observed a robust expression of alpha-smooth muscle actin and fibroblast activation protein in CAFs, whereas alpha-fetoprotein, epithelial cell adhesion molecule, platelet/endothelial cell adhesion molecule-1, and E-cadherin were not expressed in CAFs. Furthermore, CAFs showed high secretion of various cytokines, namely C-X-C motif chemokine ligand 12, interleukin (IL)-6, IL-8, and C-C motif chemokine ligand 2.
Conclusions
CAFs are abundant in the TME of HCC and play a crucial role in tumor progression. These fibroblasts secrete cytokines that promote tumor growth and metastasis.

Citations

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Rebuilding the microenvironment of primary tumors in humans: a focus on stroma
Siwon Mun, Hyun Jin Lee, Pilnam Kim
Experimental & Molecular Medicine.2024; 56(3): 527. CrossRef

Nomogram for predicting overall survival in patients with large (>5 cm) hepatocellular carcinoma based on real-world practice: Nalee Kim, Jeong Il Yu, Hee Chul Park, Jung Yong Hong, Ho Yeong Lim, Myung Ji Goh, Yong-Han Paik; J Liver Cancer. 2023;23(2):350-361. Published online September 6, 2023; DOI: https://doi.org/10.17998/jlc.2023.08.10

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Abstract PDF Supplementary Material: Background/Aim
Patients with large (>5 cm) hepatocellular carcinoma (HCC) have limited treatment options, thus necessitating the identification of prognostic factors and the development of predictive tools. This study aimed to identify prognostic factors and to construct a nomogram to predict survival outcomes in patients with large HCC.
Methods
A cohort of 438 patients, who were diagnosed with large HCC at a tertiary hospital between 2015 and 2018, was analyzed. Cox proportional hazards models were used to identify key prognosticators of overall survival (OS), and an independent set of prognostic factors was used to develop a nomogram. The discrimination and calibration abilities of the nomogram were assessed and internal validation was performed using cross-validation and bootstrapping methods.
Results
During a median follow-up of 9.3 months, the median OS was 9.9 months, and the 1-year OS rate was 43.9%. Multivariable Cox regression analysis revealed that performance status, modified albumin-bilirubin grade, tumor size, extent of portal vein tumor thrombosis, and initial treatment significantly affected OS. The newly developed nomogram incorporating these variables demonstrated favorable accuracy (Harrell’s concordance index, 0.807).
Conclusions
The newly developed nomogram facilitated the estimation of individual survival outcomes in patients with large HCC, providing an acceptable level of accuracy.

The efficacy of treatment for hepatocellular carcinoma in elderly patients: Han Ah Lee, Sangheun Lee, Hae Lim Lee, Jeong Eun Song, Dong Hyeon Lee, Sojung Han, Ju Hyun Shim, Bo Hyun Kim, Jong Young Choi, Hyunchul Rhim, Do Young Kim; J Liver Cancer. 2023;23(2):362-376. Published online September 14, 2023; DOI: https://doi.org/10.17998/jlc.2023.08.03

1,321 Views
70 Downloads

Abstract PDF Supplementary Material: Background/Aim
Despite the increasing proportion of elderly patients with hepatocellular carcinoma (HCC) over time, treatment efficacy in this population is not well established.
Methods
Data collected from the Korean Primary Liver Cancer Registry, a representative cohort of patients newly diagnosed with HCC in Korea between 2008 and 2017, were analyzed. Overall survival (OS) according to tumor stage and treatment modality was compared between elderly and non-elderly patients with HCC.
Results
Among 15,186 study patients, 5,829 (38.4%) were elderly. A larger proportion of elderly patients did not receive any treatment for HCC than non-elderly patients (25.2% vs. 16.7%). However, OS was significantly better in elderly patients who received treatment compared to those who did not (median, 38.6 vs. 22.3 months; P<0.001). In early-stage HCC, surgery yielded significantly lower OS in elderly patients compared to non-elderly patients (median, 97.4 vs. 138.0 months; P<0.001), however, local ablation (median, 82.2 vs. 105.5 months) and transarterial therapy (median, 42.6 vs. 56.9 months) each provided comparable OS between the two groups after inverse probability of treatment weighting (IPTW) analysis (all P>0.05). After IPTW, in intermediate-stage HCC, surgery (median, 66.0 vs. 90.3 months) and transarterial therapy (median, 36.5 vs. 37.2 months), and in advanced-stage HCC, transarterial (median, 25.3 vs. 26.3 months) and systemic therapy (median, 25.3 vs. 26.3 months) yielded comparable OS between the elderly and non-elderly HCC patients (all P>0.05).
Conclusions
Personalized treatments tailored to individual patients can improve the prognosis of elderly patients with HCC to a level comparable to that of non-elderly patients.

Clinical outcome of surgical resection for multifocal T2-T3 hepatocellular carcinoma up to 3 nodules: a comparative analysis with a single nodule: Sehyeon Yu, Hye-Sung Jo, Young-Dong Yu, Yoo jin Choi, Dong-Sik Kim; J Liver Cancer. 2023;23(2):377-388. Published online September 15, 2023; DOI: https://doi.org/10.17998/jlc.2023.08.24

641 Views
35 Downloads

Abstract PDF Supplementary Material: Background/Aim
s: Although the Barcelona Clinic Liver Cancer staging system seems to underestimate the impact of curative-intent surgical resection for multifocal hepatocellular carcinoma (HCC), recent studies have indicated favorable results for the surgical resection of multiple HCC. This study aimed to assess clinical outcomes and feasibility of surgical resection for multifocal HCC with up to three nodules compared with single tumor cases.
Methods
Patients who underwent surgical resection for HCC with up to three nodules between 2009 and 2020 were included, and those with the American Joint Committee on Cancer (AJCC) 8th edition, T1 and T4 stages were excluded to reduce differences in disease distribution and severity. Finally, 81 and 52 patients were included in the single and multiple treatment groups, respectively. Short- and long-term outcomes including recurrence-free survival (RFS) and overall survival (OS), were evaluated.
Results
All patients were classified as Child-Pugh class A. RFS and OS were not significantly different between the two groups (P=0.176 and P=0.966, respectively). Multivariate analysis revealed that transfusion and intrahepatic metastasis were significantly associated with recurrence (P=0.046 and P=0.005, respectively). Additionally, intrahepatic metastasis was significantly associated with OS (hazard ratio, 1.989; 95% confidence interval, 1.040-3.802; P=0.038).
Conclusions
Since there was no significant difference in survival between the single and multiple groups among patients with AJCC 8th stage T2 and T3, surgical resection with curative intent could be considered with acceptable long-term survival for selected patients with multiple HCC of up to three nodules.

Case Reports

Hepatic basidiobolomycosis masquerading as cholangiocarcinoma: a case report and literature review: Roopali Sehrawat, Nalini Bansal, Ajitabh Srivastava, Dharmender Malik, Vivek Vij; J Liver Cancer. 2023;23(2):389-396. Published online August 17, 2023; DOI: https://doi.org/10.17998/jlc.2023.06.07

1,042 Views
52 Downloads

Abstract PDF: Basidiobolus ranarum is known to cause subcutaneous mycoses; however, rare cases of hepatic and gastrointestinal involvement by basidiobolomycosis have been reported. Hepatic basidiobolomycosis may be confused with a carcinoma on imaging, and histological examination and fungal culture can help distinguish between these two. We report a rare case of basidiobolomycosis in a 16-year-old male with liver and gastrointestinal involvement.

A single hepatic mass with two tales: hepatic tuberculosis and hepatocellular carcinoma: Yi De Ian Koh, Wei-Qiang Leow; J Liver Cancer. 2023;23(2):397-401. Published online September 8, 2023; DOI: https://doi.org/10.17998/jlc.2023.08.30

706 Views
55 Downloads

Abstract PDF: Hepatic tuberculosis (HTB) is an uncommon manifestation of tuberculous infections, and there has been no proven causal link between HTB and hepatocellular carcinoma (HCC). We herein present a rare case of a synchronous presentation of HTB and HCC within a single hepatic mass. A 57-year-old Chinese gentleman with recently diagnosed sigmoid adenocarcinoma was found to have a left lower lobe pulmonary nodule and solitary hepatic mass on staging computed tomography. Biopsies showed the hepatic mass to have both HTB and HCC components. This serves as a reminder that HTB is an important differential to consider for space-occupying lesions in the liver. Histological evaluation of suspected hepatic malignancies is recommended to exclude the presence of HTB in appropriate clinical settings.

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