Journal of Liver Cancer

Volume 24(2); September 2024

Editorials

Congratulatory remarks: Kyung Sik Kim; J Liver Cancer. 2024;24(2):119-119. Published online September 13, 2024; DOI: https://doi.org/10.17998/jlc.2024.09.10

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Practical consensus multi-specialty guidelines on image-guided ablation for hepatocellular carcinoma: David S. Lu; J Liver Cancer. 2024;24(2):120-123. Published online September 27, 2024; DOI: https://doi.org/10.17998/jlc.2024.09.11

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Inter-reader agreement for LR-M imaging features: a premise for better imaging-based diagnosis in liver imaging: Jaeseung Shin; J Liver Cancer. 2024;24(2):124-125. Published online August 13, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.06

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Exploring the role of liver resection as a first-line treatment option for multinodular BCLC-A hepatocellular carcinoma: Joo Hyun Oh, Dong Hyun Sinn; J Liver Cancer. 2024;24(2):126-128. Published online August 16, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.08

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The position of loco-regional therapy in the management of hepatocellular carcinoma with extrahepatic metastases: Beom Kyung Kim; J Liver Cancer. 2024;24(2):129-130. Published online August 29, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.26

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Recommendation and Guideline

Local ablation for hepatocellular carcinoma: 2024 expert consensus-based practical recommendation of the Korean Liver Cancer Association: Seungchul Han, Pil Soo Sung, Soo Young Park, Jin Woong Kim, Hyun Pyo Hong, Jung-Hee Yoon, Dong Jin Chung, Joon Ho Kwon, Sanghyeok Lim, Jae Hyun Kim, Seung Kak Shin, Tae Hyung Kim, Dong Ho Lee, Jong Young Choi; J Liver Cancer. 2024;24(2):131-144. Published online August 30, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.04

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Abstract PDF Supplementary Material

Local ablation for hepatocellular carcinoma (HCC), a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the firstline treatment for early-stage HCC. The lack of organized evidence and expert opinions regarding patient selection, pre-procedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and posttreatment management of patients.

Citations

Citations to this article as recorded by

Practical consensus multi-specialty guidelines on image-guided ablation for hepatocellular carcinoma
David S. Lu
Journal of Liver Cancer.2024; 24(2): 120. CrossRef

Review Articles

Disease modifiers and novel markers in hepatitis B virus-related hepatocellular carcinoma: Lung-Yi Mak; J Liver Cancer. 2024;24(2):145-154. Published online August 5, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.03

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Abstract PDF: Chronic hepatitis B (CHB) infection is responsible for 40% of the global burden of hepatocellular carcinoma (HCC) with a high case fatality rate. The risk of HCC differs among CHB subjects owing to differences in host and viral factors. Modifiable risk factors include viral load, use of antiviral therapy, co-infection with other hepatotropic viruses, concomitant metabolic dysfunctionassociated steatotic liver disease or diabetes mellitus, environmental exposure, and medication use. Detecting HCC at early stage improves survival, and current practice recommends HCC surveillance among individuals with cirrhosis, family history of HCC, or above an age cut-off. Ultrasonography with or without serum alpha feto-protein (AFP) every 6 months is widely accepted strategy for HCC surveillance. Novel tumor-specific markers, when combined with AFP, improve diagnostic accuracy than AFP alone to detect HCC at an early stage. To predict the risk of HCC, a number of clinical risk scores have been developed but none of them are clinically implemented nor endorsed by clinical practice guidelines. Biomarkers that reflect viral transcriptional activity and degree of liver fibrosis can potentially stratify the risk of HCC, especially among subjects who are already on antiviral therapy. Ongoing exploration of these novel biomarkers is required to confirm their performance characteristics, replicability and practicability.

New systemic treatment options for advanced cholangiocarcinoma: Valentina Zanuso, Giulia Tesini, Elena Valenzi, Lorenza Rimassa; J Liver Cancer. 2024;24(2):155-170. Published online August 8, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.07

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Abstract PDF: Cholangiocarcinoma (CCA) is a rare and aggressive cancer, mostly diagnosed at advanced or metastatic stage, at which point systemic treatment represents the only therapeutic option. Chemotherapy has been the backbone of advanced CCA treatment. More recently, immunotherapy has changed the therapeutic landscape, as immune checkpoint inhibitors have yielded the first improvement in survival and currently, the addition of either durvalumab or pembrolizumab to standard of care cisplatin plus gemcitabine represents the new first-line treatment option. However, the use of immunotherapy in subsequent lines has not demonstrated its efficacy and therefore, it is not approved, except for pembrolizumab in the selected microsatellite instability-high population. In addition, advances in comprehensive genomic profiling have led to the identification of targetable genetic alterations, such as isocitrate dehydrogenase 1 (IDH1), fibroblast growth factor receptor 2 (FGFR2), human epidermal growth factor receptor 2 (HER2), proto-oncogene B-Raf (BRAF), neurotrophic tropomyosin receptor kinase (NTRK), rearranged during transfection (RET), Kirsten rat sarcoma virus (KRAS), and mouse double minute 2 homolog (MDM2), thus favoring the development of a precision medicine approach in previously treated patients. Despite these advances, the use of molecularly driven agents is limited to a subgroup of patients. This review aims to provide an overview of the newly approved systemic therapies, the ongoing studies, and future research challenges in advanced CCA management.

Multidisciplinary approaches to downstaging hepatocellular carcinoma: present and future: Sang-Youn Hwang, Hyunwook Choi, Wan Jeon, Ryoung-Go Kim; J Liver Cancer. 2024;24(2):171-177. Published online September 5, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.30

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Abstract PDF: Downstaging of hepatocellular carcinoma (HCC) is typically defined as the reduction in size or number of viable tumors through locoregional therapy (LRT), aiming to meet the established criteria for liver transplantation (LT). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, a subgroup of patients with BCLC-B may benefit most from downstaging therapies. The United Network Organ Sharing downstaging protocol identifies potential candidates for downstaging by setting out ‘inclusion criteria’ and defining ‘successful downstaging.’ Additionally, the protocol considers factors related to tumor biology, such as an alphafetoprotein level <500 ng/mL after LRT. Reports indicate that successful downstaging rates following LRT are about 50%, with post- LT recurrence rates comparable to those of patients within the Milan criteria. A comprehensive multicenter US study on 10-year outcomes post-LT after downstaging showed 10-year post-LT survival and recurrence rates of 52.1% and 20.6%, respectively, for patients whose disease was downstaged; this compares to 61.5% and 13.3% for those consistently within the Milan criteria. Recently, the development of effective systemic treatments for HCC, such as immuno-oncologic agents, has provided additional opportunities for downstaging. Numerous clinical trials are exploring a multidisciplinary approach (MDA) combining LRT and systemic therapy. Although concrete evidence of the superiority of MDA for HCC downstaging is lacking, some retrospective studies and phase I and II trials have shown promising results regarding the efficacy and safety of MDA for this purpose. In this review, we will also discuss the future of MDA protocols in downstaging for improved clinical outcomes.

Original Articles

Outcomes of liver resection and transarterial chemoembolization in patients with multinodular BCLC-A hepatocellular carcinoma: Jiwon Yang, Won-Mook Choi, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Deok-Bog Moon, Dong-Hwan Jung, Jonggi Choi; J Liver Cancer. 2024;24(2):178-191. Published online April 3, 2024; DOI: https://doi.org/10.17998/jlc.2024.03.25

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Abstract PDF Supplementary Material: Backgrounds/Aims
This study aimed to compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) in patients with multinodular hepatocellular carcinoma (HCC) within the Milan criteria who were not eligible for liver transplantation.
Methods
We retrospectively analyzed 483 patients with multinodular HCC within the Milan criteria, who underwent either LR or TACE as an initial therapy between 2013 and 2022. The overall survival (OS) in the entire population and recurrence-free survival (RFS) in patients who underwent LR and TACE and achieved a complete response were analyzed. Propensity score (PS) matching analysis was also used for a fair comparison of outcomes between the two groups.
Results
Among the 483 patients, 107 (22.2%) and 376 (77.8%) underwent LR and TACE, respectively. The median size of the largest tumor was 2.0 cm, and 72.3% of the patients had two HCC lesions. The median OS and RFS were significantly longer in the LR group than in the TACE group (P<0.01 for both). In the multivariate analysis, TACE (adjusted hazard ratio [aHR], 1.81 and aHR, 2.41) and large tumor size (aHR, 1.43 and aHR, 1.44) were significantly associated with worse OS and RFS, respectively. The PS-matched analysis also demonstrated that the LR group had significantly longer OS and RFS than the TACE group (PS<0.05).
Conclusions
In this study, LR showed better OS and RFS than TACE in patients with multinodular Barcelona Clinic Liver Cancer stage A HCC. Therefore, LR can be considered an effective treatment option for these patients.

Inter-reader agreement for CT/MRI LI-RADS category M imaging features: a systematic review and meta-analysis: Dong Hwan Kim, Sang Hyun Choi; J Liver Cancer. 2024;24(2):192-205. Published online April 15, 2024; DOI: https://doi.org/10.17998/jlc.2024.04.05

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Abstract PDF Supplementary Material

Backgrounds/Aims
To systematically evaluate inter-reader agreement in the assessment of individual liver imaging reporting and data system (LI-RADS) category M (LR-M) imaging features in computed tomography/magnetic resonance imaging (CT/MRI) LIRADS v2018, and to explore the causes of poor agreement in LR-M assignment.
Methods
Original studies reporting inter-reader agreement for LR-M features on multiphasic CT or MRI were identified using the MEDLINE, EMBASE, and Cochrane databases. The pooled kappa coefficient (κ) was calculated using the DerSimonian-Laird random-effects model. Heterogeneity was assessed using Cochran’s Q test and I² statistics. Subgroup meta-regression analyses were conducted to explore the study heterogeneity.
Results
In total, 24 eligible studies with 5,163 hepatic observations were included. The pooled κ values were 0.72 (95% confidence interval [CI], 0.65-0.78) for rim arterial phase hyperenhancement, 0.52 (95% CI, 0.39-0.65) for peripheral washout, 0.60 (95% CI, 0.50-0.70) for delayed central enhancement, 0.68 (95% CI, 0.57-0.78) for targetoid restriction, 0.74 (95% CI, 0.65-0.83) for targetoid transitional phase/hepatobiliary phase appearance, 0.64 (95% CI, 0.49-0.78) for infiltrative appearance, 0.49 (95% CI, 0.30-0.68) for marked diffusion restriction, and 0.61 (95% CI, 0.48-0.73) for necrosis or severe ischemia. Substantial study heterogeneity was observed for all LR-M features (Cochran’s Q test, P<0.01; I²≥89.2%). Studies with a mean observation size of <3 cm, those performed using 1.5-T MRI, and those with multiple image readers, were significantly associated with poor agreement of LR-M features.
Conclusions
The agreement for peripheral washout and marked diffusion restriction was limited. The LI-RADS should focus on improving the agreement of LR-M features.

Citations

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Inter-reader agreement for LR-M imaging features: a premise for better imaging-based diagnosis in liver imaging
Jaeseung Shin
Journal of Liver Cancer.2024; 24(2): 124. CrossRef

Re-assessing the diagnostic value of the enhancing capsule in hepatocellular carcinoma imaging: Jae Seok Bae, Jeong Min Lee, Bo Yun Hur, Jeongin Yoo, Sae-Jin Park; J Liver Cancer. 2024;24(2):206-216. Published online May 8, 2024; DOI: https://doi.org/10.17998/jlc.2024.05.01

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Abstract PDF Supplementary Material: Backgrounds/Aims
The enhancing capsule (EC) in hepatocellular carcinoma (HCC) diagnosis has received varying degrees of recognition across major guidelines. This study aimed to assess the diagnostic utility of EC in HCC detection.
Methods
We retrospectively analyzed patients who underwent pre-surgical computed tomography (CT) and hepatobiliary agent-enhanced magnetic resonance imaging (HBA-MRI) between January 2016 and December 2019. A single hepatic tumor was confirmed based on the pathology of each patient. Three radiologists independently reviewed the images according to the Liver Imaging Reporting and Data System (LI-RADS) v2018 criteria and reached a consensus. Interobserver agreement for EC before reaching a consensus was quantified using Fleiss κ statistics. The impact of EC on the LI-RADS classification was assessed by comparing the positive predictive values for HCC detection in the presence and absence of EC.
Results
In total, 237 patients (median age, 60 years; 184 men) with 237 observations were included. The interobserver agreement for EC detection was notably low for CT (κ=0.169) and HBA-MRI (κ=0.138). The presence of EC did not significantly alter the positive predictive value for HCC detection in LI-RADS category 5 observations on CT (94.1% [80/85] vs. 94.6% [88/93], P=0.886) or HBAMRI (95.7% [88/92] vs. 90.6% [77/85], P=0.178).
Conclusions
The diagnostic value of EC in HCC diagnosis remains questionable, given its poor interobserver agreement and negligible impact on positive predictive values for HCC detection. This study challenges the emphasis on EC in certain diagnostic guidelines and suggests the need to re-evaluate its role in HCC imaging.

Superselective ablative chemo-ethanol embolization for recurrent single hepatocellular carcinoma: a 6-month outcome analysis: Jae Hwan Lee, Kun Yung Kim, Chong-ho Lee, Minuk Kim, Chang Jin Yoon; J Liver Cancer. 2024;24(2):217-223. Published online May 14, 2024; DOI: https://doi.org/10.17998/jlc.2024.05.08

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Abstract PDF: Backgrounds/Aims
To evaluate the safety and effectiveness of superselective ablative chemo-ethanol embolization (SACE) for the treatment of patients with recurrent single hepatocellular carcinoma (rHCC).
Methods
This retrospective study included 22 patients (19 men; median age, 63 years [range, 38-86]) with Child-Pugh class of A/ B/C (16/3/3) that underwent SACE between January and June 2023 for recurrent single HCCs measuring ≤5 cm in diameter using a mixture of 99% ethanol and ethiodized oil/doxorubicin emulsion. The primary endpoint was the 6-month tumor response, and the secondary endpoints were the 1-month tumor response and treatment-related safety. This study was approved by our institutional review board, and the requirement for informed consent was waived.
Results
SACE was successfully performed in 22 patients (95.2%). The complete response rates at 1-month and 6-month after treatment were 100.0% and 83.3%, respectively. At 6-month, local tumor progression occurred in one patient and intrahepatic distant metastasis was found in six patients (30.0%). No 6-month mortalities were reported. No adverse events greater than grade 2 or laboratory deteriorations were observed. Biliary complications or liver abscesses were not observed.
Conclusions
SACE for a single rHCC was highly effective in achieving a favorable 6-month tumor response and showed acceptable adverse events. However, further prospective studies are required to verify these findings.

Downstaging with atezolizumab-bevacizumab: a case series: Anand V. Kulkarni, Parthasarathy Kumaraswamy, Balachandran Menon, Anuradha Sekaran, Anuhya Rambhatla, Sowmya Iyengar, Manasa Alla, Shantan Venishetty, Sumana Kolar Ramachandra, Giri V. Premkumar, Mithun Sharma, P. Nagaraja Rao, Duvvur Nageshwar Reddy, Amit G. Singal; J Liver Cancer. 2024;24(2):224-233. Published online May 27, 2024; DOI: https://doi.org/10.17998/jlc.2024.05.12

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190 Downloads
2 Citations

Abstract PDF Supplementary Material

Backgrounds/Aims
Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezo-bev remains unknown.
Methods
In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging.
Results
Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age, 58.5 years; women, 17%; Barcelona Clinic Liver Cancer stage system B/C, 5/7) had received 3-12 cycles of atezo- bev, and four of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 days (range, 54-114) following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 months (range, 4-30), none of the alive patients developed HCC recurrence or graft rejection.
Conclusions
Surgical therapy, including LT, is possible after atezo-bev therapy in well-selected patients after downstaging.

Citations

Citations to this article as recorded by

Immunotherapy Prior to a Liver Transplant: Literature Review and a Case Report of Hepatocellular Carcinoma With BRCA1 Mutation
N. E. Kostrygin, D. S. Chumachenko
Innovative Medicine of Kuban.2024; (3): 61. CrossRef
Combining liver-directed and immunotherapy in advanced hepatocellular carcinoma: A review and future directions
Pranav Kumar, Chase J. Wehrle, Keyue Sun, Chunbao Jiao, Rebecca Panconesi, Mingyi Zhang, Noah X. Tocci, Hanna Hong, Abby Gross, Erlind Allkushi, Maureen Whitsett Linganna, Andrea Schlegel, Toms Augustin, Charles Miller, David CH Kwon, Kazunari Sasaki, Fed
Surgical Oncology Insight.2024; 1(4): 100100. CrossRef

Cure can be achieved by conversion to microwave ablation following atezolizumab-bevacizumab therapy in unresectable hepatocellular carcinoma: Rene John D. Febro, Engelbert Simon S. Perillo, Akemi A. Kimura, Stephen N. Wong; J Liver Cancer. 2024;24(2):234-242. Published online June 3, 2024; DOI: https://doi.org/10.17998/jlc.2024.05.23

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108 Downloads

Abstract PDF: Backgrounds/Aims
Atezolizumab/bevacizumab is the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC) and may facilitate curative conversion through resection and locoregional therapies. However, there have been very few reports on curative conversion using microwave ablation (MWA). This study aimed to determine the curative conversion rate with MWA using atezolizumab-bevacizumab as the first-line treatment in patients with uHCC, and to compare the characteristics and survival of patients with and without curative conversion.
Methods
Consecutive patients with uHCC who were started on atezolizumab-bevacizumab from May 2021 to December 2023 in a single tertiary center were included. Objective response rate (ORR) and disease control rate (DCR) were based on the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria.
Results
Twenty consecutive patients with uHCC (60% advanced-stage) were included, 90% exceeding the up-to-7 criteria. The ORR and DCR were 35% and 60%, 35% and 55% using RECIST and mRECIST, respectively. Five patients (25%) underwent successful curative conversion with MWA (four advanced and one intermediate stage) despite a median HCC size of 6.1 cm (range, 2.4-7.3). Two of these patients were tumor and drug-free 132-133 weeks from the 1st atezolizumab-bevacizumab dose. Patients who underwent curative conversion had significantly longer survival than those who did not (P=0.024). Other factors associated with survival were male sex, Child-Pugh class A, and an objective response.
Conclusions
Despite the relatively large tumor size, successful curative conversion with MWA was achieved with first-line atezolizumab-bevacizumab in uHCC. However, data from prospective multicenter trials are required to determine whether this strategy is universally applicable.

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