Journal of Liver Cancer

Review Articles

A clinical and pathological update on hepatocellular carcinoma: Salvatore Lorenzo Renne, Luca Di Tommaso; J Liver Cancer. 2022;22(1):14-22. Published online March 31, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.18

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It is estimated that more than 1 million individuals will be affected annually by hepatocellular carcinoma (HCC) by 2025. HCC can be broadly grouped into two major molecular subgroups, each of which is characterized by specific morphological and phenotypic features that mirror the genetic background. The use of these tissue biomarkers in the daily practice of pathologists promises to better allocate patients with HCC with adequate treatments. In turn, this will likely boost the attitude of clinicians toward obtaining a pre-treatment biopsy.

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Identification of gallbladder cancer by direct near-infrared measurement of raw bile combined with two-trace two-dimensional correlation analysis
Eunjin Jang, Woosuk Sohng, Dongho Choi, Hoeil Chung
The Analyst.2023; 148(2): 374. CrossRef
Measurement of Heavy Metal and Antioxidant-Oxidant Levels in Tissues Obtained From Three Different Localizations of Explant Hepatectomy of Patients With Hepatocellular Carcinoma
Cemalettin Koc, Sami Akbulut, Kemal Baris Sarici, Muhammed Mehdi Uremis, Ufuk Gunay Dogan, Zeynep Kucukakcali, Ibrahim Umar Garzali, Ertugrul Karabulut, Yusuf Turkoz, Sezai Yilmaz
Transplantation Proceedings.2023;[Epub] CrossRef

Combination of interventional oncology local therapies and immunotherapy for the treatment of hepatocellular carcinoma: Dong-Hyun Kim; J Liver Cancer. 2022;22(2):93-102. Published online April 22, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.28

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Abstract PDF: Interventional oncology (IO) local therapies of hepatocellular carcinoma (HCC) can activate anti-cancer immunity and it is potentially leading to an anti-cancer immunity throughout the body. For the development of an effective HCC treatment regime, great emphasis has been dedicated to different IO local therapy mediated immune modulation and possible combinations with immune checkpoint inhibitor immunotherapy. In this review paper, we summarize the status of combination of IO local therapy and immunotherapy, as well as the prospective role of therapeutic carriers and locally administered immunotherapy in advanced HCC.

Case Report

Multidisciplinary treatment with immune checkpoint inhibitors for advanced stage hepatocellular carcinoma: Ahlim Lee, Jaejun Lee, Hyun Yang, Soo-Yoon Sung, Chang Ho Jeon, Su Ho Kim, Moon Hyung Choi, Young Joon Lee, Ho Jong Chun, Si Hyun Bae; J Liver Cancer. 2022;22(1):75-83. Published online March 18, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.04

1,782 Views
55 Downloads
1 Citation

Abstract PDF

Hepatocellular carcinoma (HCC) is a cytotoxic chemotherapy-resistant tumor and most HCCs arise in a background of liver cirrhosis of various causes. Although the IMBrave150 trial showed remarkable advancements in the treatment of unresectable HCC with atezolizumab plus bevacizumab (AteBeva), therapeutic outcomes were unsatisfactory in more than half of the patients. Accordingly, many ongoing trials combine conventional modalities with new drugs such as immune checkpoint inhibitors for better treatment outcomes, and they are expected to benefit patients with limited responses to conventional treatment. Here, two patients with advanced stage HCC with preserved liver function and good performance status showed partial response after treatment with combination or sequential therapy of AteBeva, hepatic arterial infusion chemotherapy, radiation therapy, and transarterial chemoembolization. These findings indicate the efficacy of multidisciplinary treatment against advanced HCC. Additional studies are required to establish optimal treatment strategies.

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Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus?
Won Hyeok Choe
Journal of Liver Cancer.2022; 22(1): 1. CrossRef

Review Article

Radioembolization for hepatocellular carcinoma: what clinicians need to know: Jin Woo Choi, Hyo-Cheol Kim; J Liver Cancer. 2022;22(1):4-13. Published online February 23, 2022; DOI: https://doi.org/10.17998/jlc.2022.01.16

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136 Downloads

Abstract PDF: Transarterial radioembolization (TARE) with yttrium 90 (⁹⁰Y) has been used in the management of hepatocellular carcinoma (HCC) for more than 10 years in Korea. There are two types of ⁹⁰Y radioactive microspheres available, namely, glass and resin microspheres, with comparable clinical outcomes. In general, TARE outperforms transarterial chemoembolization regarding post-embolization syndrome, time to progression, tumor downsizing for liver transplantation, and hospitalization stay. Although TARE is commonly recommended for patients with unresectable large HCCs, it can be an alternative to or performed in combination with ablation, surgical resection, and systemic treatment. This review aimed to address ⁹⁰Y radioactive microspheres, patient selection, clinical outcomes, simulation tests, radioembolization procedures, follow-up imaging, and complications.

Original Article

Diagnostic performance of serum exosomal miRNA-720 in hepatocellular carcinoma: Jeong Won Jang, Ji Min Kim, Hye Seon Kim, Jin Seoub Kim, Ji Won Han, Soon Kyu Lee, Heechul Nam, Pil Soo Sung, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon; J Liver Cancer. 2022;22(1):30-39. Published online March 21, 2022; DOI: https://doi.org/10.17998/jlc.2022.02.25

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87 Downloads

Abstract PDF Supplementary Material: Background
/Aim: Hepatocellular carcinoma (HCC) is associated with poor prognosis, largely due to late detection. Highly accurate biomarkers are urgently needed to detect early-stage HCC. Our study aims to explore the diagnostic performance of serum exosomal microRNA (miR)-720 in HCC.
Methods
Exosomal miRNA was measured via quantitative real-time PCR. A correlation analysis of exosomal miR-720 and tumor or clinico-demographic data of patients with HCC was performed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic capacity of serum exosomal miR-720 for HCC, in comparison with α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II).
Results
MiR-720 was chosen as a potential HCC marker via miR microarray based on significant differential expression between tumor and non-tumor samples. Serum exosomal miR-720 was significantly upregulated in patients with HCC (n=114) versus other liver diseases (control, n=30), with a higher area under the ROC curve (AUC=0.931) than the other markers. Particularly, serum exosomal miR-720 showed superior performance in diagnosing small HCC (< 5 cm; AUC=0.930) compared with AFP (AUC=0.802) or PIVKA-II (AUC=0.718). Exosomal miR-720 levels showed marginal correlation with tumor size. The proportion of elevated miR-720 also increased with intrahepatic tumor stage progression. Unlike AFP or PIVKA-II showing a significant correlation with aminotransferase levels, the exosomal miR-720 level was not affected by aminotransferase levels.
Conclusions
Serum exosomal miR-720 is an excellent biomarker for the diagnosis of HCC, with better performance than AFP or PIVKA-II. Its diagnostic utility is maintained even in small HCC and is unaffected by aminotransferase levels.

Review Article

Recent updates on the classification of hepatoblastoma according to the International Pediatric Liver Tumors Consensus: Se Un Jeong, Hyo Jeong Kang; J Liver Cancer. 2022;22(1):23-29. Published online March 17, 2022; DOI: https://doi.org/10.17998/jlc.2022.02.24

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160 Downloads

Abstract PDF: Hepatoblastoma is the most common pediatric liver malignancy and usually occurs within the first 3 years of life. In recent years, the overall incidence of hepatoblastoma has exhibited the greatest increase among all pediatric malignancies worldwide. The diagnosis of hepatoblastoma may be challenging due to the lack of a current consensus classification system. The International Pediatric Liver Tumors Consensus introduced guidelines and a consensus classification for the diagnosis of hepatoblastoma as either epithelial or mixed epithelial and mesenchymal and in the updated 5^th edition of the World Health Organization Classification of Digestive System Tumors.

Original Article

Hepatocellular Carcinoma in Korea: an Analysis of the 2015 Korean Nationwide Cancer Registry: Jun Sik Yoon, Han Ah Lee, Hwi Young Kim, Dong Hyun Sinn, Dong Ho Lee, Suk Kyun Hong, Ju-Yeon Cho, Jonggi Choi, Young Chang, Hyun-Joo Kong, Eunyang Kim, Young-Joo Won, Jeong-Hoon Lee; J Liver Cancer. 2021;21(1):58-68. Published online March 31, 2021; DOI: https://doi.org/10.17998/jlc.21.1.58; Retraction in: J Liver Cancer 2022;22(2):207

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9 Citations

Abstract PDF Supplementary Material

Background
/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related death in Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2015.
Methods
Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative sample of patients newly diagnosed with HCC in Korea, were analyzed. A total of 1,558 patients with HCC registered in the KPLCR in 2015 were investigated.
Results
The median age was 61.0 years (interquartile range, 54.0-70.0 years), and men accounted for 79.7% of the subjects. Hepatitis B virus infection was the most common underlying liver disease (58.1%). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, stage 0, A, B, C, and D HCCs accounted for 14.2%, 31.5%, 7.6%, 39.0%, and 7.8% of patients, respectively. Transarterial therapy (32.1%) was the most commonly performed initial treatment, followed by surgical resection (23.2%), best supportive care (20.2%), and local ablation therapy (10.7%). Overall, 34.5% of patients were treated in accordance with the BCLC guidelines: 59.2% in stage 0/A, 48.4% in stage B, 18.1% in stage C, and 71.6% in stage D. The 1-, 3-, and 5-year OS rates were 67.1%, 50.9%, and 27.0%, respectively.
Conclusions
In 2015, approximately 45% of Korean HCC cases were diagnosed at a very early or early stage, and 35% of patients underwent potentially curative initial treatment. BCLC guidance was followed in 34.5% of patients; in patients with stage B or C disease, there was relatively low adherence.

Citations

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Surgical resection versus ablation for early hepatocellular carcinoma: The debate is still open
Bo Hyun Kim
Clinical and Molecular Hepatology.2022; 28(2): 174. CrossRef
Cause of death and cause-specific mortality for primary liver cancer in South Korea: A nationwide population-based study in hepatitis B virus-endemic area
Bo Hyun Kim, Dahhay Lee, Kyu-Won Jung, Young-Joo Won, Hyunsoon Cho
Clinical and Molecular Hepatology.2022; 28(2): 242. CrossRef
Impact of tumor size on hepatectomy outcomes in hepatocellular carcinoma: a nationwide propensity score matching analysis
Suk Kyun Hong, Kwang-Woong Lee, Sola Lee, Su young Hong, Sanggyun Suh, Eui Soo Han, YoungRok Choi, Nam-Joon Yi, Kyung-Suk Suh
Annals of Surgical Treatment and Research.2022; 102(4): 193. CrossRef
Efficacy and feasibility of surgery and external radiotherapy for hepatocellular carcinoma with portal invasion: A meta-analysis
Han Ah Lee, Yeon Seok Seo, In-Soo Shin, Won Sup Yoon, Hye Yoon Lee, Chai Hong Rim
International Journal of Surgery.2022; 104: 106753. CrossRef
Yoon et al. Hepatocellular Carcinoma in Korea: an Analysis of the 2015 Korean Nationwide Cancer Registry
Jeong-Hoon Lee
Journal of Liver Cancer.2022; 22(2): 207. CrossRef
Surveillance for hepatocellular carcinoma: It is time to move forward
Bo Hyun Kim, Yuri Cho, Joong-Won Park
Clinical and Molecular Hepatology.2022; 28(4): 810. CrossRef
Treatment patterns for hepatocellular carcinoma in patients with Child–Pugh class B and their impact on survival: A Korean nationwide registry study
Dongsub Jeon, Gi‐Won Song, Han Chu Lee, Ju Hyun Shim
Liver International.2022; 42(12): 2830. CrossRef
Metastatic breast cancer from a hepatocellular carcinoma: a case report
Hyewon Bang, Nam-Hee Kim, Seung Hye Choi, Si Hyun Bae, Eun Sun Jung, Ki Ouk Min, Yong Hwa Eom
Korean Journal of Clinical Oncology.2022; 18(2): 93. CrossRef
Current Status and Future Directions of Hepatocellular Carcinoma Surveillance Test Based on Cost-effective Analysis
Jihyun An
The Korean Journal of Gastroenterology.2021; 78(5): 255. CrossRef

Case Report

A Case of Metastatic Melanoma in the Liver Mimicking Hepatocellular Carcinoma: Jae-Kyoung So, Ji-Yun Hong, Min-Woo Chung, Sung-Bum Cho; J Liver Cancer. 2021;21(1):92-96. Published online March 31, 2021; DOI: https://doi.org/10.17998/jlc.21.1.92

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230 Downloads

Abstract PDF: The liver is one of the most common sites of metastasis. Although most metastatic liver cancers are hypovascular, some hypervascular metastases, such as those from melanoma, need to be differentiated from hepatocellular carcinoma (HCC) because they may show similar radiologic findings due to their hypervascularity. We encountered a case of multinodular liver masses with hyperenhancement during the arterial phase and washout during the portal venous and delayed phases, which were consistent with imaging hallmarks of HCC. The patient had a history of malignant melanoma and had undergone curative resection 11 years earlier. We performed a liver biopsy for pathologic confirmation, which revealed a metastatic melanoma of the liver. Metastatic liver cancer should be considered if a patient without chronic liver disease has a history of other primary malignancies, and caution should be exercised with hypervascular cancers that may mimic HCC.

Editorial

Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus?: Won Hyeok Choe; J Liver Cancer. 2022;22(1):1-3. Published online March 31, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.15

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PDF

Review Articles

Liquid biopsy for early detection and therapeutic monitoring of hepatocellular carcinoma: Eun-Ji Choi, Young-Joon Kim; J Liver Cancer. 2022;22(2):103-114. Published online September 22, 2022; DOI: https://doi.org/10.17998/jlc.2022.09.08

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Abstract PDF Supplementary Material: Advances in our knowledge of the molecular characteristics of hepatocellular carcinoma (HCC) have enabled significant progress in the detection and therapeutic prediction of HCC. As a non-invasive alternative to tissue biopsy, liquid biopsy examines circulating cellular components such as exosomes, nucleic acids, and cell-free DNA found in body fluids (e.g., urine, saliva, ascites, and pleural effusions) and provides information about tumor characteristics. Technical advances in liquid biopsy have led to the increasing adoption of diagnostic and monitoring applications for HCC. This review summarizes the various analytes, ongoing clinical trials, and case studies of United States Food and Drug Administrationapproved in vitro diagnostic applications for liquid biopsy, and provides insight into its implementation in managing HCC.

Update on Pathologic and Radiologic Diagnosis of Combined Hepatocellular-Cholangiocarcinoma: Hyungjin Rhee, Jae Hyon Park, Young Nyun Park; J Liver Cancer. 2021;21(1):12-24. Published online March 31, 2021; DOI: https://doi.org/10.17998/jlc.21.1.12

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201 Downloads
1 Citation

Abstract PDF

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a malignant primary liver carcinoma characterized by the unequivocal presence of both hepatocytic and cholangiocytic differentiation within the same tumor. Recent research has highlighted that cHCC-CCAs are more heterogeneous than previously expected. In the updated consensus terminology and WHO 2019 classification, “classical type” and “subtypes with stem-cell features” of the WHO 2010 classification are no longer recommended. Instead, it is recommended that the presence and percentages of various histopathologic components and stem-cell features be mentioned in the pathologic report. The new terminology and classification enable the exchange of clearer and more objective information about cHCC-CCAs, facilitating multi-center and multinational research. However, there are limitations to the diagnosis of cHCC-CCA by imaging and biopsy. cHCC-CCAs showing typical imaging findings of HCC could be misdiagnosed as HCC and subjected to inappropriate treatment, if other clinical findings are not sufficiently considered. cHCC-CCAs showing at least one of the CCA-like imaging features or unusual clinical features should be subjected to biopsy. There may be a sampling error for the biopsy diagnosis of cHCC-CCA. An optimized diagnostic algorithm integrating clinical, radiological, and histopathologic information of biopsy is required to resolve these diagnostic pitfalls.

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The Human TOR Signaling Regulator Is the Key Indicator of Liver Cancer Patients’ Overall Survival: TIPRL/LC3/CD133/CD44 as Potential Biomarkers for Early Liver Cancers
Soo Young Jun, Hyang Ran Yoon, Ji-Yong Yoon, Su-Jin Jeon, Jeong-Ju Lee, Debasish Halder, Jin-Man Kim, Nam-Soon Kim
Cancers.2021; 13(12): 2925. CrossRef

Original Article

Stereotactic body radiation therapy for elderly patients with small hepatocellular carcinoma: a retrospective observational study: Jeong Yun Jang, Jinhong Jung, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Jin-hong Park, Sang Min Yoon; J Liver Cancer. 2022;22(2):136-145. Published online September 16, 2022; DOI: https://doi.org/10.17998/jlc.2022.08.18

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Abstract PDF Supplementary Material: Background
/Aim: We aimed to investigate the efficacy and safety of stereotactic body radiation therapy (SBRT) in elderly patients with small hepatocellular carcinomas (HCC).
Methods
Eighty-three patients (89 lesions) with HCC who underwent SBRT between January 2012 and December 2018 were reviewed in this retrospective observational study. The key inclusion criteria were as follows: 1) age ≥75 years, 2) contraindications for hepatic resection or percutaneous ablative therapies, 3) no macroscopic vascular invasion, and 4) no extrahepatic metastasis.
Results
The patients were 75-90 years of age, and 49 (59.0%) of them were male. Most patients (94.0%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Seventy-four patients (89.2%) had Child-Pugh class A hepatic function before SBRT. The median tumor size was 1.6 cm (range, 0.7-3.5). The overall median follow-up period was 34.8 months (range, 7.3-99.3). The 5-year local tumor control rate was 90.1%. The 3-year and 5-year overall survival rate was 57.1% and 40.7%, respectively. Acute toxicity grade ≥3 was observed in three patients (3.6%) with elevated serum hepatic enzymes; however, no patient experienced a worsening of the Child-Pugh score to ≥2 after SBRT. None of the patients developed late toxicity (grade ≥3).
Conclusions
SBRT is a safe treatment option with a high local control rate in elderly patients with small HCC who are not eligible for other curative treatments.

Review Article

Liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis: Sang Jin Kim, Jong Man Kim; J Liver Cancer. 2021;21(2):105-112. Published online September 2, 2021; DOI: https://doi.org/10.17998/jlc.2021.03.17

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140 Downloads
1 Citation

Abstract PDF

Traditionally, liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis is not recommended. However, with recent developments in locoregional therapies for hepatocellular carcinoma, more aggressive treatments have been attempted for advanced hepatocellular carcinoma. Recently, various studies on locoregional therapies for downstaging followed by living donor liver transplantation reported inspiring overall survival and recurrence-free survival of patients. These downstaging procedures included three-dimensional conformal radiation therapy, trans-arterial chemoembolization, stereotactic body radiation therapy, trans-arterial radioembolization, hepatic arterial infusion chemotherapy and combinations of these therapies. Selection of the optimal downstaging protocol should depend on tumor location, biology and background liver status. The risk factors affecting outcome include pre-downstaging alpha-fetoprotein values, delta alpha-fetoprotein values, disappearance of portal vein tumor thrombosis on imaging and meeting the Milan criteria or not after downstaging. For hepatocellular carcinoma with portal vein tumor thrombosis, downstaging procedure with liver transplantation in mind would be helpful. If the reaction of the downstaged tumor is good, liver transplantation may be performed.

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Prediction models of hepatocellular carcinoma recurrence after liver transplantation: A comprehensive review
Sang Jin Kim, Jong Man Kim
Clinical and Molecular Hepatology.2022; 28(4): 739. CrossRef

Case Report

Concurrent transarterial radioembolization and combination atezolizumab/ bevacizumab treatment of infiltrative hepatocellular carcinoma with portal vein tumor thrombosis: a case report: Min Kyung Park, Su Jong Yu; J Liver Cancer. 2022;22(1):69-74. Published online March 21, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.09

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52 Downloads
1 Citation

Abstract PDF

Treatment options for advanced hepatocellular carcinoma (HCC) have been rapidly evolving. Herein, we describe a patient with advanced HCC and portal vein tumor thrombosis (PVTT) who responded decisively to a multidisciplinary approach. The patient had an ill-defined infiltrative HCC (diffuse subtype), with several intrahepatic metastasis and tumor invasion of left portal vein. Concurrent use of transarterial radioembolization (TARE) and systemic therapeutics (atezolizumab + bevacizumab) ultimately proved successful. There was marked reduction in tumor volume after TARE and an additional three cycles of atezolizumab plus bevacizumab. This concurrent treatment was well tolerated, without adverse events during immunotherapy. The impressive results achieved suggest that concurrent TARE and combination atezolizumab/bevacizumab is a promising treatment approach for advanced HCC with PVTT.

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Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus?
Won Hyeok Choe
Journal of Liver Cancer.2022; 22(1): 1. CrossRef

Review Article

Advances in immune checkpoint inhibitors for hepatocellular carcinoma: Ji Won Han, Su-Hyung Park; J Liver Cancer. 2021;21(2):139-145. Published online September 30, 2021; DOI: https://doi.org/10.17998/jlc.2021.09.24

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73 Downloads

Abstract PDF: Hepatocellular carcinoma (HCC) is the fifth most common cancer, and the second leading cause of cancer-related death worldwide. Although recent advances in immune checkpoint inhibitor-based immunotherapy have initiated a new era for advanced HCC treatment, the majority of HCC patients receiving immune checkpoint blockades do not derive clinical benefit. Thus, there remains an urgent need for novel immunotherapeutic strategies with improved therapeutic efficacy. Here we review recent studies of immune checkpoint blockade in HCC, providing the necessary basis for the rational design of immunotherapy.

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