Journal of Liver Cancer

Review Article

Combined hepatocellular-cholangiocarcinoma: a contemporary pathologic and molecular perspective: Taek Chung; J Liver Cancer. 2026;26(1):1-8. Published online March 9, 2026; DOI: https://doi.org/10.17998/jlc.2026.03.06

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Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare primary liver carcinoma characterized by the unequivocal coexistence of hepatocytic and cholangiocytic differentiation within a single tumor. Despite its low incidence, cHCC-CCA has received considerable attention because of its marked histologic heterogeneity, diagnostic challenges, and poorer clinical outcomes than conventional hepatocellular carcinoma. Historically, the biological nature of cHCC-CCA has been controversial, with competing hypotheses, including derivation from hepatic progenitor cells, collision of independent tumors, and transdifferentiation between hepatocytic and biliary lineages. Recent advances in genomic and transcriptomic profiling have substantially improved this understanding. Accumulating evidence indicates that most cHCC-CCAs arise from a common clonal origin and subsequently undergo divergent differentiation rather than representing true collision tumors. Transcriptomic analyses further demonstrate that cHCC-CCAs span a biological continuum between hepatocellular- and cholangiocytic-like states, with intermediate tumors characterized by lineage plasticity, activation of developmental pathways, and heterogeneous tumor microenvironments. This review provides a pathology- centered overview of cHCC-CCAs, summarizing the key histopathological features and the supportive role of immunohistochemistry, followed by an integrated discussion of recent genomic, transcriptomic, and immune profiling studies. Additionally, it highlights emerging applications of artificial intelligence and digital pathology, which may assist in biological stratification. Collectively, the current evidence supports viewing cHCC-CCA not as a single static entity, but as a spectrum of primary liver carcinomas unified by lineage plasticity, underscoring the importance of integrated pathological and multi-omics approaches for future classification and research.

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Curative Effect Evaluation of Targeted Therapy and Chemotherapy for Non-Resectable Combined Hepatocellular-Cholangiocarcinoma: A Systematic Review and Meta-Analysis
永豪林
Advances in Clinical Medicine.2026; 16(05): 920. CrossRef

Original Article

Systematic review of metabolomic profiles linked to liver cancer: Bao Le Thai Tran, Ngoc Hong Cao, Tung Hoang; J Liver Cancer. 2026;26(1):124-146. Published online December 2, 2025; DOI: https://doi.org/10.17998/jlc.2025.10.27

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61 Downloads

Abstract PDF Supplementary Material: Backgrounds/Aims
Increasing evidence indicates that metabolites play a significant role in the pathogenesis of liver cancer and have potential as biomarkers for early detection. This review summarizes the current literature on the utility of metabolomic profiling as a screening strategy for early diagnosis of liver cancer.
Methods
We searched PubMed, Embase, and Web of Science for studies published between 2004 and 2024 that examined metabolite alterations in liver cancer. The metabolites differentially expressed in liver cancer versus healthy controls, cirrhosis, and hepatic B virus cases are summarized. The diagnostic performance of the metabolite-based models was also evaluated, highlighting their potential as early detection biomarkers for liver cancer.
Results
A total of 96 studies were included in this review, encompassing case-only, case-control, nested case-control, and cohort designs. The analysis identified taurine and taurochenodeoxycholic acid to be consistently associated with an increased risk of liver cancer, supported by findings from both the discovery and validation cohorts. Notably, a diagnostic model incorporating 10 metabolites including taurine and taurochenodeoxycholic acid, achieved an area under the receiver operating characteristic curve of 0.86 (95% confidence interval, 0.82-0.88), indicating strong discriminatory power for early liver cancer detection. Nevertheless, heterogeneity across studies was observed, largely owing to differences in biological sample types and metabolomic platforms.
Conclusions
This review highlights the significant roles of taurine and taurochenodeoxycholic acid in liver cancer development. Future research should prioritize the standardization of analytical methodologies, increased sample sizes, and integration of metabolomics with other omics layers to enhance our understanding of liver cancer biology and improve biomarker accuracy and clinical utility.

Review Articles

Preventing false positive imaging diagnosis of HCC: differentiating HCC from mimickers and practical strategies: Ijin Joo; J Liver Cancer. 2025;25(2):217-232. Published online July 31, 2025; DOI: https://doi.org/10.17998/jlc.2025.07.29

8,781 Views
132 Downloads
4 Citations

Abstract PDF

Noninvasive imaging-based diagnosis of hepatocellular carcinoma (HCC) in high-risk patients plays a central role in clinical practice. Current major guidelines typically rely on the radiologic hallmark of nonrim arterial phase hyperenhancement followed by nonperipheral washout, criteria designed to achieve both high positive predictive value and sufficient specificity when applied within well-defined target populations. Despite these criteria, false positive diagnoses still occur and can lead to unnecessary or inappropriate treatment, as various benign and non-HCC malignant lesions may exhibit vascular features that overlap with the classic appearance of HCC. Furthermore, treatment decisions are occasionally guided by imaging findings even in patients outside the target population who are being evaluated for possible HCC, in whom vascular patterns are less specific and the risk of false positive diagnosis is inherently higher. Minimizing the risk of false positive diagnosis requires not only adherence to validated imaging criteria but also clinical and contextual integration when findings are uncertain. This includes consideration of ancillary features, tumor markers, and, when appropriate, further evaluation through biopsy, additional imaging, or follow-up. This review outlines a range of HCC mimickers and provides practical strategies to support accurate imaging interpretation and reduce false positive diagnoses in clinical practice.

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“WBC-HBP Dissociation” Unveils Occult Xanthogranulomatous Inflammation Mimicking Hepatocellular Carcinoma in Diabetic Patients
Xuan-Yi Zhu, Kai-Chi Liu, Ze-Bin Zhu, Shu-Geng Zhang
Journal of Hepatocellular Carcinoma.2026; Volume 13: 1. CrossRef
Gadoxetate-enhanced MRI Transitional Phase Parenchymal Signal: Effect on Washout and LI-RADS Diagnostic Performance for Hepatocellular Carcinoma
Seong Hyeon Cho, Yong Jun Jung, Seung Baek Hong, Se Jin Choi, Seung Soo Lee, Jae Ho Byun, Hyung Jin Won, Yong Moon Shin, Subin Heo, Sang Hyun Choi
Radiology.2026;[Epub] CrossRef
Imaging differentiation of hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma: pitfalls and advances
Jaeseung Shin, Taek Chung, Sang Yun Ha, Hyungjin Rhee
Journal of Liver Cancer.2026; 26(1): 9. CrossRef
Advances in the Management of Hepatocellular Carcinoma: Evolving Systemic Therapy, Perioperative Strategies, and Care for Special Populations
Jing He, Xiao-Qin Wu, Zhen-Guang Wang
Journal of Clinical Question.2026; 3(2): e114. CrossRef

Public health strategies for hepatocellular carcinoma: from risk factors to prevention and control: Mei-Hsuan Lee; J Liver Cancer. 2025;25(2):204-216. Published online July 28, 2025; DOI: https://doi.org/10.17998/jlc.2025.07.25

7,627 Views
186 Downloads
13 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) remains a major global health burden, ranking as one of the leading causes of cancer-related deaths worldwide. This review synthesizes current evidence on HCC epidemiology, highlighting both modifiable and non-modifiable risk factors, including chronic hepatitis B and C virus infections, metabolic dysfunction-associated steatotic liver disease (MASLD), excessive alcohol consumption, aflatoxin exposure, and genetic susceptibility. These diverse etiologies reflect not only biological mechanisms but also broader social and environmental determinants of health, emphasizing the need for integrated, population-level preventive strategies. Effective strategies across all levels of prevention are reviewed. Primordial and primary prevention strategies include public health policies, health education to raise awareness, universal hepatitis B vaccination, expanded access to antiviral therapies for hepatitis B virus (HBV) and hepatitis C virus (HCV), lifestyle interventions targeting obesity and alcohol use, and environmental controls to reduce aflatoxin exposure. Secondary prevention focuses on early detection through viral hepatitis screening and routine HCC surveillance in high-risk populations. Tertiary prevention aims to reduce morbidity and mortality through timely treatment and multidisciplinary care. Despite the availability of effective tools, substantial implementation gaps remain persist. Underdiagnosis of viral hepatitis, low treatment uptake, inadequate surveillance coverage, and disparities in healthcare access continue to limit progress. Addressing these challenges requires a coordinated public health response grounded in health system strengthening, policy innovation, and equitable access to care. A renewed public health commitment -integrating prevention, early diagnosis, and continuity of care- is essential to reduce the global burden of HCC and bridge the gap between knowledge and action.

Citations

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Epidemiological trends and age–period–cohort analysis of alcoholic liver cancer from 1990 to 2021
Jiajia Chen, Runhua Li, Xiaojie Li, Kai Shi, Rui Zeng, Kunpeng Hu, Qingliang Wang
Hepatology International.2026; 20(2): 330. CrossRef
Multi-omics analysis of key lipid metabolism-related genes involved in the anti-hepatocellular carcinoma effect of dihydroartemisinin
Jiaqi Guo, Li Li, Yicheng Chen, Junxia Gao, Yonghui Xie, Qiang Li, Zhiqin Zhang
Discover Oncology.2026;[Epub] CrossRef
Advances in understanding of role of class III semaphorins in promoting malignant transformation of chronic liver diseases
Xiao-Xiao Xia, Hao Tang, Min Xu, Wen-Li Sai, Min Yao, Deng-Fu Yao
World Chinese Journal of Digestology.2026; 34(1): 1. CrossRef
Trends in incidence rates of hepatocellular carcinoma and stage at diagnosis by demographics in the U.S. from 2004 to 2021: a joinpoint analysis of the SEER database
Seunghee Han, Boniface Mensah, Greeshma Gaddipati, Simardeep Singh, Ramya Varesiddy, Maria Malak Bilalaga, Joseph Atarere, Haider Naqvi, Christopher Haas
Scandinavian Journal of Gastroenterology.2026; 61(5): 561. CrossRef
Impact of gastrectomy on the risk of alcohol-associated liver disease in patients with gastric cancer
Sang Yi Moon, Yang Hyun Baek, Dongwoo Kang, Jungkuk Lee, Yeo Wool Kang, Minkook Son, Hongqun Liu, Samuel S. Lee, Junho Park
Scientific Reports.2026;[Epub] CrossRef
PNPLA3 I148M is unrelated to HCC occurrence but associates with poorer tumor differentiation in Korean MASLD: a prospective cohort of 562 patients
Jaejun Lee, Dong Yeop Lee, Jung Hoon Cha, Hee Sun Cho, Keungmo Yang, Hyun Yang, Mi Young Byun, Seok Keun Cho, Seong Wook Yang, Si Hyun Bae, Pil Soo Sung
Journal of Liver Cancer.2026; 26(1): 147. CrossRef
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Aryoung Kim, Danbee Kang, Sung Chul Choi, Dong Hyun Sinn, Hye Ryoun Jang, Geum-Youn Gwak
The Journal of nutrition, health and aging.2026; 30(5): 100827. CrossRef
Alcohol-related hepatocellular carcinoma: surveillance and primary prevention
Gianni Testino
Journal of Liver Cancer.2026; 26(1): 176. CrossRef
Hepatocellular carcinoma: current aspects of multidisciplinary management. Part 2. Treatment and prevention
Yu.M. Stepanov, N.Yu. Zavhorodnia, O.M. Vlasova
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Liandong Chen, Weibo Zheng, Haojie Ying, Xinyue Chen, Han Yan, Binzhe Zhou, Yuyuan Sun, Qihui Shao, Hanyu Xu, Bowen Jin, Haonan Jin, Bin Fu
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Clinical Setting Modulates the Association Between Genetic Variants and Fibrosis Severity Across the Spectrum of MASLD
Mei‐Hsuan Lee, Maria Stepanova, Michael Estep, Yan‐Ling You, Xia‐Rong Liu, Leyla de Avila, Brian Lam, Ming‐Lung Yu, Zobair M. Younossi
Liver International.2026;[Epub] CrossRef
Investigation of the Abnormal Expression, Clinical Significance, and Molecular Biological Mechanisms of Apolipoprotein L4 in Hepatocellular Carcinoma
熙磊张
Advances in Clinical Medicine.2026; 16(06): 2074. CrossRef
Aspirin Use and Risk of HCC and Gastrointestinal Bleeding in Patients With HBV‐Related Cirrhosis: A Landmark Analysis
Mi Na Kim, Geun U. Park, Seng Chan You, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn
Journal of Gastroenterology and Hepatology.2025; 40(11): 2750. CrossRef

Insights into hepatocellular adenomas in Asia: molecular subtypes, clinical characteristics, imaging features, and hepatocellular carcinoma risks: Subin Heo, In Hye Song, Edouard Reizine, Maxime Ronot, Jean-Charles Nault, Hae Young Kim, Sang Hyun Choi, So Yeon Kim; J Liver Cancer. 2025;25(1):67-78. Published online March 7, 2025; DOI: https://doi.org/10.17998/jlc.2025.03.06

7,526 Views
177 Downloads
5 Citations

Abstract PDF

Hepatocellular adenomas (HCAs) are benign monoclonal liver tumors. Advances in molecular studies have led to the identification of distinct subtypes of HCA with unique pathways, clinical characteristics, and complication risks, underscoring the need for precise diagnosis and tailored management. Malignant transformation and bleeding remain significant concerns. Imaging plays a crucial role in the identification of these subtypes, offering a non-invasive method to guide clinical decision-making. Most studies involving patients with HCAs have been conducted in Western populations; however, the number of studies focused on Asian population has increased in recent years. HCAs exhibit distinct features in Asian population, such as a higher prevalence among male patients and specific subtypes (e.g., inflammatory HCAs). Current clinical guidelines are predominantly influenced by Western data, which may not fully capture these regional differences in epidemiology and subtype distribution. Therefore, this review presents the updated molecular classification of HCAs and their epidemiologic differences between Asian and Western populations, and discuss the role of imaging techniques, particularly magnetic resonance imaging using hepatobiliary contrast agents, in classifying the subtypes and predicting the risk of hepatocellular carcinoma.

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Daichi Ito, Ryota Hyodo, Keisuke Kurimoto, Takashi Mizuno, Akira Satou, Motoko Sasaki, Yoji Ishizu, Mami Iima, Shinji Naganawa
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Preventing false positive imaging diagnosis of HCC: differentiating HCC from mimickers and practical strategies
Ijin Joo
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Original Articles

Synergistic effects of L-arginine and argininosuccinate synthetase 1 in inducing apoptosis in hepatocellular carcinoma: Jin Sun Kim, Won-Mook Choi, Ha-Il Kim, Sung Won Chung, Jonggi Choi, Danbi Lee, Kang Mo Kim; J Liver Cancer. 2025;25(1):79-90. Published online January 14, 2025; DOI: https://doi.org/10.17998/jlc.2024.12.27

6,255 Views
124 Downloads
4 Citations

Abstract PDF

Backgrounds/Aims
Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1).
Methods
ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays.
Results
ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway.
Conclusions
Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.

Citations

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Metabolic-immune microenvironment crosstalk mediating ICI resistance in MASH-HCC
Yi Ju, Kequan Xu, Xi Chen, Tiangen Wu, Yufeng Yuan
Trends in Endocrinology & Metabolism.2026; 37(3): 262. CrossRef
L-Arginine as an Adjuvant Chemosensitizer: Enhancement of Intestinal Permeability and Cytotoxic Activity of Doxorubicin
Ghada Saad, Rana M. Alquwayi, Hanin B. Alanazi, Farah B. Aldahmashi, Aryam M. Alahmary, Shouq K. Almutairi, Fatima R. Alshammari, Ghadah T. Alshammari, Afnan J. Alrashidi, Norah K. Aldousari, Haifa F. Alsubiei, Lama H. Alanazi, Meaad H. Aldossary, Amal A.
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Impact of metabolic reprogramming on the immune response in hepatocellular carcinoma
Yang Wang, Yi-Jun Lu, Jian Zhou, Xin-Rong Yang
Hepatoma Research.2026;[Epub] CrossRef
Antitumor role of L-arginine and argininosuccinate synthetase 1 in hepatocellular carcinoma: direct and immunological mechanisms
Hyuk Soo Eun
Journal of Liver Cancer.2025; 25(1): 1. 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

6,477 Views
91 Downloads
3 Citations

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.

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Focal lesions in the cirrhotic liver: an update on LI-RADS classification and clinical implications
Antonino Andrea Blandino, Federica Vernuccio, Roberto Cannella, Aoife Kilcoyne, Leo L. Tsai, Giuseppe Brancatelli
Digestive and Liver Disease.2026; 58(6): 713. CrossRef
Enhancing Capsule on Dynamic Liver CT: Association With Hepatocellular Carcinoma Diagnosis Using LI-RADS Version 2018
Se Jin Choi, Dong Hwan Kim, Sang Hyun Choi, Yong Moon Shin, Jae Ho Byun
American Journal of Roentgenology.2026;[Epub] CrossRef
Value of enhancing capsule for diagnosing hepatocellular carcinoma on MRI: implications for simplifying LI-RADS
Se Jin Choi, Hae Young Kim, So Jung Lee, So Yeon Kim, Hyung Jin Won, Yong Moon Shin, Sang Hyun Choi, Jae Ho Byun
European Radiology.2025; 36(2): 1061. CrossRef

Review Article

Multidisciplinary approach for hepatocellular carcinoma patients: current evidence and future perspectives: Joo Hyun Oh, Dong Hyun Sinn; J Liver Cancer. 2024;24(1):47-56. Published online March 25, 2024; DOI: https://doi.org/10.17998/jlc.2024.02.27

12,562 Views
356 Downloads
28 Citations

Abstract PDF

Management of hepatocellular carcinoma (HCC) is challenging due to the complex relationship between underlying liver disease, tumor burden, and liver function. HCC is also notorious for its high recurrence rate even after curative treatment for early-stage tumor. Liver transplantation can substantially alter patient prognosis, but donor availability varies by each patient which further complicates treatment decision. Recent advancements in HCC treatments have introduced numerous potentially efficacious treatment modalities. However, high level evidence comparing the risks and benefits of these options is limited. In this complex situation, multidisciplinary approach or multidisciplinary team care has been suggested as a valuable strategy to help cope with escalating complexity in HCC management. Multidisciplinary approach involves collaboration among medical and health care professionals from various academic disciplines to provide comprehensive care. Although evidence suggests that multidisciplinary care can enhance outcomes of HCC patients, robust data from randomized controlled trials are currently lacking. Moreover, the implementation of a multidisciplinary approach necessitates increased medical resources compared to conventional cancer care. This review summarizes the current evidence on the role of multidisciplinary approach in HCC management and explores potential future directions.

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Original Article

Comparison of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma with portal vein tumor thrombosis: Jeayeon Park, Yun Bin Lee, Yunmi Ko, Youngsu Park, Hyunjae Shin, Moon Haeng Hur, Min Kyung Park, Dae-Won Lee, Eun Ju Cho, Kyung-Hun Lee, Jeong-Hoon Lee, Su Jong Yu, Tae-Yong Kim, Yoon Jun Kim, Tae-You Kim, Jung-Hwan Yoon; J Liver Cancer. 2024;24(1):81-91. Published online January 19, 2024; DOI: https://doi.org/10.17998/jlc.2023.12.25

10,713 Views
308 Downloads
12 Citations

Abstract PDF Supplementary Material

Background/Aim
Atezolizumab plus bevacizumab and lenvatinib are currently available as first-line therapy for the treatment of unresectable hepatocellular carcinoma (HCC). However, comparative efficacy studies are still limited. This study aimed to investigate the effectiveness of these treatments in HCC patients with portal vein tumor thrombosis (PVTT).
Methods
We retrospectively included patients who received either atezolizumab plus bevacizumab or lenvatinib as first-line systemic therapy for HCC with PVTT. Primary endpoint was overall survival (OS), and secondary endpoints included progressionfree survival (PFS) and disease control rate (DCR) determined by response evaluation criteria in solid tumors, version 1.1.
Results
A total of 52 patients were included: 30 received atezolizumab plus bevacizumab and 22 received lenvatinib. The median follow-up duration was 6.4 months (interquartile range, 3.9-9.8). The median OS was 10.8 months (95% confidence interval [CI], 5.7 to not estimated) with atezolizumab plus bevacizumab and 5.8 months (95% CI, 4.8 to not estimated) with lenvatinib (P=0.26 by log-rank test). There was no statistically significant difference in OS (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.34-1.49; P=0.37). The median PFS was similar (P=0.63 by log-rank test), with 4.1 months (95% CI, 3.3-7.7) for atezolizumab plus bevacizumab and 4.3 months (95% CI, 2.6-5.8) for lenvatinib (aHR, 0.93; 95% CI, 0.51-1.69; P=0.80). HRs were similar after inverse probability treatment weighting. The DCRs were 23.3% and 18.2% in patients receiving atezolizumab plus bevacizumab and lenvatinib, respectively (P=0.74).
Conclusion
The effectiveness of atezolizumab plus bevacizumab and lenvatinib was comparable for the treatment of HCC with PVTT.

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Fabio Melandro, Leonardo Centonze, Ciro Celsa, Simone Famularo, Davide Ghinolfi, Silvia Nardelli, Maria Pallozzi, Ludovico Abenavoli, Fabrizio Romano, Francesca Romana Ponziani, Francesco Paolo Russo, Quirino Lai
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Combined Transarterial Chemoembolization and External Beam Radiotherapy for Identifying Surgical Candidates for Hepatocellular Carcinoma with Macroscopic Vascular Invasion: A Propensity Score–Weighted Analysis
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Jeayeon Park, Su Jong Yu
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Tien-Shin Chou, Chun-Feng Wu, Chih-Lang Lin, Chao-Wei Hsu
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Review Article

Intrahepatic cholangiocarcinoma: histological diversity and the role of the pathologist: Mina Komuta; J Liver Cancer. 2024;24(1):17-22. Published online January 3, 2024; DOI: https://doi.org/10.17998/jlc.2023.12.11

14,834 Views
451 Downloads
7 Citations

Abstract PDF

Intrahepatic cholangiocarcinoma (iCCA) is one of the primary liver cancers and presents with tumor heterogeneity. About 50% of iCCAs comprise actionable mutations, which completely change patient management. In addition, the precise diagnosis of iCCA, including subtype, has become crucial, and pathologists play an important role in this regard. This review focuses on iCCA heterogeneity; looking at different perspectives to guide diagnosis and optimal treatment choice.

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Guido Carpino, Diletta Overi, Rocio I.R. Macias, Vincenzo Cardinale, Laura Izquierdo-Sanchez, Pilar Acedo, Marco Rengo, Michail Doukas, Timothy J. Kendall, Julien Calderaro, Lara R. Heij, Konrad Reichel, Stefano Leone, Paolo Onori, Barbara Franceschini, C
Hepatology.2026; 83(4): 753. CrossRef
Surgical management of intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma: a narrative review of principles, technical nuances, and emerging strategies
Woohyung Lee, Kwang Pyo Hong, Jae Hoon Lee, Mirang Lee, Minkyu Sung, Seung Jae Lee, Ki Byung Song, Dae Wook Hwang, Song Cheol Kim
Journal of Liver Cancer.2026; 26(1): 19. CrossRef
Trends and Disparities in Intrahepatic Cholangiocarcinoma-related Mortality in the United States from 1999 to 2020
Obaid Ur Rehman, Malik Saad Hayat, Muhammad Mukarram Shoaib, Eeman Ahmad, Zain Ali Nadeem, Ahmad Zain
Journal of Gastrointestinal Cancer.2025;[Epub] CrossRef
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Original Article

The effects of immune checkpoint modulators on the clinical course of patients with resectable hepatocellular carcinoma: Jihyun An, Hyo Jeong Kang, Eunsil Yu, Han Chu Lee, Ju Hyun Shim; J Liver Cancer. 2022;22(1):40-50. Published online March 17, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.06

7,414 Views
136 Downloads
2 Citations

Abstract PDF Supplementary Material

Background/Aim
Immune checkpoint proteins regulating T-cell mediated anti-tumor immunity have been reported to affect clinical outcomes in multiple malignancies. This study aimed to investigate the prognostic effect of histological expression of immune checkpoint proteins in patients with resected hepatocellular carcinoma (HCC).
Methods
A total of 221 patients with HCC who underwent curative resection were included. Expression of programmed-cell death ligand-1 (PD-L1) in tumor cells (tPD-L1) and tumor infiltrating mononuclear cells (TIMCs) (iPD-L1), programmed-cell death-1 in TIMCs (iPD-1), and cytotoxic T lymphocyte antigen-4 in TIMCs (iCTLA-4) were measured immunohistochemically.
Results
Histo-positivity for iCTLA-4, iPD-1, iPD-L1, and tPD-L1 was 32.1%, 42.5%, 35.3%, and 14.9%, respectively. Multivariate logistic analyses revealed that male sex and tumor >5 cm were variables related to iCTLA-4 positivity (odds ratio [OR], 0.46 and 1.94, respectively; P<0.05). Poor differentiation was related to PD-L1 expression in both tumor cells and TIMCs (OR, 2.88 and 3.46, respectively; P<0.05). Microvascular invasion was significantly associated only with iPD-L1 (OR, 2.24; P<0.05). In time-dependent outcome analyses, expression of immune checkpoint proteins in TIMCs (i.e., iCTLA-4, iPD-1, and iPD-L1) was significantly related to longer overall survival and non-cancer-related survival (all P<0.05), but not to time-to-recurrence or cancer-specific deaths. Concurrent activation of the PD-1:PD-L1 and CTLA-4 pathways predicted improved outcomes in terms of overall survival and non-cancer related survival (P=0.06 and P=0.03, respectively).
Conclusions
Immune checkpoint proteins upregulated in TIMCs in HCC tissues have individual and additive effects in prolonging the survival of patients, specifically in terms of survival not related to cancer recurrence.

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Review Article

Differences in radiotherapy application according to regional disease characteristics of hepatocellular carcinoma: Chai Hong Rim; J Liver Cancer. 2021;21(2):113-123. Published online August 11, 2021; DOI: https://doi.org/10.17998/jlc.2021.05.26

10,889 Views
124 Downloads
2 Citations

Abstract PDF

There are differences in opinion regarding the application of external beam radiotherapy in the treatment of hepatocellular carcinoma. Some major guidelines state that external beam radiotherapy is yet to attain a sufficient level of evidence. However, caution should be exercised when attempting to understand the clinical need for external beam radiotherapy solely based on the level of evidence. Previously, external beam radiotherapy had low applicability in the treatment of hepatocellular carcinoma before computed tomography-based planning was popularized. Modern external beam radiotherapy can selectively target tumor cells while sparing normal liver tissues. Recent technologies such as stereotactic body radiotherapy have enabled more precise treatment. The characteristics of hepatocellular carcinoma differ significantly according to the regional etiology. The main cause of hepatocellular carcinoma is the hepatitis B virus. It is commonly diagnosed as a locally advanced tumor but with relatively preserved hepatic function. The majority of these hepatocellular carcinoma cases are found in the East Asian population. Hepatocellular carcinoma caused by hepatitis C virus or other benign hepatitis tends to be diagnosed as a less locally aggressive tumor but with deteriorated liver function. The Western world and Japan tend to have patients with such causes. External beam radiotherapy has been more commonly performed for the former, although the use of external beam radiotherapy in the latter might have more concerns with regard to hepatic toxicity. This review discusses the above subjects along with perspectives regarding external beam radiotherapy in recent guidelines.

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Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines
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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

15,029 Views
330 Downloads
4 Citations

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.

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Review Article

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

13,484 Views
390 Downloads
12 Citations

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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Combined hepatocellular-cholangiocarcinoma: a contemporary pathologic and molecular perspective
Taek Chung
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Jaeseung Shin, Taek Chung, Sang Yun Ha, Hyungjin Rhee
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Case Report

Long-term Disease-free Survival after Trimodality Treatment of Recurrent Hepatocellular Carcinoma Involving the Inferior Vena Cava and Right Atrium: Sunmin Park, Won Sup Yoon, Hyung Joon Yim, Chai Hong Rim; J Liver Cancer. 2019;19(2):149-153. Published online September 30, 2019; DOI: https://doi.org/10.17998/jlc.19.2.149

6,380 Views
78 Downloads

Abstract PDF Supplementary Material: Hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA) is a rare and intractable disease. A standard treatment has not been established yet, owing to the rarity of disease and difficulties in the therapeutic treatment. Herein, we report the case of a patient who had recurrent HCC (after a prior lobectomy) involving both IVC and RA and underwent multimodality treatments including external beam radiotherapy and transarterial chemotherapy, followed by sorafenib treatment. The disease was well controlled with local treatments and sustained for 7 years until last follow-up after the systemic treatments. Our case shows a possibility of long-term survival for patients affected by HCC involving IVC and/or RA, after a rigorous multimodality treatment strategy.

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