Journal of Liver Cancer

Review Articles

Toward a future role for liver biopsy in HCC: literature evidence and survey-based perspectives from Korean experts: Hae Lim Lee, Su Jong Yu, Sung Hak Lee, Min Woo Lee, Han Ah Lee, Yuri Cho, Jeong-Ju Yoo, Ha Il Kim, Jae Geun Lee, Hye Won Lee, Jihyun An, Sun Young Yim, Pil Soo Sung, Jonggi Choi, Jae Hyun Yoon, Eun Ju Cho, Jinhong Jung, Dongho Hyun, Ijin Joo, Yu Rim Lee, YoungRok Choi, Bo Hyun Kim, Sung Hyun Kim, Soon Sun Kim, Jeong-Han Kim, Haeryoung Kim, Pyoung-Jae Park, Hyun Phil Shin, Ki Tae Yoon, Sang Min Yoon, Minjong Lee, Jai Young Cho, Jin-Young Choi, Do Young Kim, June Sung Lee, Mi-Sook Kim, Kyung Sik Kim; J Liver Cancer. 2026;26(2):205-219. Published online September 3, 2026; DOI: https://doi.org/10.17998/jlc.2026.08.27

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Abstract PDF: The role of liver biopsy in hepatocellular carcinoma (HCC) is being re-evaluated in the era of precision oncology and biomarker-driven systemic therapy. Although histopathological examination remains the diagnostic gold standard, HCC is unique among solid tumors in that accurate non-invasive imaging criteria allow diagnosis without routine biopsy in selected clinical settings. However, increasing biological heterogeneity, expanding therapeutic options, and the growing need for molecular stratification have renewed interest in tissue-based evaluation. Recent international guidelines have gradually broadened the indications for liver biopsy, particularly in selected diagnostic scenarios, prior to systemic therapy, and for molecular profiling. Beyond diagnostic confirmation, liver biopsy provides important information for histological subtyping, prognostic stratification, and biomarker discovery. Advances in immunohistochemistry, next-generation sequencing, and artificial intelligence-assisted pathology have further enhanced the clinical value of tumor tissue. In parallel, contemporary cohort studies indicate that liver biopsy is associated with low complication rates when modern techniques and standardized peri-procedural management are applied. Despite these advances, the integration of liver biopsy into routine clinical practice remains limited. To contextualize this gap, the Korean Liver Cancer Association conducted a nationwide survey of HCC specialists. The survey showed that liver biopsy is infrequently performed in current practice due to perceived procedural risks and limited immediate impact on therapeutic decision-making. Taken together, accumulating evidence supports a reappraisal of the clinical role of liver biopsy in HCC. Optimizing procedural safety, standardizing indications, and integrating tissue-based molecular insights into therapeutic decision-making may help bridge the gap between emerging evidence and real-world practice.

Stemness plasticity in hepatocellular carcinoma: spatial niches and therapeutic implications: Hye Ri Ahn, Sujin Kim, Hyo Jung Cho; J Liver Cancer. 2026;26(2):231-242. Published online September 3, 2026; DOI: https://doi.org/10.17998/jlc.2026.08.24

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Abstract PDF: Hepatocellular carcinoma (HCC) remains a major global health burden, with therapeutic resistance limiting the long-term efficacy of current treatments. Although cancer stem cell (CSC) models have been proposed to explain tumor initiation and relapse, strategies targeting marker-defined CSC populations have shown limited clinical benefit. Increasing evidence indicates that stemness in HCC is not a fixed cellular trait but a dynamic and reversible state that can be induced, maintained, and re-established under therapeutic pressure. This stemness plasticity is regulated by tumor-intrinsic signaling pathways, including transforming growth factor beta, Yes-associated protein/transcriptional coactivator with PDZ-binding motif, and Wnt/β-catenin, and stabilized by epigenetic and post-transcriptional mechanisms such as N6-methyladenosine modification. In parallel, spatially organized tumor microenvironmental niches composed of cancer-associated fibroblasts, macrophages, and endothelial cells provide critical signals that support stem-like phenotypes and immune evasion. These interconnected mechanisms collectively contribute to therapeutic resistance and tumor progression. This review synthesizes current evidence linking stemness plasticity to spatial niche regulation and treatment failure in HCC, and outlines a therapeutic framework that integrates targeting of intracellular regulatory programs with disruption of microenvironmental support systems. We further discuss the implications of this framework for the development of combination strategies and dynamic biomarkers that better capture the context-dependent nature of stemness. Together, these insights support a shift from targeting static cell populations toward targeting the regulatory processes that govern tumor cell plasticity in HCC.

Original Articles

Risk-based hepatocellular carcinoma surveillance thresholds using a prediction score in Asian patients with chronic hepatitis B: a nationwide cohort study: Won Sohn, Myeongcheol Lee, Danbee Kang, Ju Yeon Cho, Jung Hee Kim, Soo Jin Park, Yong-Han Paik; J Liver Cancer. 2026;26(2):253-262. Published online September 3, 2026; DOI: https://doi.org/10.17998/jlc.2026.08.23

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Abstract PDF: Background/Aims
This study aimed to quantify hepatocellular carcinoma (HCC) incidence according to a validated prediction score and to define score-based cut-offs corresponding to surveillance-relevant incidence thresholds in Asian patients with chronic hepatitis B (CHB) receiving antiviral therapy.
Methods
We conducted a nationwide population-based cohort study using the Korean National Health Insurance Service database. Adults with CHB initiating nucleos(t)ide analogue therapy between 2012 and 2023 were included; those with viral coinfections, prior malignancy, or decompensated cirrhosis were excluded. HCC risk was stratified using the HCC-RESCUE score. Incident HCC was the primary outcome. Annual HCC incidence rates and adjusted hazard ratios were estimated using multivariable Cox proportional hazards models.
Results
Among 199,143 treated patients (median follow-up, 7.3 years), 15,233 developed HCC. Adjusted annual HCC incidence increased progressively across risk strata: 0.31% (95% confidence interval [CI], 0.24-0.40) in the low-risk group, 1.09% (95% CI, 0.84-1.41) in the intermediate-risk group, and 1.85% (95% CI, 1.44-2.40) in the high-risk group. Compared with the low-risk group, adjusted hazard ratios for HCC were 3.48 (95% CI, 3.35-3.61) and 5.90 (95% CI, 5.62-6.19) in the intermediate- and high-risk groups, respectively (all P<0.001). HCC-RESCUE scores corresponding to annual HCC incidence thresholds of 0.2%, 1.5%, and 3.0% were 47, 66, and 90.
Conclusions
In a large antiviral-treated Asian CHB population, prediction score–based stratification revealed a graded spectrum of residual HCC risk and identified incidence-aligned thresholds relevant to surveillance. These findings support incidence-informed refinement of HCC surveillance strategies that complement traditional cirrhosis-based criteria in the antiviral treatment era.

Prognostic value of automated computed tomography body composition in hepatocellular carcinoma: a volumetric versus single-slice comparison: Seok Jin Hong, Jeong Hee Yoon, Jae Hyun Kim, Jeongin Yoo, Jeong Min Lee; J Liver Cancer. 2026;26(2):263-274. Published online August 21, 2026; DOI: https://doi.org/10.17998/jlc.2026.06.08

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Abstract PDF: Background/Aims
To compare the prognostic value of fully automated volumetric versus single-slice computed tomography (CT)-derived body composition analysis for predicting overall survival in patients with newly diagnosed hepatocellular carcinoma (HCC).
Methods
In this retrospective study of 448 patients with newly diagnosed HCC, deep-learning algorithm quantified volumetric (L1-L5) and single-slice (L3) skeletal muscle and adipose tissue metrics using CT images. Spearman correlation assessed the relationship between volumetric and single-slice body composition metrics. Cox proportional hazards models, adjusted for established clinical prognostic factors, were used to evaluate association between body composition parameters and overall survival. Harrell’s C-index was used to compare prognostic performance of Cox models.
Results
Strong correlations (correlation coefficient ≥0.82) were observed between volumetric and single-slice measurements for muscle attenuation, visceral fat index, and subcutaneous fat index, while muscle index demonstrated only moderate correlation (correlation coefficient= 0.50). Single-slice low muscle index (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.15-2.31; P=0.006), single-slice low muscle attenuation (HR, 1.38; 95% CI, 1.01-1.88; P=0.045) and volumetric low muscle attenuation (HR, 1.42; 95% CI, 1.03-1.95; P=0.034) were identified as independent predictors of overall survival. Median follow-up was 6.6 years. The single-slice and volumetric models showed comparable discrimination (C-index, 0.816 vs. 0.817; P=0.11).
Conclusion
Automated single-slice muscle parameters at the L3 level provide significant prognostic stratification in patients with hepatocellular carcinoma, establishing it as a viable, time-efficient tool for routine oncologic practice. In contrast, automated volumetric body composition assessment did not provide superior discrimination compared with the single-slice approach.

SINEUP-mediated enhancement of HNF4α improves metabolic function in Huh7-based bioengineered hepatic microtissues: Zohreh Hashemian, Morteza Zarrabi, Masoumeh Nouri, Abbas Piryaei, Ali Mohammad Moradi, Mohssen Nassiri Toosi, Sara Taleahmad, Mustapha Najimi, Massoud Vosough; J Liver Cancer. 2026;26(2):298-316. Published online August 21, 2026; DOI: https://doi.org/10.17998/jlc.2026.05.13

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Abstract PDF: Background/Aims
Human liver cell-based drug-screening platforms require stable hepatocyte identity and metabolic competence, but Huh7 cells show reduced hepatic function. We investigated whether SINEUP-mediated enhancement of hepatocyte nuclear factor 4 alpha (HNF4α) could improve the metabolic performance of Huh7-based three-dimensional hepatic microtissues.
Methods
Decellularized liver extracellular matrix-derived microparticles were incorporated into three-dimensional microtissues containing Huh7 cells, human umbilical vein endothelial cells, and Wharton’s jelly mesenchymal stem cells using AggreWell technology. Experimental microtissues were generated with Huh7 cells expressing a SINEUP-based long noncoding RNA targeting HNF4α and were compared with control microtissues.
Results
Enhanced HNF4α expression upregulated hepatic markers including HNF4α and albumin, decreased alpha-fetoprotein and CDH2, increased CDH1 expression, suppressed glycolytic genes, modulated lipid metabolism, and increased cytochrome P450-related gene expression. Albumin and fibrinogen secretion, urea synthesis, and glycogen storage increased, whereas alpha-fetoprotein secretion, lactate production, and cell migration decreased.
Conclusions
SINEUP-mediated enhancement of HNF4α partially restored hepatocyte-like metabolic and functional properties in Huh7-based hepatic microtissues, supporting their potential use as an in vitro platform for drug discovery and toxicity screening.

Enhancing non-LR-5 liver lesion diagnoses: the incremental value of serum alpha-fetoprotein and PIVKA-II for detecting hepatocellular carcinoma components: Junghoan Park, Jeong Min Lee, Rae Rim Ryu, Seok Jin Hong; Received December 15, 2025 Accepted May 26, 2026 Published online June 26, 2026; DOI: https://doi.org/10.17998/jlc.2026.05.26 [Accepted]

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Abstract PDF: Backgrounds/Aims
To investigate whether incorporating serum alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) into gadoxetic acid-enhanced liver MRI improves the accuracy of differentiating hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC-CC) from non-LR-5 lesions.
Methods
This retrospective study included 123 patients comprising 70 HCC, 30 ICC, and 23 cHCC-CC cases who underwent preoperative MRI and tumor marker analysis. Two abdominal radiologists independently interpreted the MRI without markers (Decision 1). Then, lesions were reclassified as HCC if either marker was elevated, regardless of the initial interpretation (Decision 2, biomarker-assisted override strategy). Outcomes included the diagnostic performance for identifying HCC versus non-HCC malignancies and distinguishing the presence of HCC components (HCC or cHCC-CC) from ICC. The McNemar’s test and Cohen’s κ compared diagnostic performance and evaluated interobserver agreement, respectively.
Results
Adding AFP and PIVKA-II (Decision 2) improved the sensitivity and accuracy of detecting HCC components from 62.4–76.3% to 81.7–90.3% (P<0.001) and 66.7–76.4% to 81.3–87.0% (P<0.001), respectively. The overall accuracy for differentiating HCC from non-HCC malignancies did not improve. However, the accuracy for detecting HCC in small tumors (<3 cm) significantly improved from 68.8–72.5% to 81.3–82.5% (P= 0.002–0.008). Interobserver agreement also increased, from moderate (κ = 0.48) to substantial (κ = 0.68) after adding tumor marker values.
Conclusions
In non-LR-5 hepatic lesions, adding AFP and PIVKA-II to MRI interpretations significantly improved the accuracy of identifying HCC components, as well as HCC detection in small tumors.

Outcomes of early-stage hepatocellular carcinoma patients treated by resection or ablation: real-life data from the French Administrative Health Care database: Marie Decraecker, Boris Guiu, Emmanuel Boleslawski, Pierre Nahon, Manel Dhaoui, Danko Stamenic, Moreau Manoel, Alicia Fravalo, Jean Frédéric Blanc; J Liver Cancer. 2026;26(2):275-286. Published online May 14, 2026; DOI: https://doi.org/10.17998/jlc.2026.04.24

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Abstract PDF: Background/Aims
Surgical resection and percutaneous ablation are considered curative treatments for hepatocellular carcinoma (HCC). However, both approaches are associated with a high risk of recurrence. Real-world data on outcomes and post-curative management remain scarce. This study aimed to assess survival and healthcare pathways of patients with HCC treated with resection or ablation in routine clinical practice.
Methods
We conducted a retrospective analysis using the French National Health Data System. Patients who underwent resection or percutaneous ablation as first-line treatment for HCC between January 2014 and December 2021 were included. The primary endpoint was overall survival (OS); secondary endpoints focused on subsequent treatment sequences and healthcare pathways
Results
Among 10,810 patients included, 5,488 underwent ablation and 5,322 resection as first-line treatment. One- and 2-year OS rates were 90% and 78% after ablation (median OS [mOS], 56 months; 95% confidence interval [CI], 54-58) and 88% and 80% after resection (mOS, 75 months; 95% CI, 72-79). Median time to next treatment or death was 20 months (95% CI, 18-21) after ablation and 29 months (95% CI, 27-30) after resection. Following initial treatment, 27% of patients in the ablation group and 39% in the resection group received no further therapy.
Conclusions
This nationwide real-world study provides comprehensive data on survival and treatment sequences after curative-intent therapy for HCC in France. Despite frequent recurrence, survival outcomes remained favourable, reflecting access to repeated and effective subsequent treatments, underscoring the importance of long-term follow-up in routine care.

Pain, analgesic use and misconceptions in patients with hepatocellular carcinoma: a cross-sectional survey: Jina Park, Jiwon Yang, Sung Won Chung, Won-Mook Choi, Ju Hyun Shim, Danbi Lee, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Jonggi Choi; J Liver Cancer. 2026;26(2):287-297. Published online April 29, 2026; DOI: https://doi.org/10.17998/jlc.2026.03.19

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1 Citation

Abstract PDF Supplementary Material

Backgrounds/Aims
Cancer-related pain remains undertreated despite established guidelines. In hepatocellular carcinoma (HCC), underlying chronic liver disease may amplify concerns regarding analgesic safety. We aimed to evaluate pain prevalence, analgesic use, pain-related perceptions, and educational needs among patients with HCC.
Methods
We conducted a cross-sectional survey of 200 adult patients with HCC receiving systemic therapy at a tertiary referral center. A 30-item questionnaire assessed pain presence and intensity using a numeric rating scale (NRS), analgesic use patterns, liver-related safety concerns, opioid-related stigma, and educational needs. Clinical characteristics, including tumor burden and liver function, were analyzed in relation to pain and perception domains.
Results
Fifty-five patients (27.5%) reported current pain (mean NRS, 3.6±2.5; mean worst pain 5.2±2.8). Among them, 31 patients (56.3%) were using analgesics; however, 51.6% reported using them only when pain became unbearable. Misconceptions regarding analgesic safety were prevalent: 70.0% believed long-term analgesic use damages the liver, 56.0% believed analgesics are unsafe with impaired liver function, 46.5% associated opioids with addiction, and 30.0% hesitated due to the term “narcotic.” These beliefs were not associated with Child-Pugh class or serum albumin level. Extrahepatic metastasis was associated with higher liver-related concern scores and a trend toward increased pain prevalence. Patients with elementary school education or less had poorer pain scale knowledge and no prior counseling.
Conclusions
Pain undertreatment and safety-related misconceptions are common in HCC and appear independent of objective liver function. Structured, proactive education, particularly for patients with untreated pain and low educational attainment, may improve pain control in this population.

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Patterns and Frequency of Opioid Use Among Individuals With a History of Gastrointestinal Malignancy: A Cross-Sectional Analysis of the 2019-2020 National Health Interview Survey (NHIS)
Mohammed D Al-Hejaili , Rami Saleh, Ghazi H Mogharbel, Dana F Maufa, Abdulmohsen Hassan, Maisa Manfaluti, Rifq S Altamimi, Linah A Murtadha , Abdulrahman I Almarwani, Renad K Alandejane
Cureus.2026;[Epub] CrossRef

Review Articles

Imaging differentiation of hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma: pitfalls and advances: Jaeseung Shin, Taek Chung, Sang Yun Ha, Hyungjin Rhee; J Liver Cancer. 2026;26(1):9-18. Published online March 5, 2026; DOI: https://doi.org/10.17998/jlc.2026.03.05

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151 Downloads

Abstract PDF: Accurate non-invasive differentiation of primary liver cancers, such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA), is crucial for optimal management but challenging due to shared risk factors and overlapping imaging phenotypes. While the Liver Imaging Reporting and Data System category M effectively captures the classic targetoid appearance of large duct type iCCA, the small duct type frequently exhibits HCC-mimicking non-rim arterial phase hyperenhancement and non-peripheral washout, potentially compromising diagnostic specificity. Furthermore, cHCC-CCA presents a formidable diagnostic dilemma, existing on a continuous imaging spectrum that reflects its histologic dominance. This continuous imaging spectrum not only blurs radiologic distinctions but also complicates tissue sampling, limiting the diagnostic accuracy of core needle biopsies and highlighting the risk of misclassification. To enhance diagnostic clarity, this review highlights their key imaging hallmarks: while HCC typically shows non-rim arterial phase hyperenhancement (APHE) and non-peripheral washout, large duct iCCA displays a classic targetoid appearance with rim APHE and progressive central enhancement. Conversely, small duct iCCA often mimics HCC, and cHCC-CCA exhibits a variable spectrum depending on its predominant histologic component. Ultimately, overcoming these diagnostic pitfalls requires a rigorous, multidisciplinary approach that synthesizes imaging findings, serologic tumor markers, and clinical contexts.

The role of radiotherapy in the management of combined hepatocellular-cholangiocarcinoma: current evidence and future perspectives: Seo Hee Choi, Woong Sub Koom, Ik Jae Lee; J Liver Cancer. 2026;26(1):55-64. Published online March 5, 2026; DOI: https://doi.org/10.17998/jlc.2026.03.04

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82 Downloads
1 Web of Science

Abstract PDF: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare and highly aggressive hybrid malignancy characterized by a poor prognosis and high recurrence rates due to its dual histological nature. In the absence of established standard-of-care protocols, clinical management strategies are frequently extrapolated from the guidelines for its components, hepatocellular carcinoma and intrahepatic cholangiocarcinoma (iCCA). This review evaluates the evolving role of radiotherapy (RT) as an integral part of the multidisciplinary care for cHCC-CCA. Adjuvant RT may be considered for patients exhibiting high-risk pathological features, such as positive or close resection margins, lymphovascular invasion, and perineural invasion. For unresectable disease unfeasible for surgery or transarterial therapies, definitive RT using intensified doses, analogous to iCCA protocols, is employed to improve local control. High-precision modalities, particularly particle therapies such as proton or carbon ion RT, are emphasized as preferred options for delivering ablative doses while minimizing toxicity and preserving functional liver reserve. Furthermore, preliminary clinical evidence suggests a potential synergy between RT and immune checkpoint inhibitors, with reported cases demonstrating complete responses or successful conversion to curative-intent resection. While current evidence remains limited to retrospective cohorts and case series, the strategic integration of precision RT offers a rational pathway for optimizing outcomes in cHCC-CCA, necessitating further prospective validation.

Systemic therapy for combined hepatocellular-cholangiocarcinoma: a comprehensive review of chemotherapy, immunotherapy, and targeted therapy: Jung Yong Hong, Dong Hyun Sinn, Sang Yun Ha; J Liver Cancer. 2026;26(1):36-44. Published online March 5, 2026; DOI: https://doi.org/10.17998/jlc.2026.03.02

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2 Web of Science
2 Citations

Abstract PDF

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver malignancy exhibiting both hepatocytic and cholangiocytic differentiation. Since the 2019 World Health Organization (WHO) reclassification, growing molecular and clinical evidence has reshaped our understanding of this entity. However, patients with cHCC-CCA have been systematically excluded from landmark clinical trials in both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), leaving clinicians without prospective evidence to guide treatment selection. This review comprehensively evaluates the current evidence on systemic therapy for advanced cHCC-CCA, encompassing cytotoxic chemotherapy, immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitors, and molecularly targeted agents. Retrospective data indicate that gemcitabine plus platinum-based chemotherapy achieves the most consistent efficacy among conventional regimens, with median overall survival of 10-16 months. ICIs demonstrate objective response rates of 20-33% with durable responses in a subset of patients, supported by the finding that approximately 57% of cHCC-CCA tumors harbor an immune-high phenotype. Nearly 25% of tumors carry potentially actionable genomic alterations, including fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and human epidermal growth factor receptor 2 (HER2) amplification. The molecular heterogeneity of cHCC-CCA, with tumors classifiable as HCC-like or CCA-like in approximately 75% of cases, provides a rational framework for personalized treatment selection. We propose an emerging molecular classification-based treatment algorithm and identify critical gaps requiring dedicated prospective investigation. For clinical settings where comprehensive genomic profiling is not feasible, we discuss a pragmatic surrogate-based approach using imaging characteristics and serum tumor markers to guide initial treatment selection. We also address post-progression treatment considerations, including phenotype-based regimen switching and the role of re-biopsy

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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
Efficacy and safety of camrelizumab combined with apatinib as second‐line and beyond treatment for advanced combined hepatocellular‐cholangiocarcinoma
Haiyun Geng, Fang Dai, Kuimin Mei, Mengran Cao, Haiqing Hua, Xinlei Gong
Clinical and Translational Discovery.2026;[Epub] CrossRef

Original Article

Liver resection versus radiofrequency ablation or transarterial chemoembolization for early multinodular BCLC-A hepatocellular carcinoma: a systematic review and meta-analysis: Maria F. F. Viana, Arthur A. Braga, Lucas B. Carvalho, Danilo C. M. S. Vasconcellos, Bianca C. M. R. Alexandrino, Felipe J. F. Coimbra; J Liver Cancer. 2026;26(1):157-168. Published online February 26, 2026; DOI: https://doi.org/10.17998/jlc.2026.02.21

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100 Downloads

Abstract PDF Supplementary Material: Backgrounds/Aims
Hepatocellularcarcinoma (HCC) is the most common form of liver cancer, with high mortality rates worldwide. The optimal treatment strategy for patients with multinodular early-stage HCC (BCLC-A) is still controversial, particularly regarding liver resection (LR), radiofrequency ablation (RFA), and transarterial chemoembolization (TACE). This meta-analysis aims to evaluate the overall survival (OS) and disease-free survival (DFS) in patients with multinodular BCLC-A HCC treated with LR compared to RFA and TACE.
Methods
A systematic literature review and meta-analysis were performed by searching PubMed, Embase, and the Cochrane Library for studies comparing LR with RFA and TACE. Pooled analyses of OS and DFS were performed using hazard ratios (HR) with 95% confidence intervals (CI).
Results
Fifteen studies, including two randomized controlled trials and 13 cohort studies, with a total of 2,869 patients, were included. LR was significantly associated with improved OS (HR, 1.38; 95% CI, 1.03-1.84; P=0.01) and DFS (HR, 2.16; 95% CI, 1.26-3.70; P=0.001) compared with RFA. Similarly, LR demonstrated superior OS (HR, 2.11; 95% CI, 1.37-3.25; P<0.0001) and DFS (HR, 2.77; 95% CI, 1.04-7.36; P=0.04) when compared with TACE. The more pronounced benefit observed for DFS likely reflects improved local tumor control achieved with surgical resection.
Conclusions
In selected patients with multinodular BCLC-A HCC and preserved liver function (predominantly Child-Pugh A or B), LR is associated with significant improvements in OS and DFS compared with RFA and TACE when liver transplantation is not feasible. These findings support reconsideration of current treatment algorithms to prioritize LR in appropriately selected candidates.

Review Articles

Immune-related adverse events in hepatocellular carcinoma: organ-specific patterns and management approaches: Sul Ki Choi, Seonjeong Woo, Hong Jae Chon; J Liver Cancer. 2026;26(1):65-82. Published online December 29, 2025; DOI: https://doi.org/10.17998/jlc.2025.12.21

4,467 Views
227 Downloads
4 Web of Science
4 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide. The recent introduction of immune checkpoint inhibitors (ICIs) has transformed the therapeutic landscape for advanced HCC. Combination regimens such as atezolizumab plus bevacizumab, durvalumab plus tremelimumab, and nivolumab plus ipilimumab have demonstrated significant survival improvements over conventional tyrosine kinase inhibitors and have become the new standard of care. However, ICIs can trigger immune-related adverse events (irAEs) through overactivation of the immune system, affecting multiple organs including the skin, gastrointestinal tract, liver, endocrine system, lungs, and heart. Patients with HCC frequently have underlying liver diseases such as chronic hepatitis or cirrhosis, placing them at higher risk of hepatic irAEs compared to that with other cancer types, which can markedly influence prognosis. The pathophysiology of irAEs is driven by a series of interconnected immune mechanisms, including excessive T-cell activation, disruption of immune tolerance, cytokine dysregulation, complement-mediated injury, and innate immune activation. Clinical decisions regarding the continuation, interruption, or discontinuation of ICIs, as well as the administration of corticosteroids or immunosuppressants, should be guided by the severity of toxicity. Organ-specific management strategies and multidisciplinary collaboration are essential, particularly for severe presentations. This review summarizes the incidence, mechanisms, and management strategies for ICI-related irAEs in advanced HCC, and provides practical insights for clinical decision-making.

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Jung Sun Kim, Thomas Yau, Hong Jae Chon
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Comparative efficacy and safety of first-line treatments for advanced hepatocellular carcinoma: a Bayesian network meta-analysis
Yun Su, Tongze Cai, Jingxuan Wei, Qiuju Huang, Chun Yao, Lei Fu, Jinghui Zheng, Hongwei Guo, Xiongbin Gui
Frontiers in Immunology.2026;[Epub] CrossRef
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Faizah M. Alotaibi, Seham A. Khashwayn, Lamia K. Alshamlani, Rayan A. Almutairi, Anas K. Alghamdi, Nawaf M. Alamer, Mohannad A. Alghamdi, Badi A. Alotaibi, Kanan Alshammari
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Regorafenib as Second-Line Versus Later-Line Therapy in Advanced Hepatocellular Carcinoma: A Multicenter Real-World Study with Exploratory Analysis of Prior Immune Checkpoint Inhibitor Exposure
Kwon Yong Tak, Hee Sun Cho, Jaejun Lee, Kyeungmo Yang, Ahlim Lee, Ji Won Han, Soon Kyu Lee, Hyun Yang, Heechul Nam, Hee Yeon Kim, Sung Won Lee, Seok-Hwan Kim, Do Seon Song, Myeong Jun Song, Jung Hyun Kwon, UIm Chang, Soon Woo Nam, Chang Wook Kim, Jeong Wo
Targeted Oncology.2026; 21(5): 761. CrossRef

Exploring single-cell and multi-omics technologies and their role in unraveling tumor heterogeneity of hepatocellular carcinoma: Charmi Jyotishi, Suresh Prajapati, Mansi Patel, Reeshu Gupta; J Liver Cancer. 2026;26(1):104-123. Published online December 17, 2025; DOI: https://doi.org/10.17998/jlc.2025.11.29

2,801 Views
89 Downloads
4 Web of Science
4 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Tumor heterogeneity is a major obstacle to effective treatment and is poorly understood using traditional bulk sequencing methods. This review highlights the transformative role of single-cell and multi-omics technologies in determining the cellular and molecular complexities of HCC. We summarize recent advances in single-cell transcriptomics, epigenomics, multi-omics, and spatial transcriptomics platforms, emphasizing their applications in characterizing tumor subclones, cancer-associated fibroblast-immune interactions, circulating tumor cells, and immune-resistant phenotypes. Spatial approaches have revealed the architecture of cancer stem cell niches and tertiary lymphoid structures, providing unprecedented insights into tumor organization and microenvironmental crosstalk. Although still in their early stages, clinical trials have begun to incorporate these technologies, underscoring their translational potential. Single-cell and spatial omics have reshaped HCC research by enabling high-resolution profiling of tumor ecosystems and driving the discovery of biomarkers, therapeutic targets, and strategies for patient stratification. However, high cost, technical expertise, and limited accessibility, particularly in resource-constrained settings, are major barriers to its widespread adoption. Addressing these challenges is critical for translating these powerful approaches into clinical practice and for advancing precision medicine for the treatment of liver cancer.

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Yule Ma, Huigang Li, Huan Chen, Jinxin Xu, Ziyi Ye, Yuhang Li, Xiang Wu, Jinyan Chen, Chenghao Cao, Peiru Zhang, Ruijie Zhao, Jun Li, Cheng Zhu, Jianyong Zhuo, Shengjun Xu, Xiao Xu, Di Lu
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Ye Tan, Jingxuan Xiang, Zehan Wang, Yu Wang, Aidong Chen, Qiwen Wu
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Unraveling the regulatory role of intercellular communication in intestinal immune cells mediated by H₂ in sepsis recovery through single-cell RNA sequencing
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Original Article

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; J Liver Cancer. 2026;26(1):147-156. Published online December 4, 2025; DOI: https://doi.org/10.17998/jlc.2025.11.16

1,837 Views
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Abstract PDF Supplementary Material: Backgrounds/Aims
The patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M variant has been implicated in metabolic dysfunction-associated steatotic liver disease (MASLD), but its role in hepatocellular carcinoma (HCC) development is unclear. This study examines the association between the PNPLA3 I148M variant and HCC occurrence.
Methods
A total of 562 MASLD patients, with and without HCC, were prospectively and consecutively enrolled at two universityaffiliated hospital between June 2024 and June 2025. Genomic DNA was extracted from buccal swabs or liver biopsy samples, and single nucleotide polymorphism genotyping was performed to determine the rs738409 genotype at codon 148 of PNPLA3. The histological grade of HCC was assessed using the Edmondson-Steiner (ES) grading system in patients who underwent core-needle liver biopsy.
Results
Among 474 non-HCC patients, the GG genotype was found in 39.9%, GC in 37.1%, and CC in 23.0%. In 88 HCC patients, these frequencies were 45.5%, 36.4%, and 18.2%, respectively. No significant differences in GG genotype distribution were observed between HCC and non-HCC groups (P=0.509), nor in subgroups by sex, age, obesity status, cirrhosis status, fibrosis-4 index, or liver stiffness measurement. However, among HCC patients with histological grading, the GG genotype was significantly associated with higher ES grades (P=0.0076).
Conclusions
The PNPLA3 I148M GG genotype was not significantly associated with increased HCC occurrence in Korean MASLD patients within the present cohort. Although the GG genotype is known to play a role in development and progression of MASLD, further studies are warranted to clarify its contribution to tumor initiation and dedifferentiation.

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