Cholangiocarcinoma (CCA) is an epithelial cell cancer of the biliary tract. CCA can be further classified into intrahepatic cholangiocarcinoma (iCCA), perihilar cholangiocarcinoma (pCCA), and distal cholangiocarcinoma (dCCA) depending on the anatomical location. Until recently, the treatment for advanced CCA has remained highly reliant on chemotherapy, with gemcitabine plus cisplatin used in first-line treatment. Recent developments have led to the addition of immune checkpoint blockade (ICB) to the chemotherapy regimen, highlighting the promising potential of immunotherapies for CCA treatment. Despite these developments, most patients still do not benefit from current treatments, and response rates to ICB monotherapy remain modest. This underscores the need to develop more effective immunotherapeutic strategies. A major obstacle to this is the highly heterogenous nature of the disease. CCA tumors exhibit high inter-tumor heterogeneity in terms of anatomical locations, driver mutations, etiologies, and tumor microenvironment (TME) composition, making each patient immunologically distinct and difficult to benefit from a one-size-fits-all approach. There is a need to stratify patients according to individual disease status to identify immunotherapies and combination therapies that are most beneficial to them. Here we describe the different ways inter-tumor heterogeneity may arise in CCA, including stromal cell abundance, anatomical location, driver mutations, etiologies, TME profile, and tertiary lymphoid structure (TLS) presence. We also discuss what these factors mean to the immune microenvironment and their potential to be used as biomarkers. Careful stratification of patients is crucial in designing personalized medicine to improve survival outcomes and treatment efficacy for CCA patients.
Citations
Citations to this article as recorded by
Integrative single-cell and machine-learning analysis identifies ac4C-related S100A13 as a causal risk gene in cholangiocarcinoma Yi Zheng, Yan Lin, Zilin Wang, Fazong Wu BMC Cancer.2026;[Epub] CrossRef
Development of a prediction model integrating cardiac ultrasound parameters for cardiac complications after distal cholangiocarcinoma surgery: a retrospective cohort study Fangfei Wang, Shan Jin, Shaocheng Lyu, Xin Zhao, Xiuzhang Lyu, Qiang He BMC Medical Imaging.2026;[Epub] CrossRef
Distinct tumor immune microenvironment modulation by anti-PD-1/PD-L1, VEGF, and CTLA-4 blockade provides a rationale for triplet therapy in hepatocellular carcinoma Hideki Iwamoto, Hironori Koga, Takumi Kawaguchi Clinical and Molecular Hepatology.2026; 32(1): e38. CrossRef
Correspondence to editorial on “Integrated molecular characterization of sarcomatoid hepatocellular carcinoma” Rong-Qi Sun, Shao-Lai Zhou Clinical and Molecular Hepatology.2025; 31(2): e192. CrossRef
Curative response to combined targeted-immunotherapy for post-hepatectomy lymph node metastasis in sarcomatoid hepatocellular carcinoma: case report and literature review Pan Liu, Song Zhang, Xiao-Ming Xin, Min Jing, Lie-Dong Wen, Xin Xiang, Shun-Hai Liu Frontiers in Oncology.2025;[Epub] CrossRef
Development of an UPLC-MS/MS method for quantification of donafenib and its metabolite in rat plasma: application to drug–drug interaction Yuxin Shen, Ruibin Li, Lu Cao, Jun Wu, Haoxin Fu, Peiqi Wang, Ren-ai Xu, Ling Ji Biochemical Pharmacology.2026; 246: 117540. CrossRef
Comparison of repeat hepatectomy with radiofrequency ablation for the survival of hepatocellular carcinoma with solitary intrahepatic recurrence after hepatectomy Jialu Fu, Jiafeng Chen, Lei Jin, Junfeng Huang, Shengwei Mao, Xuhui Zhao, Weifeng Qu, Rui Yang, Yi Wang, Yichao Bu, Zhiqi Guan, Jun Gao, Xiaoling Wu, Qianfu Zhao, Tianhao Chu, Guiqi Zhu, Yuan Fang, Yinghong Shi, Weiren Liu Clinics and Research in Hepatology and Gastroenterology.2026; 50(2): 102750. CrossRef
Integrated Bioinformatic Analysis Reveals the Oncogenic, Survival, and Prognostic Characteristics of TPX2 in Hepatocellular Carcinoma Weibin Zhang, Jia Dong, Yunfei Wu, Xiangnan Liang, Lida Suo, Liming Wang Biochemical Genetics.2025; 63(3): 2650. CrossRef
Exploring the association between air pollution and the incidence of liver cancers Xin Wu, Xin Zhang, Xiaopeng Yu, Hongyuan Liang, Shaoshan Tang, Yao Wang Ecotoxicology and Environmental Safety.2025; 290: 117437. CrossRef
α-Fetoprotein model versus Milan criteria in predicting outcomes after hepatic resection for hepatocellular carcinoma: multicentre study Chao Li, Yong-Kang Diao, Yi-Fan Li, Shao-Dong Lv, Xian-Ming Wang, Xue-Dong Wang, Qi-Xuan Zheng, Hong Wang, Han Liu, Kong-Ying Lin, Ying-Jian Liang, Ya-Hao Zhou, Wei-Min Gu, Ming-Da Wang, Lan-Qing Yao, Xin-Fei Xu, Jia-Hao Xu, Li-Hui Gu, Timothy M Pawlik, F BJS Open.2025;[Epub] CrossRef
METTL1-driven nucleotide metabolism reprograms the immune microenvironment in hepatocellular carcinoma: a multi-omics approach for prognostic biomarker discovery Xie Weng, Yangyue Huang, Zhuoya Fu, Xingli Liu, Fuli Xie, Jiale Wang, Qiaohua Zhu, Dayong Zheng Frontiers in Immunology.2025;[Epub] CrossRef
MSNs-loaded HMME and Erastin-mediated ferroptosis combined with sonodynamic therapy for HCC treatment Chang Zhao, Guchun Qin, Caixia Ling, Yang Zhao, Yunxi Huang, Zelong Jiang, Niqiang Zhou, Junjie Liu, Danke Su, Jinghang Jiang Journal of Cancer Research and Therapeutics.2025; 21(2): 465. CrossRef
SNRPB/CCNB1 axis promotes hepatocellular carcinoma progression and cisplatin resistance through enhancing lipid metabolism reprogramming Xin Jin, Xigan He, Runze Huang, Qinyu Liu, Lei Wang, Xuanci Bai, Yibin Wu, Yixiu Wang, Ziting Jiang, Yi Shi, Gautam Sethi, Lu Wang, Weiping Zhu Journal of Experimental & Clinical Cancer Research.2025;[Epub] CrossRef
Preoperative ASAP score predicts recurrence and survival following curative hepatic resection for hepatitis B virus-related hepatocellular carcinoma: A multicenter cohort study Dongxu Yin, Zixuan Wang, Chao Li, Huixuan Fan, Zichao Tu, Yongkang Diao, Zijie Tang, Yongyi Zeng, Han Wu, Lihui Gu, Lanqing Yao, Xinfei Xu, Feng Shen, Mingda Wang, Tian Yang European Journal of Surgical Oncology.2025; 51(10): 110361. CrossRef
Exosomal FOSL1 From Cancer-associated Fibroblasts Drives the Progression and Pro-tumorigenic M2 Macrophage Polarization of Hepatocellular Carcinoma By Activating PLAU Transcription Kai Bai, Ruopeng Liang, Jian Li, Kun Zhao Applied Biochemistry and Biotechnology.2025;[Epub] CrossRef
Artificial intelligence for enhancing decision-making in multidisciplinary tumor boards for HCC in China Dong Li, Haoyu Wang, Fei Gao, Xifeng Fu, Junfeng Han Hepatoma Research.2025;[Epub] CrossRef
Predictive indicators of immune therapy efficacy in hepatocellular carcinoma based on neutrophil-to-lymphocyte ratio Shengzhe Lin, Yang Wang, Xinran Cai, Yunbin Ye, Yanling Chen International Immunopharmacology.2024; 128: 111477. CrossRef
Emerging role of molecular diagnosis and personalized therapy for hepatocellular carcinoma Ming-Da Wang, Yong-Kang Diao, Lan-Qing Yao, Zhong-Qi Fan, Ke-Chun Wang, Han Wu, Li-Hui Gu, Jia-Hao Xu, Chao Li, Guo-Yue Lv, Tian Yang iLIVER.2024; 3(1): 100083. CrossRef
Cell-Membrane-Coated Metal–Organic Framework Nanocarrier Combining Chemodynamic Therapy for the Inhibition of Hepatocellular Carcinoma Proliferation Huaying Xie, Xuhua Xiao, Xiaoyuan Yi, Kunzhao Huang, Liyan Wang Pharmaceutics.2024; 16(5): 619. CrossRef
Apolipoprotein H-based prognostic risk correlates with liver lipid metabolism disorder in patients with HBV-related hepatocellular carcinoma Yaming Liu, Zeyi Wu, Yiqun Zhao, Maochuan Zhen, Yanhong Wang, Qiusong Liu Heliyon.2024; 10(10): e31412. CrossRef
Clinical significance of LINC02532 in hepatitis B virus-associated hepatocellular carcinoma and its regulatory effect on tumor progression Wei Ding, Sujuan Xi, Kewei Gao, Danping Weng, Sheng Xu, Guoping Huang, Min Yu, Haiyan Yue, Jianguo Wang Clinics and Research in Hepatology and Gastroenterology.2024; 48(7): 102403. CrossRef
Hepatocellular carcinoma (HCC) is usually accompanied by chronic liver damage, which sometimes influences the selection of HCC treatment. The Barcelona Clinic Liver Cancer (BCLC) staging system, which was first introduced in 1999, is the most commonly used worldwide. Although the intermediate-stage (BCLC stage B) includes the largest number and heterogeneous HCC patients, the recommended treatment option is transarterial chemoembolization (TACE) only. However, recent progress in radical treatments such as hepatic resection, liver transplantation, radiation therapy, and percutaneous therapy has made it possible to treat selected patients with BCLC stage B HCC. Radical treatments are expected to prolong survival time. To-date, TACE has also progressed. In addition to conventional TACE, balloon-occluded TACE and drug-eluting beads TACE are available. These new modalities of TACE will improve therapeutic efficacy and reduce adverse events. One of the most serious concerns of TACE is that repeated TACE reduces the treatment effect and induces liver function impairment. The decision on when TACE should be interrupted is complex. Many molecular targeted agents are now available, and immune checkpoint inhibitors will soon be available for HCC patients with Child-Pugh class A worldwide. Under these circumstances, in patients with TACE unsuitability, switching to molecular targeted agents before deterioration of liver function might improve the prognosis compared to repeated TACE. We should pay attention to stop TACE in TACE-unsuitable HCC patients as it can induce the deterioration of liver function.
Citations
Citations to this article as recorded by
MRI‐Based Score to Predict Retreatment Response for Viable Hepatocellular Carcinomas After Transarterial Chemoembolization Weilang Wang, Xiuming Zhang, Yixing Yu, Feng Feng, Wu Cai, Shuwei Zhou, Shuhang Zhang, Binrong Li, Tianyi Xia, Shenghong Ju, Yuan‐Cheng Wang Liver International.2026;[Epub] CrossRef
Tumor growth rate for prognostic stratification and treatment optimization in unresectable hepatocellular carcinoma treated with TACE combined with systemic therapy Guobin Chen, Meixia Wang, Xing Huang, Zhenzhen Zhang, Yanfang Wu, Xiaochun Chen, Xinkun Guo, Susu Zheng, Tanghui Zheng, Hong Chen, Jingfang Wu, Boheng Zhang BMC Gastroenterology.2026;[Epub] CrossRef
Progress in hepatoprotective strategies during TACE treatment Chenlu Qian, Yan Wu, Chuan Yin, Jie Gao Advanced Interventional Materials.2026; 1(1): 100012. CrossRef
Discovery of Novel Selenocyanate Derivatives as Histone Deacetylase 6 Inhibitors for the Treatment of Hepatocellular Carcinoma Zeping Yang, Yuanqing Wu, Feizhi Kong, Yue Zhang, Lijun Jia, Chu Tang, Fu Wang Journal of Medicinal Chemistry.2026; 69(3): 2850. CrossRef
Prognostic significance of combined PCPE-1 and α-fetoprotein for hepatocellular carcinoma Ruhua Zhang, Wanqi Chen, Xuelan Peng, Zhiguang Zhang, Shangjiu Yang, Li Zhong Translational Oncology.2025; 51: 102185. CrossRef
Prediction of treatment response and outcome of transarterial chemoembolization in patients with hepatocellular carcinoma using artificial intelligence: A systematic review of efficacy Pedram Keshavarz, Nariman Nezami, Fereshteh Yazdanpanah, Maryam Khojaste-Sarakhsi, Zahra Mohammadigoldar, Mobin Azami, Azadeh Hajati, Faranak Ebrahimian Sadabad, Jason Chiang, Justin P. McWilliams, David S.K. Lu, Steven S. Raman European Journal of Radiology.2025; 184: 111948. CrossRef
Advanced targeted microsphere embolization for arteriovenous malformations: state-of-the-art and future directions Ali Mortezaei, Khaled M. Taghlabi, Nadir Al-Saidi, Saketh Amasa, Rachael E. Whitehead, Alex Hoang, Kurt Yaeger, Amir H. Faraji, Ramanathan Kadirvel, Sherief Ghozy Neuroradiology.2025; 67(4): 1009. CrossRef
Extrahepatic Recurrence After Surgical Resection of Hepatocellular Carcinoma Without Intrahepatic Recurrence: A Multi-Institutional Observational Study Ga Ram You, Shin Young Park, Su Hyeon Cho, Sung Bum Cho, Yang Seok Koh, Chang Hun Lee, Hoon Gil Jo, Sung Kyu Choi, Jae Hyun Yoon Cancers.2025; 17(9): 1417. CrossRef
Exosomal miRNA-720 as a potential diagnostic and prognostic biomarker for hepatocellular carcinoma 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, Jeong Won Jang The Korean Journal of Internal Medicine.2025; 40(6): 939. CrossRef
Outcomes of robotic liver resection and intraoperative radiofrequency ablation for hepatocellular carcinoma in posterior segments VII and VIII Cheng-Ming Peng, Shao-Chieh Lin, Yung-Yin Cheng, Teng-Chieh Cheng, Ching-Lung Hsieh, Chia-Hong Hsieh, Mei-Fang Hsieh, Chun-Han Liao, Ming-Cheng Liu, Yi-Jui Liu World Journal of Gastrointestinal Surgery.2025;[Epub] CrossRef
Sorafenib for 9,923 Patients with Hepatocellular Carcinoma: An Analysis from National Health Insurance Claim Data in South Korea Sojung Han, Do Young Kim, Ho Yeong Lim, Jung-Hwan Yoon, Baek-Yeol Ryoo, Yujeong Kim, Kookhee Kim, Bo Yeon Kim, So Young Yi, Dong-Sook Kim, Do-Yeon Cho, Jina Yu, Suhyun Kim, Joong-Won Park Gut and Liver.2024; 18(1): 116. CrossRef
Identification of patients with favorable prognosis after resection in intermediate-stage-hepatocellular carcinoma Han Ah Lee, Minjong Lee, Jeong-Ju Yoo, Ho Soo Chun, Yewan Park, Hwi Young Kim, Tae Hun Kim, Yeon Seok Seo, Dong Hyun Sinn International Journal of Surgery.2024; 110(2): 1008. CrossRef
A refined prediction model for survival in hepatocellular carcinoma patients treated with transarterial chemoembolization Hae Lim Lee, Seok Hwan Kim, Hee Yeon Kim, Sung Won Lee, Myeong Jun Song Frontiers in Oncology.2024;[Epub] CrossRef
Clinical outcomes of transarterial chemoembolization in Child–Turcotte Pugh class A patients with a single small (≤3 cm) hepatocellular carcinoma Jungnam Lee, Young‐Joo Jin, Seung Kak Shin, Jung Hyun Kwon, Sang Gyune Kim, Jung Hwan Yu, Jin‐Woo Lee, Oh Sang Kwon, Soon Woo Nahm, Young Seok Kim Journal of Gastroenterology and Hepatology.2024; 39(9): 1924. CrossRef
Consistent efficacy of hepatic artery infusion chemotherapy irrespective of PD‑L1 positivity in unresectable hepatocellular carcinoma Ji Kim, Young Kim, Hee-Chul Nam, Chang-Wook Kim, Jae-Sung Yoo, Ji Han, Jeong Jang, Jong Choi, Seung Yoon, Ho Jong Chun, Jung Oh, Suho Kim, Sung Lee, Pil Sung Oncology Letters.2024;[Epub] CrossRef
Evolving trends in treatment patterns for hepatocellular carcinoma in Korea from 2008 to 2022: a nationwide population-based study Ji Won Han, Won Sohn, Gwang Hyeon Choi, Jeong Won Jang, Gi Hyeon Seo, Bo Hyun Kim, Jong Young Choi Journal of Liver Cancer.2024; 24(2): 274. CrossRef
Percutaneous radiofrequency ablation for stage B1 of modified Bolondi’s subclassification for intermediate-stage hepatocellular carcinoma Ragaey Ahmad Eid, Ali M. Abdel Fattah, Alaa Farouk Haseeb, Ahmed Moheyeldien Hamed, Marwa Abdallah Shaker Egyptian Liver Journal.2024;[Epub] CrossRef
Post-operative recurrence of liver cancer according to antiviral therapy for detectable hepatitis B viremia: A nationwide study Byungyoon Yun, Sang Hoon Ahn, Juyeon Oh, Jin-Ha Yoon, Beom Kyung Kim European Journal of Internal Medicine.2023; 107: 66. CrossRef
The emerging age-pattern changes of patients with hepatocellular carcinoma in Korea Yuri Cho, Bo Hyun Kim, Joong-Won Park Clinical and Molecular Hepatology.2023; 29(1): 99. CrossRef
Barriers to palliative care in hepatocellular carcinoma: A review of the literature Mostafa Abasseri, Shakira Hoque, BA Slavica Kochovska, Kim Caldwell, Linda Sheahan, Amany Zekry Journal of Gastroenterology and Hepatology.2023; 38(7): 1047. CrossRef
Clinical consensus statement: Establishing the roles of locoregional and systemic therapies for the treatment of intermediate-stage hepatocellular carcinoma in Canada Jason K. Wong, Howard J. Lim, Vincent C. Tam, Kelly W. Burak, Laura A. Dawson, Prosanto Chaudhury, Robert J. Abraham, Brandon M. Meyers, Gonzalo Sapisochin, David Valenti, Setareh Samimi, Ravi Ramjeesingh, Amol Mujoomdar, Ilidio Martins, Elijah Dixon, Maj Cancer Treatment Reviews.2023; 115: 102526. CrossRef
Factors associated with the survival outcomes of patients with untreated hepatocellular carcinoma: An analysis of nationwide data Min Jung Kwon, Soy Chang, Ji Hoon Kim, Ji Won Han, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Pil Soo Sung Frontiers in Oncology.2023;[Epub] CrossRef
Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Chinese perspective Diyang Xie, Jieyi Shi, Jian Zhou, Jia Fan, Qiang Gao Clinical and Molecular Hepatology.2023; 29(2): 206. CrossRef
Understanding the causes of recurrent HCC after liver resection and radiofrequency ablation Carlo Bosi, Margherita Rimini, andrea Casadei-Gardini, Giorgio Ercolani Expert Review of Anticancer Therapy.2023; 23(5): 503. CrossRef
The clinical management of hepatocellular carcinoma in China: Progress and challenges Shan Shan, Jidong Jia Clinical and Molecular Hepatology.2023; 29(2): 339. CrossRef
Establishment and application of a survival rate graph model based on biomarkers and imaging indexes after primary hepatocellular carcinoma resection Yue Xu, Xiaoqin Yao, Jinmei Li, Guoyuan Zhang, Guangcheng Luo, Qiang Wang Cancer Medicine.2023; 12(12): 13329. CrossRef
Comparative efficacy and safety of molecular targeted agents combined with transarterial chemoembolization in the treatment of unresectable hepatocellular carcinoma: a network meta-analysis Jiaye Long, Baoxiang Chen, Zhaohui Liu Frontiers in Oncology.2023;[Epub] CrossRef
Prediction model of hepatitis B virus-related hepatocellular carcinoma in patients receiving antiviral therapy Beom Kyung Kim, Sang Hoon Ahn Journal of the Formosan Medical Association.2023; 122(12): 1238. CrossRef
Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma in the era of chemo-diversity Hideki Iwamoto, Shigeo Shimose, Tomotake Shirono, Takashi Niizeki, Takumi Kawaguchi Clinical and Molecular Hepatology.2023; 29(3): 593. CrossRef
Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis Moon Haeng Hur, Yuri Cho, Do Young Kim, Jae Seung Lee, Gyoung Min Kim, Hyo-Cheol Kim, Dong Hyun Sinn, Dongho Hyun, Han Ah Lee, Yeon Seok Seo, In Joon Lee, Joong-Won Park, Yoon Jun Kim Clinical and Molecular Hepatology.2023; 29(3): 763. CrossRef
Risk factors associated with late hepatocellular carcinoma detection in patients undergoing regular surveillance Sangmi Jang, Young-Joo Jin, Jin-Woo Lee, Dam Kwon, Jung Hwan Yu Medicine.2023; 102(32): e34637. CrossRef
Efficacy and safety of CalliSpheres® Microsphere transcatheter-arterial chemoembolization versus conventional TACE in treating renal angiomyolipoma patients Tianshi Lyu, Jian Wang, Xiaoqiang Tong, Tianai Mi, Chao An, Yinghua Zou Journal of Cancer Research and Therapeutics.2023; 19(4): 933. CrossRef
Hepatocellular Carcinoma: Surveillance, Diagnosis, Evaluation and Management Jessica Elderkin, Najeeb Al Hallak, Asfar S. Azmi, Hussein Aoun, Jeffrey Critchfield, Miguel Tobon, Eliza W. Beal Cancers.2023; 15(21): 5118. CrossRef
Polyamines: their significance for maintaining health and contributing to diseases Mengjuan Xuan, Xinyu Gu, Juan Li, Di Huang, Chen Xue, Yuting He Cell Communication and Signaling.2023;[Epub] CrossRef
Feasibility and safety of a novel indwelling catheter system via the femoral artery for intermittent transarterial therapy for treating malignant liver tumors Hideki Iwamoto, Satoshi Itano, Osamu Itano, Masatsugu Ishii, Takashi Niizeki, Tomotake Shirono, Shigeo Shimose, Hiroyuki Suzuki, Akira Kajiwara, Taizo Yamaguchi, Hironori Koga, Takuji Torimura Japanese Journal of Radiology.2022; 40(3): 326. CrossRef
Atezolizumab/Bevacizumab vs. Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Real-World, Multi-Center Study Beom Kyung Kim, Jaekyung Cheon, Hyeyeong Kim, Beodeul Kang, Yeonjung Ha, Do Young Kim, Seong Gyu Hwang, Young Eun Chon, Hong Jae Chon Cancers.2022; 14(7): 1747. CrossRef
Effect of postoperative administration of nafamostat mesilate on posthepatectomy liver failure Boram Lee, Jai Young Cho, Ho-Seong Han, Yoo-Seok Yoon, Hae Won Lee, Jun Suh Lee, Moonhwan Kim, Yeongsoo Jo HPB.2022; 24(9): 1569. CrossRef
Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus? Won Hyeok Choe Journal of Liver Cancer.2022; 22(1): 1. CrossRef
Association between achieving textbook outcomes and better survival after laparoscopic liver resection in the anterolateral segments in patients with hepatocellular carcinoma Mizelle D'Silva, Jai Young Cho, Ho‐Seong Han, Yoo‐Seok Yoon, Hae Won Lee, Jun Suh Lee, Boram Lee, Moonhwan Kim, Yeongsoo Jo Journal of Hepato-Biliary-Pancreatic Sciences.2022; 29(8): 855. CrossRef
A Case-Matched Analysis of Laparoscopic Liver Resection for Hepatocellular Carcinoma Located in Posterosuperior Segments of the Liver According to Adaption of Developed Techniques Yujin Kwon, Boram Lee, Jai Young Cho, Ho-Seong Han, Yoo-Seok Yoon, Hae Won Lee, Jun Suh Lee, Munwhan Kim, Youngsoo Jo Medicina.2022; 58(4): 543. CrossRef
Long-Term Outcomes of Laparoscopic Liver Resection for Centrally Located Hepatocellular Carcinoma Hyo Jun Kim, Jai Young Cho, Ho-Seong Han, Yoo-Seok Yoon, Hae Won Lee, Jun Suh Lee, Boram Lee, Yeongsoo Jo, Meeyouong Kang, Yeshong Park, Eunhye Lee Medicina.2022; 58(6): 737. CrossRef
Prognostic Comparison between cTACE and H101-TACE in Unresectable Hepatocellular Carcinoma (HCC): A Propensity-Score Matching Analysis Man Yao, Simo Cheng, Xiaofeng Zhai, Hetong Zhao, Jing Hong, Xiaoyan Li, Yongbin Meng, Wei Chen, Ye Liu Applied Bionics and Biomechanics.2022; 2022: 1. CrossRef
Prognostic Impact of MAFLD Following Surgical Resection of Hepatitis B Virus-Related Hepatocellular Carcinoma: A Nationwide Cohort Study Byungyoon Yun, Sang Hoon Ahn, Juyeon Oh, Jin-Ha Yoon, Beom Kyung Kim Cancers.2022; 14(20): 5002. CrossRef
Early extrahepatic recurrence as a pivotal factor for survival after hepatocellular carcinoma resection: A 15-year observational study Jae Hyun Yoon, Sung Kyu Choi, Sung Bum Cho, Hee Joon Kim, Yang Seok Ko, Chung Hwan Jun World Journal of Gastroenterology.2022; 28(36): 5351. CrossRef
Low-grade hepatocellular carcinoma characteristics, a practical nomogram and risk stratification system: a SEER population-based study Dashuai Yang, Yang Su, Fangrui Zhao, Yong Hu, Kailiang Zhao, Xiangyun Xiong, Mingqiang Zhu, Junpeng Pei, Youming Ding Expert Review of Gastroenterology & Hepatology.2022; 16(11-12): 1115. CrossRef
The Liver Maximum Capacity Test (LiMAx) Is Associated with Short-Term Survival in Patients with Early Stage HCC Undergoing Transarterial Treatment Janett Fischer, Stella Wellhöner, Sebastian Ebel, Thomas Lincke, Albrecht Böhlig, Florian Gerhardt, Rhea Veelken, Holger Goessmann, Karen Geva Steinhoff, Timm Denecke, Osama Sabri, Thomas Berg, Florian van Bömmel Cancers.2022; 14(21): 5323. CrossRef
Suboptimal Performance of Hepatocellular Carcinoma Prediction Models in Patients with Hepatitis B Virus-Related Cirrhosis Jae Lee, Tae Lim, Hye Lee, Seung Kim, Jun Park, Do Kim, Sang Ahn, Hyun Lee, Jung Lee, Ja Kim, In Min, Beom Kim Diagnostics.2022; 13(1): 3. CrossRef
New Evidence of Oral Branched-Chain Amino Acid Supplementation on the Prognosis of Patients With Advanced Liver Disease Hankil Lee, Jeong-Ju Yoo, Sang Hoon Ahn, Beom Kyung Kim Clinical and Translational Gastroenterology.2022; 13(12): e00542. CrossRef
Realization of improved outcomes following liver resection in hepatocellular carcinoma patients aged 75 years and older Jong Man Kim, Jinsoo Rhu, Sang Yun Ha, Gyu-Seong Choi, Choon Hyuck David Kwon, Gaabsoo Kim, Jae-Won Joh Annals of Surgical Treatment and Research.2021; 101(5): 257. CrossRef
Validation of Pre-/Post-TACE-Predict Models among Patients with Hepatocellular Carcinoma Receiving Transarterial Chemoembolization David Sooik Kim, Beom Kyung Kim, Jae Seung Lee, Hye Won Lee, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Seung Up Kim Cancers.2021; 14(1): 67. CrossRef
Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1 Tae Suk Kim, Minjong Lee, Minji Park, Sae Yun Kim, Min Suk Shim, Chea Yeon Lee, Dae Hee Choi, Yuri Cho International Journal of Molecular Sciences.2021; 22(18): 10027. CrossRef
Atezolizumab/Bevacizumab vs. Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Real-World, Multi-Center Study Beom Kyung Kim, Jaekyung Cheon, Hyeyeong Kim, Beodeul Kang, Yeonjung Ha, Do Young Kim, Sung Kyu Hwang, Young Eun Chon, Hong Jae Chon SSRN Electronic Journal .2021;[Epub] CrossRef
Alcohol-induced liver disease (ALD) is a complex disorder, with a disease spectrum ranging from steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Although the pathogenesis of ALD is incompletely understood and currently no effective drugs are available for ALD, several lines of evidence suggest that complement activation and oxidative stress play crucial roles in the pathogenesis of ALD. Complement activation can regulate the production of ROS and influence oxidative stress in ALD. Precise regulation of the complement system in ALD may be a rational and novel avenue to postpone and even reverse the progression of disease and simultaneously promote the repair of liver injury. In this mini-review, we briefly summarize the recent research progress, especially focusing on the role of complement and oxidative stress-induced transfer RNA-derived fragments, which might help us to better understand the pathogenesis of ALD and provide aid in the development of novel therapeutic strategies for ALD.
Citations
Citations to this article as recorded by
The activation of microglia by the complement system in neurodegenerative diseases He Zhao, Yayun Lv, Jiasen Xu, Xiaoyu Song, Qi Wang, Xiaoyu Zhai, Xiaohui Ma, Jingjing Qiu, Limei Cui, Yan Sun Ageing Research Reviews.2025; 104: 102636. CrossRef
Novel insights into cuproptosis in alcoholic liver disease using bioinformatics analysis and experimental validation Tongtong Pan, Shijia Wu, Shouhao Wang, Xiaodong Wang, Dazhi Chen, Yongping Chen International Immunopharmacology.2025; 146: 113828. CrossRef
Can serum C3/C4 complement ratio be used in the differential diagnosis of central nervous system demyelinating diseases? Melike Cakan, Bariscan Cimen, Nazire Pınar Acar-Ozen, Yildirim Sara, Rana Karabudak, Aslı Tuncer Multiple Sclerosis and Related Disorders.2025; 95: 106312. CrossRef
Research progress on the roles of complement in liver injury Li-Li Ou, Jin-Lian Jiang, Man-Lu Guo, Jin-Hua Wu, Wei-Wei Zhong, Yi-Huai He World Journal of Hepatology.2025;[Epub] CrossRef
Gardenin A alleviates alcohol-induced oxidative stress and inflammation in HepG2 and Caco2 cells via AMPK/Nrf2 pathway Prashsti Chadha, Hiral Aghara, Delna Johnson, Dhrubjyoti Sharma, Mitalben Odedara, Manali Patel, Hemant Kumar, Vijay Thiruvenkatam, Palash Mandal Bioorganic Chemistry.2025; 161: 108543. CrossRef
Flavonoid Polyphenols as Therapeutic Agents for Fatty Liver Disease: Mechanisms, Microbiome Interactions, and Metabolic Insights Lei Li, Yanling Jin, Tiangang Li, Bijun Lv, Difen Yuan, Xiaoya Li, Jiali Yuan Molecular Nutrition & Food Research.2025;[Epub] CrossRef
Reactive Oxygen Species as Key Molecules in the Pathogenesis of Alcoholic Fatty Liver Disease and Nonalcoholic Fatty Liver Disease: Future Perspectives Zhiqing Zhang, Hong Yang, Fei Han, Peng Guo Current Issues in Molecular Biology.2025; 47(6): 464. CrossRef
Comparative mRNA profile analysis from NAc of adolescent male mice after binge-like alcohol exposure eliciting deficits in context fear extinction learning Mario E. Lloret Torres, Arelys Rivas Jiménez, Eduardo L. Tosado Rodríguez, Kiara Cardona Jordan, Xiany X. Lay Rivera, Yaren L. Peña Señeriz, Joseph L. Capella Muñiz, Marieliz Dieppa Rodríguez, Daniel F. Ruiz Bolívar, Jovangelis González Del Toro, John A. PLOS One.2025; 20(6): e0322576. CrossRef
Discovering Heterogeneous Leukocytes Subsets Associated With Alcoholic Steatohepatitis by scRNAseq Analysis Haribalan Perumalsamy, Sehee Park, Ji Eun Kim, Xiao Xiao, Hye Young Kim, Dae Won Jun, Tae‐Hyun Yoon MedComm.2025;[Epub] CrossRef
Inflammatory liver diseases and susceptibility to sepsis Hong Lu Clinical Science.2024; 138(7): 435. CrossRef
Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway Xing-Min Zhang, Yue-Chang Huang, Bai-Zhong Chen, Qian Li, Pan-Pan Wu, Wen-Hua Chen, Ri-Hui Wu, Chen Li Frontiers in Pharmacology.2024;[Epub] CrossRef
Alcohol and Periodontal Disease: A Narrative Review Utsav H Gandhi, Amit Benjamin, Shreya Gajjar, Tanvi Hirani, Khushboo Desai, Bansariben B Suhagia, Rahnuma Ahmad, Susmita Sinha, Mainul Haque, Santosh Kumar Cureus.2024;[Epub] CrossRef
Hepatocyte-derived Fetuin-A promotes alcohol-associated liver disease in mice by inhibiting autophagy-lysosome degradation of TLR and M2 macrophage polarization Shibang Lu, Hu Jin, Tiantian Nong, Dongxiao Li, Kang Long, Yanjun Chen, Yan Li, Hao Xing, Tingcai Pan, Songqing He, Keqing Jiang, Fudi Zhong Free Radical Biology and Medicine.2024; 224: 506. CrossRef
DNA methylome analysis reveals epigenetic alteration of complement genes in advanced metabolic dysfunction-associated steatotic liver disease Amal Magdy, Hee-Jin Kim, Hanyong Go, Jun Min Lee, Hyun Ahm Sohn, Keeok Haam, Hyo-Jung Jung, Jong-Lyul Park, Taekyeong Yoo, Eun-Soo Kwon, Dong Hyeon Lee, Murim Choi, Keon Wook Kang, Won Kim, Mirang Kim Clinical and Molecular Hepatology.2024; 30(4): 824. CrossRef
Shear Wave Dispersion Elastography in ALD and MASLD: Comparative Pathophysiology and Clinical Potential—A Narrative Review Tommaso Dionisi, Linda Galasso, Luigiandrea Antuofermo, Francesco Antonio Mancarella, Giorgio Esposto, Irene Mignini, Maria Elena Ainora, Antonio Gasbarrini, Giovanni Addolorato, Maria Assunta Zocco Journal of Clinical Medicine.2024; 13(24): 7799. CrossRef
Compound Probiotic Ameliorates Acute Alcoholic Liver Disease in Mice by Modulating Gut Microbiota and Maintaining Intestinal Barrier Haixia Liu, Xing Kang, Xiaodan Yang, Hao Yang, Xiaoyu Kuang, Peng Ren, Huan Yan, Xiaorong Shen, Yongbo Kang, Lin Li, Xiaohui Wang, Linzhi Guo, Mingwei Tong, Weiping Fan Probiotics and Antimicrobial Proteins.2023; 15(1): 185. CrossRef
Hepatoprotective Effect of Kaempferol: A Review of the Dietary Sources, Bioavailability, Mechanisms of Action, and Safety Maulana Yusuf Alkandahri, Barolym Tri Pamungkas, Zulpakor Oktoba, Mareetha Zahra Shafirany, Lela Sulastri, Maya Arfania, Ebta Narasukma Anggraeny, Ade Pratiwi, Fitri Dwi Astuti, Indriyani, Siti Yuliani Dewi, Salsa Zulfa Hamidah, Srinivas Mutalik Advances in Pharmacological and Pharmaceutical Sciences.2023; 2023: 1. CrossRef
Antioxidant and hepatoprotective activities of methanolic extract of Fimbristylis miliacea (L.) Vahl Roni Roy, Jony Roy, Israt Jahan Liya, Jamiuddin Ahmed, Afroza Akter, Mohammad Anwarul Basher Phytomedicine Plus.2023; 3(2): 100449. CrossRef
Hydrogen gas ameliorates acute alcoholic liver injury via anti-inflammatory and antioxidant effects and regulation of intestinal microbiota Haixia Liu, Xing Kang, Peng Ren, Xiaoyu Kuang, Xiaodan Yang, Hao Yang, Xiaorong Shen, Huan Yan, Yongbo Kang, Fan Zhang, Xiaohui Wang, Linzhi Guo, Weiping Fan International Immunopharmacology.2023; 120: 110252. CrossRef
RNA alternative splicing impacts the risk for alcohol use disorder Rudong Li, Jill L. Reiter, Andy B. Chen, Steven X. Chen, Tatiana Foroud, Howard J. Edenberg, Dongbing Lai, Yunlong Liu Molecular Psychiatry.2023; 28(7): 2922. CrossRef
Interorgan communication with the liver: novel mechanisms and therapeutic targets Jiulu Zhao, Xi Zhang, Yuan Li, Jizhang Yu, Zhang Chen, Yuqing Niu, Shuan Ran, Song Wang, Weicong Ye, Zilong Luo, Xiaohan Li, Yanglin Hao, Junjie Zong, Chengkun Xia, Jiahong Xia, Jie Wu Frontiers in Immunology.2023;[Epub] CrossRef
Métabolisme de l’alcool N. Dali-Youcef, J.-L. Schlienger EMC - Pathologie professionnelle et de l 'environnement.2023; 42(3): 1. CrossRef
Métabolisme de l’alcool N. Dali-Youcef, J.-L. Schlienger EMC - Hépatologie.2023; 38(2): 1. CrossRef
Immune cells in alcohol-related liver disease Honghai Xu, Hua Wang Liver Research.2022; 6(1): 1. CrossRef
Complement in Acute Liver Failure: The Right Timing to Give a Sincere Compliment Susanne N. Weber, Frank Lammert Cellular and Molecular Gastroenterology and Hepatology.2021; 11(5): 1546. CrossRef
Complement System in Alcohol-Associated Liver Disease Lazara Elena Santiesteban-Lores, Milena Carvalho Carneiro, Lourdes Isaac, Lorena Bavia Immunology Letters.2021; 236: 37. CrossRef
Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression Ming-Ling Chang, Zinger Yang, Sien-Sing Yang International Journal of Molecular Sciences.2020; 21(21): 8308. CrossRef
Hepatocellular carcinoma (HCC) is a major global health problem, which has a grave morbidity and mortality. Over the past few decades, no effective systemic therapeutic modalities have been established for patients with the unresectable HCC in advanced stage. Sorafenib is a small molecule that blocks cancer cell proliferation by targeting the intracellular signaling pathway at the level of Raf-1 and B-Raf serine-threonine kinases, and exerts an anti-angiogenic effect by targeting the vascular endothelial growth factor receptor-1, 2 and 3, and platelet-derived growth factor receptor-β tyrosine kinases. Recently, two clinical successful applications, SHARP and Asia-Pacific trial, of multikinase inhibitor sorafenib represent a significant advance in the treatment of advanced HCC patients without a curative chance. However, because the results of clinical trials show diverse responses in a subset of HCC patients, a molecular classification of HCC through the excavation of specific biomarkers related to its biological behavior is necessary for sorting HCC patients to each group with a biological homogeneity, ultimately leading to the most suitable individualization of molecular targeted therapy in HCC. (Korean J Hepatol 2009,15:299-308)
Citations
Citations to this article as recorded by
MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE Xin Lu, Zhiyuan Chen, Wenting Mi, Jianming Zheng, Yubin Liu Open Medicine.2024;[Epub] CrossRef
Cytotoxicities of novel hydrazone compounds with pyrrolidine moiety: inhibition of mitochondrial respiration may be a possible mechanism of action for the cytotoxicity of new hydrazones Kaan Kucukoglu, Mustafa Gul, Halise Inci Gul, Rengul Cetin-Atalay, Bernard Geny Medicinal Chemistry Research.2018; 27(9): 2116. CrossRef
Neurotensin regulation induces overexpression and activation of EGFR in HCC and restores response to erlotinib and sorafenib Zherui Wu, Antoine Galmiche, Jin Liu, Nicolas Stadler, Dominique Wendum, Evelyne Segal-Bendirdjian, Valerie Paradis, Patricia Forgez Cancer Letters.2017; 388: 73. CrossRef
Metastatic hepatocellular carcinoma presenting as facial nerve palsy and facial pain Jong In Yang, Jung Mook Kang, Hee Jin Byun, Go Eun Chung, Jeong Yoon Yim, Min Jung Park, Jeong-Hoon Lee, Jung Hwan Yoon, Hyo Suk Lee The Korean Journal of Hepatology.2011; 17(4): 319. CrossRef
Prognostic significance of co‐expression of nm23 and p57 protein in hepatocellular carcinoma Hui Guo, Kejun Nan, Tinghua Hu, Jie Meng, Wentao Hui, Xiaozhan Zhang, Haixia Qin, Chenguang Sui Hepatology Research.2010; 40(11): 1107. CrossRef
Hepatocellular carcinoma – a challenge for oncologists R. Anghel memo - Magazine of European Medical Oncology.2010; 3(3): 97. CrossRef
Current status of liver diseases in Korea: Hepatocellular carcinoma Il Han Song, Kyung Sik Kim The Korean Journal of Hepatology.2009; 15(Suppl 6): S50. CrossRef
First
Prev
