Background: To evaluate the relationship between soluble CD36 (sCD36) and type 2 diabetes mellitus complicated by hepatocellular carcinoma (T2DM-HCC), and to explore its potential clinical prognostic value.
Methods: A prospective study was conducted enrolling newly diagnosed T2DM-HCC patients from two medical centers, along with control groups including healthy individuals (HC), T2DM patients, and HCC patients. Clinical, biochemical, and pathological data were collected. Serum sCD36 levels were measured by ELISA. Univariate and multivariate analyses were used to identify recurrence risk factors, and ROC analysis was performed to evaluate diagnostic performance.
Results: Among 258 participants, the T2DM-HCC group exhibited the highest sCD36 levels, impaired liver function, lower platelets, and mild chronic inflammation. In this group, sCD36 levels positively correlated with tumor stage, size, and proliferation. In univariable analysis, it was associated with postoperative recurrence (OR = 2.57, 95% CI: 0.68-9.67). The predictive ability of sCD36 for recurrence (AUC = 0.86) was comparable to AFP (AUC = 0.89), while their combination showed the highest accuracy (AUC = 0.94).
Conclusion: sCD36 is associated with tumor progression in T2DM-HCC patients and serves as an independent risk factor for recurrence. To the best of our knowledge, this is the first study to identify sCD36 as a critical clinical biomarker for disease progression in T2DM-HCC, with strong potential for clinical application.
Trial registration: This study was registered in September 2024 with the Chinese Clinical Trial Registry (ChiCTR), registration number: ChiCTR2400089651.
{"title":"sCD36 as a Biomarker for Progression and Recurrence in Type 2 Diabetes Mellitus Associated Hepatocellular Carcinoma.","authors":"Weiwei Dai, Fan Yang, Furao Guo, Yuling Ding, Deying He, Jiajia Zhang, Ying Guo, Yingying Gao, Anhua Xiao","doi":"10.2147/JHC.S565006","DOIUrl":"10.2147/JHC.S565006","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the relationship between soluble CD36 (sCD36) and type 2 diabetes mellitus complicated by hepatocellular carcinoma (T2DM-HCC), and to explore its potential clinical prognostic value.</p><p><strong>Methods: </strong>A prospective study was conducted enrolling newly diagnosed T2DM-HCC patients from two medical centers, along with control groups including healthy individuals (HC), T2DM patients, and HCC patients. Clinical, biochemical, and pathological data were collected. Serum sCD36 levels were measured by ELISA. Univariate and multivariate analyses were used to identify recurrence risk factors, and ROC analysis was performed to evaluate diagnostic performance.</p><p><strong>Results: </strong>Among 258 participants, the T2DM-HCC group exhibited the highest sCD36 levels, impaired liver function, lower platelets, and mild chronic inflammation. In this group, sCD36 levels positively correlated with tumor stage, size, and proliferation. In univariable analysis, it was associated with postoperative recurrence (OR = 2.57, 95% CI: 0.68-9.67). The predictive ability of sCD36 for recurrence (AUC = 0.86) was comparable to AFP (AUC = 0.89), while their combination showed the highest accuracy (AUC = 0.94).</p><p><strong>Conclusion: </strong>sCD36 is associated with tumor progression in T2DM-HCC patients and serves as an independent risk factor for recurrence. To the best of our knowledge, this is the first study to identify sCD36 as a critical clinical biomarker for disease progression in T2DM-HCC, with strong potential for clinical application.</p><p><strong>Trial registration: </strong>This study was registered in September 2024 with the Chinese Clinical Trial Registry (ChiCTR), registration number: ChiCTR2400089651.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"12 ","pages":"2541-2552"},"PeriodicalIF":3.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12625760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-07eCollection Date: 2025-01-01DOI: 10.2147/JHC.S538084
Huidong Guo, Xiaojun Chen, Rong Li, Jianzhen Shen, Donghui Gan, Yue Yin, Hehui Zhang, Jiachen Xie, Longfei Xie, Yanquan Liu
Objective: This study retrospectively analyzed clinical data from adolescent primary liver cancer (PLC) cases over the past decade, summarizing clinical characteristics, diagnostic approaches, and prognostic outcomes to provide guidance for prevention, early diagnosis, and timely treatment of adolescent PLC.
Methods: Clinical data of 497 cases of adolescent PLC patients were collected from January 1, 2014, to December 31, 2024. The baseline demographic data, general condition, imaging, laboratory findings, and pathological features of these patients were described, and the diagnostic and therapeutic processes were analyzed, univariate and multivariate Cox regression analyses were conducted to identify significant prognostic factors.
Results: The age of onset for patients was 13.75 (10.25-19.00) years, with 311 males (62.58%) and 186 females (37.42%), yielding a male-to-female ratio of 1.67:1. Elevated ALT and GGT levels were observed in most patients, while all patients exhibited elevated ChE. Among all patients included in this study, 320 cases (64.39%) were infected with HBV, 469 cases (94.36%) were diagnosed with hepatocellular carcinoma (HCC), 14 cases (2.82%) with intrahepatic cholangiocarcinoma, and 14 cases (2.82%) with mixed hepatocellular-intrahepatic cholangiocarcinoma. The follow-up results showed the 1-year, 2-year, and 3-year survival rates in adolescent PLC patients were 45.27%, 20.32%, and 8.45%, respectively. The univariate Cox regression analysis revealed that adolescent PLC patients who accompanied with portal vein tumor thrombus, ascites, advanced CNLC stage, abnormalities in AFP, ALT, AST, AST/ALT ratio, GGT, ALP and TBIL, high ECOG score and non-surgical treatment had shorter OS (P < 0.05). Multivariate Cox regression analysis showed that portal vein tumor thrombus, advanced CNLC stage, abnormalities in AFP, GGT, and non-surgical treatment were independent prognostic factors influencing the OS of adolescent PLC patients (P < 0.05).
Conclusion: Clinical manifestations and symptoms of adolescent PLC patients lack specificity, and portal vein tumor thrombus, advanced CNLC stage, abnormalities in AFP, GGT, and non-surgical treatment were independent prognostic factors influencing OS in adolescent PLC.
{"title":"Clinical Implications and Novel Insights into Adolescent Primary Liver Cancer: A Nightmare for Adolescents?","authors":"Huidong Guo, Xiaojun Chen, Rong Li, Jianzhen Shen, Donghui Gan, Yue Yin, Hehui Zhang, Jiachen Xie, Longfei Xie, Yanquan Liu","doi":"10.2147/JHC.S538084","DOIUrl":"10.2147/JHC.S538084","url":null,"abstract":"<p><strong>Objective: </strong>This study retrospectively analyzed clinical data from adolescent primary liver cancer (PLC) cases over the past decade, summarizing clinical characteristics, diagnostic approaches, and prognostic outcomes to provide guidance for prevention, early diagnosis, and timely treatment of adolescent PLC.</p><p><strong>Methods: </strong>Clinical data of 497 cases of adolescent PLC patients were collected from January 1, 2014, to December 31, 2024. The baseline demographic data, general condition, imaging, laboratory findings, and pathological features of these patients were described, and the diagnostic and therapeutic processes were analyzed, univariate and multivariate Cox regression analyses were conducted to identify significant prognostic factors.</p><p><strong>Results: </strong>The age of onset for patients was 13.75 (10.25-19.00) years, with 311 males (62.58%) and 186 females (37.42%), yielding a male-to-female ratio of 1.67:1. Elevated ALT and GGT levels were observed in most patients, while all patients exhibited elevated ChE. Among all patients included in this study, 320 cases (64.39%) were infected with HBV, 469 cases (94.36%) were diagnosed with hepatocellular carcinoma (HCC), 14 cases (2.82%) with intrahepatic cholangiocarcinoma, and 14 cases (2.82%) with mixed hepatocellular-intrahepatic cholangiocarcinoma. The follow-up results showed the 1-year, 2-year, and 3-year survival rates in adolescent PLC patients were 45.27%, 20.32%, and 8.45%, respectively. The univariate Cox regression analysis revealed that adolescent PLC patients who accompanied with portal vein tumor thrombus, ascites, advanced CNLC stage, abnormalities in AFP, ALT, AST, AST/ALT ratio, GGT, ALP and TBIL, high ECOG score and non-surgical treatment had shorter OS (<i>P</i> < 0.05). Multivariate Cox regression analysis showed that portal vein tumor thrombus, advanced CNLC stage, abnormalities in AFP, GGT, and non-surgical treatment were independent prognostic factors influencing the OS of adolescent PLC patients (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>Clinical manifestations and symptoms of adolescent PLC patients lack specificity, and portal vein tumor thrombus, advanced CNLC stage, abnormalities in AFP, GGT, and non-surgical treatment were independent prognostic factors influencing OS in adolescent PLC.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"12 ","pages":"2513-2540"},"PeriodicalIF":3.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12604521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Systemic inflammatory response is reported to occupy a crucial role in the progression of hepatocellular carcinoma (HCC). The prognostic significance of SII and PNI in HCC has been explored, but the prognostic significance of aggregate index of systemic inflammation (AISI) in HCC is still unknown. This study was designed to determine the prognostic significance of AISI in HCC and explain the potential underlying mechanisms via gut microbiota and fecal metabolomic profiling.
Patients and methods: A cohort of 109 cases of HCC individuals during January 2023 to August 2024 was included into this clinical research, and the clinical information and fresh fecal samples were collected. The fecal samples were collected for 16S rRNA sequence and metabolomics analysis.
Results: Survival analysis revealed that HCC patients in low AISI group tend to experience relatively longer survival time compared with those in high AISI group. Then, we employed ROC analysis to measure the predictive performance of AISI for the survival outcome, and ROC curve showed that levels of AISI had good predictive performance for the survival status with an AUC of 0.771 (95%CI: 0.671-0.871). 16S rRNA sequencing results revealed that levels of Parabacteroides were up-regulated in the low AISI group, and levels of Fusicatenibacter were up-regulated in the high AISI group. Metabolic analysis demonstrated that cavipetin A, pemptoporphyrin, and 8-Oxo-dGMP with high VIP value were the most distinct fecal metabolites.
Conclusion: AISI is a potential prognostic biomarker in individuals with HCC. A low level of AISI was correlated with high abundance of Parabacteroides and some metabolites, indicating that AISI might affect the prognosis of HCC individuals via the regulations of gut microbes and metabolites.
{"title":"Low Aggregate Index of Systemic Inflammation Values Correlate with Favorable Prognosis and High Abundance of <i>Parabacteroides</i> in Hepatocellular Carcinoma.","authors":"Wenju Sun, Fengqin Zhou, Chengyu Shi, Congcong Xu, Zhihai Wang, Xufeng Guo","doi":"10.2147/JHC.S538192","DOIUrl":"10.2147/JHC.S538192","url":null,"abstract":"<p><strong>Purpose: </strong>Systemic inflammatory response is reported to occupy a crucial role in the progression of hepatocellular carcinoma (HCC). The prognostic significance of SII and PNI in HCC has been explored, but the prognostic significance of aggregate index of systemic inflammation (AISI) in HCC is still unknown. This study was designed to determine the prognostic significance of AISI in HCC and explain the potential underlying mechanisms via gut microbiota and fecal metabolomic profiling.</p><p><strong>Patients and methods: </strong>A cohort of 109 cases of HCC individuals during January 2023 to August 2024 was included into this clinical research, and the clinical information and fresh fecal samples were collected. The fecal samples were collected for 16S rRNA sequence and metabolomics analysis.</p><p><strong>Results: </strong>Survival analysis revealed that HCC patients in low AISI group tend to experience relatively longer survival time compared with those in high AISI group. Then, we employed ROC analysis to measure the predictive performance of AISI for the survival outcome, and ROC curve showed that levels of AISI had good predictive performance for the survival status with an AUC of 0.771 (95%CI: 0.671-0.871). 16S rRNA sequencing results revealed that levels of <i>Parabacteroides</i> were up-regulated in the low AISI group, and levels of <i>Fusicatenibacter</i> were up-regulated in the high AISI group. Metabolic analysis demonstrated that cavipetin A, pemptoporphyrin, and 8-Oxo-dGMP with high VIP value were the most distinct fecal metabolites.</p><p><strong>Conclusion: </strong>AISI is a potential prognostic biomarker in individuals with HCC. A low level of AISI was correlated with high abundance of <i>Parabacteroides</i> and some metabolites, indicating that AISI might affect the prognosis of HCC individuals via the regulations of gut microbes and metabolites.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"12 ","pages":"2491-2500"},"PeriodicalIF":3.4,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12599210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145495743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hepatocellular carcinoma (HCC) is the most common liver cancer and has a high incidence in China, largely due to the high prevalence of hepatitis B virus (HBV) infection. HBV‑related HCC often presents with aggressive characteristics but preserved liver function. Resection and ablation are approaches to achieve potentially curative outcomes. However, the recurrence rate is high, with up to 70% within five years. Curative surgery or ablation is used more broadly in China than in Western countries, so identifying patients at high risk of recurrence is essential: risk stratification can inform postoperative management, including surveillance intensity and avoidance of over- or under-treatment. Baseline characteristics provide a simple method of prediction, the impacts of which differ in early and late recurrence. To our knowledge, this is the first narrative review to comprehensively understand the identification, prevalence, and impact of risk factors for both early and late HCC recurrence in Chinese patients following curative‑intent resection or ablation. The review suggests that the most impactful risk factors for early recurrence are aggressive tumor features including tumor size, number and vascular invasion. For late recurrence, key risk factors are patient characteristics such as sex, viral infections and liver cirrhosis. As these risk factors are interrelated, several integrated predictive models like nomograms and artificial intelligence (AI) applications have been proposed, which may enhance risk stratification and inform personalized management strategies. These models should be further validated in large prospective studies to achieve clinical application.
{"title":"Risk Factors for Recurrence in Patients with Hepatocellular Carcinoma After Curative Resection or Ablation.","authors":"Fanzheng Meng, Jizhou Wang, Xiao-Dong Zhu, Meng Zhang, Xiaowu Zhang, Dantong Cheng, Xijie Zhang, Lianxin Liu","doi":"10.2147/JHC.S552316","DOIUrl":"10.2147/JHC.S552316","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most common liver cancer and has a high incidence in China, largely due to the high prevalence of hepatitis B virus (HBV) infection. HBV‑related HCC often presents with aggressive characteristics but preserved liver function. Resection and ablation are approaches to achieve potentially curative outcomes. However, the recurrence rate is high, with up to 70% within five years. Curative surgery or ablation is used more broadly in China than in Western countries, so identifying patients at high risk of recurrence is essential: risk stratification can inform postoperative management, including surveillance intensity and avoidance of over- or under-treatment. Baseline characteristics provide a simple method of prediction, the impacts of which differ in early and late recurrence. To our knowledge, this is the first narrative review to comprehensively understand the identification, prevalence, and impact of risk factors for both early and late HCC recurrence in Chinese patients following curative‑intent resection or ablation. The review suggests that the most impactful risk factors for early recurrence are aggressive tumor features including tumor size, number and vascular invasion. For late recurrence, key risk factors are patient characteristics such as sex, viral infections and liver cirrhosis. As these risk factors are interrelated, several integrated predictive models like nomograms and artificial intelligence (AI) applications have been proposed, which may enhance risk stratification and inform personalized management strategies. These models should be further validated in large prospective studies to achieve clinical application.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"12 ","pages":"2501-2511"},"PeriodicalIF":3.4,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12599226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145495791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Very early recurrence (VER), defined as recurrence within one year after curative resection of hepatocellular carcinoma (HCC), significantly impacts long-term survival. This study aimed to develop and validate the ANT Score, a novel prognostic model integrating nutrition, inflammation, and tumor burden to refine VER prediction.
Methods: A retrospective cohort of HCC patients undergoing curative liver resection was analyzed. Key predictors were identified using least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression, forming the ANT Score. Model performance was evaluated through receiver operating characteristic (ROC) curve analysis, DeLong's test, calibration curves, and decision curve analysis (DCA). The prognostic value of capsule integrity was also assessed.
Results: Among 459 included patients, 118 (25.7%) experienced VER. Patients were randomly assigned to training (70%) and test (30%) cohorts. The ANT Score, comprising albumin-to-alkaline phosphatase ratio (AAPR), neutrophil-to-albumin ratio (NPAR), and tumor burden score (TBS), demonstrated superior predictive performance (area under the curve [AUC] = 0.751, 95% confidence interval: 0.669-0.832, P < 0.05) compared to conventional markers. Capsule incompleteness was an independent risk factor but did not significantly enhance predictive accuracy (AUC = 0.76 vs 0.751, P > 0.05, DeLong test). The ANT Score-based nomogram exhibited excellent calibration and clinical utility in DCA.
Conclusion: The ANT Score is an independent and superior predictor of VER after curative HCC resection. The ANT Score-based nomogram showed promising predictive value, offering a practical tool for individualized risk assessment. External validation and prospective studies are warranted to further assess its clinical applicability.
背景:非常早期复发(VER),定义为肝细胞癌(HCC)根治性切除后一年内的复发,显著影响长期生存。本研究旨在开发和验证ANT评分,这是一种整合营养、炎症和肿瘤负担的新型预后模型,以完善VER预测。方法:对行根治性肝切除术的HCC患者进行回顾性队列分析。使用最小绝对收缩和选择算子(LASSO)回归和多元逻辑回归确定关键预测因子,形成ANT评分。通过受试者工作特征(ROC)曲线分析、德龙检验、校正曲线和决策曲线分析(DCA)评价模型的性能。还评估了胶囊完整性的预后价值。结果:459例患者中,有118例(25.7%)发生VER。患者被随机分配到训练组(70%)和测试组(30%)。由白蛋白与碱性磷酸酶比值(AAPR)、中性粒细胞与白蛋白比值(NPAR)和肿瘤负荷评分(TBS)组成的ANT评分与常规标记物相比,显示出更优越的预测性能(曲线下面积[AUC] = 0.751, 95%可信区间:0.669-0.832,P < 0.05)。胶囊不完整是独立的危险因素,但没有显著提高预测准确性(AUC = 0.76 vs 0.751, P < 0.05, DeLong检验)。基于ANT评分的图在DCA中表现出良好的校准和临床应用。结论:ANT评分是肝癌根治性切除术后VER的独立且优越的预测指标。基于ANT评分的nomogram显示了良好的预测价值,为个体化风险评估提供了实用的工具。需要外部验证和前瞻性研究来进一步评估其临床适用性。
{"title":"ANT Score Nomogram for Predicting Very Early Recurrence of Hepatocellular Carcinoma.","authors":"Zichen Yu, Hanyu Wang, Qiang Huo, Wenli Cao, Liming Jin, Jie Liu, Fangqiang Wei","doi":"10.2147/JHC.S556733","DOIUrl":"10.2147/JHC.S556733","url":null,"abstract":"<p><strong>Background: </strong>Very early recurrence (VER), defined as recurrence within one year after curative resection of hepatocellular carcinoma (HCC), significantly impacts long-term survival. This study aimed to develop and validate the ANT Score, a novel prognostic model integrating nutrition, inflammation, and tumor burden to refine VER prediction.</p><p><strong>Methods: </strong>A retrospective cohort of HCC patients undergoing curative liver resection was analyzed. Key predictors were identified using least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression, forming the ANT Score. Model performance was evaluated through receiver operating characteristic (ROC) curve analysis, DeLong's test, calibration curves, and decision curve analysis (DCA). The prognostic value of capsule integrity was also assessed.</p><p><strong>Results: </strong>Among 459 included patients, 118 (25.7%) experienced VER. Patients were randomly assigned to training (70%) and test (30%) cohorts. The ANT Score, comprising albumin-to-alkaline phosphatase ratio (AAPR), neutrophil-to-albumin ratio (NPAR), and tumor burden score (TBS), demonstrated superior predictive performance (area under the curve [AUC] = 0.751, 95% confidence interval: 0.669-0.832, P < 0.05) compared to conventional markers. Capsule incompleteness was an independent risk factor but did not significantly enhance predictive accuracy (AUC = 0.76 vs 0.751, P > 0.05, DeLong test). The ANT Score-based nomogram exhibited excellent calibration and clinical utility in DCA.</p><p><strong>Conclusion: </strong>The ANT Score is an independent and superior predictor of VER after curative HCC resection. The ANT Score-based nomogram showed promising predictive value, offering a practical tool for individualized risk assessment. External validation and prospective studies are warranted to further assess its clinical applicability.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"12 ","pages":"2477-2490"},"PeriodicalIF":3.4,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12596833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01eCollection Date: 2025-01-01DOI: 10.2147/JHC.S536629
Aoyun Hao, Changlei Li, Ruitao Sun, Bin Tan, Guanming Shao, Kun Li, Na Li, Weiyu Hu, Chao Qu, Jingyu Cao
Background: With the increasing prevalence of obesity and type 2 diabetes, the number of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) coexisting with hepatic steatosis is steadily rising. However, the impact of hepatic steatosis on tumor recurrence following radical resection remains unclear.
Methods: We retrospectively analyzed a cohort of 733 HBV-infected patients diagnosed with HCC who underwent curative liver resection. Propensity score matching (PSM) was performed at a 1:2 ratio using 12 covariates to reduce selection bias and explore the association between preoperative hepatic steatosis and recurrence-free survival (RFS). Furthermore, we constructed a postoperative recurrence prediction model based on hepatic steatosis and other clinicopathological factors using 101 combinations of machine learning algorithms. The optimal model was identified through comprehensive evaluation and validation.
Results: After PSM, survival analysis revealed that patients without hepatic steatosis had significantly better RFS compared to those with steatosis. Multivariate Cox regression analysis confirmed that preoperative hepatic steatosis was an independent risk factor for recurrence following radical resection ( P = 0.006, HR:1.564, 95% CI:1.137-2.150). A recurrence prediction model was developed using hepatic steatosis and additional clinicopathological features through machine learning. Among the 101 models tested, the Random Survival Forest (RSF) model exhibited the best predictive performance, achieving a C-index of 0.719 in the training cohort. The model demonstrated high predictive accuracy for 1-, 2-, and 3-year recurrence, with AUC of 0.782, 0.856, and 0.898, respectively. Compared to conventional staging systems such as BCLC and CNLC, our model achieved superior performance, and decision curve analysis (DCA) demonstrated favorable clinical utility.
Conclusion: Preoperative hepatic steatosis is an independent predictor of recurrence after radical resection in patients with HBV-related HCC. The RSF-based machine learning model incorporating hepatic steatosis and other clinicopathological factors effectively predicts postoperative recurrence risk and may facilitate personalized clinical decision-making in this patient population.
{"title":"Predictive Value of Hepatic Steatosis for Postoperative Recurrence in Hepatitis B-Related Hepatocellular Carcinoma: Development of a Machine Learning-Based Prognostic Model.","authors":"Aoyun Hao, Changlei Li, Ruitao Sun, Bin Tan, Guanming Shao, Kun Li, Na Li, Weiyu Hu, Chao Qu, Jingyu Cao","doi":"10.2147/JHC.S536629","DOIUrl":"10.2147/JHC.S536629","url":null,"abstract":"<p><strong>Background: </strong>With the increasing prevalence of obesity and type 2 diabetes, the number of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) coexisting with hepatic steatosis is steadily rising. However, the impact of hepatic steatosis on tumor recurrence following radical resection remains unclear.</p><p><strong>Methods: </strong>We retrospectively analyzed a cohort of 733 HBV-infected patients diagnosed with HCC who underwent curative liver resection. Propensity score matching (PSM) was performed at a 1:2 ratio using 12 covariates to reduce selection bias and explore the association between preoperative hepatic steatosis and recurrence-free survival (RFS). Furthermore, we constructed a postoperative recurrence prediction model based on hepatic steatosis and other clinicopathological factors using 101 combinations of machine learning algorithms. The optimal model was identified through comprehensive evaluation and validation.</p><p><strong>Results: </strong>After PSM, survival analysis revealed that patients without hepatic steatosis had significantly better RFS compared to those with steatosis. Multivariate Cox regression analysis confirmed that preoperative hepatic steatosis was an independent risk factor for recurrence following radical resection ( <b><i>P</i></b> = 0.006, HR:1.564, 95% CI:1.137-2.150). A recurrence prediction model was developed using hepatic steatosis and additional clinicopathological features through machine learning. Among the 101 models tested, the Random Survival Forest (RSF) model exhibited the best predictive performance, achieving a C-index of 0.719 in the training cohort. The model demonstrated high predictive accuracy for 1-, 2-, and 3-year recurrence, with AUC of 0.782, 0.856, and 0.898, respectively. Compared to conventional staging systems such as BCLC and CNLC, our model achieved superior performance, and decision curve analysis (DCA) demonstrated favorable clinical utility.</p><p><strong>Conclusion: </strong>Preoperative hepatic steatosis is an independent predictor of recurrence after radical resection in patients with HBV-related HCC. The RSF-based machine learning model incorporating hepatic steatosis and other clinicopathological factors effectively predicts postoperative recurrence risk and may facilitate personalized clinical decision-making in this patient population.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"12 ","pages":"2459-2475"},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12587867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-31eCollection Date: 2025-01-01DOI: 10.2147/JHC.S544565
Haibin Tu, Dingluan Lin, Cailong Chen
Objective: Targeted and immunotherapy offer new treatment options for patients with advanced hepatocellular carcinoma (HCC); however, the proportion of patients who benefit from these therapies remains limited. Moreover, these treatments can involve complications and add financial burdens to patients, underscoring the need to identify those who are likely to benefit. As an advanced molecular imaging technique, nuclear medicine has the potential to predict treatment efficacy in targeted and immunotherapy, though its predictive accuracy remains uncertain. This narrative review aims to summarize existing research on nuclear medicine applications in this area, providing clinicians with new perspectives.
Materials and methods: We conducted a literature review across multiple medical databases, including PubMed, Embase, Cochrane Library, Web of Science, and Scopus. Relevant studies were identified, organized, and summarized to present findings in the field.
Results: The findings indicate that metrics such as maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) correlate with the efficacy of targeted and immunotherapy. Additionally, emerging nuclear medicine techniques have shown promise in predicting PD-L1 expression.
Conclusion: Nuclear medicine holds potential for identifying patients who are likely to benefit from targeted and immunotherapy. However, further refinements are necessary to optimize its predictive capabilities.
目的:靶向和免疫治疗为晚期肝细胞癌(HCC)患者提供新的治疗选择;然而,从这些疗法中受益的患者比例仍然有限。此外,这些治疗可能涉及并发症并增加患者的经济负担,因此需要确定哪些人可能受益。核医学作为一种先进的分子成像技术,具有预测靶向治疗和免疫治疗疗效的潜力,但其预测准确性尚不确定。本文旨在对核医学在这一领域的应用进行综述,为临床医生提供新的视角。材料和方法:我们对多个医学数据库进行了文献综述,包括PubMed、Embase、Cochrane Library、Web of Science和Scopus。相关研究被确定、组织和总结,以呈现该领域的发现。结果:研究结果表明,最大标准化摄取值(SUVmax)和代谢肿瘤体积(MTV)等指标与靶向治疗和免疫治疗的疗效相关。此外,新兴的核医学技术在预测PD-L1表达方面显示出了希望。结论:核医学在识别可能受益于靶向和免疫治疗的患者方面具有潜力。然而,需要进一步改进以优化其预测能力。
{"title":"The Role of Nuclear Medicine in Predicting Treatment Response to Immunotherapy and Targeted Therapy in Hepatocellular Carcinoma: A Narrative Review.","authors":"Haibin Tu, Dingluan Lin, Cailong Chen","doi":"10.2147/JHC.S544565","DOIUrl":"10.2147/JHC.S544565","url":null,"abstract":"<p><strong>Objective: </strong>Targeted and immunotherapy offer new treatment options for patients with advanced hepatocellular carcinoma (HCC); however, the proportion of patients who benefit from these therapies remains limited. Moreover, these treatments can involve complications and add financial burdens to patients, underscoring the need to identify those who are likely to benefit. As an advanced molecular imaging technique, nuclear medicine has the potential to predict treatment efficacy in targeted and immunotherapy, though its predictive accuracy remains uncertain. This narrative review aims to summarize existing research on nuclear medicine applications in this area, providing clinicians with new perspectives.</p><p><strong>Materials and methods: </strong>We conducted a literature review across multiple medical databases, including PubMed, Embase, Cochrane Library, Web of Science, and Scopus. Relevant studies were identified, organized, and summarized to present findings in the field.</p><p><strong>Results: </strong>The findings indicate that metrics such as maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) correlate with the efficacy of targeted and immunotherapy. Additionally, emerging nuclear medicine techniques have shown promise in predicting PD-L1 expression.</p><p><strong>Conclusion: </strong>Nuclear medicine holds potential for identifying patients who are likely to benefit from targeted and immunotherapy. However, further refinements are necessary to optimize its predictive capabilities.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"12 ","pages":"2445-2457"},"PeriodicalIF":3.4,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12584814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28eCollection Date: 2025-01-01DOI: 10.2147/JHC.S549003
Tuo Zhang, Yongping Huang, Sha Hu, Yongjie Yu, Fang Qin, Yu Zhang, Zeming Cai, Haitao Wang, Peng Zhang, Jing Dai
Purpose: The study aims to further classify hepatocellular carcinoma (HCC) based on proliferative capacity, identify hub genes associated with highly proliferative HCC, and investigate its regulatory roles in HCC.
Materials and methods: Bioinformatics analysis was employed to establish classification of HCC and further identify the hub gene. Cell counting kit-8 (CCK-8) assay, colony formation assay, Western Blot assay and tumor xenograft assay were employed to detect the proliferation of HCC cells. Transwell assay and Western blot assay were employed to detect the migration of HCC cells. RNA sequencing analysis was employed to explore the signaling pathways activated by the gene and verify it through rescue experiments.
Results: We classified HCC into three more precise subtypes termed Prolifer-low, Prolifer-mid and Prolifer-high, and also found that Cms1 ribosomal small subunit homolog 1 (CMSS1) was a hub gene associated with stronger proliferative capacity subgroup of HCC. Functional studies revealed that CMSS1 overexpression significantly promoted the proliferation of HCC cells in vitro and in vivo. Additionally, CMSS1 could also promote the migration and epithelial-mesenchymal transition of HCC cells. Mechanistically, RNA sequencing analysis revealed that CMSS1 knockdown inhibited the tumor necrosis factor (TNF) and downstream nuclear factor kappa B (NF-κB) signaling pathways. More importantly, TNF or NF-κB suppression could reverse the promoting effects of CMSS1 on HCC cells proliferation and migration.
Conclusion: The study suggested that CMSS1 could be a critical modulator of HCC tumorigenesis and metastasis through the TNF/NF-κB signaling pathway, thus being considered as a potential therapeutic target for HCC. Targeting CMSS1 may offer a novel strategy to inhibit NF-κB-driven inflammatory signaling and suppress tumor progression in HCC.
{"title":"Cms1 Ribosomal Small Subunit Homolog Promotes HCC Proliferation and Migration by Modulating the TNF/NF-κB Signaling Pathway.","authors":"Tuo Zhang, Yongping Huang, Sha Hu, Yongjie Yu, Fang Qin, Yu Zhang, Zeming Cai, Haitao Wang, Peng Zhang, Jing Dai","doi":"10.2147/JHC.S549003","DOIUrl":"10.2147/JHC.S549003","url":null,"abstract":"<p><strong>Purpose: </strong>The study aims to further classify hepatocellular carcinoma (HCC) based on proliferative capacity, identify hub genes associated with highly proliferative HCC, and investigate its regulatory roles in HCC.</p><p><strong>Materials and methods: </strong>Bioinformatics analysis was employed to establish classification of HCC and further identify the hub gene. Cell counting kit-8 (CCK-8) assay, colony formation assay, Western Blot assay and tumor xenograft assay were employed to detect the proliferation of HCC cells. Transwell assay and Western blot assay were employed to detect the migration of HCC cells. RNA sequencing analysis was employed to explore the signaling pathways activated by the gene and verify it through rescue experiments.</p><p><strong>Results: </strong>We classified HCC into three more precise subtypes termed Prolifer-low, Prolifer-mid and Prolifer-high, and also found that Cms1 ribosomal small subunit homolog 1 (CMSS1) was a hub gene associated with stronger proliferative capacity subgroup of HCC. Functional studies revealed that CMSS1 overexpression significantly promoted the proliferation of HCC cells in vitro and in vivo. Additionally, CMSS1 could also promote the migration and epithelial-mesenchymal transition of HCC cells. Mechanistically, RNA sequencing analysis revealed that CMSS1 knockdown inhibited the tumor necrosis factor (TNF) and downstream nuclear factor kappa B (NF-κB) signaling pathways. More importantly, TNF or NF-κB suppression could reverse the promoting effects of CMSS1 on HCC cells proliferation and migration.</p><p><strong>Conclusion: </strong>The study suggested that CMSS1 could be a critical modulator of HCC tumorigenesis and metastasis through the TNF/NF-κB signaling pathway, thus being considered as a potential therapeutic target for HCC. Targeting CMSS1 may offer a novel strategy to inhibit NF-κB-driven inflammatory signaling and suppress tumor progression in HCC.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"12 ","pages":"2429-2443"},"PeriodicalIF":3.4,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12579455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145431854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-27eCollection Date: 2025-01-01DOI: 10.2147/JHC.S540510
Yuan Cheng, Feng Ye, Yongjun Chen
Spontaneous rupture of hepatocellular carcinoma (srHCC) is a life-threatening complication with complex pathophysiology and heterogeneous clinical presentations. This review aims to provide an up-to-date summary of the pathogenesis, clinical features, treatment strategies, prognostic factors, and emerging research in srHCC. We discuss current understanding of risk factors and rupture mechanisms, outline diagnostic and therapeutic approaches-including surgical, interventional, and systemic options-and explore postoperative management and prognosis. We also highlight recent clinical evidence and unmet research needs. Understanding the multifaceted nature of srHCC is essential to improve outcomes and guide future research directions.
{"title":"Spontaneous Rupture of Hepatocellular Carcinoma: Pathogenesis, Clinical Management, Prognostic Factors, and Future Directions.","authors":"Yuan Cheng, Feng Ye, Yongjun Chen","doi":"10.2147/JHC.S540510","DOIUrl":"10.2147/JHC.S540510","url":null,"abstract":"<p><p>Spontaneous rupture of hepatocellular carcinoma (srHCC) is a life-threatening complication with complex pathophysiology and heterogeneous clinical presentations. This review aims to provide an up-to-date summary of the pathogenesis, clinical features, treatment strategies, prognostic factors, and emerging research in srHCC. We discuss current understanding of risk factors and rupture mechanisms, outline diagnostic and therapeutic approaches-including surgical, interventional, and systemic options-and explore postoperative management and prognosis. We also highlight recent clinical evidence and unmet research needs. Understanding the multifaceted nature of srHCC is essential to improve outcomes and guide future research directions.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"12 ","pages":"2421-2428"},"PeriodicalIF":3.4,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12577586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-27eCollection Date: 2025-01-01DOI: 10.2147/JHC.S537915
Rong-Yun Mai, Zheng Tao, Hong-Yang Huang, Can Zeng, Kai-Xiang Mo, Dan-Dan Zeng, Rong Liang, Yan Lin, Xiao-Bo Wang, Tao Bai, Le-Qun Li, Jia-Zhou Ye, Guo-Bin Wu
Background: This study aimed to evaluate the clinical efficacy of postoperative adjuvant transarterial chemoembolization (PA-TACE) in cytokeratin 19-positive (CK19+) hepatocellular carcinoma (HCC) patients and to identify cases that may benefit from PA-TACE.
Methods: We conducted a retrospective analysis of 453 CK19+ HCC patients who underwent hepatectomy between November 2013 and June 2019 at our institution. We compared the recurrence-free survival (RFS) and overall survival (OS) between patients who received PA-TACE and those who did not, utilizing propensity score matching (PSM) to balance the groups.
Results: Before and after PSM, both RFS and OS were significantly greater in PA-TACE group compared to the non-TACE group. Multivariable analysis identified PA-TACE as a significantly favorable factor of RFS and OS. In subgroups analyses, PA-TACE significantly improved RFS and OS in patients with CK19+ HCC under the following conditions: alpha-fetoprotein ≥ 400 ng/mL, cirrhosis, tumor size ≥ 5 cm, multiple tumors, major resection, Edmondson-Steiner stage III-IV, macrovascular invasion and microvascular invasion. Similar results were obtained in patients with higher tumor stages. Further recurrence model analyses revealed that PA-TACE significantly reduced early recurrence in patients with high-risk of postoperative recurrence, but had little effect on late recurrence.
Conclusion: Among CK19+ HCC patients with higher recurrence of postoperative risk, PA-TACE could greatly improve RFS and OS.
{"title":"Postoperative Adjuvant Transcatheterarterial Chemoembolization Should Be Considered Selectively for Patients with Cytokeratin-19 Positive Hepatocellular Carcinoma.","authors":"Rong-Yun Mai, Zheng Tao, Hong-Yang Huang, Can Zeng, Kai-Xiang Mo, Dan-Dan Zeng, Rong Liang, Yan Lin, Xiao-Bo Wang, Tao Bai, Le-Qun Li, Jia-Zhou Ye, Guo-Bin Wu","doi":"10.2147/JHC.S537915","DOIUrl":"10.2147/JHC.S537915","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to evaluate the clinical efficacy of postoperative adjuvant transarterial chemoembolization (PA-TACE) in cytokeratin 19-positive (CK19+) hepatocellular carcinoma (HCC) patients and to identify cases that may benefit from PA-TACE.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 453 CK19+ HCC patients who underwent hepatectomy between November 2013 and June 2019 at our institution. We compared the recurrence-free survival (RFS) and overall survival (OS) between patients who received PA-TACE and those who did not, utilizing propensity score matching (PSM) to balance the groups.</p><p><strong>Results: </strong>Before and after PSM, both RFS and OS were significantly greater in PA-TACE group compared to the non-TACE group. Multivariable analysis identified PA-TACE as a significantly favorable factor of RFS and OS. In subgroups analyses, PA-TACE significantly improved RFS and OS in patients with CK19+ HCC under the following conditions: alpha-fetoprotein ≥ 400 ng/mL, cirrhosis, tumor size ≥ 5 cm, multiple tumors, major resection, Edmondson-Steiner stage III-IV, macrovascular invasion and microvascular invasion. Similar results were obtained in patients with higher tumor stages. Further recurrence model analyses revealed that PA-TACE significantly reduced early recurrence in patients with high-risk of postoperative recurrence, but had little effect on late recurrence.</p><p><strong>Conclusion: </strong>Among CK19+ HCC patients with higher recurrence of postoperative risk, PA-TACE could greatly improve RFS and OS.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"12 ","pages":"2407-2419"},"PeriodicalIF":3.4,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12577640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145431893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}