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Su Y, Liang Y, Zhong D, Yan H, Yang Q, Shang J, Chen Y, Huang X. Construction and validation of a novel liver function-tumor burden-inflammation-nutrition (LTIN) score for HCC patients underwent hepatectomy. BMC Cancer 2025; 25:504. [PMID: 40108574 PMCID: PMC11921615 DOI: 10.1186/s12885-025-13867-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 03/05/2025] [Indexed: 03/22/2025] Open
Abstract
OBJECTIVE Liver function, tumor burden, inflammation level, and nutritional status are critical factors influencing tumor onset, progression, and metastasis. This study sought to investigate the prognostic significance and clinical relevance of biomarkers associated with these factors to develop a novel liver function-tumor burden-inflammation-nutrition (LTIN) score for patients with hepatocellular carcinoma (HCC) who received hepatectomy. METHODS A retrospective analysis was conducted on 285 patients with HCC undergoing hepatectomy at two medical centers between July 2019 and July 2023. The patients were divided into a training set (n = 200) and a validation set (n = 85). The study evaluated the prognostic significance of eight relevant clinical indicators and developed an LTIN score using Least Absolute Shrinkage and Selection Operator (LASSO) regression. Kaplan-Meier survival curves and multivariate Cox regression analysis were utilized to determine the prognostic value of the LTIN score. Time-dependent receiver operating characteristic (ROC) analyses were used to compare the predictive performance of various prognostic factors. RESULTS The LTIN score, derived from the albumin-bilirubin (ALBI) grade, tumor burden score (TBS), prognostic nutritional index (PNI), and prognostic inflammatory index (PII), effectively classified patients into high- and low-risk groups based on the optimal cut-off value. Patients with low-risk scores exhibited significantly better overall survival (OS) and recurrence-free survival (RFS) than those with high-risk groups in both the training and validation sets (P < 0.001). Furthermore, the LTIN score was identified as a significant independent prognostic factor for both OS (P < 0.001) and RFS (P < 0.001). The LTIN score also exhibited superior prognostic capabilities compared to the other indicators, Tumor-Node-Metastasis (TNM) staging system, and Barcelona Clinic Liver Cancer (BCLC) staging system. CONCLUSION Our findings indicated that the preoperative LTIN score has significant potential as a reliable predictor of OS and RFS for HCC patients underwent radical surgery. The LTIN score could further effectively guide treatment decisions and optimize follow-up strategies to enhance patients prognosis.
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Affiliation(s)
- Yuhao Su
- Department of Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yuxin Liang
- Department of Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Deyuan Zhong
- Department of Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Hongtao Yan
- Department of Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Qinyan Yang
- Department of Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Jin Shang
- Department of Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yahui Chen
- Department of Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiaolun Huang
- Department of Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
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Liu L, Wang L, Ding Y, Zhang Q, Shu Y. Cost-effectiveness of atezolizumab plus bevacizumab versus sorafenib as first-line therapy in unresectable hepatocellular carcinoma in the US and Chinese setting: a modelling comparison study. BMJ Open 2025; 15:e094804. [PMID: 40050065 PMCID: PMC11887288 DOI: 10.1136/bmjopen-2024-094804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 02/05/2025] [Indexed: 03/09/2025] Open
Abstract
OBJECTIVE Atezolizumab plus bevacizumab demonstrates a significant improvement in overall survival and progression-free survival compared with sorafenib in patients with unresectable hepatocellular carcinoma (HCC). The combined usage of these two medications could result in substantial consumption of resources, primarily due to their exceptionally high costs. The current study aims to evaluate the cost-effectiveness of atezolizumab plus bevacizumab as a first-line treatment for advanced HCC from the perspective of payers in developed and developing countries. DESIGN A partitioned survival model was constructed to evaluate the cost-effectiveness of atezolizumab plus bevacizumab versus sorafenib as a first-line treatment for advanced HCC. The efficacy and safety data incorporated within the model were derived from the IMbrave150 trial. Costs and utilities were extracted from published sources. INTERVENTIONS Atezolizumab plus bevacizumab versus sorafenib. OUTCOME MEASURES Estimates were calculated for costs, life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER) for both treatment strategies. One-way sensitivity, probabilistic sensitivity, expected value of perfect information (EVPI), subgroup and scenario analyses were conducted. RESULTS The combination therapy of atezolizumab and bevacizumab results in an additional 0.72 life-years/0.57 QALYs in the USA and 0.64 life-years/0.47 QALYs in China compared with standard sorafenib treatment, although with a significant increase in costs, yielding an average ICER of US$253 247.07/QALY in the USA and US$181 552.71/QALY in China. The probability sensitivity analysis indicated that atezolizumab plus bevacizumab demonstrated a 13.60% likelihood of cost-effectiveness in the USA, whereas this likelihood is negligible (0%) in China. The expected value of uncertainty, as quantified by the EVPI, was estimated at approximately US$3658.41/patient in the USA and US$0/patient in China. The ICER was most sensitive to the cost of subsequent treatment in the USA, and most sensitive to the cost of atezolizumab in China. In scenario analyses, the atezolizumab plus bevacizumab treatment becomes favourable when the cost of atezolizumab decreases to 67.85% and 18.45% of its original price in the USA and China, respectively. CONCLUSIONS The atezolizumab plus bevacizumab is unlikely to be cost-effective compared with sorafenib for patients with unresectable HCC in the context of the USA and China. The implementation of significant reductions in drug prices may render the treatment economically viable.
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Affiliation(s)
- Lulu Liu
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Pharmacy, The Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Lei Wang
- Outpatient Department Office, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yiling Ding
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qilin Zhang
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yamin Shu
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Xiong X, Guo JJ. Cost Effectiveness of Tremelimumab Plus Durvalumab for Unresectable Hepatocellular Carcinoma in the USA. PHARMACOECONOMICS 2025; 43:271-282. [PMID: 39546248 DOI: 10.1007/s40273-024-01453-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 10/29/2024] [Indexed: 11/17/2024]
Abstract
BACKGROUND Treating unresectable hepatocellular carcinoma (uHCC) is challenging. Clinical trials have shown that Single Tremelimumab Regular Interval Durvalumab (STRIDE) offers clinical benefits as a first-line treatment for uHCC, but its cost effectiveness remains unknown in the USA. OBJECTIVE We aimed to assess the cost effectiveness of STRIDE (tremelimumab plus durvalumab) versus sorafenib and durvalumab monotherapy as the first-line treatment for uHCC in the USA. METHODS A partitioned survival model was constructed to assess the cost effectiveness of STRIDE compared to sorafenib and durvalumab monotherapy as the first-line treatment for uHCC from the US societal perspective. The time horizon was 48 months with 1-month cycles. Seven parametric survival functions replicated survival curves from clinical trials, with the best-fitting model used to calculate survival probabilities. Costs, health utilities, and adverse events were included, with quality-adjusted life-years (QALYs) as the primary effectiveness measure. Both costs and effectiveness were discounted at 3%. In the base-case analysis, the incremental cost-effectiveness ratio was compared to a willingness-to-pay threshold of $150,000 per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to examine the uncertainty of the model. RESULTS In the base-case analysis, STRIDE was cost effective compared to sorafenib, with an incremental cost-effectiveness ratio of $97,995.51 per QALY gained, based on a willingness-to-pay threshold of $150,000 per QALY gained. However, STRIDE was not cost effective compared to durvalumab monotherapy at the same threshold, with an incremental cost-effectiveness ratio of $754,408.92 per QALY gained. Deterministic sensitivity analyses were consistent with the base-case analysis. A probabilistic sensitivity analysis indicated that STRIDE was more likely to be cost effective than sorafenib and durvalumab monotherapy when the willingness-to-pay exceeded $101,000 and $713,000, respectively. CONCLUSIONS The STRIDE regimen appears to be cost effective compared to sorafenib but not compared to durvalumab for first-line uHCC treatment in the USA. However, durvalumab has not yet been approved for uHCC in the USA. Future research should focus on long-term data and economic evaluations of other recommended biologics.
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MESH Headings
- Humans
- Cost-Benefit Analysis
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/economics
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/mortality
- Liver Neoplasms/drug therapy
- Liver Neoplasms/economics
- Liver Neoplasms/pathology
- Liver Neoplasms/mortality
- United States
- Quality-Adjusted Life Years
- Antibodies, Monoclonal, Humanized/economics
- Antibodies, Monoclonal, Humanized/administration & dosage
- Sorafenib/economics
- Sorafenib/administration & dosage
- Antibodies, Monoclonal/administration & dosage
- Antibodies, Monoclonal/economics
- Antineoplastic Combined Chemotherapy Protocols/economics
- Antineoplastic Combined Chemotherapy Protocols/administration & dosage
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/adverse effects
- Models, Economic
- Cost-Effectiveness Analysis
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Affiliation(s)
- Xiaomo Xiong
- Division of Pharmacy Practice and Administrative Sciences, James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, 3255 Eden Ave, Cincinnati, OH, 45267, USA.
| | - Jeff Jianfei Guo
- Division of Pharmacy Practice and Administrative Sciences, James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, 3255 Eden Ave, Cincinnati, OH, 45267, USA
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Sangro B, Argemi J, Ronot M, Paradis V, Meyer T, Mazzaferro V, Jepsen P, Golfieri R, Galle P, Dawson L, Reig M. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol 2025; 82:315-374. [PMID: 39690085 DOI: 10.1016/j.jhep.2024.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 12/19/2024]
Abstract
Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.
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Decharatanachart P, Poovorawan K, Tangkijvanich P, Charatcharoenwitthaya P, Peeraphatdit T, Taychakhoonavudh S, Treeprasertsuk S, Chaiteerakij R. Cost-Utility Analysis of Non-Invasive Tests to Initiate Hepatocellular Carcinoma Surveillance in Metabolic Dysfunction-Associated Steatotic Liver Disease. Am J Gastroenterol 2025:00000434-990000000-01565. [PMID: 39878449 DOI: 10.14309/ajg.0000000000003332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Accepted: 01/13/2025] [Indexed: 01/31/2025]
Abstract
BACKGROUND AIMS Non-invasive tests (NITs), e.g. Fibrosis-4 Index (FIB-4) and vibration-controlled elastography (VCTE), have been used to identify metabolic dysfunction-associated steatotic liver disease (MASLD) patients at high risks for hepatocellular carcinoma (HCC). This study investigates the cost-effectiveness of NITs to identify MASLD patients with advanced liver fibrosis and initiate HCC surveillance. METHODS A cost-utility analysis using a Markov model compared no use of NITs with three NIT strategies: 1) FIB-4 and VCTE (FIB-4/VCTE), 2) FIB-4 alone, and 3) VCTE alone to identify advanced liver fibrosis and initiate HCC surveillance with biannual ultrasonography with alpha-fetoprotein in 4 MASLD populations: 1) general MASLD patients, 2) MASLD patients with body mass index (BMI) >30 kg/m2, 3) MASLD patients with diabetes, and 4) MASLD patients with three metabolic traits (diabetes, hypertension and BMI >30). RESULTS FIB-4/VCTE was the most cost-effective approach across all groups, showing the lowest ICER, followed by FIB-4 alone and VCTE alone. In the general MASLD population, both FIB-4/VCTE and FIB-4 alone were cost-effective in the US, while only FIB-4/VCTE was cost-effective in Thailand. For MASLD patients with BMI >30, all strategies were cost-effective in the US, while only FIB-4/VCTE was cost-effective in Thailand. In MASLD patients with diabetes or 3 metabolic traits, all strategies were cost-effective in the US, while FIB-4/VCTE and FIB-4 alone were cost-effective in Thailand. CONCLUSIONS Using FIB-4/VCTE to initiate HCC surveillance is cost-effective for MASLD patients. If VCTE is unavailable, FIB-4 alone is a cost-effective alternative for MASLD patients with diabetes or 3 metabolic traits.
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Affiliation(s)
| | - Kittiyod Poovorawan
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Department of Biochemistry, Chulalongkorn University, Bangkok, Thailand
| | | | - Thoetchai Peeraphatdit
- Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Suthira Taychakhoonavudh
- Department of Social and Administrative Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Du Y, Zhang H, Liu J, Duan X, Chen S, Jiang W. HK3: A potential prognostic biomarker with metastasis inhibition capabilities in hepatocellular carcinoma. Biochem Biophys Res Commun 2024; 741:151057. [PMID: 39615209 DOI: 10.1016/j.bbrc.2024.151057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 11/06/2024] [Accepted: 11/22/2024] [Indexed: 12/11/2024]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) stands as one of the prevalent malignant tumors worldwide. The effectiveness of immunotherapy frequently depends on the intricate dynamics of immunomodulation within the tumor microenvironment (TME). The current study aims to identify prognostically relevant genes and their functional roles in HCC. This is achieved by utilizing immune scores and mutations as the basis, through the application of bioinformatics and molecular biological analysis. METHODS Differentially expressed genes (DEGs) analysis was conducted using the "clusterProfiler" package for functional enrichment. Cox regression analysis and LASSO regression analysis were performed for prognostic gene screening. Kaplan-Meier curve were further utilized to verify the prognostic value of these genes. The relationship between selected genes and immune cells was analyzed using ssGSEA algorithm and TIMER. The HK3 expression in HCC cells was tested by Western blot. Additionally, wound healing and transwell assays were utilized to detect the impact of HK3 on HCC metastasis. RESULTS Patients who had higher ESTIMATE, stromal, and immune scores exhibited more favorable overall survival rates. There are 17 genes that overlap among the DEGs related to the immune-stromal-ESTIMATE scores, mutated genes, and DEGs in HCC tissues compared to normal tissues. Among the DEGs, three genes (STAB1, COL15A1 and HK3) emerged with the most profound association concerning survival outcomes. Notably, the HK3 genes displayed a pronounced correlation with immune infiltration. Concurrently, diminished expression levels of HK3 were observed in HCC tissues and upregulation of HK3 resulted in a significant reduction in HCC cell metastasis in vitro and in vivo. CONCLUSIONS HK3 emerges as a novel prognostic biomarker for HCC, exerting regulatory influence over cellular proliferation, metastasis, and invasiveness. These findings indicate that HK3 holds promise as a potential candidate for treatment and prognosis of HCC.
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Affiliation(s)
- Yexiang Du
- Department of Anatomy, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China
| | - Hongchuan Zhang
- Department of Oncology, Dianjiang People's Hospital of Chongqing, Chongqing, 408300, China
| | - Jialong Liu
- 65136, Troops Hospital of PLA, Dalian, Liaoning, 116300, China
| | - Xiaodong Duan
- Department of Anatomy, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China
| | - Suhua Chen
- Department of Clinical Laboratory, Guizhou Provincial People's Hospital, Guizhou, 550002, China
| | - Wenbin Jiang
- Department of Clinical Laboratory, Guizhou Provincial People's Hospital, Guizhou, 550002, China.
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Le QA, Pham XL, van Walsum T, Dao VH, Le TL, Franklin D, Moelker A, Le VH, Trung NL, Luu MH. Precise ablation zone segmentation on CT images after liver cancer ablation using semi-automatic CNN-based segmentation. Med Phys 2024; 51:8882-8899. [PMID: 39250658 DOI: 10.1002/mp.17373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 07/17/2024] [Accepted: 08/12/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Ablation zone segmentation in contrast-enhanced computed tomography (CECT) images enables the quantitative assessment of treatment success in the ablation of liver lesions. However, fully automatic liver ablation zone segmentation in CT images still remains challenging, such as low accuracy and time-consuming manual refinement of the incorrect regions. PURPOSE Therefore, in this study, we developed a semi-automatic technique to address the remaining drawbacks and improve the accuracy of the liver ablation zone segmentation in the CT images. METHODS Our approach uses a combination of a CNN-based automatic segmentation method and an interactive CNN-based segmentation method. First, automatic segmentation is applied for coarse ablation zone segmentation in the whole CT image. Human experts then visually validate the segmentation results. If there are errors in the coarse segmentation, local corrections can be performed on each slice via an interactive CNN-based segmentation method. The models were trained and the proposed method was evaluated using two internal datasets of post-interventional CECT images (n 1 $n_{1}$ = 22,n 2 $n_{2}$ = 145; 62 patients in total) and then further tested using an external benchmark dataset (n 3 $n_{3}$ = 12; 10 patients). RESULTS To evaluate the accuracy of the proposed approach, we used Dice similarity coefficient (DSC), average symmetric surface distance (ASSD), Hausdorff distance (HD), and volume difference (VD). The quantitative evaluation results show that the proposed approach obtained mean DSC, ASSD, HD, and VD scores of 94.0%, 0.4 mm, 8.4 mm, 0.02, respectively, on the internal dataset, and 87.8%, 0.9 mm, 9.5 mm, and -0.03, respectively, on the benchmark dataset. We also compared the performance of the proposed approach to that of five well-known segmentation methods; the proposed semi-automatic method achieved state-of-the-art performance on ablation segmentation accuracy, and on average, 2 min are required to correct the segmentation. Furthermore, we found that the accuracy of the proposed method on the benchmark dataset is comparable to that of manual segmentation by human experts ( p $p$ = 0.55, t $t$ -test). CONCLUSIONS The proposed semi-automatic CNN-based segmentation method can be used to effectively segment the ablation zones, increasing the value of CECT for an assessment of treatment success. For reproducibility, the trained models, source code, and demonstration tool are publicly available at https://github.com/lqanh11/Interactive_AblationZone_Segmentation.
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Affiliation(s)
- Quoc Anh Le
- AVITECH, VNU University of Engineering and Technology, Hanoi, Vietnam
| | - Xuan Loc Pham
- FET, VNU University of Engineering and Technology, Hanoi, Vietnam
| | - Theo van Walsum
- Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands
| | - Viet Hang Dao
- Internal Medicine Faculty, Hanoi Medical University, Hanoi, Vietnam
- The Institute of Gastroenterology and Hepatology, Hanoi, Vietnam
| | - Tuan Linh Le
- Diagnostic Imaging and Interventional Radiology Center, Hanoi Medical University Hospital, Hanoi, Vietnam
| | - Daniel Franklin
- School of Electrical and Data Engineering, University of Technology Sydney, Sydney, Australia
| | - Adriaan Moelker
- Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands
| | - Vu Ha Le
- AVITECH, VNU University of Engineering and Technology, Hanoi, Vietnam
- FET, VNU University of Engineering and Technology, Hanoi, Vietnam
| | - Nguyen Linh Trung
- AVITECH, VNU University of Engineering and Technology, Hanoi, Vietnam
| | - Manh Ha Luu
- AVITECH, VNU University of Engineering and Technology, Hanoi, Vietnam
- FET, VNU University of Engineering and Technology, Hanoi, Vietnam
- Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands
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Sun H, Liu N, Lou J. Diagnostic value of serum STIP1 in HCC and AFP-negative HCC. Lab Med 2024; 55:700-707. [PMID: 38780206 PMCID: PMC11532616 DOI: 10.1093/labmed/lmae033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2024] Open
Abstract
OBJECTIVE This study aimed to investigate the diagnostic value of stress-induced phosphoprotein 1 (STIP1) in serum for hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP)-negative HCC (ANHC). METHODS In this study, serum samples were collected from 158 HCC patients and 63 non-HCC patients. Logistic regression analysis was performed to identify independent risk factors associated with HCC and ANHC. The diagnostic values of each index for HCC and ANHC were analyzed using receiver operating characteristic (ROC) curve analysis. RESULTS The STIP1, des-γ-carboxy prothrombin (DCP), and AFP levels were higher in the HCC groups than in the non-HCC groups (P < .05). Age, DCP, STIP1, and hepatitis B virus infection were independent predictors of HCC (P < .05). The diagnostic value of STIP1 for HCC was higher than that of DCP. Additionally, age, STIP1, and hepatitis B virus infection were independent predictors for ANHC patients. The ROC curve exhibited an area under the curve value of 0.919 for STIP1, with a diagnostic cutoff value of 68.5 U/mL. Moreover, 36 ANHC patients and 19 AFP-negative non-HCC patients were included to validate the diagnostic model. A total of 20 patients had STIP1 levels greater than 68.5 U/mL, resulting in diagnostic accuracy of 67.3%, sensitivity of 55.6%, and specificity of 89.5%. CONCLUSION STIP1 demonstrates excellent diagnostic value for HCC and ANHC.
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Affiliation(s)
- Haiqing Sun
- Department of Clinical Laboratory Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Ning Liu
- Department of Clinical Laboratory Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jinli Lou
- Department of Clinical Laboratory Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
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Kong Q, Gao Q, Li W, Chen Z. The Impact of Imaging-Diagnosed Sarcopenia on Long-term Prognosis After Curative Resection for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. Acad Radiol 2024; 31:1272-1283. [PMID: 38071101 DOI: 10.1016/j.acra.2023.11.040] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 11/15/2023] [Accepted: 11/29/2023] [Indexed: 04/14/2024]
Abstract
BACKGROUND Recent research suggests that sarcopenia potentially influences the long-term postoperative prognosis of malignant tumors. Thus, the primary objective of this study was to investigate the impact of imaging-diagnosed sarcopenia on the long-term prognosis of hepatocellular carcinoma (HCC) patients after curative resection. METHODS In our approach, all studies incorporated in this study employed Cox proportional hazards models with multivariable adjusted hazard ratios. The meta-analysis was performed using R statistical software. The primary outcomes were quantified using hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS This study analyzed 30 studies, involving 7352 HCC patients after curative resection (2695 in the sarcopenia group and 4657 in the non-sarcopenia group). The meta-analysis of 28 studies indicated that patients in the sarcopenia group demonstrated notably inferior overall survival (OS) compared with the non-sarcopenia group (HR=2.20; 95% CI, 1.88-2.58; p < 0.01). Similarly, sarcopenia exhibits a significant association with poor recurrence-free survival (RFS) and disease-free survival (DFS) based on 16 and 6 studies (HR=1.50; 95% CI, 1.39-1.63; p < 0.01 and HR=1.96; 95% CI, 1.83-2.10; p < 0.01, respectively). CONCLUSION In conclusion, imaging-diagnosed sarcopenia adversely affects the long-term prognosis, including OS, RFS, and DFS, in HCC patients after curative resection. The findings hold considerable importance in guiding comprehensive healthcare procedures for HCC patients after surgery.
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Affiliation(s)
- Qingyan Kong
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, 37 Guo Xue Rd, Chengdu 610041, Sichuan Province, China
| | - Qianqian Gao
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, 37 Guo Xue Rd, Chengdu 610041, Sichuan Province, China
| | - Wenjie Li
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, 37 Guo Xue Rd, Chengdu 610041, Sichuan Province, China
| | - Zheyu Chen
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, 37 Guo Xue Rd, Chengdu 610041, Sichuan Province, China.
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Nahon P, Layese R, Ganne-Carrié N, Moins C, N'Kontchou G, Chaffaut C, Ronot M, Audureau E, Durand-Zaleski I, Natella PA. The clinical and financial burden of nonhepatocellular carcinoma focal lesions detected during the surveillance of patients with cirrhosis. Hepatology 2024; 79:813-828. [PMID: 37774387 DOI: 10.1097/hep.0000000000000615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 09/01/2023] [Indexed: 10/01/2023]
Abstract
BACKGROUND AND AIMS HCC surveillance is challenged by the detection of hepatic focal lesions (HFLs) of other types. This study aimed to describe the incidence, characteristics, outcomes, and costs of non-HCC HFL detected during surveillance. APPROACH AND RESULTS We retrospectively analyzed nonstandardized workup performed in French patients included in HCC surveillance programs recruited in 57 French tertiary centers (ANRS CirVir and CIRRAL cohorts, HCC 2000 trial). The overall cost of workup was evaluated, with an estimation of an average cost per patient for the entire population and per lesion detected. A total of 3295 patients were followed up for 59.8 months, 391 (11.9%) patients developed HCCs (5-year incidence: 12.1%), and 633 (19.2%) developed non-HCC HFLs (5-year incidence: 21.8%). Characterization of non-HCC HFL required a median additional of 0.7 exams per year. A total of 11.8% of non-HCC HFLs were not confirmed on recall procedures, and 19.6% of non-HCC HFLs remained undetermined. A definite diagnosis of benign liver lesions was made in 65.1%, and malignant tumors were diagnosed in 3.5%. The survival of patients with benign or undetermined non-HCC HFL was similar to that of patients who never developed any HFL (5-year survival 92% vs. 88%, p = 0.07). The average cost of the diagnostic workup was 1087€ for non-HCC HFL and €1572 for HCC. CONCLUSIONS Non-HCC HFLs are frequently detected in patients with cirrhosis, and do not impact prognosis, but trigger substantial costs. This burden must be considered in cost-effectiveness analyses of future personalized surveillance strategies.
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Affiliation(s)
- Pierre Nahon
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, Liver Department, Bobigny; Université Sorbonne Paris Nord, Bobigny, France
- Inserm, UMR-1138 Functional Genomics of Solid Tumors department, Centre de recherche des Cordeliers, Université de Paris, Paris, France
| | - Richard Layese
- Univ Paris Est Créteil, INSERM, IMRB, Equipe CEpiA (Clinical Epidemiology and Ageing), Unité de Recherche Clinique (URC Mondor), Public health department, Assistance Publique Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil, France
| | - Nathalie Ganne-Carrié
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, Liver Department, Bobigny; Université Sorbonne Paris Nord, Bobigny, France
- Inserm, UMR-1138 Functional Genomics of Solid Tumors department, Centre de recherche des Cordeliers, Université de Paris, Paris, France
| | - Cécile Moins
- Clinical Research Department, ANRS | Emerging Infectious Diseases, Paris, France
| | - Gisèle N'Kontchou
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, Liver Department, Bobigny; Université Sorbonne Paris Nord, Bobigny, France
- Inserm, UMR-1138 Functional Genomics of Solid Tumors department, Centre de recherche des Cordeliers, Université de Paris, Paris, France
| | - Cendrine Chaffaut
- SBIM, APHP, Hôpital Saint-Louis, Paris, Inserm, UMR-1153, ECSTRA department, Paris, France
| | - Maxime Ronot
- APHP, Hôpital Beaujon, Radiology department, Hôpital Beaujon, APHP. Nord, Clichy-Sous-Bois, & Université Paris Cité, Paris, France
| | - Etienne Audureau
- Univ Paris Est Créteil, INSERM, IMRB, Equipe CEpiA (Clinical Epidemiology and Ageing), Unité de Recherche Clinique (URC Mondor), Public health department, Assistance Publique Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil, France
| | - Isabelle Durand-Zaleski
- Université de Paris, CRESS, INSERM, INRA, URCECo department, AP-HP, Hôpital de l'Hôtel Dieu, Paris, France
| | - Pierre-André Natella
- Univ Paris Est Créteil, INSERM, IMRB, Equipe CEpiA (Clinical Epidemiology and Ageing), Unité de Recherche Clinique (URC Mondor), Public health department, Assistance Publique Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil, France
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11
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Nahon P, Ronot M, Sutter O, Natella PA, Baloul S, Durand-Zaleski I, Audureau E. Study protocol for FASTRAK: a randomised controlled trial evaluating the cost impact and effectiveness of FAST-MRI for HCC suRveillance in pAtients with high risK of liver cancer. BMJ Open 2024; 14:e083701. [PMID: 38367972 PMCID: PMC10875554 DOI: 10.1136/bmjopen-2023-083701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 01/23/2024] [Indexed: 02/19/2024] Open
Abstract
INTRODUCTION The surveillance of hepatocellular carcinoma (HCC) using semi-annual liver ultrasound (US) is justified in patients with cirrhosis. In this context, US has a low sensitivity (<30%) for the detection of HCC at the very early stage (ie, Barcelona clinic liver cancer (BCLC) 0, uninodular tumour <2 cm). The sensitivity of abbreviated liver MRI (AMRI) is reported to exceed 80%, but its use is hampered by costs and availability. Our hypothesis is that AMRI used as a screening examination in patients at high risk of HCC (>3% per year) could increase the rates of patients with a tumour detected at an early stage accessible to curative-intent treatment, and demonstrate its cost-effectiveness in this population. METHODS AND ANALYSIS The FASTRAK trial is a multicentre, randomised controlled trial with two parallel arms, aiming for superiority and conducted on patients at high risk for HCC (yearly HCC incidence >3%). Randomisation will be conducted on an individual basis with a centralised approach and stratification by centre. After inclusion in the trial, each patient will be randomly assigned to the experimental group (semi-annual US and AMRI) or the control group (semi-annual US alone). The main objective is to assess the cost/quality-adjusted life year and cost/patient detected with a BCLC 0 HCC in both arms. A total of 944 patients will be recruited in 37 tertiary French centres during a 36-month period and will be followed-up during 36 months. ETHICS AND DISSEMINATION The FASTRAK trial received ethical approval on 4 April 2022. Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences. TRIAL REGISTRATION NUMBER Clinical trial number (ClinicaTrials.gov) NCT05095714.
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Affiliation(s)
| | | | | | - Pierre-André Natella
- Clinical Epidemiology and Ageing, Hôpitaux Universitaires Henri Mondor, Creteil, France
| | - Samia Baloul
- Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Isabelle Durand-Zaleski
- University of Paris, Paris, France
- URCEco, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Etienne Audureau
- CEPIA EA7376, Universite Paris-Est Creteil Val de Marne, Creteil, France
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Decharatanachart P, Pan-ngum W, Peeraphatdit T, Tanpowpong N, Tangkijvanich P, Treeprasertsuk S, Rerknimitr R, Chaiteerakij R. Cost-Utility Analysis of Non-Contrast Abbreviated Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance in Cirrhosis. Gut Liver 2024; 18:135-146. [PMID: 37560799 PMCID: PMC10791494 DOI: 10.5009/gnl230089] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 05/01/2023] [Accepted: 05/23/2023] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND/AIMS Ultrasonography has a low sensitivity for detecting early-stage hepatocellular carcinoma (HCC) in cirrhotic patients. Non-contrast abbreviated magnetic resonance imaging (aMRI) demonstrated a comparable performance to that of magnetic resonance imaging without the risk of contrast media exposure and at a lower cost than that of full diagnostic MRI. We aimed to investigate the cost-effectiveness of non-contrast aMRI for HCC surveillance in cirrhotic patients, using ultrasonography with alpha-fetoprotein (AFP) as a reference. METHODS Cost-utility analysis was performed using a Markov model in Thailand and the United States. Incremental cost-effectiveness ratios were calculated using the total costs and quality-adjusted life years (QALYs) gained in each strategy. Surveillance protocols were considered cost-effective based on a willingness-to-pay value of $4,665 (160,000 Thai Baht) in Thailand and $50,000 in the United States. RESULTS aMRI was cost-effective in both countries with incremental cost-effectiveness ratios of $3,667/QALY in Thailand and $37,062/QALY in the United States. Patient-level microsimulations showed consistent findings that aMRI was cost-effective in both countries. By probabilistic sensitivity analysis, aMRI was found to be more cost-effective than combined ultrasonography and AFP with a probability of 0.77 in Thailand and 0.98 in the United States. By sensitivity analyses, annual HCC incidence was revealed as the most influential factor affecting cost-effectiveness. The cost-effectiveness of aMRI increased in settings with a higher HCC incidence. At a higher HCC incidence, aMRI would remain cost-effective at a higher aMRI-to-ultrasonography with AFP cost ratio. CONCLUSIONS Compared to ultrasonography with AFP, non-contrast aMRI is a cost-effective strategy for HCC surveillance and may be useful for such surveillance in cirrhotic patients, especially in those with high HCC risks.
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Affiliation(s)
| | - Wirichada Pan-ngum
- Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Thoetchai Peeraphatdit
- Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Natthaporn Tanpowpong
- Department of Radiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Yu WM, Li GW, Lou MG, Wu ZY. A meta-analysis of the prognostic impact of tissue golgi protein 73 (tGP73) in hepatocellular carcinoma. BMC Gastroenterol 2023; 23:401. [PMID: 37978447 PMCID: PMC10656938 DOI: 10.1186/s12876-023-03050-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 11/09/2023] [Indexed: 11/19/2023] Open
Abstract
INTRODUCTION To date, an increasing number of studies have revealed that GP73 may have prognostic value in liver cancer. However, most of the studies evaluated serum GP73, and the results regarding the prognostic value of tGP73 in liver cancer are still controversial. Therefore, in this meta-analysis, we aimed to determine whether tGP73 has any prognostic value in patients with HCC. MATERIALS AND METHODS Relevant publications were searched for in PubMed, EMBASE, OVID, the Cochrane Library, and the Web of Science databases up to March 2023. The hazard ratio (HR) or odds ratio (OR) with corresponding 95% confidence intervals (95% CIs) of eligible studies were assessed by fixed-effects or random-effects models. In addition, subgroup analyses were conducted to investigate the possible causes of heterogeneity, and publication bias analysis was also performed to assess the reliability of the meta-analysis results. RESULTS A total of 10 studies were included. These studies included 1569 HCC patients, and a meta-analysis was performed. The results of our meta-analysis showed that higher GP73 expression levels were significantly associated with poorer OS (HR = 1.87, 95% CI: 1.41-2.48, P < 0.0001, I2 = 58%). However, there was no significant correlation between high GP73 expression and disease-free survival (DFS) (HR: 1.43, 95% CI: 0.93-2.33, P = 0.100). In addition, abnormal GP73 expression was also related to higher tumour tissue differentiation grade (OR = 3.03, 95% CI = 2.01-4.57, P < 0.0001, I2 = 89%), later tumour stage (OR = 5.89, 95% CI = 2.31-14.99, P < 0.0001, I2 = 0%), vascular invasion (OR = 1.72, 95% CI = 1.12-2.64, P = 0.010, I2 = 0%), multiple tumours (OR = 2.44, 95% CI = 1.37-3.68, P = 0.001, I2 = 44%) and early postoperative tumour recurrence (OR = 1.92, 95% CI = 1.10-3.28, P = 0.020, I2 = 62%). CONCLUSIONS The meta-analysis showed that the overexpression of GP73 may be related to a poor prognosis of HCC, and it may also have a predictive effect on the invasion and metastasis of HCC.
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Affiliation(s)
- Wei-Ming Yu
- Department of Hepatobiliary and pancreatic surgery, The First People's Hospital of Fuyang District, Fuyang First Hospital Affiliated to Binjiang College of Zhejiang Chinese Medicine University, Hangzhou, China.
| | - Guo-Wei Li
- Department of Hepatobiliary and pancreatic surgery, The First People's Hospital of Fuyang District, Fuyang First Hospital Affiliated to Binjiang College of Zhejiang Chinese Medicine University, Hangzhou, China
| | - Ming-Geng Lou
- Department of Hepatobiliary and pancreatic surgery, The First People's Hospital of Fuyang District, Fuyang First Hospital Affiliated to Binjiang College of Zhejiang Chinese Medicine University, Hangzhou, China
| | - Zheng-Yu Wu
- Department of Hepatobiliary and pancreatic surgery, The First People's Hospital of Fuyang District, Fuyang First Hospital Affiliated to Binjiang College of Zhejiang Chinese Medicine University, Hangzhou, China
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Wang Q, Guo D, Gao W, Yuan C, Li J, Zhang Y, He N, Zhao P, Zheng J, Zhang Y. Individual surveillance by competing risk model for patients with hepatocellular carcinoma occurrence in all-cause cirrhosis. J Cancer Res Clin Oncol 2023; 149:13403-13416. [PMID: 37495731 PMCID: PMC10587216 DOI: 10.1007/s00432-023-04911-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 05/20/2023] [Indexed: 07/28/2023]
Abstract
PURPOSE It was of great significance to identify someone with a high risk of hepatocellular carcinoma (HCC) occurrence and make a diagnosis as early as possible. Therefore, we aimed to develop and validate a new, objective, and accurate prediction model, and convert it into a nomogram to make a personalized prediction of cancer occurrence in cirrhotic patients with different etiologies. METHODS The present study included 938 patients with cirrhosis from January 1, 2011, to December 31, 2012. Patients were prospectively followed-up until January 1, 2018. We used a competing risk model and the Fine-Gray test to develop and validate the prediction model and to plot a nomogram based on the model established. RESULTS At the end of follow-up, 202 (21.5%) patients developed HCC, with a 5-year incidence of 19.0% (corrected for competing risk model). Based on the competing risk regression method, we built a prediction model including age, gender, etiology, lymphocyte, and A/G ratio. Three groups with different risks were generated on account of tertiles of the 5-year risk predicted by the model. The cumulative 1-, 3-, and 5-year incidences of HCC were 2.0%, 20.8%, and 42.3% in high-risk group, 0.9%, 10.1%, and 17.7% in medium-risk group, and 0%, 2.0%, 8.5% in low-risk group (P < 0.001). The model showed excellent discrimination and calibration in predicting the risk of HCC occurrence in patients with all-cause cirrhosis. CONCLUSION The model could make an individual prediction of cancer occurrence and stratify patients based on predicted risk, regardless of the causes of cirrhosis.
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Affiliation(s)
- Qi Wang
- Research Center for Biomedical Resources, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Dandan Guo
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Wenfeng Gao
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Chunwang Yuan
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Jianjun Li
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Yinghua Zhang
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Ning He
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Peng Zhao
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Jiasheng Zheng
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Yonghong Zhang
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China.
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Campello CA, Castanha EB, Vilardo M, Staziaki PV, Francisco MZ, Mohajer B, Watte G, Moraes FY, Hochhegger B, Altmayer S. Machine learning for malignant versus benign focal liver lesions on US and CEUS: a meta-analysis. Abdom Radiol (NY) 2023; 48:3114-3126. [PMID: 37365266 DOI: 10.1007/s00261-023-03984-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 06/10/2023] [Accepted: 06/12/2023] [Indexed: 06/28/2023]
Abstract
OBJECTIVES To perform a meta-analysis of the diagnostic performance of learning (ML) algorithms (conventional and deep learning algorithms) for the classification of malignant versus benign focal liver lesions (FLLs) on US and CEUS. METHODS Available databases were searched for relevant published studies through September 2022. Studies met eligibility criteria if they evaluate the diagnostic performance of ML for the classification of malignant and benign focal liver lesions on US and CEUS. The pooled per-lesion sensitivities and specificities for each modality with 95% confidence intervals were calculated. RESULTS A total of 8 studies on US, 11 on CEUS, and 1 study evaluating both methods met the inclusion criteria with a total of 34,245 FLLs evaluated. The pooled sensitivity and specificity of ML for the malignancy classification of FLLs were 81.7% (95% CI, 77.2-85.4%) and 84.8% (95% CI, 76.0-90.8%) for US, compared to 87.1% (95% CI, 81.8-91.0%) and 87.0% (95% CI, 83.1-90.1%) for CEUS. In the subgroup analysis of studies that evaluated deep learning algorithms, the sensitivity and specificity of CEUS (n = 4) increased to 92.4% (95% CI, 88.5-95.0%) and 88.2% (95% CI, 81.1-92.9%). CONCLUSIONS The diagnostic performance of ML algorithms for the malignant classification of FLLs was high for both US and CEUS with overall similar sensitivity and specificity. The similar performance of US may be related to the higher prevalence of DL models in that group.
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Affiliation(s)
- Carlos Alberto Campello
- School of Medicine, Universidade Federal do Mato Grosso, 2367 Quarenta e Nove St, Cuiabá, Brazil
| | - Everton Bruno Castanha
- School of Medicine, Universidade Federal de Pelotas, 538 Prof. Dr. Araújo St. Pelotas, Pelotas, Brazil
| | - Marina Vilardo
- School of Medicine, Universidade Catolica de Brasilia, QS 07, Brasília, Brazil
| | - Pedro V Staziaki
- Department of Radiology, University of Vermont Medical Center, 111 Colchester Ave, Burlington, USA
| | - Martina Zaguini Francisco
- Department of Radiology, Universidade Federal de Ciencias da Saude de Porto Alegre, 245 Sarmento Leite St, Porto Alegre, Brazil
| | - Bahram Mohajer
- Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 N Caroline St, Baltimore, USA
| | - Guilherme Watte
- Department of Radiology, Universidade Federal de Ciencias da Saude de Porto Alegre, 245 Sarmento Leite St, Porto Alegre, Brazil
| | - Fabio Ynoe Moraes
- Department of Oncology, Queen's University, 76 Stuart St, Kingston, Canada
| | - Bruno Hochhegger
- Department of Radiology, University of Florida, 1600 SW Archer Rd, Gainesville, USA
| | - Stephan Altmayer
- Department of Radiology, Stanford University, 300 Pasteur Drive, Suite H1330, Stanford, USA.
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Zhang YH, Chen XL, Wang YR, Hou YW, Zhang YD, Wang KJ. Prevention of malignant digestive system tumors should focus on the control of chronic inflammation. World J Gastrointest Oncol 2023; 15:389-404. [PMID: 37009320 PMCID: PMC10052658 DOI: 10.4251/wjgo.v15.i3.389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 01/17/2023] [Accepted: 02/07/2023] [Indexed: 03/14/2023] Open
Abstract
Chronic inflammation, through a variety of mechanisms, plays a key role in the occurrence and development of digestive system malignant tumors (DSMTs). In this study, we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation. The development and evaluation of cancer prevention strategies is a longstanding process. Cancer prevention, especially in the early stage of life, should be emphasized throughout the whole life course. Issues such as the time interval for colon cancer screening, the development of direct-acting antiviral drugs for liver cancer, and the Helicobacter pylori vaccine all need to be explored in long-term, large-scale experiments in the future.
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Affiliation(s)
- Yue-Hua Zhang
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Xiao-Lin Chen
- Department of Prenatal Diagnosis Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Yi-Ran Wang
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Yu-Wei Hou
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Yao-Dong Zhang
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Kai-Juan Wang
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
- Henan Children’s Hospital Zhengzhou Children’s Hospital, Children’s Hospital Affiliated to Zhengzhou University, Key Laboratory of Tumor Epidemiology of Henan Province, State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
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Roa-Colomo A, López Garrido MÁ, Molina-Vallejo P, Rojas A, Sanchez MG, Aranda-García V, Salmeron J, Romero-Gomez M, Muntane J, Padillo J, Alamo JM, Lorente JA, Serrano MJ, Garrido-Navas MC. Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception. Front Mol Biosci 2022; 9:1074277. [PMID: 36518850 PMCID: PMC9742249 DOI: 10.3389/fmolb.2022.1074277] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 11/16/2022] [Indexed: 09/24/2023] Open
Abstract
Purpose: Lack of diagnostic and prognostic biomarkers in hepatocellular carcinoma impedes stratifying patients based on their risk of developing cancer. The aim of this study was to evaluate phenotypic and genetic heterogeneity of circulating epithelial cells (CECs) based on asialoglycoprotein receptor 1 (ASGR1) and miR-122-5p expression as potential diagnostic and prognostic tools in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Methods: Peripheral blood samples were extracted from LC and HCC patients at different disease stages. CECs were isolated using positive immunomagnetic selection. Genetic and phenotypic characterization was validated by double immunocytochemistry for cytokeratin (CK) and ASGR1 or by in situ hybridization with miR-122-5p and CECs were visualized by confocal microscopy. Results: The presence of CECs increased HCC risk by 2.58-fold, however, this was only significant for patients with previous LC (p = 0.028) and not for those without prior LC (p = 0.23). Furthermore, the number of CECs lacking ASGR1 expression correlated significantly with HCC incidence and absence of miR-122-5p expression (p = 0.014; r = 0.23). Finally, overall survival was significantly greater for patients at earlier cancer stages (p = 0.018), but this difference was only maintained in the group with the presence of CECs (p = 0.021) whereas progression-free survival was influenced by the absence of ASGR1 expression. Conclusion: Identification and characterization of CECs by ASGR1 and/or miR-122-5p expression may be used as a risk-stratification tool in LC patients, as it was shown to be an independent prognostic and risk-stratification marker in LC and early disease stage HCC patients.
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Affiliation(s)
- Amparo Roa-Colomo
- Clinical Medicine and Public Health Doctoral Program, University of Granada, Granada, Spain
- Gastroenterology and Hepatology Department, San Cecilio University Hospital, Granada, Spain
| | | | - Pilar Molina-Vallejo
- Genyo-Centro Pfizer-Universidad De Granada-Junta De Andalucía De Genómica e Investigación Oncológica, Granada, Spain
| | - Angela Rojas
- Seliver Group, Institute of Biomedicine of Seville (IBiS)/ Hospital Universitario Virgen Del Rocío/CSIC/Universidad De Sevilla, Seville, Spain
- Spanish Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute (ISCIII), Madrid, Spain
| | - Mercedes González Sanchez
- Gastroenterology and Hepatology Department, Virgen De Las Nieves University Hospital, Granada, Spain
| | - Violeta Aranda-García
- Statistician at Fundación para la Investigación Biosanitaria Andalucía Oriental Alejandro Otero (FIBAO), Hospital Virgen de las Nieves, Granada, Spain
| | - Javier Salmeron
- Gastroenterology and Hepatology Department, San Cecilio University Hospital, Granada, Spain
| | - Manuel Romero-Gomez
- Seliver Group, Institute of Biomedicine of Seville (IBiS)/ Hospital Universitario Virgen Del Rocío/CSIC/Universidad De Sevilla, Seville, Spain
- Spanish Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute (ISCIII), Madrid, Spain
| | - Jordi Muntane
- Spanish Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute (ISCIII), Madrid, Spain
- Institute of Biomedicine of Seville (IBiS), Hospital University Virgen del Rocío/CSIC/University of Seville, Seville, Spain
- Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain
| | - Javier Padillo
- General and Gastrointestinal Surgery Division, Virgen del Rocío University Hospital, Sevilla, Spain
| | - Jose María Alamo
- General and Gastrointestinal Surgery Division, Virgen del Rocío University Hospital, Sevilla, Spain
| | - Jose A. Lorente
- Genyo-Centro Pfizer-Universidad De Granada-Junta De Andalucía De Genómica e Investigación Oncológica, Granada, Spain
- Legal Medicine Department, Medicine School, University of Granada, Granada, Spain
| | - María José Serrano
- Genyo-Centro Pfizer-Universidad De Granada-Junta De Andalucía De Genómica e Investigación Oncológica, Granada, Spain
- Comprehensive Oncology Division, Clinical University Hospital, Virgen de las Nieves-IBS, Granada, Spain
- Department of Pathological Anatomy, Faculty of Medicine, University of Granada, Granada, Spain
| | - M. Carmen Garrido-Navas
- Genyo-Centro Pfizer-Universidad De Granada-Junta De Andalucía De Genómica e Investigación Oncológica, Granada, Spain
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Liang Y, Zhang Z, Zhong D, Lai C, Dai Z, Zou H, Feng T, Shang J, Shi Y, Huang X. The prognostic significance of inflammation-immunity-nutrition score on postoperative survival and recurrence in hepatocellular carcinoma patients. Front Oncol 2022; 12:913731. [PMID: 36016629 PMCID: PMC9396284 DOI: 10.3389/fonc.2022.913731] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 07/21/2022] [Indexed: 12/24/2022] Open
Abstract
Background Inflammation, immunity, and nutrition status play important roles in tumorigenesis, progression, and metastasis. This study aimed to evaluate the prognostic value of Inflammation-Immunity-Nutrition Score (IINS) for overall survival (OS) and progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC) undergoing radical surgery. Methods A total of 204 HCC patients who met the criteria were included in this retrospective study: 144 in the prediction model and 60 in the validation model. IINS was constructed based on the sum of classification scores of preoperative high-sensitivity C-reactive protein (hsCRP), lymphocyte (LYM), and albumin (ALB). The associations between the IINS group and the clinicopathologic characteristics were analyzed using Pearson’s χ2 test or Fisher’s exact test. Multivariate Cox regression analysis was used to evaluate variables significant on univariate analysis. Kaplan-Meier survival curves were conducted to investigate the prognostic values of IINS, Alpha-fetoprotein (AFP) and IINS-AFP classification. The prognostic performances of all the potential prognostic factors were further compared by receiver operating characteristic (ROC) curve, and time-dependent ROC curve. The internal validation and external validation were used to ensure the credibility of this prediction model. Results The patients were divided into low and high IINS groups according to the median of IINS. According to multivariate Cox regression analyses, the Barcelona Clinic Liver Cancer (BCLC) Stage (P=0.003), AFP (P=0.013), and IINS (P=0.028) were independent prognostic factors for OS, and BCLC Stage (P=0.009), microvascular invasion (P=0.030), and IINS (P=0.031) were independent prognostic factors for PFS. High IINS group were associated with significantly worse OS and PFS compared with low IINS group (P<0.001; P=0.004). In terms of clinical prognosis, IINS-AFP classification was good in group I, moderate in group II, and poor in group III. Group I had a longer OS (P<0.001) and PFS (P=0.008) compared with group II and III. ROC analysis revealed that IINS-AFP classification had a better prognostic performance for OS (AUC: 0.767) and PFS (AUC: 0.641) than other predictors, excluding its slightly lower predictive power for PFS than IINS. The time-dependent ROC curves also showed that both IINS (12-month AUC: 0.650; 24-month AUC: 0.670; 36-month AUC: 0.880) and IINS-AFP classification (12-month AUC: 0.720; 24-month AUC: 0.760; 36-month AUC: 0.970) performed well in predicting OS for HCC patients. Furthermore, the internal validation and external validation proved that IINS had good predictive performance, strong internal validity and external applicability, and could be used to establish the prediction model. Conclusion Inflammation-immunity-nutrition score could be a powerful clinical prognostic indicator in HCC patients undergoing radical surgery. Furthermore, IINS-AFP classification presents better prognostic performance than IINS or AFP alone, and might serve as a practical guidance to help patients adjust treatment and follow-up strategies to improve future outcomes.
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Affiliation(s)
- Yuxin Liang
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province and Organ Transplant Research Institute, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Zilong Zhang
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province and Organ Transplant Research Institute, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Deyuan Zhong
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province and Organ Transplant Research Institute, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Chunyou Lai
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province and Organ Transplant Research Institute, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Zonglin Dai
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province and Organ Transplant Research Institute, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Haibo Zou
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province and Organ Transplant Research Institute, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Tianhang Feng
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province and Organ Transplant Research Institute, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Jin Shang
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province and Organ Transplant Research Institute, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Ying Shi
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province and Organ Transplant Research Institute, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
- *Correspondence: Xiaolun Huang, ; Ying Shi,
| | - Xiaolun Huang
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province and Organ Transplant Research Institute, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
- *Correspondence: Xiaolun Huang, ; Ying Shi,
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Yakovchenko V, Morgan TR, Miech EJ, Neely B, Lamorte C, Gibson S, Beste LA, McCurdy H, Scott D, Gonzalez R, Park A, Powell BJ, Bajaj JS, Dominitz JA, Chartier M, Ross D, Chinman MJ, Rogal SS. Core implementation strategies for improving cirrhosis care in the Veterans Health Administration. Hepatology 2022; 76:404-417. [PMID: 35124820 PMCID: PMC9288973 DOI: 10.1002/hep.32395] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 01/11/2022] [Accepted: 01/14/2022] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIMS The Veterans Health Administration (VHA) provides care for more than 80,000 veterans with cirrhosis. This longitudinal, multimethod evaluation of a cirrhosis care quality improvement program aimed to (1) identify implementation strategies associated with evidence-based, guideline-concordant cirrhosis care over time, and (2) use qualitative interviews to operationalize strategies for a manualized intervention. APPROACH AND RESULTS VHA providers were surveyed annually about the use of 73 implementation strategies to improve cirrhosis care in fiscal years 2018 (FY18) and 2019 (FY19). Implementation strategies linked to guideline-concordant cirrhosis care were identified using bivariate statistics and comparative configurational methods. Semistructured interviews were conducted with 12 facilities in the highest quartile of cirrhosis care to specify the successful implementation strategies and their mechanisms of change. A total of 106 VHA facilities (82%) responded at least once over the 2-year period (FY18, n = 63; FY19, n = 100). Facilities reported using a median of 12 (interquartile range [IQR] 20) implementation strategies in FY18 and 10 (IQR 19) in FY19. Of the 73 strategies, 35 (48%) were positively correlated with provision of evidence-based cirrhosis care. Configurational analysis identified multiple strategy pathways directly linked to more guideline-concordant cirrhosis care. Across both methods, a subset of eight strategies was determined to be core to cirrhosis care improvement and specified using qualitative interviews. CONCLUSIONS In a national cirrhosis care improvement initiative, a multimethod approach identified a core subset of successful implementation strategy combinations. This process of empirically identifying and specifying implementation strategies may be applicable to other implementation challenges in hepatology.
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Affiliation(s)
- Vera Yakovchenko
- Center for Healthcare Organization and Implementation Research, VA Bedford Healthcare System, Bedford, MA
| | - Timothy R. Morgan
- Gastroenterology Section, VA Long Beach Healthcare System, Long Beach, CA,Division of Gastroenterology, Department of Medicine, University of California, Irvine, CA
| | - Edward J. Miech
- Department of Veterans Affairs, Roudebush VA Medical Center, HSR&D Center for Health Information & Communication, VA PRIS-M QUERI, Indianapolis, IN,Regenstrief Institute, Indianapolis, IN
| | - Brittney Neely
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, PA
| | - Carolyn Lamorte
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, PA
| | - Sandra Gibson
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, PA,Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA
| | - Lauren A. Beste
- Division of General Internal Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA,General Medicine Service, VA Puget Sound Health Care System, Seattle, WA
| | | | - Dawn Scott
- Department of Medicine, Central Texas Veterans Healthcare System, Temple, TX
| | - Rachel Gonzalez
- Department of Veterans Affairs, Sierra Pacific Veterans Integrated Service Network, Pharmacy Benefits Management, Mather, CA
| | - Angela Park
- Office of Healthcare Transformation, Department of Veterans Affairs, Washington, DC
| | - Byron J. Powell
- Brown School, Washington University in St. Louis, St. Louis, MO
| | - Jasmohan S. Bajaj
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA,Division of Gastroenterology, Central Virginia Veterans Affairs Healthcare System, Richmond, VA
| | - Jason A. Dominitz
- Gastroenterology Section, Veterans Affairs Puget Sound Health Care System, Seattle, WA,Division of Gastroenterology, Department of Medicine, University of Washington School of Medicine, Seattle, WA
| | - Maggie Chartier
- HIV, Hepatitis, and Related Conditions Programs, Office of Specialty Care Services, Veterans Health Administration, Washington, DC
| | - David Ross
- HIV, Hepatitis, and Related Conditions Programs, Office of Specialty Care Services, Veterans Health Administration, Washington, DC
| | - Matthew J. Chinman
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, PA,RAND Corporation, Pittsburgh, PA
| | - Shari S. Rogal
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, PA,Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA,Department of Surgery, University of Pittsburgh, Pittsburgh, PA
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20
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Wang Y, Li X, Yu J, Cheng Z, Hou Q, Liang P. Prognostic Nutritional Index in Hepatocellular Carcinoma Patients With Hepatitis B Following US-Guided Percutaneous Microwave Ablation: A Retrospective Study With 1,047 Patients. Front Surg 2022; 9:878737. [PMID: 35846958 PMCID: PMC9276976 DOI: 10.3389/fsurg.2022.878737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 06/03/2022] [Indexed: 12/24/2022] Open
Abstract
ObjectiveSeveral studies have revealed that the prognostic nutritional index (PNI) was associated with survival in several cancers. However, the prognostic value of PNI in hepatocellular carcinoma (HCC) patients following ultrasound-guided percutaneous microwave ablation (US-PMWA) remains unknown, especially in patients with hepatitis B virus (HBV) infection. Therefore, the present study aimed to evaluate the potential prognostic value of PNI in these patients.MaterialsThe medical records of 1,047 HCC patients with HBV infection following US-PMWA were retrospectively reviewed. The association between preoperative PNI and overall survival (OS), as well as other clinical characteristics of HCC, were analyzed using the Kaplan–Meier plot, log-rank test, multi-parameter Cox proportional hazards model, restricted cubic spline (RCS), and time-dependent receiver operating characteristic (ROC) curve analyses.ResultsPatients with a preoperative PNI more than 45 were verified to have better OS than patients with a PNI less than 45. In the multi-parameter Cox proportional hazards models, the log-transformed PNI was verified as an independent prognostic factor for OS. The result of the RCS analysis revealed that there was a nearly linear relationship between PNI and OS. The area under the time-dependent ROC curve for PNI in predicting OS was 0.56, which is relatively stable.ConclusionPreoperative PNI represents a convenient, noninvasive, and independent prognostic indicator in HCC patients with HBV infection following US-PMWA.
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21
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Ramtohul T, Vilgrain V, Soubrane O, Bouattour M, Luciani A, Kobeiter H, Mule S, Tacher V, Laurent A, Amaddeo G, Regnault H, Bulsei J, Nault JC, Nahon P, Durand-Zaleski I, Seror O. Impact of Extended Use of Ablation Techniques in Cirrhotic Patients with Hepatocellular Carcinoma: A Cost-Effectiveness Analysis. Cancers (Basel) 2022; 14:2634. [PMID: 35681618 PMCID: PMC9179352 DOI: 10.3390/cancers14112634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 05/22/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND To evaluate the cost-effectiveness of the extended use of ablation for the treatment of hepatocellular carcinoma (HCC) with cirrhosis in an expert ablation center when compared to the non-extended use of ablation in equivalent tertiary care centers. METHODS Consecutive cirrhotic patients with non-metastatic HCC, no prior treatment, and referred to three tertiary care centers between 2012 and 2016 were retrospectively identified. The Bondy group, including all of the patients treated at Jean Verdier Hospital, where the extended use of ablation is routinely performed, was compared to the standard of care (SOC) group, including all of the patients treated at the Beaujon and Mondor Hospitals, using propensity score matching. A cost-effectiveness analysis was carried out from the perspective of French health insurance using a Markov model on a lifetime horizon. RESULTS 532 patients were matched. The Bondy group led to incremental discounted lifetime effects of 0.8 life-years gained (LYG) (95% confidence interval: 0.4, 1.3) and a decrease in lifetime costs of EUR 7288 (USD 8016) (95% confidence interval: EUR 5730 [USD 6303], EUR 10,620 [USD 11,682]) per patient, compared with the SOC group, resulting in a dominant mean incremental cost-effectiveness ratio (ICER). A compliance with the Barcelona Clinic Liver Classification (BCLC) guidelines for earlier stage contributed to the greater part of the ICER. CONCLUSION The extended use of ablation in cirrhotic patients with HCC was more effective and less expensive than the non-extended use of the ablation strategy.
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Affiliation(s)
- Toulsie Ramtohul
- AP-HP, Health Economics Research Unit, 75004 Paris, France; (T.R.); (J.B.); (I.D.-Z.)
- AP-HP, Department of Radiology, Jean Verdier Hospital, 93140 Bondy, France
| | - Valérie Vilgrain
- AP-HP, Department of Radiology, Beaujon Hospital, 92110 Clichy, France;
- INSERM U1149, Centre de Recherche Biomédicale Bichat-Beaujon, CRB3, 75018 Paris, France
| | - Olivier Soubrane
- AP-HP, Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, 92110 Clichy, France;
| | - Mohamed Bouattour
- AP-HP, Department of Digestive Oncology, Beaujon Hospital, 92110 Clichy, France;
| | - Alain Luciani
- INSERM IMRB Unit U 955, Equipe 18, 94010 Créteil, France; (A.L.); (S.M.); (V.T.); (A.L.); (G.A.); (H.R.)
- AP-HP, Department of Radiology, Henri Mondor Hospital, 94000 Créteil, France;
| | - Hicham Kobeiter
- AP-HP, Department of Radiology, Henri Mondor Hospital, 94000 Créteil, France;
| | - Sébastien Mule
- INSERM IMRB Unit U 955, Equipe 18, 94010 Créteil, France; (A.L.); (S.M.); (V.T.); (A.L.); (G.A.); (H.R.)
- AP-HP, Department of Radiology, Henri Mondor Hospital, 94000 Créteil, France;
| | - Vania Tacher
- INSERM IMRB Unit U 955, Equipe 18, 94010 Créteil, France; (A.L.); (S.M.); (V.T.); (A.L.); (G.A.); (H.R.)
- AP-HP, Department of Radiology, Henri Mondor Hospital, 94000 Créteil, France;
| | - Alexis Laurent
- INSERM IMRB Unit U 955, Equipe 18, 94010 Créteil, France; (A.L.); (S.M.); (V.T.); (A.L.); (G.A.); (H.R.)
- AP-HP, Department of Liver Surgery, Henri Mondor Hospital, 94000 Créteil, France
| | - Giuliana Amaddeo
- INSERM IMRB Unit U 955, Equipe 18, 94010 Créteil, France; (A.L.); (S.M.); (V.T.); (A.L.); (G.A.); (H.R.)
- AP-HP, Department of Hepatology, Henri Mondor Hospital, 94000 Créteil, France
| | - Hélène Regnault
- INSERM IMRB Unit U 955, Equipe 18, 94010 Créteil, France; (A.L.); (S.M.); (V.T.); (A.L.); (G.A.); (H.R.)
- AP-HP, Department of Hepatology, Henri Mondor Hospital, 94000 Créteil, France
| | - Julie Bulsei
- AP-HP, Health Economics Research Unit, 75004 Paris, France; (T.R.); (J.B.); (I.D.-Z.)
| | - Jean-Charles Nault
- AP-HP, Department of Hepatology, Jean Verdier Hospital, 93140 Bondy, France; (J.-C.N.); (P.N.)
- Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale, 75010 Paris, France
| | - Pierre Nahon
- AP-HP, Department of Hepatology, Jean Verdier Hospital, 93140 Bondy, France; (J.-C.N.); (P.N.)
- Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale, 75010 Paris, France
- French League Against Cancer, Education and Research in Health Medicine and Human Biology, University Paris 13, Sorbonne Paris Cité, 75005 Paris, France
| | - Isabelle Durand-Zaleski
- AP-HP, Health Economics Research Unit, 75004 Paris, France; (T.R.); (J.B.); (I.D.-Z.)
- ECEVE, UMRS 1123, French National Institute of Health and Medical Research, 75010 Paris, France
- AP-HP, Department of Public Health, Henri Mondor Hospital, 94000 Creteil, France
| | - Olivier Seror
- AP-HP, Department of Radiology, Jean Verdier Hospital, 93140 Bondy, France
- Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale, 75010 Paris, France
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22
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Dadoun H, Rousseau AL, de Kerviler E, Correas JM, Tissier AM, Joujou F, Bodard S, Khezzane K, de Margerie-Mellon C, Delingette H, Ayache N. Deep Learning for the Detection, Localization, and Characterization of Focal Liver Lesions on Abdominal US Images. Radiol Artif Intell 2022; 4:e210110. [PMID: 35652113 DOI: 10.1148/ryai.210110] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 02/08/2022] [Accepted: 02/16/2022] [Indexed: 12/24/2022]
Abstract
Purpose To train and assess the performance of a deep learning-based network designed to detect, localize, and characterize focal liver lesions (FLLs) in the liver parenchyma on abdominal US images. Materials and Methods In this retrospective, multicenter, institutional review board-approved study, two object detectors, Faster region-based convolutional neural network (Faster R-CNN) and Detection Transformer (DETR), were fine-tuned on a dataset of 1026 patients (n = 2551 B-mode abdominal US images obtained between 2014 and 2018). Performance of the networks was analyzed on a test set of 48 additional patients (n = 155 B-mode abdominal US images obtained in 2019) and compared with the performance of three caregivers (one nonexpert and two experts) blinded to the clinical history. The sign test was used to compare accuracy, specificity, sensitivity, and positive predictive value among all raters. Results DETR achieved a specificity of 90% (95% CI: 75, 100) and a sensitivity of 97% (95% CI: 97, 97) for the detection of FLLs. The performance of DETR met or exceeded that of the three caregivers for this task. DETR correctly localized 80% of the lesions, and it achieved a specificity of 81% (95% CI: 67, 91) and a sensitivity of 82% (95% CI: 62, 100) for FLL characterization (benign vs malignant) among lesions localized by all raters. The performance of DETR met or exceeded that of two experts and Faster R-CNN for these tasks. Conclusion DETR demonstrated high specificity for detection, localization, and characterization of FLLs on abdominal US images. Supplemental material is available for this article. RSNA, 2022Keywords: Computer-aided Diagnosis (CAD), Ultrasound, Abdomen/GI, Liver, Tissue Characterization, Supervised Learning, Transfer Learning, Convolutional Neural Network (CNN).
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Affiliation(s)
- Hind Dadoun
- Université Côte d'Azur, Inria, Epione Team, Sophia Antipolis, 2004 Route des Lucioles, 06902 Valbonne, France (H. Dadoun, H. Delingette, N.A.); Department of Vascular Surgery, Georges Pompidou European Hospital APHP, Université de Paris, Paris, France (A.L.R.); NHance.ngo, Saint Germain en Laye, France (A.L.R.); Department of Radiology, Hôpital Saint Louis APHP, Université de Paris, Paris, France (E.d.K., F.J., K.K., C.d.M.M.); and Department of Adult Radiology, Université de Paris and Université de l'Hôpital Necker, Paris, France (J.M.C., A.M.T., S.B.)
| | - Anne-Laure Rousseau
- Université Côte d'Azur, Inria, Epione Team, Sophia Antipolis, 2004 Route des Lucioles, 06902 Valbonne, France (H. Dadoun, H. Delingette, N.A.); Department of Vascular Surgery, Georges Pompidou European Hospital APHP, Université de Paris, Paris, France (A.L.R.); NHance.ngo, Saint Germain en Laye, France (A.L.R.); Department of Radiology, Hôpital Saint Louis APHP, Université de Paris, Paris, France (E.d.K., F.J., K.K., C.d.M.M.); and Department of Adult Radiology, Université de Paris and Université de l'Hôpital Necker, Paris, France (J.M.C., A.M.T., S.B.)
| | - Eric de Kerviler
- Université Côte d'Azur, Inria, Epione Team, Sophia Antipolis, 2004 Route des Lucioles, 06902 Valbonne, France (H. Dadoun, H. Delingette, N.A.); Department of Vascular Surgery, Georges Pompidou European Hospital APHP, Université de Paris, Paris, France (A.L.R.); NHance.ngo, Saint Germain en Laye, France (A.L.R.); Department of Radiology, Hôpital Saint Louis APHP, Université de Paris, Paris, France (E.d.K., F.J., K.K., C.d.M.M.); and Department of Adult Radiology, Université de Paris and Université de l'Hôpital Necker, Paris, France (J.M.C., A.M.T., S.B.)
| | - Jean-Michel Correas
- Université Côte d'Azur, Inria, Epione Team, Sophia Antipolis, 2004 Route des Lucioles, 06902 Valbonne, France (H. Dadoun, H. Delingette, N.A.); Department of Vascular Surgery, Georges Pompidou European Hospital APHP, Université de Paris, Paris, France (A.L.R.); NHance.ngo, Saint Germain en Laye, France (A.L.R.); Department of Radiology, Hôpital Saint Louis APHP, Université de Paris, Paris, France (E.d.K., F.J., K.K., C.d.M.M.); and Department of Adult Radiology, Université de Paris and Université de l'Hôpital Necker, Paris, France (J.M.C., A.M.T., S.B.)
| | - Anne-Marie Tissier
- Université Côte d'Azur, Inria, Epione Team, Sophia Antipolis, 2004 Route des Lucioles, 06902 Valbonne, France (H. Dadoun, H. Delingette, N.A.); Department of Vascular Surgery, Georges Pompidou European Hospital APHP, Université de Paris, Paris, France (A.L.R.); NHance.ngo, Saint Germain en Laye, France (A.L.R.); Department of Radiology, Hôpital Saint Louis APHP, Université de Paris, Paris, France (E.d.K., F.J., K.K., C.d.M.M.); and Department of Adult Radiology, Université de Paris and Université de l'Hôpital Necker, Paris, France (J.M.C., A.M.T., S.B.)
| | - Fanny Joujou
- Université Côte d'Azur, Inria, Epione Team, Sophia Antipolis, 2004 Route des Lucioles, 06902 Valbonne, France (H. Dadoun, H. Delingette, N.A.); Department of Vascular Surgery, Georges Pompidou European Hospital APHP, Université de Paris, Paris, France (A.L.R.); NHance.ngo, Saint Germain en Laye, France (A.L.R.); Department of Radiology, Hôpital Saint Louis APHP, Université de Paris, Paris, France (E.d.K., F.J., K.K., C.d.M.M.); and Department of Adult Radiology, Université de Paris and Université de l'Hôpital Necker, Paris, France (J.M.C., A.M.T., S.B.)
| | - Sylvain Bodard
- Université Côte d'Azur, Inria, Epione Team, Sophia Antipolis, 2004 Route des Lucioles, 06902 Valbonne, France (H. Dadoun, H. Delingette, N.A.); Department of Vascular Surgery, Georges Pompidou European Hospital APHP, Université de Paris, Paris, France (A.L.R.); NHance.ngo, Saint Germain en Laye, France (A.L.R.); Department of Radiology, Hôpital Saint Louis APHP, Université de Paris, Paris, France (E.d.K., F.J., K.K., C.d.M.M.); and Department of Adult Radiology, Université de Paris and Université de l'Hôpital Necker, Paris, France (J.M.C., A.M.T., S.B.)
| | - Kemel Khezzane
- Université Côte d'Azur, Inria, Epione Team, Sophia Antipolis, 2004 Route des Lucioles, 06902 Valbonne, France (H. Dadoun, H. Delingette, N.A.); Department of Vascular Surgery, Georges Pompidou European Hospital APHP, Université de Paris, Paris, France (A.L.R.); NHance.ngo, Saint Germain en Laye, France (A.L.R.); Department of Radiology, Hôpital Saint Louis APHP, Université de Paris, Paris, France (E.d.K., F.J., K.K., C.d.M.M.); and Department of Adult Radiology, Université de Paris and Université de l'Hôpital Necker, Paris, France (J.M.C., A.M.T., S.B.)
| | - Constance de Margerie-Mellon
- Université Côte d'Azur, Inria, Epione Team, Sophia Antipolis, 2004 Route des Lucioles, 06902 Valbonne, France (H. Dadoun, H. Delingette, N.A.); Department of Vascular Surgery, Georges Pompidou European Hospital APHP, Université de Paris, Paris, France (A.L.R.); NHance.ngo, Saint Germain en Laye, France (A.L.R.); Department of Radiology, Hôpital Saint Louis APHP, Université de Paris, Paris, France (E.d.K., F.J., K.K., C.d.M.M.); and Department of Adult Radiology, Université de Paris and Université de l'Hôpital Necker, Paris, France (J.M.C., A.M.T., S.B.)
| | - Hervé Delingette
- Université Côte d'Azur, Inria, Epione Team, Sophia Antipolis, 2004 Route des Lucioles, 06902 Valbonne, France (H. Dadoun, H. Delingette, N.A.); Department of Vascular Surgery, Georges Pompidou European Hospital APHP, Université de Paris, Paris, France (A.L.R.); NHance.ngo, Saint Germain en Laye, France (A.L.R.); Department of Radiology, Hôpital Saint Louis APHP, Université de Paris, Paris, France (E.d.K., F.J., K.K., C.d.M.M.); and Department of Adult Radiology, Université de Paris and Université de l'Hôpital Necker, Paris, France (J.M.C., A.M.T., S.B.)
| | - Nicholas Ayache
- Université Côte d'Azur, Inria, Epione Team, Sophia Antipolis, 2004 Route des Lucioles, 06902 Valbonne, France (H. Dadoun, H. Delingette, N.A.); Department of Vascular Surgery, Georges Pompidou European Hospital APHP, Université de Paris, Paris, France (A.L.R.); NHance.ngo, Saint Germain en Laye, France (A.L.R.); Department of Radiology, Hôpital Saint Louis APHP, Université de Paris, Paris, France (E.d.K., F.J., K.K., C.d.M.M.); and Department of Adult Radiology, Université de Paris and Université de l'Hôpital Necker, Paris, France (J.M.C., A.M.T., S.B.)
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Gao Q, Zeng Q, Wang Z, Li C, Xu Y, Cui P, Zhu X, Lu H, Wang G, Cai S, Wang J, Fan J. Start of an era: circulating cell-free DNA for early detection of cancers. Innovation (N Y) 2022; 3:100259. [PMID: 35647572 PMCID: PMC9133648 DOI: 10.1016/j.xinn.2022.100259] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 05/02/2022] [Indexed: 11/29/2022] Open
Abstract
Effective screening modalities are currently available for only a small subset of cancers, and they generally have suboptimal performance with complicated procedures. Therefore, there is an urgent need to develop simple, accurate, and non-invasive methods for early detection of cancers. Genetic and epigenetic alterations in plasma circulating cell-free DNA (cfDNA) have shown the potential to revolutionize methods of early detection of cancers and facilitate subsequent diagnosis to improve survival of patients. The medical interest in cfDNA assays has been inspired by emerging single- and multi-early detection of cancers studies. This review summarizes current technological and clinical advances, in the hopes of providing insights into the development and applications of cfDNA assays in various cancers and clinical scenarios. The key phases of clinical development of biomarkers are highlighted, and the future developments of cfDNA-based liquid biopsies in early detection of cancers are outlined. It is hoped that this study can boost the potential integration of cfDNA-based early detection of cancers into the current clinical workflow.
Liquid biopsy, characterized by minimal invasiveness and user friendliness, can identify multiple cancers at the early stage and localize the tissue of origin The state-of-the-art technology facilitates the application of circulating cell-free DNA (cfDNA) assays in the early detection of cancers cfDNA assays are expected to be integrated into the clinical workflow after technological refinement and clinical trial validation The development and application strategies of cfDNA assays in various cancers and clinical scenarios can vary, and the harm-and-benefit should be balanced carefully
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Affiliation(s)
- Qiang Gao
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China
- Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
| | - Qiang Zeng
- Health Management Institute, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China
| | - Zhijie Wang
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, China
| | | | - Yu Xu
- Burning Rock Biotech, Guangzhou 510320, China
| | - Peng Cui
- Burning Rock Biotech, Guangzhou 510320, China
| | - Xin Zhu
- Burning Rock Biotech, Guangzhou 510320, China
| | - Huafei Lu
- Burning Rock Biotech, Guangzhou 510320, China
| | | | - Shangli Cai
- Burning Rock Biotech, Guangzhou 510320, China
- Corresponding author
| | - Jie Wang
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, China
- Corresponding author
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China
- Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
- Corresponding author
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24
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Stefanini B, Tonnini M, Serio I, Renzulli M, Tovoli F. Surveillance for hepatocellular carcinoma: current status and future perspectives for improvement. Expert Rev Anticancer Ther 2022; 22:371-381. [PMID: 35263211 DOI: 10.1080/14737140.2022.2052276] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 03/08/2022] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is a globally relevant medical problem. Fortunately, risk factors for this tumor have been identified, and surveillance protocols developed. Patients with liver cirrhosis have the highest risk of developing HCC and have historically been included in surveillance programs. Special categories have also emerged in recent years, especially patients with eradicated HCV infection or nonalcoholic fatty liver disease. Novel serum biomarkers and magnetic resonance imaging protocols are currently being proposed to refine existing surveillance protocols. AREAS COVERED We discuss the rationale of surveillance programs for HCC and report the most recent recommendations from international guidelines about this topic. Gray areas, such as nonalcoholic fatty liver disease and the role of intrahepatic cholangiocellular carcinoma, are also discussed. EXPERT OPINION Surveillance is recognized as a tool to favor early diagnosis of HCC, access to curative treatment, and increase survival, even if the supporting evidence is mainly based on observational studies. As new randomized clinical trials are difficult to propose, future challenges will include optimizing implementation in the primary care setting and a more personalized approach, balancing the opportunities and risks of overdiagnosis of novel techniques and biomarkers.
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Affiliation(s)
- Bernardo Stefanini
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Matteo Tonnini
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Ilaria Serio
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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25
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Singal AG, El-Serag HB. Rational HCC screening approaches for patients with NAFLD. J Hepatol 2022; 76:195-201. [PMID: 34508791 PMCID: PMC8688224 DOI: 10.1016/j.jhep.2021.08.028] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 08/24/2021] [Accepted: 08/30/2021] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of developing hepatocellular carcinoma (HCC), especially among those who have cirrhosis or advanced fibrosis, but 20-30% of cases of NAFLD-related HCC occur in the absence of advanced fibrosis. The prevalence of NAFLD-related HCC is increasing in most countries worldwide. There are few direct data to support or refute the efficacy or effectiveness of HCC surveillance in NAFLD or to guide its application. We use evidence on surveillance in other conditions and studies on the clinical course of patients with NAFLD to arrive at recommendations for rational approaches to HCC surveillance in this growing cohort of patients. We also outline gaps in research and practice, including opportunities to advance the field.
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Affiliation(s)
- Amit G Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Hashem B El-Serag
- Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA.
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26
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Nahon P, Aubé C, Moga L, Chalaye J, Guiu B, Luciani A, Rode A, Ronot M, Seror O, Soussan M, Sutter O, Bourlière M, Bureau C, de Lédinghen V, Ganne-Carrié N. Non-invasive diagnosis and follow-up of primary malignant liver tumours. Clin Res Hepatol Gastroenterol 2022; 46:101766. [PMID: 34332137 DOI: 10.1016/j.clinre.2021.101766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 07/23/2021] [Indexed: 02/04/2023]
Abstract
Among a wide range of malignant liver tumours, hepatocellular carcinoma (HCC) developed on a background of cirrhosis represents the most frequent clinical situation. In this setting, HCC is one of the rare solid tumours for which histological confirmation is not mandatory. The convergence of multiple arguments obtained by non-invasive parameters using radiological findings allows to avoid liver biopsy in a large proportion of patients when a diagnosis of underlying cirrhosis is ascertained. Conversely, in case of atypical presentation or in order to exclude other rare malignant tumours mostly developed in the absence of cirrhosis, liver biopsy will then be essential. Based on typical radiological patterns described by contrast-enhanced imaging, numerous clinical guidelines have endorsed non-invasive diagnosis, staging and monitoring of HCC patients under treatment since 20 years. These algorithms have evolved over the years, taking into account progress in radiological technology and advances in curative or palliative procedures. Large cohort studies have also helped to refine diagnostic criteria and prognostication in the setting of complex therapeutic strategy. Unsupervised multi-analysis approaches both at the biological and radiological levels will in the future enrich the panel of non-invasive markers useful in clinical practice to manage HCC and other malignant tumours.
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Affiliation(s)
- Pierre Nahon
- Service d'hépatologie, Hôpital Avicenne, APHP, Université Sorbonne Paris Nord, Bobigny; INSERM UMR 1138, Centre de recherche des Cordeliers, Université de Paris
| | | | - Lucile Moga
- Service d'Hépatologie, Hôpital Beaujon, APHP, Clichy
| | - Julia Chalaye
- Service de médecine nucléaire, Hôpital Henri-Mondor, APHP, Créteil
| | - Boris Guiu
- Département de radiologie, Hôpital Saint-Eloi, CHU Angers
| | - Alain Luciani
- Service d'imagerie médicale, Hôpital Henri-Mondor, APHP, Créteil
| | - Agnès Rode
- Service d'imagerie médicale, Hôpital de la Croix Rousse, Hospices Civiles de Lyon, Lyon
| | - Maxime Ronot
- Service d'imagerie médicale, Hôpital Beaujon, APHP, Clichy
| | - Olivier Seror
- INSERM UMR 1138, Centre de recherche des Cordeliers, Université de Paris; Département de Radiologie Interventionnelle, Hôpital Avicenne, APHP, Université Sorbonne Paris Nord, Bobigny
| | - Michael Soussan
- Service de médecine nucléaire, Hôpital Avicenne, APHP, Université Sorbonne Paris Nord, Bobigny
| | - Olivier Sutter
- Département de Radiologie Interventionnelle, Hôpital Avicenne, APHP, Université Sorbonne Paris Nord, Bobigny
| | - Marc Bourlière
- Service d'hépato-gastroentérologie, Hôpital Saint Joseph, Marseille
| | | | - Victor de Lédinghen
- Service d'Hépatologie, CHU Bordeaux, Pessac & INSERM U1053, Université de Bordeaux, Bordeaux
| | - Nathalie Ganne-Carrié
- Service d'hépatologie, Hôpital Avicenne, APHP, Université Sorbonne Paris Nord, Bobigny; INSERM UMR 1138, Centre de recherche des Cordeliers, Université de Paris.
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27
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Nahon P, Najean M, Layese R, Zarca K, Segar LB, Cagnot C, Ganne-Carrié N, N’Kontchou G, Pol S, Chaffaut C, Carrat F, Ronot M, Audureau E, Durand-Zaleski I. Early hepatocellular carcinoma detection using magnetic resonance imaging is cost-effective in high-risk patients with cirrhosis. JHEP Rep 2022; 4:100390. [PMID: 34977518 PMCID: PMC8683591 DOI: 10.1016/j.jhepr.2021.100390] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 10/02/2021] [Accepted: 10/20/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND & AIMS Reinforced hepatocellular carcinoma (HCC) surveillance using magnetic resonance imaging (MRI) could increase early tumour detection but faces cost-effectiveness issues. In this study, we aimed to evaluate the cost-effectiveness of MRI for the detection of very early HCC (Barcelona Clinic Liver Cancer [BCLC] 0) in patients with an annual HCC risk >3%. METHODS French patients with compensated cirrhosis included in 4 multicentre prospective cohorts were considered. A scoring system was constructed to identify patients with an annual risk >3%. Using a Markov model, the economic evaluation estimated the costs and life years (LYs) gained with MRI vs. ultrasound (US) monitoring over a 20-year period. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the incremental costs by the incremental LYs. RESULTS Among 2,513 patients with non-viral causes of cirrhosis (n = 840) and/or cured HCV (n = 1,489)/controlled HBV infection (n = 184), 206 cases of HCC were detected after a 37-month follow-up. When applied to training (n = 1,658) and validation (n = 855) sets, the construction of a scoring system identified 33.4% and 37.5% of patients with an annual HCC risk >3% (3-year C-Indexes 75 and 76, respectively). In patients with a 3% annual risk, the incremental LY gained with MRI was 0.4 for an additional cost of €6,134, resulting in an ICER of €15,447 per LY. Compared to US monitoring, MRI detected 5x more BCLC 0 HCC. The deterministic sensitivity analysis confirmed the impact of HCC incidence. At a willingness to pay of €50,000/LY, MRI screening had a 100% probability of being cost-effective. CONCLUSIONS In the era of HCV eradication/HBV control, patients with annual HCC risk >3% represent one-third of French patients with cirrhosis. MRI is cost-effective in this population and could favour early HCC detection. LAY SUMMARY The early identification of hepatocellular carcinoma in patients with cirrhosis is important to improve patient outcomes. Magnetic resonance imaging could increase early tumour detection but is more expensive and less accessible than ultrasound (the standard modality for surveillance). Herein, using a simple score, we identified a subgroup of patients with cirrhosis (accounting for >one-third), who were at increased risk of hepatocellular carcinoma and for whom the increased expense of magnetic resonance imaging would be justified by the potential improvement in outcomes.
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Key Words
- AFP, alpha-fetoprotein
- AMRI, abbreviated magnetic resonance imaging
- BCLC, Barcelona Clinic Liver Cancer
- HCC, hepatocellular carcinoma
- HR, hazard ratio
- ICER, incremental cost-effectiveness ratio
- LY, life years
- LYG, life years gained
- MRI
- MRI, magnetic resonance imaging
- NAFLD, non-alcoholic fatty liver disease
- QALY, quality-adjusted life year
- RFA, radiofrequency ablation
- SHR, subdistribution hazard ratio
- TACE, transarterial chemoembolization
- US, ultrasound
- cirrhosis
- cost-effectiveness
- liver cancer risk
- surveillance
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Affiliation(s)
- Pierre Nahon
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, Liver Unit, Bobigny, France
- Université Sorbonne Paris Nord, F-93000 Bobigny, France
- Inserm, UMR-1138 “Functional Genomics of Solid Tumors”, Centre de recherche des Cordeliers, Université de Paris, Paris, France
| | - Marie Najean
- Université de Paris, CRESS, INSERM, INRA, URCEco, AP-HP, Hôpital de l’Hôtel Dieu, F-75004, Paris, France
| | - Richard Layese
- Univ Paris Est Créteil, INSERM, IMRB, Equipe CEpiA (Clinical Epidemiology and Ageing), Unité de Recherche Clinique (URC Mondor), Service de Santé Publique, Assistance Publique Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, F-94000, Créteil, France
| | - Kevin Zarca
- Université de Paris, CRESS, INSERM, INRA, URCEco, AP-HP, Hôpital de l’Hôtel Dieu, F-75004, Paris, France
| | - Laeticia Blampain Segar
- Université de Paris, CRESS, INSERM, INRA, URCEco, AP-HP, Hôpital de l’Hôtel Dieu, F-75004, Paris, France
| | - Carole Cagnot
- Clinical Research Department, ANRS | Emerging Infectious Diseases, Paris, France
| | - Nathalie Ganne-Carrié
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, Liver Unit, Bobigny, France
- Université Sorbonne Paris Nord, F-93000 Bobigny, France
- Inserm, UMR-1138 “Functional Genomics of Solid Tumors”, Centre de recherche des Cordeliers, Université de Paris, Paris, France
| | - Gisèle N’Kontchou
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, Liver Unit, Bobigny, France
- Université Sorbonne Paris Nord, F-93000 Bobigny, France
- Inserm, UMR-1138 “Functional Genomics of Solid Tumors”, Centre de recherche des Cordeliers, Université de Paris, Paris, France
| | - Stanislas Pol
- Université de Paris, département d’hépatologie/Addictologie, Hôpital Cochin, APHP, Paris, France
| | - Cendrine Chaffaut
- SBIM, APHP, Hôpital Saint-Louis, Paris, France
- Inserm, UMR-1153, ECSTRA Team, Paris, France
| | - Fabrice Carrat
- Sorbonne Université, Inserm, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Saint-Antoine, Unité de Santé Publique, Paris, France
| | - Maxime Ronot
- AP-HP, Hôpital Beaujon, Service de Radiologie, Clichy, France
| | - Etienne Audureau
- Univ Paris Est Créteil, INSERM, IMRB, Equipe CEpiA (Clinical Epidemiology and Ageing), Unité de Recherche Clinique (URC Mondor), Service de Santé Publique, Assistance Publique Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, F-94000, Créteil, France
| | - Isabelle Durand-Zaleski
- Université de Paris, CRESS, INSERM, INRA, URCEco, AP-HP, Hôpital de l’Hôtel Dieu, F-75004, Paris, France
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28
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Cho JY, Kwon SH, Lee EK, Lee JH, Kim HL. Cost-Effectiveness of Adjuvant Immunotherapy With Cytokine-Induced Killer Cell for Hepatocellular Carcinoma Based on a Randomized Controlled Trial and Real-World Data. Front Oncol 2021; 11:728740. [PMID: 34926248 PMCID: PMC8682810 DOI: 10.3389/fonc.2021.728740] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 11/16/2021] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Studies using data from randomized controlled trials (RCTs) and real-world data (RWD) have suggested that adjuvant cytokine-induced killer (CIK) cell immunotherapy after curative treatment for hepatocellular carcinoma (HCC) prolongs recurrence-free survival (RFS) and overall survival (OS). However, the cost-effectiveness of CIK cell immunotherapy as an adjuvant therapy for HCC compared to no adjuvant therapy is uncertain. METHODS We constructed a partitioned survival model to compare the expected costs, life-year (LY), and quality-adjusted life-year (QALY) of a hypothetical population of 10,000 patients between CIK cell immunotherapy and no adjuvant therapy groups. Patients with HCC aged 55 years who underwent a potentially curative treatment were simulated with the model over a 20-year time horizon, from a healthcare system perspective. To model the effectiveness, we used OS and RFS data from RCTs and RWD. We estimated the incremental cost-effectiveness ratios (ICERs) and performed extensive sensitivity analyses. RESULTS Based on the RCT data, the CIK cell immunotherapy incrementally incurred a cost of $61,813, 2.07 LYs, and 1.87 QALYs per patient compared to no adjuvant therapy, and the estimated ICER was $33,077/QALY. Being less than the willingness-to-pay threshold of $50,000/QALY, CIK cell immunotherapy was cost-effective. Using the RWD, the ICER was estimated as $25,107/QALY, which is lower than that obtained using RCT. The time horizon and cost of productivity loss were the most influential factors on the ICER. CONCLUSION We showed that receiving adjuvant CIK cell immunotherapy was more cost-effective than no adjuvant therapy in patients with HCC who underwent a potentially curative treatment, attributed to prolonged survival, reduced recurrence of HCC, and better prognosis of recurrence. Receiving CIK cell immunotherapy may be more cost-effective in real-world clinical practice.
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Affiliation(s)
- Jeong-Yeon Cho
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Sun-Hong Kwon
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Eui-Kyung Lee
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Hye-Lin Kim
- College of Pharmacy, Sahmyook University, Seoul, South Korea
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29
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Lim YS. Role of Tumor Biomarkers in the Surveillance of Hepatocellular Carcinoma. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2021; 78:284-288. [PMID: 34824186 DOI: 10.4166/kjg.2021.137] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 10/17/2021] [Accepted: 10/18/2021] [Indexed: 11/03/2022]
Abstract
Biomarkers are key components of the clinical management of cancer patients because they have contributed to significant survival improvements in these patients. They allow the classification of patients based on common features and facilitate risk stratification, early detection, diagnosis, and prediction of the prognosis or treatment response. In hepatocellular carcinoma (HCC), there are few biomarkers incorporated in clinical practice. Despite this, this has been an extensive area of research in recent years, with increasing efforts to identify the biomarkers across the cancer care continuum from risk stratification to early detection to prognostication and treatment response. The heterogeneous nature of HCCs has restricted the performance of biomarkers. HCC biomarkers have limited roles in risk stratification, diagnosis, and treatment response. Currently, the main role of biomarkers is in the surveillance of HCC to detect it at an earlier stage and reduce mortality, which is the focus of this review.
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Affiliation(s)
- Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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30
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An J. [Current Status and Future Directions of Hepatocellular Carcinoma Surveillance Test Based on Cost-effective Analysis]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2021; 78:255-260. [PMID: 34824183 DOI: 10.4166/kjg.2021.142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 11/22/2021] [Accepted: 11/22/2021] [Indexed: 12/25/2022]
Abstract
Detection of hepatocellular carcinoma (HCC) at an early stage enables patients to receive curative treatment with survival gains. Current international liver society guidelines recommend the enrollment of patients at high risk for HCC in surveillance programs. In Korea, surveillance for HCC advocated for patients with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis. The established surveillance tool for HCC is liver ultrasonography plus serum alpha-fetoprotein measurement every 6 months. However, there would be obstacles to the improvement of efficacy and cost-effectiveness of the HCC surveillance test. Assessing who is at risk of developing HCC remains incompletely validated. Also, which surveillance tools to use according to patients' characteristics are controversial. The present paper reviews the latest knowledge regarding the strategies and cost-effectiveness of HCC surveillance.
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Affiliation(s)
- Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
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31
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Crouchet E, Schuster C, Baumert TF. Liver cell circuits and therapeutic discovery for advanced liver disease and cancer. C R Biol 2021; 344:233-248. [PMID: 35786628 PMCID: PMC7613418 DOI: 10.5802/crbiol.64] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 10/11/2021] [Indexed: 11/24/2022]
Abstract
Hepatocellular carcinoma (HCC) is a major global health challenge with rising incidence. Despite the previous approval of several novel therapeutic approaches, HCC remains the second common cause of cancer-related death worldwide. The vast majority of HCCs arises in the context of chronic fibrotic liver diseases caused by viral or metabolic etiologies. In patients with advanced liver disease the risk of HCC persists even after viral cure or control of infection. Moreover, given the change in the lifestyle and increase of obesity and metabolic disorders, HCC incidence is predicted to drastically augment in the next decade. Early detection, improvement of the screening method in patient at-risk and development of chemopreventive strategies are therefore urgently needed to reduce HCC risk. This review summarizes the major challenges in the identification of patient at risk for HCC and the emergent strategies for HCC prevention to improve patients’ outcome.
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Huang XC, Pang FX, Ou SS, Wei XJ, Xu YJ, Lai YH. Risk Score Based on Two microRNAs as a Prognostic Marker of Hepatocellular Carcinoma and the Corresponding Competitive Endogenous RNA Network. Int J Gen Med 2021; 14:3377-3385. [PMID: 34285562 PMCID: PMC8286150 DOI: 10.2147/ijgm.s318516] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 06/28/2021] [Indexed: 12/15/2022] Open
Abstract
Purpose Liver transplantation (LT) currently yields the best outcomes for hepatocellular carcinoma (HCC). However, tumor recurrence still occurs in some patients. Identifying markers that predict HCC recurrence after LT is an unmet medical need. Methods In this study, differential expression analysis was used to identify differentially expressed microRNAs (DEmiRs) between HCC and liver tissues in the The Cancer Genome Atlas database and in data from patients with recurrent or non-recurrent HCC in the GSE64989 dataset. The expression profiles of the overlap DEmiRs were used to construct an miRNA-based risk score to predict prognosis using Cox regression analysis. The target genes of the miRNAs of interest were predicted, and they were analyzed for functional enrichment. Furthermore, we used the miRNAs of interest to construct a competitive endogenous RNA (ceRNA) network of long non-coding RNAs (lncRNAs), miRs and mRNAs. Results Four up-regulated and three down-regulated miRNAs in HCC and recurrent HCC after LT were considered as candidate miRs. MiR-3200-3p and miR-3690 were selected to construct the miR-based risk score, which was found to be associated with poor overall survival and progression-free survival. Furthermore, it proved to be an independent prognostic factor after adjusting for other clinicopathological factors. The corresponding ceRNA networks of these two miRs that we constructed may help to understand their regulatory mechanisms in HCC. Conclusion We propose a risk score based on miR-3200-3p and miR-3690 that may be useful as a prognostic marker to predict HCC recurrence after LT. We generated a ceRNA network involving these miRNAs, which may help reveal their regulatory roles in HCC.
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Affiliation(s)
- Xiao-Chun Huang
- Department of Transplantation, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People's Republic of China.,Guangxi Academy Of Medical Sciences, Nanning, Guangxi, 530021, People's Republic of China
| | - Fei-Xiong Pang
- Department of Transplantation, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People's Republic of China.,Guangxi Academy Of Medical Sciences, Nanning, Guangxi, 530021, People's Republic of China
| | - Sheng-Song Ou
- Department of Transplantation, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People's Republic of China.,Guangxi Academy Of Medical Sciences, Nanning, Guangxi, 530021, People's Republic of China
| | - Xiao-Jiao Wei
- Department of Transplantation, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People's Republic of China.,Guangxi Academy Of Medical Sciences, Nanning, Guangxi, 530021, People's Republic of China
| | - Yu-Ju Xu
- Department of Transplantation, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People's Republic of China.,Guangxi Academy Of Medical Sciences, Nanning, Guangxi, 530021, People's Republic of China
| | - Yan-Hua Lai
- Department of Transplantation, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People's Republic of China.,Guangxi Academy Of Medical Sciences, Nanning, Guangxi, 530021, People's Republic of China
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Metallomic profile in non-cirrhotic hepatocellular carcinoma supports a phenomenon of metal metabolism adaptation in tumor cells. Sci Rep 2021; 11:14195. [PMID: 34244548 PMCID: PMC8271004 DOI: 10.1038/s41598-021-93369-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 06/18/2021] [Indexed: 01/31/2023] Open
Abstract
We have previously described a form of hepatocellular carcinoma (HCC) in non-cirrhotic liver (HCC-NC) developed by Peruvian patients. We analyzed the metallomic profile in hepatic tissues from two independent cohorts exhibiting HCC-NC. Clinical, histopathological data, and HCC and non-tumoral liver (NTL) samples of 38 Peruvian and 38 French HCC-NC patients, were studied. Twelve metals were quantified using ICP/MS: Mn, Fe, Cu, Co, Zn, As, Se, Rb, Mo, Cd, Pb, and Sn. Associations between metals and survival were assessed. Our data showed significant differences between cohorts. Mean ages were 40.6 ± 20, 67.5 ± 9 years old for Peruvians and French, respectively. Fifty percent of the Peruvian patients were positive for the HBsAg, versus 3% in French patients. Mn, Cu, Zn, As, Se, Rb, Mo, Cd, Sn metal concentrations were higher in NTL of Peruvians. Importantly, metal concentrations were lower in HCC areas compared to NTL tissues in both cohorts, except for Cu for which mean concentration was higher in HCC (p < 0.05). Se concentration in HCC was associated with extended survival only in Peruvians. Our data, obtained in Peruvian and French HCC-NC cohorts, highlights similarity in the metallomic profile of HCC compared to NTL during the hepatic tumorigenesis in these specific groups of patients.
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Avanceña AL, Miller N, Uttal SE, Hutton DW, Mellinger JL. Cost-effectiveness of alcohol use treatments in patients with alcohol-related cirrhosis. J Hepatol 2021; 74:1286-1294. [PMID: 33326815 PMCID: PMC8177741 DOI: 10.1016/j.jhep.2020.12.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 11/24/2020] [Accepted: 12/03/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS Alcohol use treatment such as medication-assisted therapies (MATs) and counseling are available and effective in promoting alcohol abstinence. We sought to explore the cost-effectiveness of different alcohol use treatments among patients with compensated alcohol-related cirrhosis (AC). METHODS We simulated a cohort of patients with compensated AC receiving care from a hepatology clinic over their lifetimes. We estimated costs (in 2017 US$) and benefits in terms of quality-adjusted life years (QALYs) gained from healthcare and societal perspectives. Transition probabilities, costs, and health utility weights were taken from the literature. Treatment effects of FDA-approved MATs (acamprosate and naltrexone) and non-FDA approved MATs (baclofen, gabapentin, and topiramate) and counseling were based on a study of employer-insured patients with AC. We calculated incremental cost-effectiveness ratios (ICERs) and performed one-way and probabilistic sensitivity analyses to understand the impact of parameter uncertainty. RESULTS Compared to a do-nothing scenario, MATs and counseling were found to be cost-saving from a healthcare perspective, which means that they provide more benefits with less costs than no intervention. Compared to other interventions, acamprosate and naltrexone cost the least and provide the most QALYs. If the effectiveness of MATs and counseling decreased, these interventions would still be cost-effective based on the commonly used $100,000 per QALY gained threshold. Several sensitivity and scenario analyses showed that our main findings are robust. CONCLUSIONS Among patients with compensated AC, MATs and counseling are extremely cost-effective, and in some cases cost-saving, interventions to prevent decompensation and improve health. Health policies (e.g. payer reimbursement) should emphasize and appropriately compensate for these interventions. LAY SUMMARY Alcohol use treatments, including physician counseling and medication-assisted therapies (MATs), improve the outcomes of patients with compensated alcohol-related cirrhosis, though use and access have remained suboptimal. In this study, we found that counseling and MATs are extremely cost-effective, and in some cases cost-saving, interventions to help patients with alcohol-related cirrhosis abstain from alcohol and improve their health. Wider use of these interventions should be encouraged.
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Affiliation(s)
- Anton L.V. Avanceña
- Department of Health Management and Policy, School of Public Health, University of Michigan, Ann Arbor, MI, USA,Corresponding author: Anton Avanceña, Department of Health Management and Policy, University of Michigan School of Public Health, 1415 Washington Heights, SPH II, Ann Arbor, MI 48109. . Phone: +1-734-0287. Fax: +1-734-764-4338
| | - Nicholas Miller
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA
| | - Sarah E. Uttal
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - David W. Hutton
- Department of Health Management and Policy, School of Public Health, University of Michigan, Ann Arbor, MI, USA,Department of Industrial and Operations Engineering, College of Engineering, University of Michigan, Ann Arbor, MI, USA
| | - Jessica L. Mellinger
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
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Rogal SS, Yakovchenko V, Gonzalez R, Park A, Beste LA, Rozenberg-Ben-Dror K, Bajaj JS, Scott D, McCurdy H, Comstock E, Sidorovic M, Gibson S, Lamorte C, Nobbe A, Chartier M, Ross D, Dominitz JA, Morgan TR. The Hepatic Innovation Team Collaborative: A Successful Population-Based Approach to Hepatocellular Carcinoma Surveillance. Cancers (Basel) 2021; 13:cancers13092251. [PMID: 34067177 PMCID: PMC8125814 DOI: 10.3390/cancers13092251] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 04/24/2021] [Accepted: 04/26/2021] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Liver cancer is a growing problem that largely impacts people with cirrhosis. This article describes the Veterans Health Administration’s national cirrhosis quality improvement program and its focus on early detection of liver cancer. Abstract After implementing a successful hepatitis C elimination program, the Veterans Health Administration’s (VHA) Hepatic Innovation Team (HIT) Collaborative pivoted to focus on improving cirrhosis care. This national program developed teams of providers across the country and engaged them in using systems redesign methods and population health approaches to improve care. The HIT Collaborative developed an Advanced Liver Disease (ALD) Dashboard to identify Veterans with cirrhosis who were due for surveillance for hepatocellular carcinoma (HCC) and other liver care, promoted the use of an HCC Clinical Reminder in the electronic health record, and provided training and networking opportunities. This evaluation aimed to describe the VHA’s approach to improving cirrhosis care and identify the facility factors and HIT activities associated with HCC surveillance rates, using a quasi-experimental design. Across all VHA facilities, as the HIT focused on cirrhosis between 2018–2019, HCC surveillance rates increased from 46% (IQR 37–53%) to 51% (IQR 42–60%, p < 0.001). The median HCC surveillance rate was 57% in facilities with high ALD Dashboard utilization compared with 45% in facilities with lower utilization (p < 0.001) and 58% in facilities using the HCC Clinical Reminder compared with 47% in facilities not using this tool (p < 0.001) in FY19. Increased use of the ALD Dashboard and adoption of the HCC Clinical Reminder were independently, significantly associated with HCC surveillance rates in multivariate models, controlling for other facility characteristics. In conclusion, the VHA’s HIT Collaborative is a national healthcare initiative associated with significant improvement in HCC surveillance rates.
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Affiliation(s)
- Shari S. Rogal
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, University Drive (151C), Pittsburgh, PA 15240, USA; (S.G.); (C.L.)
- Departments of Medicine and Surgery, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15240, USA
- Correspondence: ; Tel.: +1-412-360-6177
| | - Vera Yakovchenko
- Center for Healthcare Organization and Implementation Research, VA Bedford Healthcare System, 200 Springs Road (152), Building 70, Bedford, MA 01730, USA;
| | - Rachel Gonzalez
- Department of Veterans Affairs, Sierra Pacific Veterans Integrated Service Network, Pharmacy Benefits Management, Mather, CA 94523, USA;
| | - Angela Park
- Office of Healthcare Transformation, Department of Veterans Affairs, 810 Vermont Avenue, Washington, DC 20420, USA;
| | - Lauren A. Beste
- Division of General Internal Medicine, Department of Medicine, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA;
- General Medicine Service, VA Puget Sound Health Care System, 1660 S Columbian Way, Seattle, WA 98108, USA
| | - Karine Rozenberg-Ben-Dror
- Veteran Affairs Great Lakes Health Care System, VISN 12 PBM, 11301 W Cermak Road, Ste 810, Westchester, IL 60154, USA;
| | - Jasmohan S. Bajaj
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, 1200 E Broad Street, West Hospital, 14th Floor, Box 980341, Richmond, VA 23298, USA;
- Division of Gastroenterology, Central Virginia Veterans Affairs Healthcare System, 1201 Broad Rock Blvd, Richmond, VA 23249, USA
| | - Dawn Scott
- Department of Medicine, Central Texas Veterans Healthcare System, 1901 Veterans Memorial Drive, Temple, TX 76504, USA;
| | - Heather McCurdy
- VA Ann Arbor Healthcare System, 2215 Fuller Rd, Ann Arbor, MI 48105, USA;
| | - Emily Comstock
- Department of Infectious Diseases, Baltimore VA Medical Center, 10 N Greene Street, Baltimore, MD 21201, USA;
| | - Michael Sidorovic
- Salisbury VA Medical Center, 1601 Brenner Avenue, Salisbury, NC 28144, USA;
| | - Sandra Gibson
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, University Drive (151C), Pittsburgh, PA 15240, USA; (S.G.); (C.L.)
| | - Carolyn Lamorte
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, University Drive (151C), Pittsburgh, PA 15240, USA; (S.G.); (C.L.)
| | - Anna Nobbe
- Digestive Disease Section, Cincinnati VA Medical Center, 3200 Vine Street, Cincinnati, OH 45220, USA;
| | - Maggie Chartier
- HIV, Hepatitis, and Related Conditions, Office of Specialty Care Services (10P11I), Department of Veterans Affairs, 810 Vermont Avenue, Washington, DC 20420, USA; (M.C.); (D.R.)
| | - David Ross
- HIV, Hepatitis, and Related Conditions, Office of Specialty Care Services (10P11I), Department of Veterans Affairs, 810 Vermont Avenue, Washington, DC 20420, USA; (M.C.); (D.R.)
| | - Jason A. Dominitz
- Gastroenterology Section, Veterans Affairs Puget Sound Health Care System, 1660 S Columbian Way, Seattle, WA 98108, USA;
- Division of Gastroenterology, Department of Medicine, RR-512, Health Sciences Building, University of Washington School of Medicine, Box 356420, 1959 NE Pacific Street, Seattle, WA 98195, USA
| | - Timothy R. Morgan
- Gastroenterology Section, VA Long Beach Healthcare System, 5901 E 7th Street, Long Beach, CA 90822, USA;
- Division of Gastroenterology, Department of Medicine, University of California, 333 City Blvd. West, Suite 400, Orange, CA 92868, USA
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Nguyen ALT, Nguyen HTT, Yee KC, Palmer AJ, Blizzard CL, de Graaff B. A Systematic Review and Narrative Synthesis of Health Economic Evaluations of Hepatocellular Carcinoma Screening Strategies. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2021; 24:733-743. [PMID: 33933243 DOI: 10.1016/j.jval.2020.11.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 09/24/2020] [Accepted: 11/17/2020] [Indexed: 05/02/2023]
Abstract
OBJECTIVES Many economic evaluations of hepatocellular carcinoma (HCC) screenings have been conducted; however, these vary substantially with regards to screening strategies, patient group, and setting. This review aims to report the current knowledge of the cost-effectiveness of screening and describe the published data. METHODS We conducted a search of biomedical and health economic databases up to July 2020. We included full and partial health economic studies if they evaluated the costs or outcomes of HCC screening strategies. RESULTS The review included 43 studies. Due to significant heterogeneity in key aspects across the studies, a narrative synthesis was conducted. Most studies reported using ultrasound or alpha fetoprotein as screening strategies. Screening intervals were mostly annual or biannual. Incidence, diagnostic performance, and health state utility values were the most critical parameters affecting the cost-effectiveness of screening. The majority of studies reported HCC screening to be cost-effective, with the biannual ultrasound + alpha fetoprotein standing out as the most cost-effective strategy. However, few studies considered the utilization rate, and none considered the diagnostic performance of ultrasound in the context of central adiposity. Computed tomography and magnetic resonance imaging were also evaluated, but its cost-effectiveness was still controversial. CONCLUSIONS Although many studies suggested HCC screening was cost-effective, substantial limitations of the quality of these studies means the results should be interpreted with caution. Future modeling studies should consider the impact of central adiposity on the precision of ultrasound, real-world utilization rates and projections of increased HCC incidence.
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Affiliation(s)
- Anh Le Tuan Nguyen
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
| | - Hoa Thi Thu Nguyen
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
| | - Kwang Chien Yee
- School of Medicine, University of Tasmania, Hobart, Tasmania, Australia
| | - Andrew J Palmer
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia; Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia
| | | | - Barbara de Graaff
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Zhang X, Wang J, Shi J, Jia X, Dang S, Wang W. Cost-effectiveness of Atezolizumab Plus Bevacizumab vs Sorafenib for Patients With Unresectable or Metastatic Hepatocellular Carcinoma. JAMA Netw Open 2021; 4:e214846. [PMID: 33825837 PMCID: PMC8027915 DOI: 10.1001/jamanetworkopen.2021.4846] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 02/08/2021] [Indexed: 02/06/2023] Open
Abstract
IMPORTANCE Atezolizumab plus bevacizumab as a first-line therapy for patients with unresectable or metastatic hepatocellular carcinoma has been shown to improve overall and progression-free survival compared with standard sorafenib treatment. However, because of the high cost of atezolizumab plus bevacizumab, assessment of its value by considering both efficacy and cost is needed. OBJECTIVE To evaluate the cost-effectiveness of atezolizumab plus bevacizumab vs sorafenib for patients with unresectable or metastatic hepatocellular carcinoma from a US payer perspective. DESIGN, SETTING, AND PARTICIPANTS This economic evaluation was performed from June through September 2020, with a 6-year investment time period. Hypothetical patients were male and female adults 18 years or older who had a diagnosis of locally advanced metastatic or unresectable hepatocellular carcinoma confirmed by histologic or clinical features. MAIN OUTCOMES AND MEASURES Health care costs (adjusted to 2020 US dollars), life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) of atezolizumab plus bevacizumab vs sorafenib were examined using a partitioned survival model. One-way deterministic and probabilistic sensitivity analyses were used to examine model uncertainty. The model was also used to estimate price reductions of atezolizumab plus bevacizumab that would achieve more favorable cost-effectiveness. RESULTS In the base case analysis of a hypothetical sample of 424 patients, atezolizumab plus bevacizumab was associated with an increase of 0.623 life-years (1.840 vs 1.218 life-years) and 0.484 QALYs (1.412 vs 0.928 QALYs) and with an incremental cost of $156 210 per patient compared with sorafenib. The ICER was $322 500 per QALY (5th to 95th percentile, $149 364-$683 744 per QALY), with 0.6% and 5.1% chance of being cost-effective at willingness-to-pay thresholds of $100 000 and $150 000 per QALY, respectively. The ICER never decreased below $150 000 per QALY in the 1-way sensitivity analyses. To achieve more favorable cost-effectiveness under the thresholds of $150 000 to $100 000 per QALY, the prices of atezolizumab and bevacizumab would need to be reduced by 37% to 47%. CONCLUSIONS AND RELEVANCE In this economic evaluation, atezolizumab plus bevacizumab was associated with clinical benefit but was not cost-effective compared with sorafenib for first-line treatment of unresectable or metastatic hepatocellular carcinoma from a US payer perspective. A substantial reduction in price for atezolizumab plus bevacizumab would be needed to achieve favorable cost-effectiveness for this new therapy.
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Affiliation(s)
- Xin Zhang
- Department of Hepatology and Infectious Diseases,
Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jingjing Wang
- Department of Pediatrics, Second Affiliated Hospital
of Xi’an Jiaotong University, Xi’an, China
| | - Juanjuan Shi
- Department of Hepatology and Infectious Diseases,
Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xiaoli Jia
- Department of Hepatology and Infectious Diseases,
Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Shuangsuo Dang
- Department of Hepatology and Infectious Diseases,
Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Wenjun Wang
- Department of Hepatology and Infectious Diseases,
Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Rigopoulou EI, Dalekos GN. Current Trends and Characteristics of Hepatocellular Carcinoma in Patients with Autoimmune Liver Diseases. Cancers (Basel) 2021; 13:1023. [PMID: 33804480 PMCID: PMC7957658 DOI: 10.3390/cancers13051023] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 02/17/2021] [Accepted: 02/24/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC), the commonest among liver cancers, is one of the leading causes of mortality among malignancies worldwide. Several reports demonstrate autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) to confer increased risk of hepatobiliary malignancies, albeit at lower frequencies compared to other liver diseases. Several parameters have been recognized as risk factors for HCC development in AIH and PBC, including demographics such as older age and male sex, clinical features, the most decisive being cirrhosis and other co-existing factors, such as alcohol consumption. Moreover, biochemical activity and treatment response have been increasingly recognized as prognostic factors for HCC development in AIH and PBC. As available treatment modalities are effective only when HCC diagnosis is established early, surveillance has been proven essential for HCC prognosis. Considering that the risk for HCC is not uniform between and within disease groups, refinement of screening strategies according to prevailing demographic, clinical, and molecular risk factors is mandated in AILDs patients, as personalized HCC risk prediction will offer significant advantage in patients at high and/or medium risk. Furthermore, future investigations should draw attention to whether modification of immunosuppression could benefit AIH patients after HCC diagnosis.
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Affiliation(s)
| | - George N. Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, 41110 Larissa, Greece;
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Wang D, Hu X, Xiao L, Long G, Yao L, Wang Z, Zhou L. Prognostic Nutritional Index and Systemic Immune-Inflammation Index Predict the Prognosis of Patients with HCC. J Gastrointest Surg 2021; 25:421-427. [PMID: 32026332 PMCID: PMC7904713 DOI: 10.1007/s11605-019-04492-7] [Citation(s) in RCA: 127] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 11/23/2019] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Systemic nutrition and inflammation are the critical factors in cancer initiation, evolution, and progression. This study aimed to evaluate the prognostic value of the prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) in hepatocellular carcinoma (HCC) patients who underwent liver resection. METHODS A total of 202 HCC patients met the criteria and were included in the study. The receiver operating characteristic (ROC) curve was used to calculate the optimal PNI and SII cutoff values. The relationship between PNI/SII and clinicopathologic parameters was analyzed. The effect of PNI and SII on recurrence-free survival (RFS) and overall survival (OS) was investigated by Kaplan-Meier curves and Cox proportional hazards models. RESULTS The areas under the ROC curve for PNI and SII were 0.64 and 0.58. The ideal preoperative PNI and SII cutoff values were 50.25 and 461.5, respectively. Multivariate Cox regression analysis identified that the PNI (P = 0.001) and tumor diameter (P = 0.018) were significant prognostic markers for RFS, and that the PNI (P = 0.049), SII (P = 0.039) and tumor diameter (P = 0.001) were significant prognostic markers for OS. The median RFS in the PNI-low and PNI-high groups was 13.5 months and 23 months (P = 0.001), and that in the SII-low and SII-high groups was 18 months and 15 months (P = 0.03), respectively. The median OS in the PNI-low and PNI-high groups was 24 months and 39 months (P = 0.001), and that in the SII-low and SII-high groups was 36 months and 22 months (P = 0.002), respectively. CONCLUSION Interestingly, we found that PNI and SII could be important prognostic parameters for HCC patients who under hepatectomy.
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Affiliation(s)
- Dong Wang
- Department of General Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Xi Hu
- Department of General Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Liang Xiao
- Department of General Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Guo Long
- Department of General Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Lei Yao
- Department of General Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China
| | - ZhiMing Wang
- Department of General Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China
| | - LeDu Zhou
- Department of General Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.
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Kim DH, Choi JI. Current status of image-based surveillance in hepatocellular carcinoma. Ultrasonography 2021; 40:45-56. [PMID: 33045812 PMCID: PMC7758104 DOI: 10.14366/usg.20067] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/17/2020] [Accepted: 07/25/2020] [Indexed: 12/24/2022] Open
Abstract
Although the overall prognosis of patients with hepatocellular carcinoma (HCC) remains poor, curative treatment may improve the survival of patients diagnosed at an early stage through surveillance. Accordingly, ultrasonography (US)-based HCC surveillance programs proposed in international society guidelines are now being implemented and regularly updated based on the latest evidence to improve their efficacy. Recently, other imaging modalities such as magnetic resonance imaging have shown potential as alternative surveillance tools based on individualized risk stratification. In this review article, we describe the current status of US-based surveillance for HCC and summarize the supporting evidence. We also discuss alternative surveillance imaging modalities that are currently being studied to validate their diagnostic performance and cost-effectiveness.
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Affiliation(s)
- Dong Hwan Kim
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Joon-Il Choi
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Audureau E, Carrat F, Layese R, Cagnot C, Asselah T, Guyader D, Larrey D, De Lédinghen V, Ouzan D, Zoulim F, Roulot D, Tran A, Bronowicki JP, Zarski JP, Riachi G, Calès P, Péron JM, Alric L, Bourlière M, Mathurin P, Blanc JF, Abergel A, Chazouillères O, Mallat A, Grangé JD, Attali P, d'Alteroche L, Wartelle C, Dao T, Thabut D, Pilette C, Silvain C, Christidis C, Nguyen-Khac E, Bernard-Chabert B, Zucman D, Di Martino V, Sutton A, Pol S, Nahon P. Personalized surveillance for hepatocellular carcinoma in cirrhosis - using machine learning adapted to HCV status. J Hepatol 2020; 73:1434-1445. [PMID: 32615276 DOI: 10.1016/j.jhep.2020.05.052] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Revised: 04/21/2020] [Accepted: 05/14/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Refining hepatocellular carcinoma (HCC) surveillance programs requires improved individual risk prediction. Thus, we aimed to develop algorithms based on machine learning approaches to predict the risk of HCC more accurately in patients with HCV-related cirrhosis, according to their virological status. METHODS Patients with compensated biopsy-proven HCV-related cirrhosis from the French ANRS CO12 CirVir cohort were included in a semi-annual HCC surveillance program. Three prognostic models for HCC occurrence were built, using (i) Fine-Gray regression as a benchmark, (ii) single decision tree (DT), and (iii) random survival forest for competing risks survival (RSF). Model performance was evaluated from C-indexes validated externally in the ANRS CO22 Hepather cohort (n = 668 enrolled between 08/2012-01/2014). RESULTS Out of 836 patients analyzed, 156 (19%) developed HCC and 434 (52%) achieved sustained virological response (SVR) (median follow-up 63 months). Fine-Gray regression models identified 6 independent predictors of HCC occurrence in patients before SVR (past excessive alcohol intake, genotype 1, elevated AFP and GGT, low platelet count and albuminemia) and 3 in patients after SVR (elevated AST, low platelet count and shorter prothrombin time). DT analysis confirmed these associations but revealed more complex interactions, yielding 8 patient groups with varying cancer risks and predictors depending on SVR achievement. On RSF analysis, the most important predictors of HCC varied by SVR status (non-SVR: platelet count, GGT, AFP and albuminemia; SVR: prothrombin time, ALT, age and platelet count). Externally validated C-indexes before/after SVR were 0.64/0.64 [Fine-Gray], 0.60/62 [DT] and 0.71/0.70 [RSF]. CONCLUSIONS Risk factors for hepatocarcinogenesis differ according to SVR status. Machine learning algorithms can refine HCC risk assessment by revealing complex interactions between cancer predictors. Such approaches could be used to develop more cost-effective tailored surveillance programs. LAY SUMMARY Patients with HCV-related cirrhosis must be included in liver cancer surveillance programs, which rely on ultrasound examination every 6 months. Hepatocellular carcinoma (HCC) screening is hampered by sensitivity issues, leading to late cancer diagnoses in a substantial number of patients. Refining surveillance periodicity and modality using more sophisticated imaging techniques such as MRI may only be cost-effective in patients with the highest HCC incidence. Herein, we demonstrate how machine learning algorithms (i.e. data-driven mathematical models to make predictions or decisions), can refine individualized risk prediction.
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Affiliation(s)
- Etienne Audureau
- AP-HP, Hôpital Henri Mondor, Département de Santé Publique, and Université Paris-Est, A-TVB DHU, CEpiA (Clinical Epidemiology and Ageing) Unit EA7376, UPEC, F-94000, Créteil, France
| | - Fabrice Carrat
- Sorbonne Université, Inserm, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; AP-HP, Hôpital Saint-Antoine, Unité de Santé Publique, Paris, France
| | - Richard Layese
- AP-HP, Hôpital Henri Mondor, Département de Santé Publique, and Université Paris-Est, A-TVB DHU, CEpiA (Clinical Epidemiology and Ageing) Unit EA7376, UPEC, F-94000, Créteil, France
| | - Carole Cagnot
- Unit for Basic and Clinical research on Viral Hepatitis, ANRS (France REcherche Nord & sud Sida-HIV Hépatites-FRENSH)
| | - Tarik Asselah
- AP-HP, Hôpital Beaujon, Service d'Hépatologie, Clichy
| | | | | | | | - Denis Ouzan
- Institut Arnaud Tzanck, Service d'Hépatologie, St Laurent du Var
| | - Fabien Zoulim
- Hospices Civils de Lyon, Service d'Hépatologie; INSERM U1052 - CRCL; Université de Lyon, Lyon
| | | | - Albert Tran
- CHU de Nice, Service d'Hépatologie, F-06202, Cedex 3, Nice; Inserm U1065, C3M, Team 8, "Hepatic Complications in Obesity", F-06204, Cedex 3, Nice
| | | | | | | | - Paul Calès
- CHU d'Angers, Service d'Hépato-Gastroentérologie, Angers
| | | | - Laurent Alric
- CHU Toulouse, Service de Médecine Interne-Pôle Digestif UMR 152, Toulouse
| | | | | | - Jean-Frédéric Blanc
- Hôpital St André, Service d'Hépatologie, Bordeaux et Hôpital Haut-Lévêque, CHU Bordeaux, 33604 Pessac
| | - Armand Abergel
- Hôpital Hôtel Dieu, Service d'Hépatologie, Clermont-Ferrand
| | - Olivier Chazouillères
- AP-HP, Hôpital Saint-Antoine, Service d'Hépatologie, and Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, Paris
| | - Ariane Mallat
- AP-HP, Hôpital Henri Mondor, Service d'Hépatologie, Créteil
| | | | - Pierre Attali
- AP-HP, Hôpital Paul Brousse, Service d'Hépatologie, Villejuif
| | | | - Claire Wartelle
- Hôpital d'Aix-En-Provence, Service d'Hépatologie, Aix-En-Provence
| | - Thông Dao
- Hôpital de la Côte de Nacre, Service d'Hépatologie, Caen
| | - Dominique Thabut
- AP-HP, Groupe Hospitalier de La Pitié-Salpêtrière, Service d'Hépatologie, Paris
| | | | | | | | | | | | - David Zucman
- Hôpital Foch, Service de Médecine Interne, Suresnes
| | | | - Angela Sutton
- CRB (liver disease biobank) Groupe Hospitalier Paris Seine-Saint-Denis BB-0033-00027; AP-HP, Hôpital Jean Verdier, Service de Biochimie, Bondy; Inserm U1148, Université Paris 13, Bobigny
| | - Stanislas Pol
- AP-HP, Hôpital Cochin, Département d'Hépatologie; Inserm UMS20 et U1223, Institut Pasteur, Université Paris Descartes, Paris
| | - Pierre Nahon
- AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy; Université Paris 13, Sorbonne Paris Cité, "Equipe labellisée Ligue Contre le Cancer", F-93206 Saint-Denis; Inserm, UMR-1162, "Génomique fonctionnelle des tumeur solides", F-75000, Paris, France.
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Understanding Gaps in the Hepatocellular Carcinoma Cascade of Care: Opportunities to Improve Hepatocellular Carcinoma Outcomes. J Clin Gastroenterol 2020; 54:850-856. [PMID: 33030855 DOI: 10.1097/mcg.0000000000001422] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality. Existing studies have highlighted significant disparities in HCC outcomes, particularly among vulnerable populations, including ethnic minorities, safety-net populations, underinsured patients, and those with low socioeconomic status and high risk behaviors. The majority of these studies have focused on HCC surveillance. Although HCC surveillance is one of the most important first steps in HCC monitoring and management, it is only one step in the complex HCC cascade of care that evolves from surveillance to diagnosis and tumor staging that leads to access to HCC therapies. In this current review, we explore the disparities that exist along this complex HCC cascade of care and further highlight potential interventions that have been implemented to improve HCC outcomes. These interventions focus on patient, provider, and system level factors and provide a potential framework for health systems to implement quality improvement initiatives to improve HCC monitoring and management.
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Rogal SS, Yakovchenko V, Morgan T, Bajaj JS, Gonzalez R, Park A, Beste L, Miech EJ, Lamorte C, Neely B, Gibson S, Malone PS, Chartier M, Taddei T, Garcia-Tsao G, Powell BJ, Dominitz JA, Ross D, Chinman MJ. Getting to implementation: a protocol for a Hybrid III stepped wedge cluster randomized evaluation of using data-driven implementation strategies to improve cirrhosis care for Veterans. Implement Sci 2020; 15:92. [PMID: 33087156 PMCID: PMC7579930 DOI: 10.1186/s13012-020-01050-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Accepted: 10/05/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Cirrhosis is a rapidly increasing cause of global mortality. To improve cirrhosis care, the Veterans Health Administration (VHA) developed the Hepatic Innovation Team (HIT) Collaborative to support VA Medical Centers (VAMCs) to deliver evidence-based cirrhosis care. This randomized HIT program evaluation aims to develop and assess a novel approach for choosing and applying implementation strategies to improve the quality of cirrhosis care. METHODS Evaluation aims are to (1) empirically determine which combinations of implementation strategies are associated with successful implementation of evidence-based practices (EBPs) for Veterans with cirrhosis, (2) manualize these "data-driven" implementation strategies, and (3) assess the effectiveness of data-driven implementation strategies in increasing cirrhosis EBP uptake. Aim 1 will include an online survey of all VAMCs' use of 73 implementations strategies to improve cirrhosis care, as defined by the Expert Recommendations for Implementing Change taxonomy. Traditional statistical as well as configurational comparative methods will both be employed to determine which combinations of implementation strategies are associated with site-level adherence to EBPs for cirrhosis. In aim 2, semi-structured interviews with high-performing VAMCs will be conducted to operationalize successful implementation strategies for cirrhosis care. These data will be used to inform the creation of a step-by-step guide to tailoring and applying the implementation strategies identified in aim 1. In aim 3, this manualized implementation intervention will be assessed using a hybrid type III stepped-wedge cluster randomized design. This evaluation will be conducted in 12 VAMCs, with four VAMCs crossing from control to intervention every 6 months, in order to assess the effectiveness of using data-driven implementation strategies to improve guideline-concordant cirrhosis care. DISCUSSION Successful completion of this innovative evaluation will establish the feasibility of using early evaluation data to inform a manualized, user-friendly implementation intervention for VAMCs with opportunities to improve care. This evaluation will provide implementation support tools that can be applied to enhance the implementation of other evidence-based practices. TRIAL REGISTRATION This project was registered at ClinicalTrials.Gov ( NCT04178096 ) on 4/29/20.
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Affiliation(s)
- Shari S Rogal
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Research Office Building (151R), University Drive C, Pittsburgh, PA, 15240, USA. .,Departments of Medicine and Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
| | - Vera Yakovchenko
- Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial VA Hospital, Bedford, MA, USA
| | - Timothy Morgan
- Gastroenterology Section, VA Long Beach Healthcare System, Long Beach, CA, USA.,Division of Gastroenterology, Department of Medicine, University of California, Irvine, CA, USA
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA, USA.,Division of Gastroenterology, Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA
| | - Rachel Gonzalez
- Department of Veterans Affairs, Sierra Pacific Veterans Integrated Service Network, Pharmacy Benefits Management, Mather, CA, USA
| | - Angela Park
- Office of Healthcare Transformation, Veterans Engineering Resource Center, Washington, DC, USA
| | - Lauren Beste
- Division of General Internal Medicine, Department of Medicine, VA Puget Sound Healthcare System, Seattle, WA, USA.,Division of General Internal Medicine, University of Washington, Seattle, WA, USA
| | - Edward J Miech
- Department of Veterans Affairs, Roudebush VA Medical Center, HSR&D Center for Health Information & Communication, VA PRIS-M QUERI, Indianapolis, IN, USA
| | - Carolyn Lamorte
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Research Office Building (151R), University Drive C, Pittsburgh, PA, 15240, USA
| | - Brittney Neely
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Research Office Building (151R), University Drive C, Pittsburgh, PA, 15240, USA
| | - Sandra Gibson
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Research Office Building (151R), University Drive C, Pittsburgh, PA, 15240, USA
| | | | - Maggie Chartier
- HIV, Hepatitis and Related Conditions Programs, Office of Specialty Care Services, Veterans Health Administration, Washington, DC, USA
| | - Tamar Taddei
- VA Connecticut Healthcare System, West Haven, CT, USA.,Department of Medicine, Yale University, West Haven, CT, USA
| | - Guadalupe Garcia-Tsao
- VA Connecticut Healthcare System, West Haven, CT, USA.,Department of Medicine, Yale University, West Haven, CT, USA
| | - Byron J Powell
- Brown School, Washington University in St. Louis, St. Louis, MO, USA
| | - Jason A Dominitz
- Gastroenterology Section, VA Puget Sound Health Care System, Seattle, WA, USA.,Department of Medicine, University of Washington, Seattle, WA, USA
| | - David Ross
- HIV, Hepatitis and Related Conditions Programs, Office of Specialty Care Services, Veterans Health Administration, Washington, DC, USA
| | - Matthew J Chinman
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Research Office Building (151R), University Drive C, Pittsburgh, PA, 15240, USA.,RAND Corporation, Pittsburgh, PA, USA
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Dai J, Zhao J, Du Y, Zhuang L, Ma Y, Chongsuvivatwong V. Clinico-Psychosocial Factors Predicting Hepatocellular Carcinoma Related Knowledge Among Patients with Chronic Liver Disease. JOURNAL OF CANCER EDUCATION : THE OFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER EDUCATION 2020; 35:937-945. [PMID: 31090039 DOI: 10.1007/s13187-019-01545-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Regular clinical surveillance for hepatocellular carcinoma (HCC) among high-risk patients could lead to early detection and cure. Patient's knowledge and attitude are important to the uptake rate of this surveillance. This study is aimed at assessing the level of HCC-related knowledge among patients with chronic liver disease (CLD) who are at risk of HCC and determine predictors for poor knowledge. A cross-sectional study was conducted among inpatients with CLD at the Third People's Hospital of Kunming in China. Questionnaires were used to measure patient's sociodemographic characteristics, HCC-related knowledge, and patient-doctor-related psychometric factors. Factor analysis was performed to explore the underlying domains captured by the knowledge questionnaire. Univariate and multivariate analyses were performed to identify independent predictors for each domain. Three common factors were derived from the exploratory factor analysis, namely, "Surveillance," "Lifestyle," and "Prognosis." Patients with low educational background and a short period of having CLD were at a significantly low level of HCC-related knowledge of all three domains. On the other hand, surveillance and lifestyle but not prognosis, were associated with patient's communication confidence with doctors. Over two-thirds of high-risk patients had low knowledge of HCC. Medical providers should pay more attention to low educational groups and newly diagnosed CLD patients.
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Affiliation(s)
- Jingyi Dai
- The Third People's Hospital of Kunming City, Kunming, Yunnan, China
- Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand
| | - Jun Zhao
- School of Public Health and Administration, Hubei University of Medicine, Shiyan, Hubei, China
| | - Yingrong Du
- The Third People's Hospital of Kunming City, Kunming, Yunnan, China
| | - Lin Zhuang
- The Third People's Hospital of Kunming City, Kunming, Yunnan, China
| | - Yanli Ma
- The Third People's Hospital of Kunming City, Kunming, Yunnan, China
| | - Virasakdi Chongsuvivatwong
- Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand.
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Blueberry malvidin-3-galactoside modulated gut microbial dysbiosis and microbial TCA cycle KEGG pathway disrupted in a liver cancer model induced by HepG2 cells. FOOD SCIENCE AND HUMAN WELLNESS 2020. [DOI: 10.1016/j.fshw.2020.04.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Fukuda H, Sato D, Moriwaki K, Ishida H. Differences in healthcare expenditure estimates according to statistical approach: A nationwide claims database study on patients with hepatocellular carcinoma. PLoS One 2020; 15:e0237316. [PMID: 32790706 PMCID: PMC7425973 DOI: 10.1371/journal.pone.0237316] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 07/25/2020] [Indexed: 01/01/2023] Open
Abstract
AIM Disease-associated healthcare expenditures are generally calculated using matched comparisons or regression-based analyses, but little is known about their differences in estimates. This aim of this study was to compare the differences between disease-associated healthcare expenditures estimated using these 2 methods. METHODS In this retrospective cohort study, a matched comparison was first conducted by matching cases with controls using sex, age, and comorbidities to estimate disease-associated expenditures. The cases were then used in a fixed-effects analysis that compared expenditures before and after disease occurrence. The subjects were adults (≥20 years) with primary hepatocellular carcinoma (HCC) who underwent treatment (including surgical resection, locoregional therapy, transcatheter arterial chemoembolization, and transarterial embolization) at a Japanese hospital between April 2010 and March 2018. We calculated the total healthcare expenditures per patient per month according to treatment and disease phase (initial, continuing, and terminal). RESULTS There were 14,923 cases in the initial/continuing phases and 15,968 cases in the terminal phase. In the initial/continuing phases, 3,552 patients underwent surgical resection only, with HCC-associated expenditures of $5,555 according to the matched comparison and $5,889 according to the fixed-effects analysis (proportional difference: 94.3%). The initial phase expenditures were approximately 9% higher in the fixed-effects analysis, whereas the continuing phase expenditures were approximately 7% higher in the matched comparison. The expenditures in the terminal phase were 93.1% higher in the fixed-effects analysis. CONCLUSIONS The 2 methods produced similar estimates of HCC-associated healthcare expenditures in the initial/continuing phases. However, terminal phase expenditures were substantially different between the methods.
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Affiliation(s)
- Haruhisa Fukuda
- Department of Health Care Administration and Management, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Daisuke Sato
- Center for Next Generation of Community Health, Chiba University Hospital, Chiba, Japan
| | - Kensuke Moriwaki
- Comprehensive Unit for Health Economic Evidence Review and Decision Support, Ritsumeikan University, Kyoto, Japan
| | - Haku Ishida
- Department of Medical Informatics & Decision Sciences, Yamaguchi University, Yamaguchi, Japan
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Wu Q, Liao W, Zhang M, Huang J, Zhang P, Li Q. Cost-Effectiveness of Tucatinib in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer From the US and Chinese Perspectives. Front Oncol 2020; 10:1336. [PMID: 32850425 PMCID: PMC7417356 DOI: 10.3389/fonc.2020.01336] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Accepted: 06/26/2020] [Indexed: 02/05/2023] Open
Abstract
Background: The clinical evaluation of HER2CLIMB trial showed a 21. 9-month median overall survival with the triplet regimens of tucatinib, capecitabine, and trastuzumab (TXT) for patients with human epidermal growth factor receptor 2 (HER2) –overexpressing metastatic breast cancer. From the payer's perspective of the United States and China, a cost-effectiveness analysis was conducted to evaluate the costs and benefits of adding tucatinib in this study. Methods: We constructed a Markov model for the economic evaluation of adding tucatinib to trastuzumab plus capecitabine in patients with HER-2 positive metastatic breast cancer in the United States and China. The model was conducted with a 10-year time horizon, and the health status was divided into three states: progression-free survival, progressing disease, and death. The health utility scores were consistent with published literature with similar patient status. The transition probabilities were derived from the survival data of the HER2CLIMB study. The unit prices of medicines were obtained from the West China Hospital, Red Book, and published literature. Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio, which robustness was evaluated by deterministic and probabilistic sensitivity analyses. Results: Compared with the two-drug regimen of trastuzumab plus capecitabine (TX), the addition of tucatinib increased 0.21 QALY, with an increasing cost of $146,995.05 and $19,022.97 in the United States and China, respectively. The incremental cost-effectiveness ratios (ICERs) for the TXT versus TX was $699,976.43 in the U.S. and $90,585.57 in China, both of which are higher than their respective threshold of willingness to play. Deterministic sensitivity analysis shows that the price of tucatinib is the parameter that has the most significant impact on ICERs, but it does not change the results of the model. Probability sensitivity analysis shows that the probability of cost-effective for TXT is 0 in the base case. Conclusion: In the United States and China, tucatinib combined with trastuzumab and capecitabine is not cost-effective for patients with HER-2 positive metastatic breast cancer.
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Affiliation(s)
- Qiuji Wu
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,West China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Weiting Liao
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,West China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Mengxi Zhang
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,West China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Jiaxing Huang
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,West China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Pengfei Zhang
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,West China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Qiu Li
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,West China Biomedical Big Data Center, Sichuan University, Chengdu, China
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Wang T, Jin H, Hu J, Li X, Ruan H, Xu H, Wei L, Dong W, Teng F, Gu J, Qin W, Luo X, Hao Y. COL4A1 promotes the growth and metastasis of hepatocellular carcinoma cells by activating FAK-Src signaling. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2020; 39:148. [PMID: 32746865 PMCID: PMC7398077 DOI: 10.1186/s13046-020-01650-7] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 07/21/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Collagens are the most abundant proteins in extra cellular matrix and important components of tumor microenvironment. Recent studies have showed that aberrant expression of collagens can influence tumor cell behaviors. However, their roles in hepatocellular carcinoma (HCC) are poorly understood. METHODS In this study, we screened all 44 collagen members in HCC using whole transcriptome sequencing data from the public datasets, and collagen type IV alpha1 chain (COL4A1) was identified as most significantly differential expressed gene. Expression of COL4A1 was detected in HCC samples by quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry (IHC). Finally, functions and potential mechanisms of COL4A1 were explored in HCC progression. RESULTS COL4A1 is the most significantly overexpressed collagen gene in HCC. Upregulation of COL4A1 facilitates the proliferation, migration and invasion of HCC cells through FAK-Src signaling. Expression of COL4A1 is upregulated by RUNX1 in HCC. HCC cells with high COL4A1 expression are sensitive to the treatment with FAK or Src inhibitor. CONCLUSION COL4A1 facilitates growth and metastasis in HCC via activation of FAK-Src signaling. High level of COL4A1 may be a potential biomarker for diagnosis and treatment with FAK or Src inhibitor for HCC.
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Affiliation(s)
- Ting Wang
- Shanghai Medical College of Fudan University, Shanghai, 200032, People's Republic of China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, People's Republic of China
| | - Haojie Jin
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, People's Republic of China
| | - Jingying Hu
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, People's Republic of China
| | - Xi Li
- The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, 519000, People's Republic of China.,Changzheng Hospital, Navy Medical University, Shanghai, 200003, People's Republic of China
| | - Haoyu Ruan
- Shanghai Medical College of Fudan University, Shanghai, 200032, People's Republic of China
| | - Huili Xu
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, People's Republic of China
| | - Lin Wei
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, People's Republic of China
| | - Weihua Dong
- Changzheng Hospital, Navy Medical University, Shanghai, 200003, People's Republic of China
| | - Fei Teng
- Changzheng Hospital, Navy Medical University, Shanghai, 200003, People's Republic of China
| | - Jianren Gu
- Shanghai Medical College of Fudan University, Shanghai, 200032, People's Republic of China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, People's Republic of China
| | - Wenxin Qin
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, People's Republic of China
| | - Xiaoying Luo
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, People's Republic of China.
| | - Yujun Hao
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, People's Republic of China.
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Kong J, Yao C, Ding X, Dong S, Wu S, Sun W, Zheng L. ATPase Inhibitory Factor 1 Promotes Hepatocellular Carcinoma Progression After Insufficient Radiofrequency Ablation, and Attenuates Cell Sensitivity to Sorafenib Therapy. Front Oncol 2020; 10:1080. [PMID: 32670888 PMCID: PMC7330926 DOI: 10.3389/fonc.2020.01080] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Accepted: 05/29/2020] [Indexed: 12/20/2022] Open
Abstract
Epithelial-mesenchymal transition (EMT) and angiogenesis is involved in tumor progression after radiofrequency ablation (RFA). ATPase inhibitory factor 1 (IF1) is a bad predictor of prognosis. Sorafenib inhibited EMT of hepatocellular carcinoma (HCC) after RFA. Whether IF1 promotes the EMT and angiogenesis of HCC and attenuates the effect of sorafenib after insufficient RFA is investigated. In this study, higher expression of IF1 was found in residual tumor after insufficient RFA. Hep3B or Huh7 cells after insufficient RFA were designated as Hep3B-H or Huh7-H cells in vitro. Hep3B-H or Huh7-H cells exhibited enhanced capacities of colony formation, migration, and increased expression of EMT associated markers and IF1 compared with Hep3B or Huh7 cells. IF1 knockdown in Hep3B-H or Huh7-H cells decreased the colony formation and migratory capacity, and IF1 overexpression in Hep3B or Huh7 cells increased these capacities. IF1 in HCC cells directly and indirectly affected angiogenesis of TAECs after insufficient RFA. IF1 promoted HCC cells growth and metastasis after insufficient RFA. IF1 increased HCC cells resistance after insufficient RFA to sorafenib. Higher IF1 expression indicated poor disease survival in HCC patients after sorafenib therapy. NF-κB activation induced by IF1 attenuated the effect of sorafenib on HCC cells after insufficient RFA. Our results demonstrated that IF1 promotes the EMT and angiogenesis, and attenuates HCC cell sensitivity to sorafenib after insufficient RFA through NF-κB signal pathway.
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Affiliation(s)
- Jian Kong
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Changyu Yao
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xuemei Ding
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Shuying Dong
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Shilun Wu
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Wenbing Sun
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Lemin Zheng
- Key Laboratory of Molecular Cardiovascular Science of Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of Health, Beijing Key Laboratory of Cardiovascular Receptors Research, School of Basic Medical Sciences, The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Tiantan Hospital, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
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Ispas S, So S, Toy M. Barriers to Disease Monitoring and Liver Cancer Surveillance Among Patients with Chronic Hepatitis B in the United States. J Community Health 2020; 44:610-625. [PMID: 30539329 DOI: 10.1007/s10900-018-00604-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Chronic hepatitis B infection (CHB) is a condition that needs ongoing care such as monitoring for liver enzymes (ALT) and HBV DNA tests in treated and untreated patients, and annual imaging evaluation for liver cancer. Although follow-up care and treatment might seem straight forward, an estimated two-thirds of those who are aware of their infection are not seeing a health care provider, and more than half of those who are eligible for treatment do not receive it. This study aimed to compile and examine studies related to the barriers of disease monitoring, treatment, and liver cancer surveillance for CHB patients in the United States (US). A total of 4439 studies on monitoring and surveillance of CHB published between 2007 and 2018 were identified through a search of electronic databases. After critical assessment, the authors included 42 studies, divided into categories: 'patient-related barriers'; 'provider-related barriers'; and 'system-related barriers'. Among the patient-related barriers, one of the most frequent factors invoked in failing to have adequate surveillance was lack of patient's knowledge. In the provider-related barrier category, a lack of disease knowledge and adherence to guidelines was frequently reported. For the system-related barrier category, the only recurrent mention was a lack of clarity in guidelines or lack of guidelines from certain national institutions. This review summarizes and highlights the need for long-term disease management improvement of chronic hepatitis B infection for patients and healthcare providers that care for them.
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Affiliation(s)
- Simona Ispas
- Asian Liver Center, Department of Surgery, Stanford University School of Medicine, 780 Welch Road, CJ 130, Palo Alto, CA, 94304-5787, USA
| | - Samuel So
- Asian Liver Center, Department of Surgery, Stanford University School of Medicine, 780 Welch Road, CJ 130, Palo Alto, CA, 94304-5787, USA
| | - Mehlika Toy
- Asian Liver Center, Department of Surgery, Stanford University School of Medicine, 780 Welch Road, CJ 130, Palo Alto, CA, 94304-5787, USA.
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