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Liu R, Wu S, Yu HY, Zeng K, Liang Z, Li S, Hu Y, Yang Y, Ye L. Prediction model for hepatocellular carcinoma recurrence after hepatectomy: Machine learning-based development and interpretation study. Heliyon 2023; 9:e22458. [PMID: 38034691 PMCID: PMC10687050 DOI: 10.1016/j.heliyon.2023.e22458] [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: 05/24/2023] [Revised: 09/10/2023] [Accepted: 11/13/2023] [Indexed: 12/02/2023] Open
Abstract
Background Identifying patients with hepatocellular carcinoma (HCC) at high risk of recurrence after hepatectomy can help to implement timely interventional treatment. This study aimed to develop a machine learning (ML) model to predict the recurrence risk of HCC patients after hepatectomy. Methods We retrospectively collected 315 HCC patients who underwent radical hepatectomy at the Third Affiliated Hospital of Sun Yat-sen University from April 2013 to October 2017, and randomly divided them into the training and validation sets at a ratio of 7:3. According to the postoperative recurrence of HCC patients, the patients were divided into recurrence group and non-recurrence group, and univariate and multivariate logistic regression were performed for the two groups. We applied six machine learning algorithms to construct the prediction models and performed internal validation by 10-fold cross-validation. Shapley additive explanations (SHAP) method was applied to interpret the machine learning model. We also built a web calculator based on the best machine learning model to personalize the assessment of the recurrence risk of HCC patients after hepatectomy. Results A total of 13 variables were included in the machine learning models. The multilayer perceptron (MLP) machine learning model was proved to achieve optimal predictive value in test set (AUC = 0.680). The SHAP method displayed that γ-glutamyl transpeptidase (GGT), fibrinogen, neutrophil, aspartate aminotransferase (AST) and total bilirubin (TB) were the top 5 important factors for recurrence risk of HCC patients after hepatectomy. In addition, we further demonstrated the reliability of the model by analyzing two patients. Finally, we successfully constructed an online web prediction calculator based on the MLP machine learning model. Conclusion MLP was an optimal machine learning model for predicting the recurrence risk of HCC patients after hepatectomy. This predictive model can help identify HCC patients at high recurrence risk after hepatectomy to provide early and personalized treatment.
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Affiliation(s)
- Rongqiang Liu
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Shinan Wu
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Hao yuan Yu
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Kaining Zeng
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhixing Liang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Siqi Li
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yongwei Hu
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Linsen Ye
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Wang L, Cong R, Chen Z, Li D, Feng B, Liang M, Wang S, Ma X, Zhao X. Determination of prognostic predictors in patients with solitary hepatocellular carcinoma: histogram analysis of multiparametric MRI. Abdom Radiol (NY) 2023; 48:3362-3372. [PMID: 37561148 DOI: 10.1007/s00261-023-04015-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Revised: 07/20/2023] [Accepted: 07/24/2023] [Indexed: 08/11/2023]
Abstract
PURPOSE To evaluate the histogram parameters of preoperative multiparametric magnetic resonance imaging (MRI) and clinical-radiological (CR) characteristics as prognostic predictors in patients with solitary hepatocellular carcinoma ≤ 5 cm and to determine the optimal time window for histogram analysis. METHODS We retrospectively included 151 patients who underwent preoperative MRI between January 2012 and December 2017. All patients were randomly separated into training and validation cohorts (n = 105 and 46). Eight whole-lesion histogram parameters were extracted from T2-weighted images, apparent diffusion coefficient maps, and dynamic contrast-enhanced images. Univariate and multivariate logistic regression analyses were performed to evaluate these histogram parameters and CR variables related to early recurrence (ER) and recurrence-free survival. A nomogram was derived from the clinical-radiological-histogram (CRH) model that incorporated these risk factors. Kaplan-Meier survival analysis was performed to evaluate the prognostic performance of the CRH model. RESULTS In total, 151 patients (male: female, 130: 21; median age, 54.46 ± 9.09 years) were evaluated. Multivariate logistic regression analysis revealed that the significant risk factors of ER were Mean Absolute Deviation and Minimum in the histogram analysis of the delayed phase images, as well as three important CR variables: albumin-bilirubin grade, microvascular invasion, and tumor size. The nomogram built by incorporating these risk factors showed satisfactory predictive ability in the training and validation cohorts with AUC values of 0.747 and 0.765, respectively. Furthermore, the prognostic nomogram can effectively classify patients into high- and low-risk groups (p < 0.05). CONCLUSION Multiparametric MRI-derived histogram parameters provide additional value in predicting patient prognosis. The CRH model may be a useful and noninvasive method for achieving prognostic stratification and personalized disease management.
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Affiliation(s)
- Leyao Wang
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Rong Cong
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zhaowei Chen
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Dengfeng Li
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Bing Feng
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Meng Liang
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Sicong Wang
- Magnetic Resonance Imaging Research, General Electric Healthcare (China), Beijing, 100176, China
| | - Xiaohong Ma
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Xinming Zhao
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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Kudo M, Finn RS, Cheng AL, Zhu AX, Ducreux M, Galle PR, Sakamoto N, Kato N, Nakano M, Jia J, Vogel A. Albumin-Bilirubin Grade Analyses of Atezolizumab plus Bevacizumab versus Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: A Post Hoc Analysis of the Phase III IMbrave150 Study. Liver Cancer 2023; 12:479-493. [PMID: 37901766 PMCID: PMC10601852 DOI: 10.1159/000529996] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 02/27/2023] [Indexed: 10/31/2023] Open
Abstract
Introduction Atezolizumab + bevacizumab showed survival benefit in patients with unresectable hepatocellular carcinoma (HCC) versus sorafenib in the Phase III IMbrave150 study. This exploratory analysis examined the prognostic impact of a baseline albumin-bilirubin (ALBI) score. Methods Patients with treatment-naïve unresectable HCC, ≥1 measurable untreated lesion, and Child-Pugh class A liver function were randomized 2:1 to receive atezolizumab 1,200 mg + bevacizumab 15 mg/kg every 3 weeks or sorafenib 400 mg twice daily. Overall survival (OS) and progression-free survival (PFS) were assessed in the intention-to-treat population by ALBI/modified (m)ALBI grade. Time to deterioration (TTD; defined as time to 0.5-point increase from the baseline ALBI score over 2 visits or death) of liver function and safety were investigated. Results Of 501 enrolled patients, 336 were randomized to receive atezolizumab + bevacizumab (ALBI grade [G] 1: n = 191; G2: n = 144 [mALBI G2a: n = 72, G2b: n = 72]; missing ALBI grade: n = 1) and 165 to sorafenib (ALBI G1: n = 87; G2: n = 78 [mALBI G2a: n = 37; G2b: n = 41]). Median follow-up was 15.6 months. OS and PFS improved with atezolizumab + bevacizumab versus sorafenib in patients with ALBI G1 (OS HR: 0.50 [95% CI: 0.35, 0.72]; PFS HR: 0.61 [95% CI: 0.45, 0.82]). In patients with ALBI G2 or mALBI G2a or G2b, PFS was numerically longer with atezolizumab + bevacizumab versus sorafenib, but no OS benefit was seen. Median TTD in the intention-to-treat population was 10.2 months (95% CI: 8.0, 11.0) with atezolizumab + bevacizumab versus 8.6 months (95% CI: 6.2, 11.8) with sorafenib (HR: 0.82 [95% CI: 0.65, 1.03]). Safety profiles of atezolizumab and bevacizumab were consistent with previous analyses, regardless of ALBI grade. Conclusion ALBI grade appeared to be prognostic for outcomes with both atezolizumab + bevacizumab and sorafenib treatment in patients with HCC. Atezolizumab + bevacizumab preserved liver function for a numerically longer duration than sorafenib.
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Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Richard S. Finn
- Division of Hematology and Oncology, Department of Medicine, Jonsson Comprehensive Cancer Center, Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Ann-Lii Cheng
- Department of Oncology, National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan
| | - Andrew X. Zhu
- Harvard Medical School, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
- Jiahui International Cancer Center, Jiahui Health, Shanghai, China
| | - Michel Ducreux
- Department of Medical Oncology, Gustave Roussy Cancer Center, Paris-Saclay University, Inserm U1279, Villejuif, France
| | - Peter R. Galle
- Department of Internal Medicine, University Medical Center Mainz, Mainz, Germany
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | | | - Jing Jia
- Hoffmann-La Roche Limited, Mississauga, ON, Canada
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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Jeng LB, Chan WL, Teng CF. Prognostic Significance of Serum Albumin Level and Albumin-Based Mono- and Combination Biomarkers in Patients with Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:cancers15041005. [PMID: 36831351 PMCID: PMC9953807 DOI: 10.3390/cancers15041005] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 01/31/2023] [Accepted: 02/03/2023] [Indexed: 02/08/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer. Although many surgical and nonsurgical therapeutic options have been established for treating HCC, the overall prognosis for HCC patients receiving different treatment modalities remains inadequate, which causes HCC to remain among the most life-threatening human cancers worldwide. Therefore, it is vitally important and urgently needed to develop valuable and independent prognostic biomarkers for the early prediction of poor prognosis in HCC patients, allowing more time for more timely and appropriate treatment to improve the survival of patients. As the most abundant protein in plasma, human serum albumin (ALB) is predominantly expressed by the liver and exhibits a wide variety of essential biological functions. It has been well recognized that serum ALB level is a significant independent biomarker for a broad spectrum of human diseases including cancer. Moreover, ALB has been commonly used as a potent biomaterial and therapeutic agent in clinical settings for the treatment of various human diseases. This review provides a comprehensive summary of the evidence from the up-to-date published literature to underscore the prognostic significance of serum ALB level and various ALB-based mono- and combination biomarkers in the prediction of the prognosis of HCC patients after treatment with different surgical, locoregional, and systemic therapies.
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Affiliation(s)
- Long-Bin Jeng
- Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan
- Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan
- Cell Therapy Center, China Medical University Hospital, Taichung 404, Taiwan
| | - Wen-Ling Chan
- Department of Bioinformatics and Medical Engineering, Asia University, Taichung 413, Taiwan
- Epigenome Research Center, China Medical University Hospital, Taichung 404, Taiwan
| | - Chiao-Fang Teng
- Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan
- Program for Cancer Biology and Drug Development, China Medical University, Taichung 404, Taiwan
- Research Center for Cancer Biology, China Medical University, Taichung 404, Taiwan
- Correspondence: ; Tel.: +886-4-2205-2121; Fax: +886-4-2202-9083
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Toyoda H, Johnson PJ. The ALBI score: From liver function in patients with HCC to a general measure of liver function. JHEP Rep 2022; 4:100557. [PMID: 36124124 PMCID: PMC9482109 DOI: 10.1016/j.jhepr.2022.100557] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/21/2022] [Accepted: 07/22/2022] [Indexed: 01/27/2023] Open
Abstract
The (albumin-bilirubin) ‘ALBI’ score is an index of ‘liver function’ that was recently developed to assess prognosis in patients with hepatocellular carcinoma, irrespective of the degree of underlying liver fibrosis. Other measures of liver function, such as model for end-stage liver disease (MELD) and Child-Pugh score, which were introduced for specific clinical scenarios, have seen their use extended to other areas of hepatology. In the case of ALBI, its application has been increasingly extended to chronic liver disease in general and in some instances to non-liver diseases where it has proven remarkably accurate in terms of prognosis. With respect to chronic liver disease, numerous publications have shown that ALBI is highly prognostic in patients with all types and stages of chronic liver disease. Outside of liver disease, ALBI has been reported as being of prognostic value in conditions ranging from chronic heart failure to brain tumours. Whilst in several of these reports, explanations for the relationship of liver function to a clinical condition have been proposed, it has to be acknowledged that the specificity of ALBI for liver function has not been clearly demonstrated. Nonetheless, and similar to the MELD and Child-Pugh scores, the lack of any mechanistic basis for ALBI’s clinical utility does not preclude it from being clinically useful in certain situations. Why albumin and bilirubin levels, or a combination thereof, are prognostic in so many different diseases should be studied in the future.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Philip J Johnson
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
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Zhang X, Xin Y, Yang Y, Chen Y, Cao XJ, Wang Y, Fan Q, Zhou X, Li X. Aspartate aminotransferase-to-platelet ratio index for predicting late recurrence of hepatocellular carcinoma after radiofrequency ablation. Int J Hyperthermia 2022; 39:437-445. [PMID: 35249443 DOI: 10.1080/02656736.2022.2043457] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Affiliation(s)
- Xinyuan Zhang
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yujing Xin
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Yang
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Chen
- Department of Interventional Radiology, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Xiao-jing Cao
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yanan Wang
- Department of Radiology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Qingsheng Fan
- Department of Oncology, Capital Medical University Affiliated Beijing Hospital of Traditional Chinese Medicine, Beijing, China
| | - Xiang Zhou
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Xin Y, Zhang X, Yang Y, Chen Y, Wang Y, Zhou X, Li X. Prediction of late recurrence after radiofrequency ablation of HBV-related hepatocellular carcinoma with the age-male-albumin-bilirubin-platelets (aMAP) risk score: a multicenter study. J Gastrointest Oncol 2021; 12:2930-2942. [PMID: 35070419 PMCID: PMC8748026 DOI: 10.21037/jgo-21-506] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 11/03/2021] [Indexed: 09/07/2023] Open
Abstract
BACKGROUND Long-term survivals of patients with HBV-related hepatocellular carcinoma are limited by the high incidence of tumor recurrence after radiofrequency ablation (RFA), identification of the risk factors and understanding the patterns of recurrence can help to improve the comprehensive management of patients after RFA. Therefore, the purpose of the study is to explore the prognostic value of the age-male-albumin-bilirubin-platelets (aMAP) score in patients with early-stage HBV-related hepatocellular carcinoma (HCC) receiving RFA; investigate the risk factors and patterns of late recurrence (LR); and develop a nomogram to predict recurrence-free survival (RFS). METHODS A retrospective review of HBV-related HCC patients who underwent primary RFA from March 2012 to December 2020 was conducted. The prognostic value of the aMAP score was evaluated in a primary cohort (n=302) and then further validated in an independent validation cohort (n=143). The optimal threshold of aMAP scores was calculated by X-tile 3.6.1 software. A prognostic nomogram was constructed from multivariate analysis and validated in an external validation cohort. RESULTS Patients with aMAP scores ≤63.8, 63.8-67.8, and >67.8 were classified into low-, medium-, and high-recurrence risk groups, respectively. The C-index to predict LR was 0.76 (95% CI: 0.700-0.810). The high-risk group was associated with the worst RFS (HR: 5.298; 95% CI, 2.697-10.408; P<0.001) and overall survival (OS) (HR: 2.639; 95% CI, 1.097-6.344; P=0.03) compared with medium- and low-risk groups. The aMAP score, multiple tumors and preoperative HBV DNA level were independent risk factors for LR. The proposed nomogram had excellent performance in predicting LR of HBV-related HCC [C-index: 0.82 (95% CI: 0.772-0.870)]. CONCLUSIONS This study demonstrated that the aMAP score can serve as an objective predictor of LR for HBV-related HCC patients after RFA. The nomogram based on preoperative HBV DNA level, aMAP score, and number of tumors can reliably help clinicians to stratify the recurrence risk of HCC patients after RFA.
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Affiliation(s)
- Yujing Xin
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinyuan Zhang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Yang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Chen
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Interventional Radiology, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Yanan Wang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiang Zhou
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Tsai YC, Sou FM, Liu YW, Wu YJ, Yong CC, Chen DW, Huang PY, Cho WR, Chuang CH, Hsiao CC, Hu TH, Tsai MC. Preoperative ALBI grade predicts the outcomes in non-B non-C HCC patients undergoing primary curative resection. BMC Gastroenterol 2021; 21:386. [PMID: 34666694 PMCID: PMC8524867 DOI: 10.1186/s12876-021-01944-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 09/27/2021] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND The albumin-bilirubin (ALBI) grade has been validated as a significant prognostic predictor for hepatocellular carcinoma (HCC). However, there is little information about the ALBI grade in patients with non-B non-C HCC (NBNC-HCC) receiving surgery. AIM This study aimed to evaluate the prognostic significance of the ALBI grade in patients with NBNC-HCC after primary curative resection. METHOD From January 2010 to April 2016, 2137 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 168 NBNC-HCC patients who received primary curative resection were analyzed. The impacts of the ALBI grade on disease-free survival (DFS) and overall survival (OS) were analyzed by multivariate analysis. RESULTS There were 66 (39.3%), 98 (58.3%), and 4 (2.4%) patients with an ALBI grade of I, II, and III, respectively. Patients with an ALBI grade II/III were older (p = 0.002), more likely to have hypoalbuminemia (p < 0.001), and more commonly had Child-Pugh class B (p = 0.009) than patients with an ALBI grade I. After a median follow-up of 76 months, 74 (44%) patients experienced recurrence, and 72 (42.9%) patients died. Multivariate analysis revealed that alpha-fetoprotein (AFP) > 200 ng/mL (p = 0.021), number of tumors (p = 0.001), and tumor stage (p = 0.007) were independent prognostic factors for DFS. Additionally, AFP > 200 ng/mL (p = 0.002), ALBI grade II/III (p = 0.002), and tumor stage (p < 0.001) were independent risk factors for poor OS. CONCLUSION The preoperative ALBI grade can be used to predict mortality in patients with NBNC-HCC after primary curative resection.
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Affiliation(s)
- Yu-Chieh Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, 83301, Taiwan
| | - Fai-Meng Sou
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, 83301, Taiwan
| | - Yueh-Wei Liu
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Ju Wu
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chee-Chien Yong
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ding-Wei Chen
- Center for Translational Research in Biomedical Sciences, Liver Transplantation Program and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Pao-Yuan Huang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, 83301, Taiwan
| | - Wei-Ru Cho
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, 83301, Taiwan
| | | | - Chang-Chun Hsiao
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, 83301, Taiwan
| | - Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, 83301, Taiwan. .,Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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Demirtas CO, D’Alessio A, Rimassa L, Sharma R, Pinato DJ. ALBI grade: Evidence for an improved model for liver functional estimation in patients with hepatocellular carcinoma. JHEP Rep 2021; 3:100347. [PMID: 34505035 PMCID: PMC8411239 DOI: 10.1016/j.jhepr.2021.100347] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 07/19/2021] [Accepted: 07/22/2021] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) usually arises in the context of a chronically damaged liver. Liver functional estimation is of paramount importance in clinical decision making. The Child-Pugh score (CPS) can be used to categorise patients into 3 classes (A to C) based on the severity of liver functional impairment according to 5 parameters (albumin, bilirubin, prothrombin time, presence of ascites and hepatic encephalopathy). The albumin-bilirubin (ALBI) grade has emerged as an alternative, reproducible and objective measure of liver functional reserve in patients with HCC, defining worsening liver impairment across 3 grades (I to III). The ALBI score can identify different subgroups of patients with different prognoses across the diverse Barcelona Clinic Liver Cancer stages and CP classes, making it an appealing clinical predictor. In patients treated with potentially curative approaches (resection, transplantation, radiofrequency ablation, microwave ablation), ALBI grade has been shown to correlate with survival, tumour relapse, and post-hepatectomy liver failure. ALBI grade also predicts survival, toxicity and post-procedural liver failure in patients treated with transarterial chemoembolisation, radioembolisation, external beam radiotherapy as well as multi-kinase inhibitors (sorafenib, lenvatinib, cabozantinib, regorafenib) and immune checkpoint inhibitor therapy. In this review, we summarise the body of evidence surrounding the role of ALBI grade as a biomarker capable of optimising patient selection and therapeutic sequencing in HCC.
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Key Words
- ALBI, albumin-bilirubin
- APRI, aspartate aminotransferase to platelet count index
- BCLC, Barcelona Clinic Liver Cancer
- CLD, chronic liver disease
- CPS, Child-Pugh score
- Child-Pugh
- HCC
- HCC, hepatocellular carcinoma
- ICIs, immune checkpoint inhibitors
- LT, liver transplantation
- MELD, model for end-stage liver disease
- ORR, objective response rate
- OS, overall survival
- PHLF, post-hepatectomy liver failure
- RFS, recurrence-free survival
- TACE, transarterial chemoembolisation
- TARE, transarterial radioembolisation
- cirrhosis
- liver function
- mAb, monoclonal antibody
- prognosis
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Affiliation(s)
- Coskun O. Demirtas
- Marmara University, School of Medicine, Department of Gastroenterology, Istanbul, Turkey
| | - Antonio D’Alessio
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Rohini Sharma
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK
| | - David J. Pinato
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK
- Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
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10
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Yonemura Y, Yoshizumi T, Tomiyama T, Iseda N, Morinaga A, Yugawa K, Harada N, Takeishi K, Toshima T, Nagao Y, Elshawy M, Ninomiya M, Iguchi T, Itoh S, Mimori K, Mori M. Clinicopathologic Features of Patients With Primary Hepatocellular Carcinoma Surviving Without Recurrence More Than 10 Years After Primary Hepatic Resection. Int Surg 2021; 105:533-542. [DOI: 10.9738/intsurg-d-20-00034.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Objective:
The aim of this study was to clarify the predictive factors of recurrence-free time more than 10 years after primary hepatic resection for hepatocellular carcinoma (HCC).
Summary of background data:
Surgical resection is a curative treatment for HCC patients with hepatic functional reserve; however, the high recurrence rate must be addressed.
Methods:
The study included 595 patients who had undergone curative resection for HCC. Multivariate analysis was performed to identify factors associated with recurrence-free survival at more than 10 years.
Results:
Multivariate analysis revealed that tumor size ≤2 cm (P = 0.004), albumin-bilirubin (ALBI) grade 1 (P = 0.03), Fibrosis-4 (FIB-4) index ≤3.3 (P = 0.002), and histologic inflammation grade ≤1 (P = 0.03) were independent predictive factors for recurrence-free survival for more than 10 years. Predictive points were scored as follows: 2 points, tumor size ≤2 cm or FIB-4 index ≤3.3; and 1 point, ALBI grade 1 or histologic inflammation grade ≤1. Patients were divided into 3 groups according to their total points: group 1, 0 to 2 points (n = 317); group 2, 3 to 4 points (n = 239); and group 3, 5 to 6 points (n = 39). Recurrence-free survival rates among the 3 groups were significantly different (P < 0.0001).
Conclusions:
Tumor size, ALBI, FIB-4 index, and histologic inflammation grade were independent predictive factors for recurrence-free survival longer than 10 years after curative hepatic resection for HCC.
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Affiliation(s)
- Yusuke Yonemura
- Department of Surgery, Kyushu University Beppu Hospital, Oita, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takahiro Tomiyama
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Norifumi Iseda
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Akinari Morinaga
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kyohei Yugawa
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Noboru Harada
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kazuki Takeishi
- Department of Surgery, Kyushu University Beppu Hospital, Oita, Japan
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiro Nagao
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Mohamed Elshawy
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Mizuki Ninomiya
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomohiro Iguchi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Koshi Mimori
- Department of Surgery, Kyushu University Beppu Hospital, Oita, Japan
| | - Masaki Mori
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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11
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Bannaga A, Arasaradnam RP. Neutrophil to lymphocyte ratio and albumin bilirubin grade in hepatocellular carcinoma: A systematic review. World J Gastroenterol 2020; 26:5022-5049. [PMID: 32952347 PMCID: PMC7476180 DOI: 10.3748/wjg.v26.i33.5022] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 08/10/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a frequent cause of cancer related death globally. Neutrophil to lymphocyte ratio (NLR) and albumin bilirubin (ALBI) grade are emerging prognostic indicators in HCC.
AIM To study published literature of NLR and ALBI over the last five years, and to validate NLR and ALBI locally in our centre as indicators of HCC survival.
METHODS A systematic review of the published literature on PubMed of NLR and ALBI in HCC over the last five years. The search followed the guidelines of the preferred reporting items for systematic reviews and meta-analyses. Additionally, we also investigated HCC cases between December 2013 and December 2018 in our centre.
RESULTS There were 54 studies describing the relation between HCC and NLR and 95 studies describing the relation between HCC and ALBI grade over the last five years. Our local cohort of patients showed NLR to have a significant negative relationship to survival (P = 0.011). There was also significant inverse relationship between the size of the largest HCC nodule and survival (P = 0.009). Median survival with alpha fetoprotein (AFP) < 10 KU/L was 20 mo and with AFP > 10 KU/L was 5 mo. We found that AFP was inversely related to survival, this relationship was not statically significant (P = 0.132). Mean survival for ALBI grade 1 was 37.7 mo, ALBI grade 2 was 13.4 months and ALBI grade 3 was 4.5 mo. ALBI grades performed better than Child Turcotte Pugh score in detecting death from HCC.
CONCLUSION NLR and ALBI grade in HCC predict survival better than the conventional alpha fetoprotein. ALBI grade performs better than Child Turcotte Pugh score. These markers are done as part of routine clinical care and in cases of normal alpha fetoprotein, these markers could give a better understanding of the patient disease progression. NLR and ALBI grade could have a role in modified easier to learn staging and prognostic systems for HCC.
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Affiliation(s)
- Ayman Bannaga
- Department of Gastroenterology and Hepatology, University Hospital Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, West Midlands, United Kingdom
- Warwick Medical School, University of Warwick, Coventry CV4 7HL, West Midlands, United Kingdom
| | - Ramesh P Arasaradnam
- Department of Gastroenterology and Hepatology, University Hospital Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, West Midlands, United Kingdom
- Warwick Medical School, University of Warwick, Coventry CV4 7HL, West Midlands, United Kingdom
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12
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WANG X, ZHANG Z, WU Z, SUN Y, ZHANG Y, GONG M, JI F. [Prediction model of mid-term fatality risk after radical resection in patients with hepatocellular carcinoma based on ALBI-grade]. Zhejiang Da Xue Xue Bao Yi Xue Ban 2020; 49:375-382. [PMID: 32762166 PMCID: PMC8800794 DOI: 10.3785/j.issn.1008-9292.2020.06.04] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 04/09/2020] [Indexed: 06/11/2023]
Abstract
OBJECTIVE To establish a clinical prediction model of the mid-term fatality risk after radical resection in patients with primary hepatocellular carcinoma (HCC) based on the albumin-bilirubin (ALBI) grade and to assess its prediction value. METHODS Clinical data of 533 patients who received HCC radical resection in Jinhua Hospital of Zhejiang University, Jinhua People's Hospital, Jinhua Hospital of Traditional Chinese Medicine and Jinhua Guangfu Hospital from January 2010 to August 2016 were retrospectively reviewed. In the training group ( n=407), Cox model was used to screen the clinical risk factors of postoperative death, and a predictive model based on ALBI grade was established and then examined in the validation group ( n=126). The value of the prediction model was assessed by ROC curve and calibration curve; the prediction results of the model were visualized by the nomogram for the convenience of clinical use. RESULTS Cox model showed that ALT ≥ 80 U/L, tumor maximum diameter ≥ 5 cm, portal vein tumor thrombus and ALBI grade 2 were independent risk factors for the prognosis of patients with HCC radical resection. The prognosis index (PI) was 0.550×ALT+0.512×ALBI grade+0.872×maximum tumor diameter+1.377×portal vein tumor thrombus. The AUCs for predicting the risk of death in 12, 36 and 60 months were 0.872, 0.814 and 0.810, respectively (all P < 0.01), and the goodness of fit ( r 2) of the established model were 0.953, 0.976 and 0.994. AUC of the established model for predicting risk of death in 36 months after resection was 0.814, which was higher than those of ALBI (AUC=0.683), BCLC (AUC=0.713), CLIP (AUC=0.689), Child-Pugh (AUC=0.645), TNM (AUC=0.612) ( P < 0.05 or P < 0.01). CONCLUSIONS ALT ≥ 80 U/L, maximum tumor diameter ≥ 5 cm, portal vein tumor thrombus and ALBI grade 2 are independent risk factors of patients after HCC resection, and ALBI grade-based prediction model is satisfactory in prediction of mid-term death risk of the patients.
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