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Zeng J, Chen G, Zeng J, Liu J, Zeng Y. Development of nomograms to predict outcomes for large hepatocellular carcinoma after liver resection. Hepatol Int 2025; 19:428-440. [PMID: 39760822 DOI: 10.1007/s12072-024-10754-7] [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: 07/17/2024] [Accepted: 11/09/2024] [Indexed: 01/07/2025]
Abstract
BACKGROUND Large hepatocellular carcinoma (HCC) is difficult to resect and accompanied by poor outcome. The aim was to evaluate the short-term and long-term outcomes of patients who underwent liver resection for large HCC, eventually drawing prediction models for short-term and long-term outcomes. METHODS 1710 large HCC patients were recruited and randomly divided into the training (n = 1140) and validation (n = 570) cohorts in a 2:1 ratio. Independent risk factors were identified by regression model and used to establish three nomograms for surgical risk, overall survival (OS), and recurrence-free survival (RFS) in the training cohort. Model performances were assessed by discrimination and calibration. The three models were also compared with six other staging systems. RESULTS Platelet (PLT), gamma-glutamyl transpeptidase (GGT), albumin-bilirubin (ALBI) grade, blood transfusion and loss, resection margin, tumor size, and tumor number were established in a nomogram to evaluate surgical risk ( https://largehcc.shinyapps.io/largehcc-morbidity/ ). The model had a good prediction capability with a C-index of 0.764 and 0.773 in the training and validation cohorts. Alpha-fetoprotein (AFP), resection margin, tumor size, tumor number, microvascular invasion, Edmondson-Steiner grade, tumor capsular, and satellite nodules were considered to construct a prognostic nomogram to predict the 1-, 3- and 5-year OS ( https://largehcc.shinyapps.io/largehcc-os/ ). The C-index of the model was 0.709 and 0.702 for the training and validation cohorts. Liver cirrhosis, albumin (ALB), total bilirubin (TBIL), AFP, tumor size, tumor number, microvascular invasion, and tumor capsular were used to draw a prognostic nomogram to predict the 1-, 3- and 5-year RFS ( https://largehcc.shinyapps.io/largehcc-rfs/ ). The C-index of the model was 0.695 and 0.675 in the training and validation cohorts. The discrimination showed that the models had significantly better predictive performances than six other staging systems. CONCLUSIONS Three novel nomograms were developed to predict short-term and long-term outcomes in patients with large HCC who underwent curative resection with adequate performance. These predictive models could help to design therapeutic interventions and surveillance for patients with large HCC.
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Affiliation(s)
- Jianxing Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
- Hepatobiliary Medical Center of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Guixiang Chen
- Department of Operating Theatre, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
- Hepatobiliary Medical Center of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Jinhua Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
- Hepatobiliary Medical Center of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Jingfeng Liu
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
- Hepatobiliary Medical Center of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Yongyi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China.
- Hepatobiliary Medical Center of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China.
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Wu PS, Lee KC, Li CY, Hsieh YC, Huo TI, Lin HC, Hou MC. Paracentesis exceeding three liters increases risks of acute kidney injury even in cirrhotic patients with albumin infused refractory ascites. J Formos Med Assoc 2025:S0929-6646(25)00002-6. [PMID: 39779410 DOI: 10.1016/j.jfma.2025.01.002] [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: 06/27/2024] [Revised: 12/05/2024] [Accepted: 01/02/2025] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Cirrhotic patients with refractory ascites exhibit severe portal hypertension and hemodynamic disturbances. The risks associated modest-volume paracentesis (<5 L) for refractory ascites remains unclear. We aimed to explore the impact of modest-volume paracentesis in refractory ascites. METHODS Cirrhotic patients with refractory ascites undergoing paracentesis <5 L with albumin infusion were retrospectively enrolled. Patients were categorized into two groups based on the volume of paracentesis: ≥3 L and <3 L. Logistic regression analyses were used to determine risk factors for post-paracentesis complications, while Kaplan-Meier analysis was used to assess 28-day survival rates. RESULTS Among 116 patients, 40 (34.5%) experienced post-paracentesis complications within one week, predominantly acute kidney injury (AKI) (19.8%). Twenty patients had paracentesis ≥3 L and 96 patients had <3 L. Overall complications were comparable between two groups (50% vs. 31.3%, p = 0.109), but ≥3 L group had more AKI (40% vs. 15.6%, p = 0.013). Additionally, paracentesis ≥3 L is an independent risk factor for AKI [Odds ratio (OR) = 4.15, p = 0.012], while higher MELD scores (OR = 1.14, p = 0.001) and older age (OR = 1.03, p = 0.047) are risk factors for overall complications. Furthermore, patients with post-paracentesis complications had significantly poorer 28-day survival. CONCLUSION Cirrhotic patients with refractory ascites face a high risk of complications from modest-volume paracentesis, even with albumin infusion. Paracentesis ≥3 L increases AKI risks, while higher MELD scores are linked to greater overall complications, leading to poor short-term survival.
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Affiliation(s)
- Pei-Shan Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan; Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Kuei-Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Chih-Yu Li
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yun-Cheng Hsieh
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Teh-Ia Huo
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan; Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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Allaire M, Garcia H, Meyblum L, Mouri S, Spitzer E, Goumard C, Lucidarme O, Rudler M, Scatton O, Roux C, Wagner M, Thabut D. Non selective beta-blockers prevent PHT-related complications occurrence in HCC patients with esophageal varices treated by TACE. Clin Res Hepatol Gastroenterol 2025; 49:102496. [PMID: 39547469 DOI: 10.1016/j.clinre.2024.102496] [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: 08/26/2024] [Revised: 10/28/2024] [Accepted: 11/08/2024] [Indexed: 11/17/2024]
Abstract
INTRODUCTION We aimed to investigate the parameters associated with portal hypertension (PHT)-related complications occurrence in hepatocellular carcinoma (HCC) patients treated by transarterial chemoembolization (TACE), with a focus on non-selective beta blockers (NSBBs) due to their impact on preventing liver decompensation. METHODS We included all patients with HCC for whom endoscopy was available the day of first TACE (2013-2023). The occurrence of PHT-related complications was defined as the appearance of ascites, acute variceal bleeding or hepatic encephalopathy (HE) post-TACE treatment and prior to HCC progression. Inappropriate treatment by NSBBs was defined by the lack of NSBBs in patients with small/large esophageal varices (EV). RESULTS 109 patients were included (age 67 years, 80 % male) and 65 % had EV. No NSBBs prescription despite indication was observed in 32 % and 81 % of patients with large and small size EV, respectively. Median progression free survival and overall survival were 10 and 23 months, respectively, and 27 % of patients underwent LT. During the follow-up, 20 patients presented PHT-related complications with an incidence of 18 % at 12months (90 % with EV,67 % not treated by NSBB while indicated). Among them, 11 presented HCC progression, 2 were transplanted and 78 % presented liver decompensation that impaired the access to further HCC treatment. In multivariate analysis, a history of HE (HR=55.39,95 %CI[7.42-413.26]) and inappropriate NSBBs treatment (HR=4.16,95 %CI[1.45-11.81]) were associated with PHT-related complications occurrence. CONCLUSION The lack of NSBBs was independently associated with PHT-related complications after TACE, precluding access to further HCC treatment in 78 % of patients with HCC progression. Appropriate screening and PHT prophylaxis are needed in HCC patients who undergo TACE to improve their outcomes.
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Affiliation(s)
- Manon Allaire
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France; INSERM UMR 1138, Centre de recherche des Cordeliers, 75006 Paris, France.
| | - Hélène Garcia
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service de radiologie diagnostique, Paris, France
| | - Louis Meyblum
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service de radiologie interventionnelle, Paris, France
| | - Sarah Mouri
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France
| | - Eléonore Spitzer
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France
| | - Claire Goumard
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service de chirurgie digestive, HPB et transplantation hépatique, Paris, France; Sorbonne Université, UMRS-938, Centre de recherche Saint-Antoine (CRSA), INSERM, Paris, France
| | - Olivier Lucidarme
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service de radiologie diagnostique, Paris, France
| | - Marika Rudler
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France; Sorbonne Université, UMRS-938, Centre de recherche Saint-Antoine (CRSA), INSERM, Paris, France
| | - Olivier Scatton
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service de chirurgie digestive, HPB et transplantation hépatique, Paris, France; Sorbonne Université, UMRS-938, Centre de recherche Saint-Antoine (CRSA), INSERM, Paris, France
| | - Charles Roux
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service de radiologie interventionnelle, Paris, France
| | - Mathilde Wagner
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service de radiologie diagnostique, Paris, France
| | - Dominique Thabut
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France; Sorbonne Université, UMRS-938, Centre de recherche Saint-Antoine (CRSA), INSERM, Paris, France
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Pagano AP, Sicchieri JMF, Morgado ASDM, Meira Filho LF, Gonzalez MC, Prado CM, Elias Junior J, Teixeira AC, Chiarello PG. Phase Angle but Not Psoas Muscle Predicts Nutritional Risk and Prognosis in Males with Hepatocellular Carcinoma. Nutr Cancer 2024; 76:963-973. [PMID: 39012155 DOI: 10.1080/01635581.2024.2378504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 07/03/2024] [Accepted: 07/05/2024] [Indexed: 07/17/2024]
Abstract
Despite those with hepatocellular carcinoma (HCC) being at increased risk of malnutrition, there is a notable absence of practical approaches for nutritional assessment in clinical practice. We investigated the usefulness of phase angle (PhA) and Total Psoas Area Index (TPAI) for indicating nutritional risk and HCC prognosis. Weight, height, body mass index (BMI), adductor pollicis muscle thickness (APMT), and handgrip strength (HGS) were assessed. The Nutritional Risk Index (NRI) was calculated. Body composition was assessed using bioimpedance spectroscopy and magnetic resonance imaging. The Child-Turcotte-Pugh (CTP) score and Barcelona-Clinic Liver Cancer (BCLC) classification determined the prognosis. Fifty-one males with HCC were enrolled (CTP C = 11.8%). PhA showed a moderate positive correlation with APMT (r = 0.450; p < 0.001) and HGS (r = 0.418; p = 0.002) and a weak positive correlation with TPAI (r = 0.332; p = 0.021). PhA had a strong positive correlation with NRI (r = 0.614; p < 0.001). Mean PhA values were significantly different according to disease severity (CTP C p = 0.001, and BCLC D p = 0.053). TPAI had no significant correlation with HGS, CTP, or BCLC. PhA was a superior approach for predicting nutritional risk and prognosis in HCC than TPAI. Lower PhA is associated with disease progression, lower muscle mass and function, greater severity of nutritional risk, and increased mortality in HCC.
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Affiliation(s)
- Ana Paula Pagano
- Hospital das Clínicas, Ribeirão Preto Medical School, Department of Health Sciences, Division of Nutrition and Metabolism, University of São Paulo, Ribeirão Preto, Brazil
- Human Nutrition Research Unit, Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Juliana Maria Faccioli Sicchieri
- Hospital das Clínicas, Ribeirão Preto Medical School, Department of Health Sciences, Division of Nutrition and Metabolism, University of São Paulo, Ribeirão Preto, Brazil
| | - Alexandre Souto de Moraes Morgado
- Hospital das Clínicas, Ribeirão Preto Medical School, Department of Medical Images, Hematology, and Oncology, University of São Paulo, Ribeirão Preto, Brazil
| | - Luiz Fernando Meira Filho
- School of Economics, Business Administration and Accounting, University of São Paulo, Ribeirão Preto, Brazil
| | | | - Carla M Prado
- Human Nutrition Research Unit, Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Jorge Elias Junior
- Hospital das Clínicas, Ribeirão Preto Medical School, Department of Medical Images, Hematology, and Oncology, University of São Paulo, Ribeirão Preto, Brazil
| | - Andreza Correa Teixeira
- Hospital das Clínicas, Ribeirão Preto Medical School, Department of Internal Medicine, Division of Gastroenterology, University of São Paulo, Ribeirão Preto, Brazil
| | - Paula Garcia Chiarello
- Hospital das Clínicas, Ribeirão Preto Medical School, Department of Health Sciences, Division of Nutrition and Metabolism, University of São Paulo, Ribeirão Preto, Brazil
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Liu G, Zhu D, He Q, Zhou C, He L, Li Z, Jiang Z, Huang M, Chang B, Wu C. Hepatic Arterial Infusion Chemotherapy Combined with Lenvatinib and PD-1 Inhibitors for Managing Arterioportal Shunt in Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective Cohort Study. J Hepatocell Carcinoma 2024; 11:1415-1428. [PMID: 39045397 PMCID: PMC11264130 DOI: 10.2147/jhc.s456460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 06/25/2024] [Indexed: 07/25/2024] Open
Abstract
Purpose This study aimed to assess the effectiveness and safety of combining hepatic arterial infusion chemotherapy (HAIC) with lenvatinib (LEN) and PD-1 inhibitors in treating arterioportal shunt (APS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Patients and Methods Conducted retrospectively, the study enrolled 54 HCC patients with APS and PVTT treated with HAIC, LEN, and PD-1 inhibitors at our center between January 2021 and October 2023. APS improvement, APS recanalization, tumor response, PVTT response rate, overall survival (OS), intrahepatic progression-free survival (InPFS), and adverse events were evaluated. Results APS improvement was observed in 42 patients (77.8%), with all improvement occurring within two treatment sessions. Complete APS occlusion was achieved in 40 patients (74.1%), and no recanalization occurred. The best objective response rate (ORR) and ORR after two HAIC sessions were 74.1% and 66.7%, respectively. The best PVTT response and PVTT response after two HAIC sessions were 98.1% and 94.4%, respectively. The median OS and InPFS were 10.0 months and 5.0 months, respectively. OS and InPFS were longer in patients with APS occlusion compared to those without (OS 12.1 vs 4.4 months, P<0.001, InPFS 6.2 vs 2.3 months, P=0.049). ALBI grade, extrahepatic spread, APS disappearance were potential prognostic factors for OS, while APS grade and extrahepatic spread being independently associated with InPFS. No treatment-related mortality occurred. Conclusion Combining HAIC with LEN and PD-1 inhibitors proves to be both effective and safe in managing APS in HCC with PVTT, potentially improving patient survival.
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Affiliation(s)
- Guanxiong Liu
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China
| | - Duo Zhu
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China
| | - Quansheng He
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China
| | - Churen Zhou
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China
| | - Li He
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China
| | - Zhengran Li
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China
| | - Zaibo Jiang
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China
| | - Mingsheng Huang
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China
| | - Boyang Chang
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China
| | - Chun Wu
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China
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Salman SS, Thirunavukkarasu B, Yadav R, Chauhan VS, Peddinti RS, Shalimar, Gamanagatti S. Diagnosis of peritoneal metastasis in an unruptured hepatocellular carcinoma on ascitic fluid cytology: A rare scenario with brief review of literature. Diagn Cytopathol 2024; 52:E54-E58. [PMID: 38031825 DOI: 10.1002/dc.25259] [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: 09/17/2023] [Revised: 10/26/2023] [Accepted: 11/21/2023] [Indexed: 12/01/2023]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy in adults occurring in a background of cirrhosis. Peritoneal dissemination of HCC is an unusual presentation with an incidence of 2%-16%. Peritoneal metastasis of an unruptured HCC is extremely uncommon. Despite low yield, ascitic fluid cytology serves as a valuable tool for diagnostic evaluation in a patient of cirrhosis with suspicion of malignant transformation. We present a rare case scenario in an elderly female with cirrhosis where the diagnosis of peritoneal metastasis was established on ascitic fluid cytology and confirmed by immunocytochemistry. This report illustrates the unique clinical presentation of an unruptured HCC with its cytological features and a brief review of literature.
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Affiliation(s)
- Syed Saad Salman
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | | | - Rajni Yadav
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Vishal Singh Chauhan
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Raja Shekar Peddinti
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
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Chen C, Li Z, Xiong X, Yao A, Wang S, Liu X, Liu X, Wang J. Intraperitoneal PD-1 monoclonal antibody for the treatment of advanced primary liver cancer with malignant ascites: a single-arm, single-center, phase Ib trial. ESMO Open 2024; 9:102206. [PMID: 38194882 PMCID: PMC10820330 DOI: 10.1016/j.esmoop.2023.102206] [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: 10/18/2023] [Revised: 11/27/2023] [Accepted: 11/27/2023] [Indexed: 01/11/2024] Open
Abstract
BACKGROUND Advanced primary liver cancer patients with malignant ascites have a poor prognosis and lack effective treatment plans. This phase Ib study aims to explore the safety and clinical efficacy of intraperitoneal anti-programmed cell death protein 1 (PD-1) antibody in these patients. PATIENTS AND METHODS Patients received sintilimab 100 mg intraperitoneally plus best supportive care on days 1, 8, and 15 in three cycles of 4 weeks. The course was repeated every 28 days until intolerable toxicity had developed or disease progression. The primary endpoint was safety, while the secondary endpoints were objective response rate (ORR), ascites control rate (ACR), and overall survival (OS). RESULTS From February 2021 through November 2022, a total of 21 patients (14 hepatocellular carcinoma and 7 cholangiocarcinoma) were enrolled to receive intraperitoneal sintilimab. Twelve patients had adverse events (AEs). The most common grade 3 AEs were fatigue, rash, and abdominal pain. No grade ≥4 AEs occurred in any patients. ORR was only evaluated in 13 patients, including partial response in 4, stable disease in 7, and progressive disease in 2. A reduction in the median maximum diameter of the tumor after treatment was observed; however, there was no statistical significance among patients. The objective remission rate of ascites was 43.75%, and the median OS for all 21 patients was 17.6 weeks. CONCLUSIONS This exploratory study represents the first trial to demonstrate the safety and clinical efficacy of intraperitoneal anti-PD-1 antibody administration. No unexpected safety concerns were identified. A large, multicenter, prospective study is needed to confirm the promising clinical efficacy.
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Affiliation(s)
- C Chen
- Department of Oncology, Jinling Hospital, Nanjing Medical University, Nanjing
| | - Z Li
- Department of Oncology, Jinling Hospital, Nanjing Medical University, Nanjing
| | - X Xiong
- Department of Hepatology, Jinling Hospital, Nanjing Medical University, Nanjing
| | - A Yao
- Department of Research Institute of General Surgery, Jinling Hospital, Nanjing Medical University, Nanjing
| | - S Wang
- Department of Research Institute of General Surgery, Jinling Hospital, Nanjing Medical University, Nanjing
| | - X Liu
- Department of Oncology, Jinling Hospital, Nanjing Medical University, Nanjing
| | - X Liu
- Department of Oncology, Jinling Hospital, Nanjing Medical University, Nanjing.
| | - J Wang
- Department of Hematology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing; Yizheng Hospital of Nanjing Drum Tower Hospital Group, Yizheng, PR China.
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Badheeb AM, Al Sedran MK, Ahmed F, Al Sidran IK, Al Qurayshah MH, Abu Bakar A, Obied HY, Seada IA, Aman A, Badheeb M. Clinical Characteristics and Survival of Hepatocellular Carcinoma: Insights from Single-Centre Experience in Saudi Arabia. Cureus 2024; 16:e52608. [PMID: 38374854 PMCID: PMC10875600 DOI: 10.7759/cureus.52608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/20/2024] [Indexed: 02/21/2024] Open
Abstract
Background Hepatocellular carcinoma (HCC) represents the most common primary liver malignancy, with a high fatality rate. Relatively, Saudi Arabia has a high incidence of HCC, which is detected in later stages with a poor prognosis. This study aims to investigate the patterns, outcomes, and mortality predictors of HCC in Saudi Arabia. Method A retrospective study from April 2018 to June 2022 included patients with HCC who were diagnosed and managed at the Najran Oncology Center, Saudi Arabia. Through our cancer registry, the patients' clinical, laboratory, radiological, and survival profiles were extracted and analyzed to assess factors associated with mortality using a univariate analysis. The overall survival was calculated by the Kaplan-Meier method. Results The study involved 52 patients with an average age of 74.6 years, predominantly male (the male-to-female ratio is 2.25:1). Viral infections were the primary cause of liver disease in 40.3% (n=21) of patients. At diagnosis, the Child-Pugh class distribution included 23.1% (n=12) patients in class A, 36.5% (n=19) patients in class B, and 40.4% (n=21) patients in class C. Uninodular tumors with ≤50% liver extension were observed in 65.4% (n=34) of cases, and 30.8% (n=16) had portal vein thrombosis. Elevated alpha-fetoprotein (AFP) levels were noted in 48.1% (n=25) of patients, with 23.1% (n=12) exceeding 400 ng/mL. Curative resection was performed in 32.7% (n=17) of patients. The mean survival time was 23±11.8 months (median of 22.5 months, minimum of six, and maximum of 49 months). Relapse occurred in seven (13.5%) cases, while new metastasis occurred in 20 (38.5%) cases. During the study period, 26 (50.0%) patients died. The main cause of death was disease progression in 15 (28.8%) patients. Univariate analysis showed that AFP>400 ng/mL (OR: 4.68; 95% CI: 1.87-11.66, p=0.001), presence of relapse (OR: 0.16; 95% CI: 0.03-0.78, p=0.023), abdominal ascites (OR: 3.38; 95% CI: 1.25-9.14, p=0.016), advanced the Cancer of the Liver Italian Program (CLIP) score (OR: 0.60; 95% CI: 0.41-0.88, p=0.009) were associated with higher mortality rate and were statistically significant. Conclusion Most cases of HCC in our patients were attributed to viral hepatitis, with the majority having liver cirrhosis. Higher AFP (>400 ng/mL), relapse, abdominal ascites, and a higher cancer CLIP score were associated with poorer outcomes. Targeted screening and health education should be advocated; in addition, social determinants should be proactively addressed.
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Affiliation(s)
- Ahmed M Badheeb
- Oncology, King Khalid Hospital, Oncology Center, Najran, SAU
| | | | | | | | | | | | | | - Islam A Seada
- Cardiothoracic Surgery, King Khalid Hospital, Najran, SAU
| | - Abdelaziz Aman
- Internal Medicine, King Khalid University Hospital, Nagran, SAU
| | - Mohamed Badheeb
- Internal Medicine, Yale New Haven Health, Bridgeport Hospital, Bridgeport, USA
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9
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Liao JI, Ho SY, Liu PH, Hsu CY, Huang YH, Su CW, Hou MC, Huo TI. Prognostic Prediction for Patients with Hepatocellular Carcinoma and Ascites: Role of Albumin-Bilirubin (ALBI) Grade and Easy (EZ)-ALBI Grade. Cancers (Basel) 2023; 15:753. [PMID: 36765711 PMCID: PMC9913159 DOI: 10.3390/cancers15030753] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 01/17/2023] [Indexed: 01/27/2023] Open
Abstract
Patients with hepatocellular carcinoma (HCC) often have co-existing ascites, which is a hallmark of liver decompensation. The albumin-bilirubin (ALBI) grade and EZ (easy)-ALBI grade are used to assess liver functional reserve in HCC, but the predictive accuracy of these two models in HCC patients with ascites is unclear. We aimed to determine the prognostic role of ALBI and EZ-ALBI grades in these patients. A total of 4431 HCC patients were prospectively enrolled and retrospectively analyzed. Independent prognostic predictors were identified by the multivariate Cox proportional hazards model. Of all patients, 995 (22.5%) patients had ascites. Grade 1, 2, and 3 ascites were found in 16%, 4%, and 3% of them, respectively. A higher ascites grade was associated with higher ALBI and EZ-ALBI scores and linked with decreased overall survival. In the Cox multivariate analysis, serum bilirubin level > 1.1 mg/dL, creatinine level ≥ 1.2 mg/dL, α-fetoprotein ≥ 20 ng/mL, total tumor volume > 100 cm3, vascular invasion, distant metastasis, poor performance status, ALBI grade 2 and 3, EZ-ALBI grade 2 and 3, and non-curative treatments were independently associated with increased mortality (all p < 0.05) among HCC patients with ascites. The ALBI and EZ-ALBI grade can adequately stratify overall survival in both the entire cohort and specifically in patients with ascites. Ascites is highly prevalent and independently predict patient survival in HCC. The ALBI and EZ-ALBI grade are feasible markers of liver dysfunction and can stratify long-term survival in HCC patients with ascites.
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Affiliation(s)
- Jia-I Liao
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
| | - Shu-Yein Ho
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- Division of Gastroenterology and Hepatology, Min-Sheng General Hospital, Taoyuan 330, Taiwan
| | - Po-Hong Liu
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Chia-Yang Hsu
- Department of Medicine, Renown Regional Medical Center, Reno, NV 89502, USA
| | - Yi-Hsiang Huang
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
| | - Chien-Wei Su
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
| | - Teh-Ia Huo
- Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan
- Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
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10
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Larrey E, Campion B, Evain M, Sultanik P, Blaise L, Giudicelli H, Wagner M, Cluzel P, Rudler M, Ganne-Carrié N, Thabut D, Allaire M. A history of variceal bleeding is associated with further bleeding under atezolizumab-bevacizumab in patients with HCC. Liver Int 2022; 42:2843-2854. [PMID: 36254617 DOI: 10.1111/liv.15458] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 09/22/2022] [Accepted: 10/13/2022] [Indexed: 12/18/2022]
Abstract
BACKGROUND Atezolizumab-bevacizumab is the new standard for advanced hepatocellular carcinoma (HCC) but its impact on portal hypertension (PHT) is unknown. We aimed to identify predictive factors of acute variceal bleeding (AVB) and to monitor PHT parameters under treatment. METHODS We conducted a prospective study including all cirrhotic patients treated with atezolizumab-bevacizumab since 2020. We performed monitoring of PHT using upper endoscopy at inclusion and at 6 months and hepatic venous pressure gradient (HVPG) at inclusion, 3 and 6 months after the beginning of treatment. We also included a retrospective series of patients treated with sorafenib. Time-to-events data were estimated by Kaplan-Meier with the log-rank test, along with Cox models. RESULTS Forty-three patients treated with atezolizumab-bevacizumab were included (male 79.1%, Child-Pugh A 86%). At baseline, 48.8% were treated with curative anticoagulation, 16.3% already experienced AVB and 25.6% had large oesophageal varices (EV). Sorafenib group characteristics were similar. Vascular invasion was present in 60.5% and median was HVPG 8.5 mm Hg. No significant modification in HVPG and EV size was observed at 6 months in the whole cohort but also when considering vascular invasion and radiological response. 14% presented AVB within a median time of occurrence of 3 months, without bleeding-related death. In multivariate analysis, history of AVB (HR = 10.58, p = .03) was associated with AVB. AVB incidence was higher in atezolizumab-bevacizumab compared to sorafenib group (21% vs. 5% at 1 year, p = .02). CONCLUSIONS Atezolizumab-bevacizumab treatment was associated with a higher risk of AVB compared to sorafenib. A history of AVB was associated with AVB during follow-up, which questions the use of bevacizumab in this setting.
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Affiliation(s)
- Edouard Larrey
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France
| | - Bertille Campion
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France
| | - Manon Evain
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France
| | - Philippe Sultanik
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France
| | - Lorraine Blaise
- AP-HP Sorbonne Paris Nord, Hôpitaux Universitaire Paris Seine Saint-Denis, Service d'Hépatologie, Bobigny, France
| | - Héloïse Giudicelli
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France
| | - Mathilde Wagner
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service de radiologie diagnostique, Paris, France
| | - Philippe Cluzel
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service de radiologie interventionnelle, Paris, France
| | - Marika Rudler
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France.,Sorbonne Université, INSERM, Centre de recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Nathalie Ganne-Carrié
- AP-HP Sorbonne Paris Nord, Hôpitaux Universitaire Paris Seine Saint-Denis, Service d'Hépatologie, Bobigny, France.,INSERM UMR 1138, Centre de recherche des Cordeliers, Paris, France
| | - Dominique Thabut
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France.,Sorbonne Université, INSERM, Centre de recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Manon Allaire
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France.,INSERM UMR 1138, Centre de recherche des Cordeliers, Paris, France
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11
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Cai Z, Xi D, Zhu X, Li R. Causal discoveries for high dimensional mixed data. Stat Med 2022; 41:4924-4940. [PMID: 35968913 DOI: 10.1002/sim.9544] [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: 06/04/2021] [Revised: 06/28/2022] [Accepted: 07/21/2022] [Indexed: 11/08/2022]
Abstract
Causal relationships are of crucial importance for biological and medical research. Algorithms have been proposed for causal structure learning with graphical visualizations. While much of the literature focuses on biological studies where data often follow the same distribution, for example, the normal distribution for all variables, challenges emerge from epidemiological and clinical studies where data are often mixed with continuous, binary, and ordinal variables. We propose to use a mixed latent Gaussian copula model to estimate the underlying correlation structure via the rank correlation for mixed data. This correlation structure is then incorporated into a popular causal discovery algorithm, the PC algorithm, to identify causal structures. The proposed algorithm, called the latent-PC algorithm, is able to discover the true causal structure consistently under mild conditions in high dimensional settings. From simulation studies, the latent-PC algorithm delivers a competitive performance in terms of a similar or higher true positive rate and a similar or lower false positive rate, compared with other variants of the PC algorithm. In the high dimensional settings where the number of variables is more than the number of observations, the causal graphs identified by the latent-PC algorithm are closer to the true causal structures, compared to other competing algorithms. Further, we demonstrate the utility of the latent-PC algorithm in a real dataset for hepatocellular carcinoma. Causal structures for patient survival are visualized and connected with clinical interpretations in the literature.
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Affiliation(s)
- Zhanrui Cai
- Department of Statistics, Iowa State University, Ames, Iowa, USA
| | - Dong Xi
- Gilead Sciences, Foster City, California, USA
| | - Xuan Zhu
- Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA
| | - Runze Li
- Department of Statistics, The Pennsylvania State University, University Park, Pennsylvania, USA
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12
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Arvanitakis K, Koufakis T, Kotsa K, Germanidis G. The effects of sodium-glucose cotransporter 2 inhibitors on hepatocellular carcinoma: From molecular mechanisms to potential clinical implications. Pharmacol Res 2022; 181:106261. [PMID: 35588918 DOI: 10.1016/j.phrs.2022.106261] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 05/11/2022] [Accepted: 05/12/2022] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma (HCC) occurs in the setting of prolonged liver inflammation, hepatocyte necrosis and regeneration in patients with cirrhosis. Despite the progress made in the medical management of the disorder during the past decades, the available pharmacological options remain limited, leading to poor survival rates and quality of life for patients with HCC. Sodium-glucose cotransporter 2 inhibitors (SGLT2) originally emerged as drugs for the treatment of hyperglycemia; however, they soon demonstrated important extra-glycemic properties, which led to their evaluation as potential treatments for a wide range of non-metabolic disorders. Evidence from animal studies suggests that SGLT2i have the potential to modulate molecular pathways that affect hallmarks of HCC, including inflammatory responses, cell proliferation, and oxidative stress. The impressive benefits of neurohormonal modulation observed with SGLT2i in congestive heart failure set the stage for human trials in cirrhotic ascites. However, future studies need to evaluate several aspects of the benefit to risk ratio of such a therapeutic strategy, including the co-administration with antineoplastic agents and diuretics, infections, use in hospitalized individuals, renal safety and hypovolemia. In this narrative review, we discuss the putative role of SGLT2i in the treatment of patients with HCC, starting with the mechanisms that could justify a possible benefit and ending with potential clinical implications and areas for future research.
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Affiliation(s)
- Konstantinos Arvanitakis
- First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Theocharis Koufakis
- Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece
| | - Kalliopi Kotsa
- Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece
| | - Georgios Germanidis
- First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece.
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13
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Chi X, Jiang L, Yuan Y, Huang X, Yang X, Hochwald S, Liu J, Huang H. A comparison of clinical pathologic characteristics between alpha-fetoprotein negative and positive hepatocellular carcinoma patients from Eastern and Southern China. BMC Gastroenterol 2022; 22:202. [PMID: 35461226 PMCID: PMC9034573 DOI: 10.1186/s12876-022-02279-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 04/11/2022] [Indexed: 11/30/2022] Open
Abstract
Background Alpha-fetoprotein (AFP) is a biomarker used in clinical management of hepatocellular carcinoma (HCC), however, approximately 40% of HCC patients do not present with elevated serum AFP levels. This study aimed to investigate the clinical and pathologic characteristics between AFP positive and negative HCC patients to allow for improved clinical management and prognostication of the disease. Methods This study observed a cohort of HCC patients from Eastern and Southern China with comparisons of the clinical and pathologic features between serum AFP positive and negative patient groups; patients with decompensated hepatic cirrhosis, those with chronic hepatitis B, and hepatitis B virus (HBV) asymptomatic carrier patients were used as controls. Data included the laboratory results, pathology diagnosis, clinical staging and scores were obtained from routine clinical diagnostic methods. Results Patients with HCC, larger tumor sizes, liver cancer with hepatic cirrhosis, portal vein thrombosis, metastasis, high Child–Pugh score, high Barcelona-Clínic Liver Cancer (BCLC) stage, and advanced clinical stage had significantly higher serum AFP levels. Also, patients with HBsAg and HBeAg positive, high HBV DNA levels had significantly higher serum AFP levels. Patients with high serum AFP levels had higher protein induced by vitamin K absence or antagonist-II (PIVKA-II), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-l-fucosidase (AFU), gamma-glutamyl transpeptidase (γ-GT), γ-GT /ALT, direct bilirubin (DBIL), indirect bilirubin (IDBIL), fibrinogen, and D-dimer levels. Patients with AFP positive had higher white blood cells (WBC), neutrophil, monocyte, and platelet count and neutrophil to lymphocyte ratio (NLR). Conclusions The are significant differences in clinical pathologic characteristics between AFP positive and negative HCC patients which may be helpful for the management and prognostication of the disease. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-022-02279-w.
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14
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Urinary BA Indices as Prognostic Biomarkers for Complications Associated with Liver Diseases. Int J Hepatol 2022; 2022:5473752. [PMID: 35402050 PMCID: PMC8986411 DOI: 10.1155/2022/5473752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 02/25/2022] [Indexed: 11/17/2022] Open
Abstract
Hepatobiliary diseases and their complications cause the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues, which may exacerbate the underlying condition and lead to unfavorable prognosis. To develop and validate prognostic biomarkers for the prediction of complications of cholestatic liver disease based on urinary BA indices, liquid chromatography-tandem mass spectrometry was used to analyze urine samples from 257 patients with cholestatic liver diseases during a 7-year follow-up period. The urinary BA profile and non-BA parameters were monitored, and logistic regression models were used to predict the prognosis of hepatobiliary disease-related complications. Urinary BA indices were applied to quantify the composition, metabolism, hydrophilicity, and toxicity of the BA profile. We have developed and validated the bile-acid liver disease complication (BALDC) model based on BA indices using logistic regression model, to predict the prognosis of cholestatic liver disease complications including ascites. The mixed BA and non-BA model was the most accurate and provided higher area under the receiver operating characteristic (ROC) and smaller akaike information criterion (AIC) values compared to both non-BA and MELD (models for end stage liver disease) models. Therefore, the mixed BA and non-BA model could be used to predict the development of ascites in patients diagnosed with liver disease at early stages of intervention. This will help physicians to make a better decision when treating hepatobiliary disease-related ascites.
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15
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de Castro T, Jochheim LS, Bathon M, Welland S, Scheiner B, Shmanko K, Roessler D, Ben Khaled N, Jeschke M, Ludwig JM, Marquardt JU, Weinmann A, Pinter M, Lange CM, Vogel A, Saborowski A. Atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma with impaired liver function and prior systemic therapy: a real-world experience. Ther Adv Med Oncol 2022; 14:17588359221080298. [PMID: 35251317 PMCID: PMC8891886 DOI: 10.1177/17588359221080298] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 01/28/2022] [Indexed: 12/13/2022] Open
Abstract
Objective Evaluation of the efficacy and safety of atezolizumab/bevacizumab in a real-world HCC cohort, including patients with impaired liver function and prior systemic therapy. Methods Retrospective analysis of 147 HCC patients treated with atezolizumab/bevacizumab at six sites in Germany and Austria. Results The overall response rate and disease control rate were 20.4% and 51.7%, respectively. Seventy-three patients (49.7%) met at least one major exclusion criterion of the IMbrave150 trial (IMbrave-OUT), whereas 74 patients (50.3%) were eligible (IMbrave-IN). Median overall survival (mOS) as well as median progression-free survival (mPFS) was significantly longer in IMbrave-IN versus IMbrave-OUT patients [mOS: 15.0 months (95% confidence interval (CI): 10.7-19.3] versus 6.0 months (95% CI: 3.2-8.9; p < 0.001) and mPFS: 8.7 months (95% CI: 5.9-11.5) versus 3.7 months (95% CI: 2.7-4.7; p < 0.001)]. Prior systemic treatment did not significantly affect mOS [hazard ratio (HR): 1.32 (95% CI: 0.78-2.23; p = 0.305)]. mOS according to ALBI grades 1/2/3 were 15.0 months (95% CI: not estimable), 8.6 months (95% CI: 5.4-11.7), and 3.2 months (95% CI: 0.3-6.1), respectively. ALBI grade and ECOG score were identified as independent prognostic factors [ALBI grade 2 versus 1; HR: 2.40 (95% CI: 1.34 - 4.30; p = 0.003), ALBI grade 3 versus 1; HR: 7.28 (95% CI: 3.30-16.08; p < 0.001), and ECOG ⩾2 versus 0; HR: 2.09 (95% CI: 1.03 - 4.23; p = 0.042)], respectively. Sixty-seven patients (45.6%) experienced an adverse event classified as CTCAE grade ⩾3. Patients in the IMbrave-OUT group were at increased risk of hepatic decompensation with encephalopathy (13.7% versus 1.4%, p = 0.004) and/or ascites (39.7% versus 9.5%; p < 0.001). Conclusion In this real-world cohort, efficacy was comparable to the results of the IMbrave150 study and not affected by prior systemic treatment. ALBI grade and ECOG score were independently associated with survival. IMbrave-OUT patients were more likely to experience hepatic decompensation.
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Affiliation(s)
- Tiago de Castro
- Department of Gastroenterology, Hepatology and
Endocrinology, Hannover Medical School, Hannover, Germany
| | - Leonie S. Jochheim
- Department of Gastroenterology and Hepatology,
Essen University Hospital, Essen, Germany
| | - Melanie Bathon
- Department of Gastroenterology, Hepatology and
Endocrinology, Hannover Medical School, Hannover, Germany
| | - Sabrina Welland
- Department of Gastroenterology, Hepatology and
Endocrinology, Hannover Medical School, Hannover, Germany
| | - Bernhard Scheiner
- Division of Gastroenterology & Hepatology,
Department of Internal Medicine III, Medical University of Vienna, Vienna,
Austria
| | - Kateryna Shmanko
- Department of Internal Medicine I, University
Medical Center of the Johannes Gutenberg University Mainz, Mainz,
Germany
| | - Daniel Roessler
- Department of Medicine II, University Hospital
of the Ludwig-Maximilians-University Munich, Munich, Germany
| | - Najib Ben Khaled
- Department of Medicine II, University Hospital
of the Ludwig-Maximilians-University Munich, Munich, Germany
| | - Matthias Jeschke
- Department of Gastroenterology and Hepatology,
Essen University Hospital, Essen, Germany
| | - Johannes M. Ludwig
- Institute of Diagnostic and Interventional
Radiology and Neuroradiology, Faculty of Medicine, Essen University
Hospital, Essen, Germany
| | - Jens U. Marquardt
- Department of Medicine I, University Hospital
Schleswig-Holstein, Lübeck, Germany
| | - Arndt Weinmann
- Department of Internal Medicine I, University
Medical Center of the Johannes Gutenberg University Mainz, Mainz,
Germany
| | - Matthias Pinter
- Division of Gastroenterology & Hepatology,
Department of Internal Medicine III, Medical University of Vienna, Vienna,
Austria
| | - Christian M. Lange
- Department of Gastroenterology and Hepatology,
Essen University Hospital, Essen, Germany
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology and
Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625
Hannover, Germany
| | - Anna Saborowski
- Department of Gastroenterology, Hepatology and
Endocrinology, Hannover Medical School, Hannover, Germany
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Ho SY, Liu PH, Hsu CY, Huang YH, Liao JI, Su CW, Hou MC, Huo TI. A New Tumor Burden Score and Albumin-Bilirubin Grade-Based Prognostic Model for Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:649. [PMID: 35158917 PMCID: PMC8833827 DOI: 10.3390/cancers14030649] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 01/20/2022] [Accepted: 01/24/2022] [Indexed: 02/08/2023] Open
Abstract
The prognosis of hepatocellular carcinoma (HCC) varies widely due to variable tumor extent and liver reserve. We aimed to develop and validate a new prognostic model based on tumor burden score (TBS) and albumin-bilirubin (ALBI) grade for HCC. We prospectively identified 3794 HCC patients who were randomized into derivation and validation groups. Survival predictors were evaluated by a multivariate Cox model. The TBS-ALBI system allocated two points for high TBS and ALBI grade 3, and one point each for the presence of ascites, serum α-fetoprotein ≥ 400 ng/mL, vascular invasion or distant metastasis, performance status 2-4, medium TBS, and ALBI grade 2, with a maximal score of 8 points. Significant survival differences were found across different TBS-ALBI score groups in the validation cohort (all p < 0.001). The TBS-ALBI system had the lowest corrected Akaike information criterion (AICc) and the highest homogeneity compared with other proposed staging models. The discriminative ability of the TBS-ALBI system was consistently stable across different viral etiologies, cancer stages, and treatment strategies. Conclusions: This new TBS-ALBI system is a feasible and robust prognostic system in comparison with other systems; it is a user-friendly tool for long-term outcome assessment independent of treatment modality and cancer stage in HCC.
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Affiliation(s)
- Shu-Yein Ho
- Division of Gastroenterology and Hepatology, Min-Sheng General Hospital, Taoyuan 330, Taiwan;
- Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan; (P.-H.L.); (C.-Y.H.); (Y.-H.H.); (J.-I.L.); (C.-W.S.); (M.-C.H.)
| | - Po-Hong Liu
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan; (P.-H.L.); (C.-Y.H.); (Y.-H.H.); (J.-I.L.); (C.-W.S.); (M.-C.H.)
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Chia-Yang Hsu
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan; (P.-H.L.); (C.-Y.H.); (Y.-H.H.); (J.-I.L.); (C.-W.S.); (M.-C.H.)
- Veterans Affairs Sierra Nevada Healthcare System, Reno, NV 89502, USA
| | - Yi-Hsiang Huang
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan; (P.-H.L.); (C.-Y.H.); (Y.-H.H.); (J.-I.L.); (C.-W.S.); (M.-C.H.)
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan
| | - Jia-I Liao
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan; (P.-H.L.); (C.-Y.H.); (Y.-H.H.); (J.-I.L.); (C.-W.S.); (M.-C.H.)
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
| | - Chien-Wei Su
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan; (P.-H.L.); (C.-Y.H.); (Y.-H.H.); (J.-I.L.); (C.-W.S.); (M.-C.H.)
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
| | - Ming-Chih Hou
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan; (P.-H.L.); (C.-Y.H.); (Y.-H.H.); (J.-I.L.); (C.-W.S.); (M.-C.H.)
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
| | - Teh-Ia Huo
- Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan; (P.-H.L.); (C.-Y.H.); (Y.-H.H.); (J.-I.L.); (C.-W.S.); (M.-C.H.)
- Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan
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17
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Sidali S, Nault JC. Portal hypertension and hepatocellular carcinoma: Navigating uncharted waters. United European Gastroenterol J 2022; 10:8-9. [PMID: 34997990 PMCID: PMC8830280 DOI: 10.1002/ueg2.12193] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Affiliation(s)
- Sabrina Sidali
- Université de Paris, Assistance-Publique Hôpitaux de Paris, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Clichy, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, Team Functional Genomics of Solid Tumors, Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
| | - Jean-Charles Nault
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, Team Functional Genomics of Solid Tumors, Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France.,Liver Unit, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France.,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France
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18
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Briones-Orta MA, Delgado-Coello B, Gutiérrez-Vidal R, Sosa-Garrocho M, Macías-Silva M, Mas-Oliva J. Quantitative Expression of Key Cancer Markers in the AS-30D Hepatocarcinoma Model. Front Oncol 2021; 11:670292. [PMID: 34737944 PMCID: PMC8561839 DOI: 10.3389/fonc.2021.670292] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 09/14/2021] [Indexed: 11/13/2022] Open
Abstract
Hepatocellular carcinoma is one of the cancers with the highest mortality rate worldwide. HCC is often diagnosed when the disease is already in an advanced stage, making the discovery and implementation of biomarkers for the disease a critical aim in cancer research. In this study, we aim to quantify the transcript levels of key signaling molecules relevant to different pathways known to participate in tumorigenesis, with special emphasis on those related to cancer hallmarks and epithelial-mesenchymal transition, using as a model the murine transplantable hepatocarcinoma AS-30D. Using qPCR to quantify the mRNA levels of genes involved in tumorigenesis, we found elevated levels for Tgfb1 and Spp1, two master regulators of EMT. A mesenchymal signature profile for AS-30D cells is also supported by the overexpression of genes encoding for molecules known to be associated to aggressiveness and metastatic phenotypes such as Foxm1, C-met, and Inppl1. This study supports the use of the AS-30D cells as an efficient and cost-effective model to study gene expression changes in HCC, especially those associated with the EMT process.
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Affiliation(s)
- Marco A Briones-Orta
- Department of Infectious Disease, Imperial College London, London, United Kingdom
| | - Blanca Delgado-Coello
- Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Roxana Gutiérrez-Vidal
- Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Marcela Sosa-Garrocho
- Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Marina Macías-Silva
- Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Jaime Mas-Oliva
- Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
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19
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Lu HL, Xuan FF, Luo YC, Qin X. Efficacy and safety of transjugular intrahepatic portosystemic shunt combined with transcatheter embolization/chemoembolization in hepatocellular carcinoma with portal hypertension and arterioportal shunt. Abdom Radiol (NY) 2021; 46:5417-5427. [PMID: 34302511 DOI: 10.1007/s00261-021-03214-5] [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: 03/16/2021] [Revised: 07/11/2021] [Accepted: 07/12/2021] [Indexed: 11/09/2022]
Abstract
OBJECTIVES This study seeks to assess the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with transarterial embolization/transarterial chemoembolization (TAE/TACE) in hepatocellular carcinoma (HCC) with portal hypertension and arterioportal shunt (APS). METHODS Consecutive hospitalized patients having HCC accompanied by portal hypertension and APS were retrospectively analyzed. A total of 103 patients were enrolled. Of them, 26 patients were in Group A and 77 patients were in Group B according to the treatment protocol (Group A: TIPS plus TAE/TACE; Group B: TAE/TACE alone). The clinical outcomes and survival rate were compared between the two groups. RESULTS The mean survival time in Group A and Group B were 14 mo and 9.9 mo, respectively, with statistical difference (p = 0.043). The immediate APS improvement rate was 95.2% in Group A and 91.9% in Group B, respectively, with no signficant difference (p = 1.000). However, the first follow-up consultation revealed that APS improvement rate in Group A was more obvious (66.7% vs 27.4%, p = 0.001). Objective response rate of HCC tended to be greater in Group A compared with Group B (65.4% vs 38.7%, p = 0.019). Liver function parameters significantly increased in Group A than those in Group B. After TIPS placement, the mean portal pressure gradient decreased from 32.61 ± 8.87 mmHg to 15.61 ± 8.15 mmHg, with significant difference (p = 0.000). The rate of absorption of ascites and control of variceal bleeding were statistically different between the two groups (p = 0.045 and 0.039, respectively). CONCLUSION Our research suggests that TIPS combined with TAE/TACE seems to be safe and efficacious in patients with HCC accompanied by portal hypertension and APS, albeit may be accompanied by liver function damage.
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20
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Yang SW, Chen WL, Wu WT, Wang CC. Investigation on returning to work in liver cancer survivors in Taiwan: a 5-year follow-up study. BMC Public Health 2021; 21:1846. [PMID: 34641825 PMCID: PMC8507177 DOI: 10.1186/s12889-021-11872-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 09/28/2021] [Indexed: 12/09/2022] Open
Abstract
BACKGROUND Primary liver cancer is the fifth most common malignancy and limits patients' quality of life and working ability. Return to work after cancer treatment is an important step in social recovery. In addition, return to work represents the recovery of financial ability and improvements in self-confidence. The purpose of this article is to discuss the relationship between return to work and various covariables in workers with liver cancer. METHODS The national registry cohort study collected adult workers newly diagnosed with liver cancer from 2004 to 2010 in Taiwan. There were 2451 workers included in our study. Primary liver cancer was diagnosed by using the International Classification of Diseases for Oncology code. Return to work after liver cancer survival was determined as returning to the same work or reemployment within five years after cancer diagnosis. The associations between independent variables and return to work were analyzed by Cox proportional hazard models. RESULTS Workers who underwent surgery were more likely to return to work not only in the 2nd year but also in the 5th year. A lower survival rate was noted in the non-return-to-work group (p < 0.001) among all patients with liver cancer. The completely adjusted model identified that the rate of return to work was related to all-cause mortality with a hazard ratio of 0.244 (95% Confidence Intervals: 0.235-0.253). CONCLUSIONS Our study indicated the impacts of treatment on the return to work of liver cancer survivors. In addition, in patient with liver cancer, return to work had positive effect on the survival rate.
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Affiliation(s)
- Shih-Wei Yang
- Department of Orthopedic, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Department of General Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Wei-Liang Chen
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Wei-Te Wu
- National Institute of Environmental Health Science, National Health Research Institutes, Miaoli, Taiwan, Republic of China
| | - Chung-Ching Wang
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China. .,Division of Environmental Health & Occupational Medicine, Department of Family & Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
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21
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Allaire M, Rudler M, Thabut D. Portal hypertension and hepatocellular carcinoma: Des liaisons dangereuses…. Liver Int 2021; 41:1734-1743. [PMID: 34051060 DOI: 10.1111/liv.14977] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 05/17/2021] [Accepted: 05/24/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS Portal hypertension (PHT) and hepatocellular carcinoma (HCC) are major complication of cirrhosis which significantly contribute to morbidity and mortality. In this review, we aim to describe the consequences of both angiogenesis and inflammation in the pathogenesis of PHT and HCC, but also the difficulty to propose adapted treatment when PHT and HCC coexist in the same patients. METHODS Studies for review in this article were retrieved from the PubMed database using literature published in English until March 2021. RESULTS Portal hypertension occurs secondary to an increase of intrahepatic vascular resistances, the opening of portosystemic collateral vessels and the formation of neovessels, related to vascular endothelial growth factor (VEGF). Recently, bacterial translocation-mediated inflammation was also identified as a major contributor to PHT. Interestingly, VEGF and chronic inflammation also contribute to HCC occurrence. As PHT and HCC often coexist in the same patient, management of PHT and its related complications as well as HCC treatment appear more complex. Indeed, PHT-related complications such as significant ascites may hamper the access to HCC treatment and the presence of HCC is also independently associated with poor prognosis in patients with acute variceal bleeding related to PHT. Due to their respective mechanism of action, the combination of Atezolizumab and Bevacizumab for advanced HCC may impact the level of PHT and its related complications and to date, no real-life data are available. CONSLUSIONS Appropriate evaluation and treatment of PHT remains a major issue in order to improve the outcome of HCC patients.
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Affiliation(s)
- Manon Allaire
- Service d'Hépatolo-gastroentérologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Sorbonne Université, Paris, France.,Inserm U1149, Centre de Recherche sur l'Inflammation, France Faculté de Médecine Xavier Bichat, Université Paris Diderot, Paris, France
| | - Marika Rudler
- Service d'Hépatolo-gastroentérologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Sorbonne Université, Paris, France.,INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, France
| | - Dominique Thabut
- Service d'Hépatolo-gastroentérologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Sorbonne Université, Paris, France.,INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, France
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22
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Kudo M, Ikeda M, Galle PR, Yamashita T, Finn RS, Liang K, Wang C, Sakaguchi S, Abada P, Widau RC, Zhu AX. Ramucirumab in patients with advanced hepatocellular carcinoma and elevated α-fetoprotein: Outcomes by treatment-emergent ascites. Hepatol Res 2021; 51:715-721. [PMID: 33743189 DOI: 10.1111/hepr.13638] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 02/17/2021] [Accepted: 03/12/2021] [Indexed: 12/30/2022]
Abstract
AIM The REACH and REACH-2 trials investigated ramucirumab versus placebo in patients with advanced hepatocellular carcinoma (HCC). Ascites is common in HCC and is associated with poorer outcomes. This exploratory, pooled meta-analysis of patients with baseline α-fetoprotein (AFP) ≥400 ng/ml investigated outcomes by treatment-emergent (TE) ascites in REACH and REACH-2. METHODS A pooled meta-analysis of independent patient data for participants (N = 542) with baseline AFP ≥400 ng/ml (stratified by study) from REACH and REACH-2 was carried out. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier estimator, and OS further assessed by Cox models. The effect of TE ascites on OS was evaluated by multivariate Cox models. RESULTS Treatment-emergent ascites developed in 66 patients (20.9%) in the ramucirumab group and 33 patients (14.8%) in the placebo group. When adjusted for treatment duration, the incidence rates per 100 patient-years of any grade TE ascites were 59.1 and 71.9 for the ramucirumab and placebo groups, respectively, and the incidence of grade ≥3 TE ascites were 13.4 and 19.6, respectively. Treatment-emergent ascites was associated with TE hypoalbuminemia (odds ratio 4.9; 95% confidence interval 2.5-9.3), but not TE proteinuria or hypertension. One patient discontinued ramucirumab treatment due to TE ascites. Ramucirumab treatment improved OS and PFS compared with placebo, irrespective of TE ascites. CONCLUSIONS When adjusted for treatment duration, the incidence of TE ascites was no higher in patients who received ramucirumab than in those who received placebo. Ramucirumab was well tolerated and provided a survival benefit irrespective of the development of TE ascites.
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Affiliation(s)
| | | | - Peter R Galle
- Medizinische Klinik und Poliklinik, Universitätsmedizin, Mainz, Germany
| | | | - Richard S Finn
- University of California, Los Angeles Medical Center, Los Angeles, California, USA
| | - Kun Liang
- Eli Lilly and Company, Indianapolis, Indiana, USA
| | | | | | - Paolo Abada
- Eli Lilly and Company, Indianapolis, Indiana, USA
| | - Ryan C Widau
- Eli Lilly and Company, Indianapolis, Indiana, USA
| | - Andrew X Zhu
- Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.,Jiahui International Cancer Center, Jiahui Health, Shanghai, China
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23
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Ho SY, Hsu CY, Liu PH, Lee RC, Ko CC, Huang YH, Su CW, Hou MC, Huo TI. Albumin-Bilirubin (ALBI) Grade-Based Nomogram for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization. Dig Dis Sci 2021; 66:1730-1738. [PMID: 32548811 DOI: 10.1007/s10620-020-06384-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 06/01/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND/AIM The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is highly heterogeneous because of variable characteristics of tumor burden and liver dysfunction. We aimed to propose and validate an albumin-bilirubin (ALBI) grade-based prognostic nomogram for HCC patients undergoing TACE. METHODS A total of 1051 patients with HCC undergoing TACE were randomly assigned to derivation (n = 525) and validation (n = 526) set in this retrospective study based on prospective data. The multivariate Cox proportional hazards model in derivation set was used to generate the nomogram. The predictive accuracy of the nomogram was evaluated by discrimination and calibration tests. RESULTS In multivariate analysis, presence of ascites, ALBI grade 2-3, serum ɑ-fetoprotein level ≥ 400 ng/mL, total tumor volume ≥ 396 cm3, presence of vascular invasion, and poor performance status were independently associated with decreased survival of patients in the derivation set. Each patient had an individualized score from 0 to 41 by adding up the points from these six prognostic predictors. The nomogram generated from the derivation set had a concordance index of 0.72 (95% confidence interval [CI] 0.63-0.82). Discrimination test in the validation set provided a good concordance index 0.72 (95% CI 0.62-0.81), and the calibration plots consistently matched the ideal 45-degree reference line for 3- and 5-year survival prediction. CONCLUSIONS The ALBI grade-based prognostic model can well discriminate the survival in HCC patients undergoing TACE. The proposed easy-to-use nomogram may accurately predict the survival at 3 and 5 years for individual HCC patient in the precision medicine era.
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Affiliation(s)
- Shu-Yein Ho
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chia-Yang Hsu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Po-Hong Liu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chih-Chieh Ko
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chien-Wei Su
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ming-Chih Hou
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Teh-Ia Huo
- Department of Medical Research, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Taipei, 11217, Taiwan. .,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan. .,Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
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24
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Zhou D, Liu X, Wang X, Yan F, Wang P, Yan H, Jiang Y, Yang Z. A prognostic nomogram based on LASSO Cox regression in patients with alpha-fetoprotein-negative hepatocellular carcinoma following non-surgical therapy. BMC Cancer 2021; 21:246. [PMID: 33685417 PMCID: PMC7938545 DOI: 10.1186/s12885-021-07916-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Accepted: 02/15/2021] [Indexed: 12/14/2022] Open
Abstract
Background Alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (< 8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of patients with AFP-NHCC. Methods A total of 410 AFP-negative patients with clinical diagnosed with HCC following non-surgical therapy as a primary cohort; 148 patients with AFP-NHCC following non-surgical therapy as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by Forward Stepwise Cox regression were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort. Results The C-index of nomogram1was 0.708 (95%CI: 0.673–0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606–0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690–0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691–0.813; AUC: 0.784, 95%CI: 0.709–0.847). The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively. Conclusions Novel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-NHCC following non-surgical therapy. This model could help patients with AFP-NHCC following non-surgical therapy facilitate a personalized prognostic evaluation.
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Affiliation(s)
- Dongdong Zhou
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Xiaoli Liu
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Xinhui Wang
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Fengna Yan
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Peng Wang
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Huiwen Yan
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China.,First Clinical Medical College, Beijing University of Chinese Medicine, Chaoyang District, Beijing, 100029, People's Republic of China
| | - Yuyong Jiang
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Zhiyun Yang
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China.
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25
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Antitumor and immunomodulatory effects of a novel multitarget inhibitor, CS2164, in mouse hepatocellular carcinoma models. Anticancer Drugs 2020; 30:909-916. [PMID: 30998512 PMCID: PMC6749973 DOI: 10.1097/cad.0000000000000791] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
As a novel orally active multitarget small molecule inhibitor, CS2164 has shown broad antitumor activities against several human tumor xenograft models in immune-compromised mice. However, the ability of CS2164 to modulate antitumor immunity in an immune-competent mouse tumor model remains undefined, although antiangiogenic treatment has been reported to affect immune cell infiltration and remodel the tumor immune microenvironment. In the present study, the subcutaneous and ascites hepatocellular carcinoma (HCC) models in syngeneic Balb/c mice established by inoculation of an H22 hepatoma cell line were utilized to investigate the antitumor and immunomodulatory effects of CS2164. Although the antitumor effects of CS2164 were validated in both subcutaneous and ascites HCC models in syngeneic mice, CS2164 treatment consistently modulated immune cell populations, both in the periphery and in tumor microenvironments, with upregulation of CD4+ and CD8+ T cells in the spleen, but downregulation of immunosuppressive populations including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages in the spleen and tumor tissues. Furthermore, CS2164 increased the relative gene expression and protein production of several proinflammatory cytokines in tumor-related ascites. These results indicate that CS2164 exerts an antitumor effect associated with its immunomodulatory activities in mouse HCC models, and may also provide evidence for the immunotherapy potentiation of CS2164 in future cancer treatment.
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26
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Survival of Patients with Hepatocellular Carcinoma in Renal Insufficiency: Prognostic Role of Albumin-Bilirubin Grade. Cancers (Basel) 2020; 12:cancers12051130. [PMID: 32366000 PMCID: PMC7281166 DOI: 10.3390/cancers12051130] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 04/22/2020] [Accepted: 04/28/2020] [Indexed: 02/08/2023] Open
Abstract
Renal insufficiency (RI) is commonly seen in patients with hepatocellular carcinoma (HCC). The prognostic role of albumin-bilirubin (ALBI) grade in this special setting is unclear. We aimed to investigate the role of ALBI grade associated with the impact of RI on HCC. A prospective cohort of 3690 HCC patients between 2002 and 2016 were retrospectively analyzed. The Kaplan-Meier method and multivariate Cox proportional hazards model were used to determine survival and independent prognostic predictors. Of all patients, RI was an independent predictor associated with decreased survival. In multivariate Cox analysis for patients with RI, α-fetoprotein level ≥20 ng/mL, tumor size >3 cm, vascular invasion, distant metastasis, presence of ascites, performance status 1-2, performance status 3-4, and ALBI grade 2 and grade 3 were independent predictors of decreased survival (all p < 0.05). In subgroup analysis of patients with RI undergoing curative and non-curative treatments, the ALBI grade remained a significant prognostic predictor associated with decreased survival (p < 0.001). In summary, HCC patients with RI have decreased survival compared to those without RI. The ALBI grade can discriminate the survival in patients with RI independent of treatment strategy and is a feasible prognostic tool in this special patient population.
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Ho SY, Liu PH, Hsu CY, Hsia CY, Su CW, Huang YH, Lei HJ, He YJ, Hou MC, Huo TI. An Albumin-Bilirubin (ALBI) Grade-based Prognostic Model For Patients With Hepatocellular Carcinoma Within Milan Criteria. Am J Clin Oncol 2020; 42:698-704. [PMID: 31335351 DOI: 10.1097/coc.0000000000000581] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE The Milan criteria are recommended as the major reference for liver transplantation in patients with small hepatocellular carcinoma (HCC). However, alternative anticancer treatments are often utilized due to severe donor organ shortage. This study aimed to develop and validate an albumin-bilirubin (ALBI) grade-based prognostic model to stratify survival in patients within Milan criteria undergoing nontransplant therapy. PATIENTS AND METHODS A total of 1655 patients were assigned into the derivation and validation cohort according to treatment modalities. Multivariate analysis was used to identify independent predictors of survival in the derivation cohort. An ALBI-based model was evaluated in the validation cohort. RESULTS In the Cox multivariate model, age 65 years or older (hazard ratio [HR]=1.576, P<0.001), serum α-fetoprotein (AFP) level >100 ng/mL (HR=1.671, P<0.001), ascites (HR=1.808, P<0.001), performance status 1 to 4 (HR=1.738, P<0.001), ALBI grade 2 (HR=1.827, P<0.001), and ALBI grade 3 (HR=3.589, P<0.001) were independent predictors of poor survival in the derivation cohort. An ALBI-based prognostic model with a total of 0 to 6 points was derived with the sum of 5 variables: 1 point each for age 65 years or older, AFP >100 ng/mL, presence of ascites, performance status 1 to 4, and ALBI grade 2, and 2 points for ALBI grade 3. This model can accurately predict long-term outcome in the validation cohort (P<0.001) and discriminate survival in patients stratified by curative and noncurative treatments (both P<0.001). CONCLUSION The proposed ALBI grade-based model is feasible in predicting survival in HCC patients within the Milan criteria, and helps identify high-risk patients who need timely liver transplantation.
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Affiliation(s)
- Shu-Yein Ho
- Departments of Medicine.,Faculty of Medicine
| | - Po-Hong Liu
- Faculty of Medicine.,Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
| | - Chia-Yang Hsu
- Faculty of Medicine.,Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | | | | | - Yi-Hsiang Huang
- Departments of Medicine.,Faculty of Medicine.,Institute of Clinical Medicine
| | | | | | | | - Teh-Ia Huo
- Faculty of Medicine.,Medical Research, Taipei Veterans General Hospital.,Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
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Li Q, Lyu Z, Wang L, Li F, Yang Z, Ren W. Albumin-to-Alkaline Phosphatase Ratio Associates with Good Prognosis of Hepatitis B Virus-Positive HCC Patients. Onco Targets Ther 2020; 13:2377-2384. [PMID: 32256088 PMCID: PMC7093105 DOI: 10.2147/ott.s242034] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 02/26/2020] [Indexed: 12/13/2022] Open
Abstract
Purpose The aim of this study was to investigate the prognostic significance of preoperative AAPR in hepatitis B virus-related hepatocellular carcinoma patients after curative hepatectomy. Patients and Methods A total of 221 patients with hepatitis B virus-related HCC patients who received curative liver resection were included. After propensity matching analysis, 188 patients were enrolled in the final analysis. COX regression analyses were used to analyze the prognosis value of AAPR and other prognostic factors. The overall survival (OS) and recurrence-free survival (RFS) curves were constructed and compared between different groups. Results The optimal cutoff of AAPR was defined as 0.40 with X-tile software. According to cutoff value, patients were divided into low-AAPR group (≤0.40) and high-AAPR group (>0.40). The cumulative 1-, 3-, and 5-year OS rates were 97.1%, 78.2%, and 67.3% in patients with AAPR>0.40 group, respectively, which were significantly higher than those in the AAPR≤0.40 group (80.2%, 54.4%, and 40.1%, respectively) (P <0.001). In the multivariate COX regression analysis, AAPR, tumor number, ascites, and portal vein tumor thrombus (PVTT) were independent risk factors for OS and RFS. Conclusion AAPR shows promise as a reliable prognostic factor in patients with hepatitis B virus-related HCC after curative hepatectomy, which could be used as a routine inspection of HCC patients before surgery.
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Affiliation(s)
- Qun Li
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, People's Republic of China
| | - Zhuozhen Lyu
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, People's Republic of China
| | - Liguang Wang
- Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, People's Republic of China
| | - Feifei Li
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, People's Republic of China
| | - Zhen Yang
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, People's Republic of China
| | - Wanhua Ren
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, People's Republic of China
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Ho SY, Liu PH, Hsu CY, Hsia CY, Huang YH, Su CW, Lei HJ, Lee RC, Hou MC, Huo TI. A New Prognostic Model Based on Albumin-Bilirubin Grade for Hepatocellular Carcinoma Beyond the Milan Criteria. Dig Dis Sci 2020; 65:658-667. [PMID: 31659612 DOI: 10.1007/s10620-019-05813-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 08/20/2019] [Indexed: 12/26/2022]
Abstract
BACKGROUND The survival of patients with advanced hepatocellular carcinoma (HCC) is highly variable due to heterogeneous tumoral characteristics. We proposed and validated an albumin-bilirubin (ALBI)-based model for HCC beyond Milan criteria, the ALBI-HOME, for these patients. METHODS A total of 2186 patients were enrolled and randomly assigned to the derivation cohort (n = 1093) and validation cohort (n = 1093). Multivariate Cox proportional hazards model was used to determine significant prognostic factors in the derivation cohort. The performance of ALBI-HOME was evaluated in the validation cohort. RESULTS In the Cox model, six factors were identified as independent predictors of poor survival: ALBI grade 2 [hazard ratio (HR) 1.848, 95% confidence incidence (CI) 1.556-2.195, p < 0.001], ALBI grade 3 (HR 3.266, 95% CI 2.531-4.215, p < 0.001), serum AFP ≥ 100 ng/ml (HR 1.482, 95% CI 1.279-1.717, p < 0.001), total tumor volume ≥ 250 cm3 (HR 1.503, 95% CI 1.294-1.746, p < 0.001), ascites (HR 1.400, 95% CI 1.187-1.561, p < 0.001), performance status 0-1 (HR 1.756, 95% CI 1.485-2.076 p < 0.001), and vascular invasion or metastasis (HR 2.110, 95% CI 1.809-2.0, p < 0.001). The ALBI-HOME is based on these six parameters, and the score ranges from 0 to 7. This model was associated with the best prognostic ability among different HCC staging systems to predict survival in patients beyond Milan criteria; its ability remained consistently stable in different treatment subgroups and viral etiologies. CONCLUSIONS The proposed ALBI-HOME is a simple and feasible predictive model for HCC beyond Milan criteria. It demonstrates superior prognostic performance among the currently used staging systems and may help identify at-risk patients to undergo more aggressive treatments.
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Affiliation(s)
- Shu-Yein Ho
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Po-Hong Liu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Chia-Yang Hsu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Cheng-Yuan Hsia
- Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chien-Wei Su
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Hao-Jan Lei
- Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ming-Chih Hou
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Teh-Ia Huo
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
- Department of Medical Research, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Taipei, 11217, Taiwan.
- Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
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Zhang Q, He Y, Luo N, Patel SJ, Han Y, Gao R, Modak M, Carotta S, Haslinger C, Kind D, Peet GW, Zhong G, Lu S, Zhu W, Mao Y, Xiao M, Bergmann M, Hu X, Kerkar SP, Vogt AB, Pflanz S, Liu K, Peng J, Ren X, Zhang Z. Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma. Cell 2019; 179:829-845.e20. [PMID: 31675496 DOI: 10.1016/j.cell.2019.10.003] [Citation(s) in RCA: 976] [Impact Index Per Article: 162.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 06/14/2019] [Accepted: 10/03/2019] [Indexed: 02/08/2023]
Abstract
The immune microenvironment of hepatocellular carcinoma (HCC) is poorly characterized. Combining two single-cell RNA sequencing technologies, we produced transcriptomes of CD45+ immune cells for HCC patients from five immune-relevant sites: tumor, adjacent liver, hepatic lymph node (LN), blood, and ascites. A cluster of LAMP3+ dendritic cells (DCs) appeared to be the mature form of conventional DCs and possessed the potential to migrate from tumors to LNs. LAMP3+ DCs also expressed diverse immune-relevant ligands and exhibited potential to regulate multiple subtypes of lymphocytes. Of the macrophages in tumors that exhibited distinct transcriptional states, tumor-associated macrophages (TAMs) were associated with poor prognosis, and we established the inflammatory role of SLC40A1 and GPNMB in these cells. Further, myeloid and lymphoid cells in ascites were predominantly linked to tumor and blood origins, respectively. The dynamic properties of diverse CD45+ cell types revealed by this study add new dimensions to the immune landscape of HCC.
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Affiliation(s)
- Qiming Zhang
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China
| | - Yao He
- Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
| | - Nan Luo
- Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Ninth School of Clinical Medicine, Peking University, Beijing 100038, China
| | - Shashank J Patel
- Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA
| | - Yanjie Han
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China
| | - Ranran Gao
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China
| | - Madhura Modak
- Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharma, Birkendorfer Str. 65, 88400 Biberach, Germany
| | - Sebastian Carotta
- Department of Cancer Cell Signaling, Boehringer Ingelheim RCV GmBH & Co KG., Dr. Boehringer Gasse 5-11, 1120 Vienna, Austria
| | - Christian Haslinger
- Department of Computational Biology and Genomics, Boehringer Ingelheim Pharma, Birkendorfer Str. 65, 88400 Biberach, Germany
| | - David Kind
- Department of Computational Biology and Genomics, Boehringer Ingelheim Pharma, Birkendorfer Str. 65, 88400 Biberach, Germany
| | - Gregory W Peet
- Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA
| | - Guojie Zhong
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China
| | - Shuangjia Lu
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China
| | - Weihua Zhu
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College Hospital, Beijing 100730, China
| | - Mengmeng Xiao
- Department of Retroperitoneal Tumor Surgery, Peking University International Hospital, Beijing 102206, China
| | - Michael Bergmann
- Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Xueda Hu
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China
| | - Sid P Kerkar
- Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA
| | - Anne B Vogt
- Department of Human Cancer Immunology, Boehringer Ingelheim RCV GmBH & Co KG., Dr. Boehringer Gasse 5-11, 1120 Vienna, Austria
| | - Stefan Pflanz
- Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharma, Birkendorfer Str. 65, 88400 Biberach, Germany
| | - Kang Liu
- Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
| | - Jirun Peng
- Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Ninth School of Clinical Medicine, Peking University, Beijing 100038, China.
| | - Xianwen Ren
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China.
| | - Zemin Zhang
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
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Zhang H, Song Y, Li L, Zhang SY, Wu Q, Mei WJ, Liu HM, Wang XC. Phenanthroimidazole derivatives act as potentinducer of autophagy by activating DNA damage pathway. Bioorg Chem 2019; 88:102940. [PMID: 31028991 DOI: 10.1016/j.bioorg.2019.102940] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Revised: 03/21/2019] [Accepted: 04/18/2019] [Indexed: 12/21/2022]
Abstract
A series of imidazo[4,5f][1,10]phenanthroline derivatives (1-6) have been synthesized in this study, and their inhibitory activity was evaluated by MTT assay. Results showed that all of these compounds demonstrate a promising inhibitory activity against a panel of human cancer cell lines. The 6, the most effective compound with IC50 of approximately 2.3 ± 0.1 µM, was against the growth and could induce autophagy of HepG2 cells. This condition was confirmed by abundant autophagic vacuoles appearing in cells and evident ultrastructural changes observed under transmission electron microscopy. The autophage induced by 6 has also been demonstrated by up-regulating LC3-II and Beclin1. The apoptosis and G2/M phase cell cycle arrest through DSB damage have also been confirmed after the HepG2 cells were treated by 6. These multiple effects, especially induction apoptosis and autophagy, indicate the potential of 6 for development as a novel anticancer drug.
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Affiliation(s)
- Hao Zhang
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510006, PR China
| | - Yue Song
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510006, PR China
| | - Li Li
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China; Guangdong Province Engineering Technology Centre for Molecular Probe and Biomedicine Imagining, Guangzhou 510006, PR China
| | - Shuang-Yan Zhang
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China; Guangdong Province Engineering Technology Centre for Molecular Probe and Biomedicine Imagining, Guangzhou 510006, PR China
| | - Qiong Wu
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China; Guangdong Province Engineering Technology Centre for Molecular Probe and Biomedicine Imagining, Guangzhou 510006, PR China.
| | - Wen-Jie Mei
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China; Guangdong Province Engineering Technology Centre for Molecular Probe and Biomedicine Imagining, Guangzhou 510006, PR China; Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model Systems, Guangdong Pharmaceutical University, Guangzhou 510006, China.
| | - Hui-Min Liu
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510006, PR China
| | - Xi-Cheng Wang
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
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Wang XB, Chen J, Xiang BD, Wu FX, Li LQ. High CONUT score predicts poor survival and postoperative HBV reactivation in HBV-related hepatocellular carcinoma patients with low HBV-DNA levels. Eur J Surg Oncol 2018; 45:782-787. [PMID: 30503048 DOI: 10.1016/j.ejso.2018.11.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 10/31/2018] [Accepted: 11/06/2018] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Postoperative hepatitis B virus (HBV) reactivation (PHR) is associated with resection-induced immunosuppression in patients with HBV-related hepatocellular carcinoma (HCC). Controlling Nutritional Status (CONUT) score is an effective index for evaluating immune-nutrition function. However, the value of COUNT in predicting PHR in HBV-HCC patients remains unknown. METHODS Totally, 209 HCC patients were enrolled. RESULTS Preoperative immune function (CD3+CD4+, CD3+CD8+, IgG and IgM) in patients with high CONUT score was significantly worse than that in patients with low CONUT score (P<0.05). Blood test results on postoperative day 7 showed the same trend. In addition, patients with high CONUT score experienced a significantly larger decrease in the proportions of CD3+CD4+ and CD3+CD8+ than those with low CONUT score (P < 0.05). In patients with high CONUT score, the incidence of overall complications was also significantly higher (P = 0.029) and hospital-stay was significantly longer (P = 0.020). Besides, overall survival and recurrence free survival in patients with high CONUT score were significantly worse than those in patients with low CONUT score (48.32 vs. 38.12 months, P<0.001; 36.08 vs. 27.03 months, P = 0.001). The incidence of PHR was significantly higher in patients with high COUNT score (P<0.001), and CONUT score was strongly associated with PHR (P<0.001). Additionally, the fellow subgroup results also demonstrated that COUNT score was more effective in predicting PHR in patients with HBV-DNA level <500 copies/ml than patients with HBV-DNA 500-1000 copies/ml. CONCLUSION CONUT score is an effective indicator predicting survival and PHR in HBV-HCC patients, especially in those with HBV-DNA levels <500 copies/ml.
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Affiliation(s)
- Xiao-Bo Wang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, China
| | - Jie Chen
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, China
| | - Fei-Xiang Wu
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, China.
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Active Treatments Prolong the Survival in Patients With Hepatocellular Carcinoma and Performance Status 3 or 4: A Propensity Score Analysis. J Clin Gastroenterol 2015; 49:878-84. [PMID: 25710525 DOI: 10.1097/mcg.0000000000000300] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
GOALS AND BACKGROUNDS Best supportive care is suggested as the standard treatment for hepatocellular carcinoma (HCC) patients with performance status (PS) 3-4 by the Barcelona Clinic Liver Cancer (BCLC) system. To investigate the rationale of treatment allocation. STUDY A total of 2660 HCC patients were reviewed. One-to-one matched pairs between PS 3 and 4 patients receiving supportive care and anti-HCC treatments were generated by using the propensity score with matching model. The survival analysis was performed with the Kaplan-Meier method and log-rank test. The hazard ratio was calculated with the Cox proportional hazards model. RESULTS Among 328 patients with PS 3-4, 38% of patients received active anti-HCC treatments against the BCLC system. Compared with patients undergoing supportive care, patients receiving anti-HCC treatments more often had milder cirrhosis, smaller tumor burden, and lower serum α-fetoprotein levels (all P<0.05). Patients undergoing supportive care had significantly decreased survival (P<0.0001). With propensity scores, 101 pairs of similar HCC patients with PS 3-4 were selected from different treatment groups. They were comparable in age, sex, etiologies of liver disease, severity of cirrhosis, tumor burden, and prevalence of diabetes mellitus (all P>0.05) at baseline. In the matching model, patients with PS 3-4 undergoing supportive care had significantly shortened survival with an adjusted hazard ratio of 4.711 (confidence interval: 3.041-7.297, P<0.0001). CONCLUSIONS Over one-third of patients with PS 3-4 receive active anti-HCC treatments against the BCLC allocation algorithm in this study. Active anticancer therapies rather than best supportive care should be performed if there is no apparent contraindication.
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Chen C, Chen DP, Gu YY, Hu LH, Wang D, Lin JH, Li ZS, Xu J, Wang G. Vascular invasion in hepatitis B virus-related hepatocellular carcinoma with underlying cirrhosis: possible associations with ascites and hepatitis B viral factors? Tumour Biol 2015; 36:6255-63. [PMID: 25833692 DOI: 10.1007/s13277-015-3311-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Accepted: 03/05/2015] [Indexed: 02/06/2023] Open
Abstract
Vascular invasion is one of the most important prognostic factors for patients with hepatocellular carcinoma (HCC). The objective of the current, retrospective study was to determine the associations of ascites and hepatitis B viral factors (HBeAg and anti-HBe status and HBV DNA levels), as well as tumor-related factors (size, tumor number, grade, and location) with micro- or macroscopic vascular invasion in patients with HCC that developed as a result of hepatitis B virus (HBV)-related cirrhosis. A total of 336 consecutive patients were included. Potential factors associated with micro- or macroscopic vascular invasion were analyzed by logistic regression. Ascites were more commonly detected in patients with micro- or macroscopic vascular invasion, and the presence of ascites was independently associated with vascular invasion. Among patients with mild-to-moderate or severe ascites, the odds ratio for macroscopic vascular invasion was 4.83 (95 % confidence interval [CI] 2.29-10.16) and 11.87 (95 % CI 4.53-31.07), respectively. Similarly, the presence of ascites was associated with microscopic vascular invasion (OR 5.00; 95 % CI 1.23-20.31). In contrast, hepatitis B viral factors were not significantly associated with vascular invasion. The presence of ascites was associated with vascular invasion in patients with HBV-related cirrhotic HCC. Thus, patients with ascites, vascular invasion should be considered and more frequent surveillance should be performed after curative treatment.
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Affiliation(s)
- Chuan Chen
- Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, No. 10 Changjiang Zhi Rd, Chongqing, 400042, China
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Hsu CY, Liu PH, Lee YH, Hsia CY, Huang YH, Lin HC, Chiou YY, Lee FY, Huo TI. Using serum α-fetoprotein for prognostic prediction in patients with hepatocellular carcinoma: what is the most optimal cutoff? PLoS One 2015; 10:e0118825. [PMID: 25738614 PMCID: PMC4349891 DOI: 10.1371/journal.pone.0118825] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Accepted: 01/08/2015] [Indexed: 02/08/2023] Open
Abstract
Background and Aims The prognostic ability of α-fetoprotein (AFP) for patients with hepatocellular carcinoma (HCC) was examined by using different cutoff values. The optimal AFP cutoff level is still unclear. Methods A total of 2579 HCC patients were consecutively enrolled in Taiwan, where hepatitis B is the major etiology of chronic liver disease. Four frequently used AFP cutoff levels, 20, 200, 400, 1000 ng/mL, were investigated. One-to-one matched pairs between patients having AFP higher and lower than the cutoffs were selected by using the propensity model. The adjusted hazard ratios of survival difference were calculated with Cox proportional hazards model. Results Patients with a higher AFP level were associated with more severe cirrhosis, more frequent vascular invasion, higher tumor burden and poorer performance status (all p<0.0001). In the propensity model, 4 groups of paired patients were selected, and there was no difference found in the comparison of baseline characteristics (all p>0.05). Patients with AFP <20 ng/mL had significantly better long-term survival than patients with AFP ≧20 ng/mL (p<0.0001), and patients with AFP <400 ng/mL had significantly better overall outcome than patients with AFP ≧400 ng/mL (p = 0.0186). There was no difference of long-term survival between patients divided by AFP levels of 200 and 1000 ng/mL. The adjusted hazard ratios of AFP ≧20 ng/mL and AFP ≧400 ng/mL were 1.545 and 1.471 (95% confidence interval: 1.3–1.838 and 1.178–1.837), respectively. Conclusions This study shows the independently predictive ability of baseline serum AFP level in HCC patients. AFP levels of 20 and 400 ng/mL are considered feasible cutoffs to predict long-term outcome in unselected HCC patients.
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Affiliation(s)
- Chia-Yang Hsu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Biostatistics, University of California Los Angeles, Los Angeles, California, United States of America
| | - Po-Hong Liu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yun-Hsuan Lee
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Cheng-Yuan Hsia
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Han-Chieh Lin
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-You Chiou
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Fa-Yauh Lee
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Teh-Ia Huo
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- * E-mail:
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Hsu CY, Liu PH, Lee YH, Hsia CY, Huang YH, Chiou YY, Tsai YJ, Nagaria TS, Huo TI. Aggressive Therapeutic Strategies Improve the Survival of Hepatocellular Carcinoma Patients with Performance Status 1 or 2: A Propensity Score Analysis. Ann Surg Oncol 2014; 22:1324-31. [DOI: 10.1245/s10434-014-4151-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Indexed: 12/12/2022]
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Abstract
GOALS/BACKGROUND Macrovascular invasion (MaVI) is often detected by radiologic imaging in hepatocellular carcinoma (HCC) patients and may affect their long-term survival. We aimed to investigate the prevalence, determinants, and prognostic impact of MaVI in patients with HCC receiving curative and noncurative therapies. STUDY A total of 2654 HCC patients in a single center were identified. The risk factors and prognostic determinants of MaVI were determined. RESULTS A total of 928 (35%) patients had MaVI. Old age, lower serum α-fetoprotein level, higher serum sodium level, good performance status, smaller total tumor volume, and better liver functional reserve were significantly associated with a lower risk for VI. In the Cox proportional hazards model, patients with lower serum albumin level, higher serum bilirubin and α-fetoprotein level, worse performance status, the presence of ascites, and MaVI independently predicted a decreased long-term survival in patients undergoing both curative and noncurative treatments. In addition, lower sodium level and larger tumor size were independently associated with a poor outcome in the noncurative treatment group. Of the patients with MaVI, the 1-year survival rates for patients receiving surgical treatment, local ablation, transarterial chemoembolization, and supportive care were 83%, 75%, 57%, and 24%, respectively (P<0.001). CONCLUSIONS MaVI represents a distinct tumor phenotype of HCC and is associated with younger age, aggressive tumor behavior, poor liver functional reserve, and poor performance status. It adversely affects the survival of HCC patients independent of treatment strategy. Intensive anticancer therapy should be proposed to achieve a better long-term survival for the at-risk patients.
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Hsu CY, Lee YH, Liu PH, Hsia CY, Huang YH, Lin HC, Chiou YY, Lee FY, Huo TI. Decrypting cryptogenic hepatocellular carcinoma: clinical manifestations, prognostic factors and long-term survival by propensity score model. PLoS One 2014; 9:e89373. [PMID: 24586728 PMCID: PMC3933535 DOI: 10.1371/journal.pone.0089373] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2013] [Accepted: 01/18/2014] [Indexed: 02/06/2023] Open
Abstract
Background and Aims The clinical aspects of cryptogenic hepatocellular carcinoma (HCC), defined as HCC in patients without hepatitis B, C or alcoholism, are not clear. We investigated its clinical presentations, long-term survival and prognostic predictors. Methods A total of 2645 HCC patients were studied. One-to-one matched pairs between viral/alcoholic and cryptogenic HCC patients were generated by using the propensity model. The survival analysis was performed with the Kaplan-Meier method and log-rank test, and hazard ratios were calculated with Cox proportional hazards model. Results Among 366 (14%) patients with cryptogenic HCC, 34% of patients were presented with abdominal discomfort, and 31% of patients were identified incidentally. Compared to patients with viral/alcoholic HCC, cryptogenic HCC patients were significantly older (p<0.0001), with poorer performance status (p = 0.0031) and less often underwent curative treatment (p = 0.0041). They also had larger tumor burden (p<0.0001), poorer renal function (p<0.0001), lower α-fetoprotein level (p<0.0001), and more advanced Barcelona Clinic Liver Cancer stages (p<0.0001). With propensity score model, 366 pairs of similar HCC patients were selected and similar long-term survival between the two groups of patients was found (p = 0.1038). For cryptogenic HCC patients, α-fetoprotein ≧49 ng/mL (hazard ratio [HR]: 1.955, p = 0.0002), Child-Turcotte-Pugh class B/C (HR: 2.798, p<0.0001), performance status ≧1 (HR: 2.463, p<0.0001) and vascular invasion (HR: 1.608, p = 0.0257) were independent predictors of poor prognosis. Conclusions Patients with cryptogenic HCC are usually diagnosed with poor general condition at late stages. However, cryptogenic HCC patients have similar prognostic predictors and long-term survival compared with viral/alcoholic HCC patients. Diagnosis at an early stage may improve their clinical outcomes.
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Affiliation(s)
- Chia-Yang Hsu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Biostatistics, UCLA, Los Angeles, California, United States of America
| | - Yun-Hsuan Lee
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Po-Hong Liu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Cheng-Yuan Hsia
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Han-Chieh Lin
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-You Chiou
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Fa-Yauh Lee
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Teh-Ia Huo
- Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- * E-mail:
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