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Heo S, Yang J, Park J, Hui RWH, Song BG, Song IH, Yoon YI, Cheung TT, Chung SW, Choi J, Lee D, Shim JH, Kim KM, Lim YS, Lee HC, Seto WK, Lee JH, Choi WM. Association Between Viral Replication Activity and Postoperative Recurrence of HBV-Related Hepatocellular Carcinoma. Aliment Pharmacol Ther 2025. [PMID: 40091291 DOI: 10.1111/apt.70085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 10/23/2024] [Accepted: 03/06/2025] [Indexed: 03/19/2025]
Abstract
BACKGROUND Baseline viral replication activity influences the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B virus (HBV) infection. AIMS To evaluate the impact of baseline viral replication activity on recurrence in HBV-related HCC after curative resection. METHODS A multinational retrospective cohort of 2384 patients with very early or early-stage HBV-related HCC who consecutively underwent curative resection and received antiviral therapy (AVT) between 2010 and 2018 was analysed. Patients were categorised into ongoing-AVT (previously on AVT with viral suppression) and initiation-AVT (initiated AVT at the time of resection) groups. HCC recurrence was compared between these two groups based on baseline viral replication activity. RESULTS During a median follow-up of 4.9 years, 1188 (49.8%) patients developed recurrence. Multivariable analysis showed similar recurrence risk between the ongoing-AVT and initiation-AVT groups (HR, 1.09; 95% CI, 0.96-1.24). However, in cirrhotic patients, the initiation-AVT group had a higher recurrence risk than the ongoing-AVT group (HR, 1.22; 95% CI, 1.02-1.45) but not in non-cirrhotic patients (HR, 0.90; 95% CI, 0.73-1.09). Intriguingly, in the non-cirrhotic initiation-AVT group, a parabolic association was observed between baseline HBV DNA levels and the risk of recurrence, with those having 5-6 log10 IU/mL HBV DNA levels showing significantly higher recurrence risk compared to the ongoing-AVT group (HR, 1.78; 95% CI, 1.32-2.42). CONCLUSIONS The association between HBV replication activity and the risk of HCC recurrence varied depending on cirrhosis, providing important insights for optimising the timing of AVT and post-operative surveillance strategies.
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Affiliation(s)
- Subin Heo
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jiwon Yang
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jeayeon Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Rex Wan-Hin Hui
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Byeong Geun Song
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - In-Hye Song
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Tan-To Cheung
- Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Sung Won Chung
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jonggi Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Danbi Lee
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Kang Mo Kim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Han Chu Lee
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Wai-Kay Seto
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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Bi X, Zhao H, Zhao H, Li G, Wang X, Chen B, Zhang W, Che X, Huang Z, Han Y, Jiang L, Sun Y, Yang Z, Zhou J, Zhang Y, Zhu Z, Chen M, Cheng S, Cai J. Consensus of Chinese Experts on Neoadjuvant and Conversion Therapies for Hepatocellular Carcinoma: 2023 Update. Liver Cancer 2024:1-16. [DOI: 10.1159/000541249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a common malignancy in China, with high recurrence rate and low resection rate among patients first diagnosed. Preoperative treatments including neoadjuvant and conversion therapy have the potential to overcome these challenges. In December 2021, Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma was published. With the emersion of new evidence regarding the neoadjuvant and conversion therapies for HCC, the cooperative group brought together multidisciplinary researchers and scholars with experience in related fields to update the new edition (2023 Edition) for reference in China, including principle of the treatment strategies, the potential populations selection, treatment methods, multidisciplinary team, and future research for preoperative treatments. The new consensus aims to provide guidance for clinical application. Through the use of neoadjuvant therapy and conversion therapy, we can enhance the resection rate and reduce the recurrence of intermediate-to-advanced HCC patients, thereby improving survival outcomes.
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Kim MN, Kim BK, Cho H, Goh MJ, Roh YH, Yu SJ, Sinn DH, Park SY, Kim SU. Similar recurrence after curative treatment of HBV-related HCC, regardless of HBV replication activity. PLoS One 2024; 19:e0307712. [PMID: 39186715 PMCID: PMC11346930 DOI: 10.1371/journal.pone.0307712] [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: 05/17/2024] [Accepted: 07/09/2024] [Indexed: 08/28/2024] Open
Abstract
BACKGROUND AND AIMS Antiviral therapy (AVT) is required in patients with newly diagnosed hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), if HBV DNA is detectable. We compared the risk of recurrence according to HBV replication activity at the curative treatment of HBV-related HCC. METHODS Patients with HBV-related HCC who underwent surgical resection or radiofrequency ablation between 2013 and 2018 were enrolled in this retrospective cohort study. Patients were categorized into two groups according to HBV replication activity at the curative treatment of HBV-related HCC (group 1: patients who met the AVT indication for HBV-related HCC due to detectable HBV DNA but did not meet the AVT indication if without HCC; group 2: patients who met the AVT indication, regardless of HCC). RESULTS In the entire cohort (n = 911), HCC recurred in 303 (33.3%) patients during a median follow-up of 4.7 years. After multivariate adjustment, group 2 showed a statistically similar risk of HCC recurrence (adjusted hazard ratio [aHR] = 1.18, P = 0.332) compared to that of group 1. In addition, group 2 showed statistically similar risks of early (< 2 years; aHR = 1.31) and late (≥ 2 years; aHR = 0.83) recurrence than that of group 1 (all P>0.05). Propensity score matching and inverse probability of treatment weighting analysis also yielded similar risks of HCC recurrence between the two groups (all P>0.05, log-rank tests). CONCLUSIONS The risk of HCC recurrence in patients who received curative treatment for newly diagnosed HBV-related HCC was similar regardless of HBV replication activity, if AVT was properly initiated.
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Affiliation(s)
- Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Heejin Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Myung Ji Goh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yun Ho Roh
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Soo Young Park
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
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Suddle A, Reeves H, Hubner R, Marshall A, Rowe I, Tiniakos D, Hubscher S, Callaway M, Sharma D, See TC, Hawkins M, Ford-Dunn S, Selemani S, Meyer T. British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults. Gut 2024; 73:1235-1268. [PMID: 38627031 PMCID: PMC11287576 DOI: 10.1136/gutjnl-2023-331695] [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: 12/06/2023] [Accepted: 03/19/2024] [Indexed: 05/01/2024]
Abstract
Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.
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Affiliation(s)
- Abid Suddle
- King's College Hospital NHS Foundation Trust, London, UK
| | - Helen Reeves
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - Richard Hubner
- Department of Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | | | - Ian Rowe
- University of Leeds, Leeds, UK
- St James's University Hospital, Leeds, UK
| | - Dina Tiniakos
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Stefan Hubscher
- Department of Pathology, University of Birmingham, Birmingham, UK
| | - Mark Callaway
- Division of Diagnostics and Therapies, University Hospitals Bristol NHS Trust, Bristol, UK
| | | | - Teik Choon See
- Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Maria Hawkins
- Department of Medical Physics and Biomedical Engineering, University College London, London, UK
| | | | - Sarah Selemani
- King's College Hospital NHS Foundation Trust, London, UK
| | - Tim Meyer
- Department of Oncology, University College, London, UK
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Mu F, Hu LS, Xu K, Zhao Z, Yang BC, Wang YM, Guo K, Shi JH, Lv Y, Wang B. Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection: How to achieve a better outcome. World J Gastrointest Oncol 2024; 16:1833-1848. [PMID: 38764825 PMCID: PMC11099449 DOI: 10.4251/wjgo.v16.i5.1833] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 01/25/2024] [Accepted: 02/18/2024] [Indexed: 05/09/2024] Open
Abstract
BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) have been proven, researchers have not confirmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time (at least 24 wk) and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC. AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC. METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to June 2019 was conducted. Considering the history of antiviral therapy, patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups. RESULTS Kaplan-Meier analysis revealed significant differences in overall survival (P < 0.0001) and disease-free survival (P = 0.035) between the two groups. Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival (hazard ratio = 0.27; 95% confidence interval: 0.08-0.88; P = 0.030). CONCLUSION In patients with HBV-related HCC, it is ideal to receive preoperative long-term antiviral therapy, which helps patients tolerate more extensive hepatectomy; however, remedial antiviral therapy, which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL, can also result in improved outcomes.
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Affiliation(s)
- Fan Mu
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Liang-Shuo Hu
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Kun Xu
- Department of Anaesthesiology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Zhen Zhao
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Bai-Cai Yang
- Department of Gynaecology, Wenzhou Medical University Affiliated Jiaxing Women and Children Hospital, Jiaxing 314000, Zhejiang Province, China
| | - Yi-Meng Wang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Kun Guo
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Jian-Hua Shi
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Yi Lv
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Bo Wang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
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Liang Y, Zhong D, Zhang Z, Su Y, Yan S, Lai C, Yao Y, Shi Y, Huang X, Shang J. Impact of preoperative antiviral therapy on the prognosis of hepatitis B virus-related hepatocellular carcinoma. BMC Cancer 2024; 24:291. [PMID: 38438842 PMCID: PMC10913258 DOI: 10.1186/s12885-024-12031-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Accepted: 02/21/2024] [Indexed: 03/06/2024] Open
Abstract
BACKGROUND For chronic hepatitis B virus (HBV) infection patients, increasing evidence has demonstrated the effectiveness of expanding the indications and applicable population for antiviral therapy. However, the expanded indication of antiviral therapy for hepatocellular carcinoma (HCC) remains to be further explored. METHODS 196 HBV-related HCC patients who received radical hepatectomy and nucleos(t)ide analogues (NAs) therapy at Sichuan Provincial People's Hospital were enrolled in this study. HCC recurrence, overall survival (OS), early virological (VR) and biochemical responses (BR) of patients were compared between different NAs therapy and the use of anti-programmed cell death protein 1 (PD-1) therapy. RESULTS NAs therapy at different timing of surgery was a strong independent risk factor for postoperative recurrence and overall mortality of HBV-related HCC patients. Furthermore, in HCC patients who received postoperative anti-PD-1 therapy, patients with HBV DNA < 1000 copy/mL had significantly better recurrence-free survival (RFS) and OS than those with HBV DNA ≥ 1000 copy/mL (HR: 7.783; P = 0.002; HR: 6.699; P < 0.001). However, the differences of RFS and OS rates between entecavir group and tenofovir disoproxil fumarate group were not statistically significant. Similar results were also observed in the rates of early VR, BR and combined VR and BR. CONCLUSION Timely and reasonable preoperative NAs therapy showed clinical benefit in improving the prognosis of patients with HBV-related HCC, even in the case of normal alanine aminotransferase (ALT) level and negative hepatitis e antigen (HBeAg). Furthermore, a possible synergistic effect between antiviral therapy and anti-PD-1 therapy was founded and need further verification.
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Affiliation(s)
- Yuxin Liang
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province & Organ Transplant Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China
| | - Deyuan Zhong
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province & Organ Transplant Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China
| | - Zilong Zhang
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China
- Department of Hepatobiliary-Pancreatic and Hernia Surgery, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430033, China
| | - Yuhao Su
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China
| | - Su Yan
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China
| | - Chunyou Lai
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province & Organ Transplant Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China
| | - Yutong Yao
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province & Organ Transplant Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China
| | - Ying Shi
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province & Organ Transplant Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China
| | - Xiaolun Huang
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China.
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province & Organ Transplant Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China.
| | - Jin Shang
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China.
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province & Organ Transplant Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China.
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Cho WT, Yoo T, Lee JM, Lee JW, Kim H, Lee JS, Han SH. Hepatitis B Virus DNA-Level Change is Associated With Tumor Recurrence in Patients With Resected Hepatitis B Virus Hepatocellular Carcinoma. J Surg Res 2024; 295:231-239. [PMID: 38041902 DOI: 10.1016/j.jss.2023.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 09/07/2023] [Accepted: 10/07/2023] [Indexed: 12/04/2023]
Abstract
INTRODUCTION To investigate the significance of perioperative hepatitis B virus (HBV) DNA changes for predicting recurrence in patients with HBV-related hepatocellular carcinoma (HCC) undergoing liver resection (LR). METHODS From 2013 to 2020, 241 patients with HBV-related HCC who underwent LR in five Hallym university-affiliated hospitals were enrolled. The serum HBV DNA level, together with other clinicopathological variables, was analyzed for association with HCC recurrence. RESULTS Preoperatively, 99 patients had undetectable HBV DNA and 142 had detectable viral levels. Of those with detectable viral levels, 72 rapidly progressed to undetectable levels within 3 mo after LR (Rapid group), and 70 showed persistently detectable levels (Nonrapid group). The Rapid group had a better recurrence-free survival (RFS) rate than the Nonrapid group (1-y, 3-y RFS = 75.4%, 57.3%, versus 54.7%, 39.9%, respectively, P = 0.012). In the subgroup analysis, the Rapid group had a better RFS rate in early stages (1-y, 3-y RFS = 82.6%, 68.5%, versus 62.8%, 45.8%, respectively, P = 0.005); however, the RFS rates between the two groups were comparable in the advanced stage (1-y, 3-y RFS = 61.1%, 16.7% versus 45.5%, 22.7%, respectively, P = 0.994). Among the 142 patients with preoperatively detectable HBV DNA, persistently detectable HBV DNA within 3 mo postoperatively (hazard ratio [HR] = 1.7, P = 0.022), large tumor size (HR = 2.7, P < 0.001), multiple tumors (HR = 3.2, P < 0.001), and microvascular invasion (HR = 1.7, P = 0.028) were independent risk factors for RFS in multivariate analysis. CONCLUSIONS Rapidly undetectable HBV DNA after LR is associated with a better prognosis for recurrence in patients with HCC. Therefore, appropriate treatment and/or screening may be necessary for patients who do not return to undetectable HBV DNA after LR.
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Affiliation(s)
- Won Tae Cho
- Department of Surgery, Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si, Gyeonggi-do, Republic of Korea
| | - Tae Yoo
- Department of Surgery, Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si, Gyeonggi-do, Republic of Korea.
| | - Jung Min Lee
- Department of Surgery, Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si, Gyeonggi-do, Republic of Korea
| | - Jung Woo Lee
- Department of Surgery, Hallym University Sacred Heart Hospital, Anyang-si, Gyeonggi-do, Republic of Korea
| | - Hanbaro Kim
- Department of Surgery, Hallym University Kangnam Sacred Heart Hospital, Seoul, Republic of Korea; Department of Surgery, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon-si, Gangwon-do, Republic of Korea
| | - Ji Soo Lee
- Department of Surgery, Kangdong Sacred Heart Hospital, Seoul, Republic of Korea
| | - Sang Hyup Han
- Department of Surgery, Kangdong Sacred Heart Hospital, Seoul, Republic of Korea
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Peng W, Yi M, Qi X, Qi W, Li C, Wen T. The effect of switch therapy to tenofovir versus entecavir maintenance on recurrence of hepatocellular carcinoma after surgery (SWITE): study protocol for a randomized controlled trial. Trials 2023; 24:781. [PMID: 38042834 PMCID: PMC10693690 DOI: 10.1186/s13063-023-07822-y] [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: 04/03/2023] [Accepted: 11/22/2023] [Indexed: 12/04/2023] Open
Abstract
BACKGROUND Antiviral therapy has been reported to be associated with lower recurrence rate of hepatocellular carcinoma (HCC) for patients with hepatitis B virus (HBV) infection. While entecavir (ETV) and tenofovir disoproxil fumarate (TDF) were both recommended as first-line therapies for HBV patients, recent retrospective studies proposed a lower incidence rate of HCC occurrence or recurrence in those receiving TDF compared ETV. However, the survival benefits of switching to TDF therapy after prolonged ETV treatment before surgery remain uncertain. We delineate the rationale and design of SWITE, a randomized, open-label, phase III trial contrasting TDF switch therapy versus ETV maintenance in HBV-related HCC patients. METHODS AND ANALYSIS This is a prospective, randomized, controlled, single-center study with two parallel groups of patients with HBV-related HCC who have received long-term ETV therapy before surgery. West China Hospital will enroll 238 patients, randomized in a 1:1 ratio to TDF switch therapy or ETV maintenance after surgery. The primary endpoint of this study is 3-year recurrence free survival (RFS), with the secondary endpoint being 3-year overall survival (OS) after curative surgery of HCC. Safety events will be diligently recorded. ETHICS AND DISSEMINATION The study protocol aligns with the ethical guidelines of the 1975 Declaration of Helsinki. It was approved by ethics committee of West China Hospital (approval number: 2022-074) and was registered with chictr.org.cn (chiCTR2200057867). Informed consent will be obtained from all participants. The results of this trial will be published in peer-reviewed journals and presentations at national and international conferences relevant to this topic. TRIAL REGISTRATION chiCTR2200057867 . Date of registration is March 20 2022.
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Affiliation(s)
- Wei Peng
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China
- Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu, China
| | - Mengshi Yi
- Deparment of Hepatobiliary Surgery, the First Affiliated Hospital of Army Medical University, Chongqing, China
| | - Xin Qi
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Weili Qi
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Chuan Li
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Tianfu Wen
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
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9
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Lu Y, Liang L, Lu WF, Cheng J, Yao WF, Xie YM, Wang DD, Xu FQ, Xiao ZQ, Zhang JG, Liu JW, Zhang CW, Huang DS. The prognosis of elderly patients with hepatocellular carcinoma after curative hepatectomy a multicenter competing risk analysis. Clin Res Hepatol Gastroenterol 2023; 47:102147. [PMID: 37245639 DOI: 10.1016/j.clinre.2023.102147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 05/25/2023] [Accepted: 05/25/2023] [Indexed: 05/30/2023]
Abstract
BACKGROUND Non-cancer-specific death (NCSD) is an important factor that needs to be considered in patients with malignancy, as it can affect their long-term prognosis. In particular, the effect of age on patients with hepatocellular carcinoma (HCC) after hepatectomy requires clarification. This study aims to examine the impact of age on patients with HCC after hepatectomy and to identify independent risk factors of survival. METHODS Patients with HCC that fell within the Milan Criteria and had undergone curative hepatectomy were included in this study. The patients were divided into two groups: young patients (age <70) and elderly patients (age ≥70). Perioperative complications, cancer-specific death (CSD), recurrence, and NCSD were all recorded and analyzed. Multivariate analyses were performed to identify independent risk factors of survival using Fine and Gray's competing-risk regression model. RESULTS Among 1,354 analytic patients, 1,068 (78.7%) were stratified into the young group and 286 (21.3%) into the elderly group. The elderly group had a higher 5-year cumulative incidence of NCSD (12.6% vs. 3.7% for the young group, P < 0.001), but lower 5-year cumulative incidences of recurrence (20.3% vs. 21.1% for the young group, P = 0.041) and CSD (14.3% vs. 15.5% for the young group, P = 0.066). Multivariate competing-risk regression analyses revealed that age was independently associated with NCSD (subdistribution hazard ratio (SHR) 3.003, 95%CI: 2.082-4.330, P < 0.001), but not with recurrence (SHR 0.837, 95%CI: 0.659-1.060, P = 0.120) or CSD (SHR 0.736, 95%CI: 0.537-1.020, P = 0.158). CONCLUSION For patients with early-stage HCC after hepatectomy, older age was independently associated with NCSD, but not recurrence and CSD.
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Affiliation(s)
- Yi Lu
- Department of Clinical Medicine, Medical College of Soochow University, Suzhou, China; General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Lei Liang
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
| | - Wen Feng Lu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Jian Cheng
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Wei Feng Yao
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Ya Ming Xie
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Dong Dong Wang
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Fei Qi Xu
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Zun Qiang Xiao
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Jun Gang Zhang
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Jun Wei Liu
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Cheng Wu Zhang
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Dong Sheng Huang
- Department of Clinical Medicine, Medical College of Soochow University, Suzhou, China; General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China; Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
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10
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Roma K, Chandler TM, Dossaji Z, Patel A, Gupta K, Minacapelli CD, Rustgi V, Gish R. A Review of the Systemic Manifestations of Hepatitis B Virus Infection, Hepatitis D Virus, Hepatocellular Carcinoma, and Emerging Therapies. GASTRO HEP ADVANCES 2023; 3:276-291. [PMID: 39129946 PMCID: PMC11308766 DOI: 10.1016/j.gastha.2023.06.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 06/26/2023] [Indexed: 08/13/2024]
Abstract
Chronic hepatitis B virus (HBV) infection affects about 262 million people worldwide, leading to over 820,000 deaths each year primarily due to cirrhosis and hepatocellular carcinoma. The World Health Organization has pledged to eliminate HBV as a health threat by 2030, but currently, no countries are on track to achieve this goal. One of the barriers to HBV elimination is stigma, causing shame, denial, self-isolation, self-rejection, and depression leading to those with chronic HBV less likely to get tested or seek treatment and more likely to conceal their infection. Other barriers include limited access to care and complicated and restrictive clinical practice guidelines. Increasing public and political efforts are necessary to raise awareness, increase access to care, and change screening and treatment guidelines. The current guidance of the American Association for the Study of Liver Diseases (AASLD) recommends testing only if patients are considered at risk, but this has proven to be ineffective. We propose a simplified "test all and treat all" approach with a 5-line guideline for HBV infection. Universal screening and treatment of adults is cost-effective and can prevent transmission by effectively managing chronic HBV. All patients who are hepatitis B surface antigen (HBsAg) positive with detectable HBV-DNA should receive treatment until HBsAg is undetectable for 12 months, as HBV-DNA transmission via blood transfusion can occur even at low viral loads of 16 copies/mL, and mother-to-child transmission is still a risk even with passive-active immunoprophylaxis. Furthermore, clinical outcomes after HBsAg clearance are significantly better than the clinical outcomes of those who remain HBsAg positive.
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Affiliation(s)
- Katerina Roma
- Internal Medicine, Kirk Kerkorian School of Medicine at the University of Nevada, Las Vegas, Nevada
| | - Toni-Marie Chandler
- Division of Gastroenterology and Hepatology, Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences (RBHS), New Brunswick, New Jersey
| | - Zahra Dossaji
- Internal Medicine, Kirk Kerkorian School of Medicine at the University of Nevada, Las Vegas, Nevada
| | - Ankoor Patel
- Internal Medicine, Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences (RBHS), Rutgers University, New Brunswick, New Jersey
| | - Kapil Gupta
- Division of Gastroenterology and Hepatology, Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences (RBHS), New Brunswick, New Jersey
| | - Carlos D. Minacapelli
- Division of Gastroenterology and Hepatology, Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences (RBHS), New Brunswick, New Jersey
- Center for Liver Diseases and Masses, Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences (RBHS), New Brunswick, New Jersey
| | - Vinod Rustgi
- Division of Gastroenterology and Hepatology, Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences (RBHS), New Brunswick, New Jersey
- Center for Liver Diseases and Masses, Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences (RBHS), New Brunswick, New Jersey
| | - Robert Gish
- Hepatitis B Foundation, Doylestown, Pennsylvania
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11
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Wang P, Wang X, Liu X, Yan F, Yan H, Zhou D, Yu L, Wang X, Yang Z. Primary non-response to antiviral therapy affects the prognosis of hepatitis B virus-related hepatocellular carcinoma. BMC Cancer 2023; 23:564. [PMID: 37340357 PMCID: PMC10280839 DOI: 10.1186/s12885-023-11059-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 06/12/2023] [Indexed: 06/22/2023] Open
Abstract
BACKGROUND AND AIM Although antiviral treatments have been shown to affect the recurrence and long-term survival of patients with hepatocellular carcinoma (HCC) who have high viral loads, the effect of different responses to antiviral therapy on the clinical outcomes remains unclear. This study aimed to assess the effect of primary non-response (no-PR) to antiviral therapy on the survival or prognosis of patients with HCC with a high load of hepatitis B virus (HBV) DNA. METHODS A total of 493 HBV-HCC patients hospitalized at Beijing Ditan Hospital of Capital Medical University were admitted to this retrospective study. Patients were divided into two groups based on viral response (no-PR and primary response). Kaplan-Meier (KM) curves were used to compare the overall survival of the two cohorts. Serum viral load comparison and subgroup analysis were performed. Additionally, risk factors were screened and the risk score chart was created. RESULTS This study consisted of 101 patients with no-PR and 392 patients with primary response. In the different categories based on hepatitis B e antigen and HBV DNA, no-PR group had a poor 1-year overall survival (OS). In addition, in the alanine aminotransferase < 50 IU/L and cirrhosis groups, primary nonresponse was related to poor overall survival and progression-free survival. Based on multivariate risk analysis, primary non-response (hazard ratio (HR) = 1.883, 95% CI 1.289-2.751, P = 0.001), tumor multiplicity (HR = 1.488, 95% CI 1.036-2.136, P = 0.031), portal vein tumor thrombus (HR = 2.732, 95% CI 1.859-4.015, P < 0.001), hemoglobin < 120 g/L (HR = 2.211, 95% CI 1.548-3.158, P < 0.001) and tumor size ≥ 5 cm (HR = 2.202, 95% CI 1.533-3.163, P < 0.001) were independent risk factors for 1-year OS. According to the scoring chart, patients were divided into three risk groups (high-, medium-, and low-risk groups) with mortality rates of 61.7%, 30.5%, and 14.1%, respectively. CONCLUSIONS The level of viral decline at 3 months post-antiviral treatment may predict the OS of patients with HBV-related HCC, and primary non-response may shorten the median survival time of patients with high HBV-DNA levels.
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Affiliation(s)
- Peng Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Xinhui Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Xiaoli Liu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Fengna Yan
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Huiwen Yan
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Dongdong Zhou
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Lihua Yu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Xianbo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Zhiyun Yang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China.
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12
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Kao WY, Tan ECH, Lee HL, Huang YH, Huo TI, Chang CC, Chiou JF, Hou MC, Wu JC, Su CW. Entecavir versus tenofovir on prognosis of hepatitis B virus-related hepatocellular carcinoma after curative hepatectomy. Aliment Pharmacol Ther 2023; 57:1299-1312. [PMID: 36914943 DOI: 10.1111/apt.17438] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 01/27/2023] [Accepted: 02/15/2023] [Indexed: 03/16/2023]
Abstract
BACKGROUND There is still controversy about whether tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have different effects on the outcomes of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). AIMS The aim of this study was to compare the prognoses between ETV and TDF treatment among patients with HBV-related HCC after hepatectomy. METHODS An analysis was done on data from the Taiwan Cancer Registry, which was linked to Taiwan National Health Insurance Research Database, for the years 2011-2016. We identified 7107 patients with HBV-related HCC after curative hepatectomy, and 25.3% of them used ETV or TDF after surgery. After propensity score overlap weighting, 1797 patients treated with ETV (n = 1365) or TDF (n = 432) were included for analyses. Cox proportional hazards models were used to compare the efficacy of ETV and TDF for recurrence and overall survival (OS). RESULTS After hepatectomy, the recurrence rate per 100 person-years was 14.87 for the ETV group and 9.25 for the TDF group. The risk of recurrence was similar in the TDF group and the ETV group (HR [95% CI]: 0.91 [0.69-1.19; p = 0.479]), as was the risk of all-cause mortality (HR [95% CI]: 0.67 [0.42-1.07]; p = 0.091). When considering early recurrence (<2 years) and late recurrence (≧2 years), the TDF and ETV groups showed no significant differences. Subgroup analyses and sensitivity analyses demonstrated consistent results. CONCLUSION Both TDF and ETV showed similar health benefits in terms of recurrence and OS in patients with HBV-related HCC patients after hepatectomy.
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Affiliation(s)
- Wei-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.,TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan
| | - Elise Chia-Hui Tan
- Department of Health Service Administration, College of Public Health, China Medical University, Taichung, Taiwan
| | - Hsin-Lun Lee
- Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.,Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan.,Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Internal Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Teh-Ia Huo
- Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan
| | - Jeng-Fong Chiou
- Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.,Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan.,Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Internal Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jaw-Ching Wu
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Internal Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Division of Holistic and Multidisciplinary Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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13
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2023; 23:1-120. [PMID: 37384024 PMCID: PMC10202234 DOI: 10.17998/jlc.2022.11.07] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 06/30/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Affiliation(s)
- Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
- Corresponding author: KLCA-NCC Korea Practice Guideline Revision Committee (KPGRC) (Committee Chair: Joong-Won Park) Center for Liver and Pancreatobiliary Cancer, Division of Gastroenterology, Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel. +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
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14
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Yang YQ, Wen ZY, Liu XY, Ma ZH, Liu YE, Cao XY, Hou L, Xie H. Current status and prospect of treatments for recurrent hepatocellular carcinoma. World J Hepatol 2023; 15:129-150. [PMID: 36926237 PMCID: PMC10011906 DOI: 10.4254/wjh.v15.i2.129] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 11/13/2022] [Accepted: 01/23/2023] [Indexed: 02/24/2023] Open
Abstract
Owing to its heterogeneous and highly aggressive nature, hepatocellular carcinoma (HCC) has a high recurrence rate, which is a non-negligible problem despite the increasing number of available treatment options. Recent clinical trials have attempted to reduce the recurrence and develop innovative treatment options for patients with recurrent HCC. In the event of liver remnant recurrence, the currently available treatment options include repeat hepatectomy, salvage liver transplantation, tumor ablation, transcatheter arterial chemoembolization, stereotactic body radiotherapy, systemic therapies, and combination therapy. In this review, we summarize the strategies to reduce the recurrence of high-risk tumors and aggressive therapies for recurrent HCC. Additionally, we discuss methods to prevent HCC recurrence and prognostic models constructed based on predictors of recurrence to develop an appropriate surveillance program.
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Affiliation(s)
- Yu-Qing Yang
- Department of Epidemiology and Biostatistics, Jilin University, Changchun 130021, Jilin Province, China
| | - Zhen-Yu Wen
- Department of Occupational and Environmental Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Xiao-Yan Liu
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Zhen-Hu Ma
- Senior Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Yan-E Liu
- Department of Epidemiology and Biostatistics, Jilin University, Changchun 130021, Jilin Province, China
| | - Xue-Ying Cao
- Senior Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Li Hou
- Senior Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Hui Xie
- Senior Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
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15
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Giri S, Agrawal D, Afzalpurkar S, Gopan A, Angadi S, Sundaram S. Tenofovir versus entecavir for tertiary prevention of hepatocellular carcinoma in chronic hepatitis B infection after curative therapy: A systematic review and meta-analysis. J Viral Hepat 2023; 30:108-115. [PMID: 36321967 DOI: 10.1111/jvh.13766] [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: 06/30/2022] [Revised: 09/20/2022] [Accepted: 10/24/2022] [Indexed: 11/07/2022]
Abstract
Entecavir (ETV) and Tenofovir disoproxil fumarate (TDF) are the first-line drugs for the treatment of chronic hepatitis B virus (HBV). However, the impact of these two antiviral agents on the outcome of HBV-related hepatocellular carcinoma (HCC) after curative therapy remains to be explored. The purpose of the present study was to compare the effect of ETV and TDF on recurrence and mortality after curative treatment for HBV-related HCC. A comprehensive literature search of multiple electronic databases was conducted from 2000 to January 2022 for studies comparing ETV and TDF for HBV-related HCC patients after curative therapy. The adjusted hazard ratios (aHR) were pooled using a random-effects model. A total of nine studies with 5298 patients were included in the final meta-analysis. TDF was associated with a lower risk of HCC recurrence [aHR 0.73, 95% confidence interval (CI) 0.65-0.81] compared to HCC. TDF reduced the risk of late recurrence compared to ETV (aHR 0.58, 95% CI 0.45-0.76) but not early recurrence (aHR 0.88, 95% CI 0.76-1.02). The mortality risk was also lower with TDF compared to ETV (aHR 0.62, 95% CI 0.50-0.77). TDF was associated with a lower risk of recurrence and mortality than ETV after resection or ablation of HBV-related HCC. Further prospective randomized controlled studies are warranted to validate these results.
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Affiliation(s)
- Suprabhat Giri
- Department of Gastroenterology, Nizam's Institute of Medical Sciences, Hyderabad, India
| | - Dhiraj Agrawal
- Department of Gastroenterology, PACE Hospital, Hyderabad, India
| | - Shivaraj Afzalpurkar
- Institute of Gastrosciences and Liver, Apollo Multispecialty Hospital, Kolkata, India
| | - Amrit Gopan
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India
| | - Sumaswi Angadi
- Department of Gastroenterology, Nizam's Institute of Medical Sciences, Hyderabad, India
| | - Sridhar Sundaram
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
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16
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Zhang D, Feng D, Ren M, Bai Y, Liu Z, Wang H. Preoperative serum hepatitis B virus DNA was a risk factor for hepatocellular carcinoma recurrence after liver transplantation. Ann Med 2022; 54:2213-2221. [PMID: 35930293 PMCID: PMC9455325 DOI: 10.1080/07853890.2022.2107233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Tumour characteristics and orthotopic liver transplantation (OLT) criteria are risks for recurrence of hepatocellular carcinoma (HCC). In Asia, most HCC is caused by chronic hepatitis B infection. Whether hepatitis B virus DNA (HBV DNA) is a risk factor for HCC recurrence after OLT is not clear. PATIENTS AND METHODS In this retrospective study, we classified patients into groups of detectable and undetectable HBV DNA, non-HCC recurrence, and recurrence and performed analyses on differed characteristics between groups and risk factors for HCC recurrence after OLT. RESULTS Among patients who underwent OLT for HCC, 117 were secondary to CHB infection. CHB was not a risk, but advanced tumour characteristics were risk factor for HCC recurrence. In patients with CHB-HCC, 24 (20.5%) of 117 patients had HCC recurrence. Compared to patients with HBV DNA undetectable (n = 75), patients with detectable HBV DNA (n = 42) had higher AFP concentration (p < .001), higher proportion of macrovascular invasion (p = .014), greater tumour diameter (p < .001), poorer TNM stage (p = .017), and higher proportion of extended OLT criteria (p = .011) and HCC recurrence (p = .036). Preoperative HBV DNA >2000 IU/mL was an independent risk factor for HCC recurrence (OR = 8.35, 95% CI 1.40, 50.00, p = .020). HBV DNA detectable was not a risk for HCC-related death. CONCLUSION Individuals with preoperative undetectable HBV DNA had advanced tumour characteristics and a higher proportion of HCC recurrence. Antiviral treatment for HCC should be performed, and HBV DNA undetectable should be obtained before OLT. But for an urgent OLT, preoperative detectable HBV DNA may not affect long-term survival.KEY MESSAGESPatients with HBV DNA detectable had advanced tumour characteristics, a higher proportion of extended OLT criteria, and HCC-recurrence.HBV DNA >2000 IU/mL was a risk factor for HCC recurrence.HBV DNA detectable was not a risk for HCC related death; extended OLT criteria affected long-term survival.
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Affiliation(s)
- Dali Zhang
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Danni Feng
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Minjuan Ren
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Ying Bai
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Zhenwen Liu
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Hongbo Wang
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
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17
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2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2022; 23:1126-1240. [PMID: 36447411 PMCID: PMC9747269 DOI: 10.3348/kjr.2022.0822] [Citation(s) in RCA: 74] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Li Z, Tan C, Liu X, Feng Z, Li K. Early and late recurrence after hepatectomy in patients with low-level HBV-DNA hepatocellular carcinoma under antiviral therapy. Infect Agent Cancer 2022; 17:56. [DOI: 10.1186/s13027-022-00468-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 11/08/2022] [Indexed: 11/18/2022] Open
Abstract
Abstract
Background
Antiviral therapy has been shown to benefit long-term survival after curative hepatectomy in patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) with high levels of HBV-DNA, but the impact of antiviral therapy on patient recurrence in patients with low levels of HBV-DNA remains less clear.
Methods
This was a retrospective cohort study analyzing 296 patients with HBV-associated HCC with HBV-DNA levels < 2000 IU/mL who underwent hepatectomy at Zhongnan Hospital of Wuhan University between March 2013 and December 2017, of whom 157 patients received antiviral therapy (antiviral group) and 139 patients did not receive antiviral therapy (non-antiviral group), propensity score matching was used for survival analysis of patients in both groups, and subgroup analysis of major risk factors was performed.
Results
The baseline characteristics of the two groups were comparable. At a median follow-up of 54 months, the 1-, 3-, and 5-year overall survival rates after propensity score matching (PSM) were 94.9%, 80.8%, 66.5%, and 90.9%, 64.6%, 49.4% for the antiviral and non-antiviral groups, respectively, p = 0.009, and the corresponding 1-, 3-, and 5-year RFS for the two groups were 81.8%, 76.8%, 76.8%, and 67.7%, 55.6%, 55.6%, respectively. p = 0.001, and the overall survival and recurrence-free survival were significantly better in the antiviral group than in the non-antiviral group. Multi-factor COX regression analysis showed that prothrombin time ≥ 13 s, methemoglobin level ≥ 20 ng/ml, platelet count ≥ 100 × 109/L, tumor size > 5 cm, tumor multiplicity was associated with early recurrence, and antiviral treatment was an independent protective factor for early recurrence of HCC (HR, 0.431; 95% CI 0.274–0.679; p < 0.001), but not associated with a low risk of late relapse (HR, 0.822; 95% CI 0.526–1.284; p = 0.389), and the main risk factors for late relapse included AST levels > 40 IU/ml, ALP levels > 130 IU/L, and the presence of satellite nodules, and subgroup analysis showed that compared to HBeAg-positive patients, antiviral therapy could significantly prolonged the recurrence-free survival of HBeAg-negative patients.
Conclusion
Antiviral therapy reduces early tumor recurrence after hepatectomy in patients with low levels of HBV-DNA.
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022; 28:583-705. [PMID: 36263666 PMCID: PMC9597235 DOI: 10.3350/cmh.2022.0294] [Citation(s) in RCA: 161] [Impact Index Per Article: 53.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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20
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Hu Z, Zeng H, Hou J, Wang J, Xu L, Zhang Y, Chen M, Zhou Z. Tenofovir vs. Entecavir on Outcomes of Hepatitis B Virus-Related Hepatocellular Carcinoma after Radiofrequency Ablation. Viruses 2022; 14:v14040656. [PMID: 35458386 PMCID: PMC9024443 DOI: 10.3390/v14040656] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/10/2022] [Accepted: 03/19/2022] [Indexed: 01/01/2023] Open
Abstract
For patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) treated with curative radiofrequency ablation (RFA), the effect of entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF) on recurrence-free survival (RFS) and overall survival (OS) remains unclear. We aimed to compare the outcomes of patients receiving ETV or TDF after RFA. This study consecutively collected patients who were treated with ETV (n = 202) or TDF (n = 102) for chronic hepatitis B (CHB) after curative RFA of HCC from December 2015 to January 2021 at Sun Yat-sen University Cancer Center. There were 130 patients in the ETV group and 77 patients in the TDF group after we performed 1-to-n propensity score matching. Kaplan−Meier and Cox regression analyses were performed to validate possible risk factors for RFS and OS. In addition, we estimated the curative effect of ETV and TDF for HBV-related hepatitis by recording the change in serum HBV DNA and ALBI grade after RFA. During the study period (median 34.1 (interquartile range: 19.6−47.4 months) months), 123 (40.5%) patients suffered HCC recurrence, and 15 (4.9%) died. In the full cohort, the probability of HCC recurrence (41.6% vs. 37.3%, p = 0.49) and overall survival (95% vs. 95.1%, p = 0.39) at 5 years were similar between the ETV and TDF groups. In the matched cohort, HCC recurrence (40.8% vs. 40.3%, p = 0.35) and overall survival (96.9% vs. 93.5%, p = 0.12) at 5 years were similar between the ETV and TDF groups. Furthermore, the early RFS (<2 years) did not differ significantly between the two groups in the full and matched cohorts (p = 0.26, p = 0.13). Compared with the ALBI grade before RFA, the ALBI grade of 80 patients (41%) remained stable or improved in the ETV group and 64 patients (64%) in the TDF group (p < 0.001). The mean time of serum HBV DNA reduction to 0 was 9.13 (95% CI: 5.92−12.33) and 2.75 (95% CI: 2.01−3.49) months in the ETV and TDF groups, respectively (p = 0.015). The RFS and OS of patients after curative RFA for HCC were not significantly different between the ETV and TDF groups. TDF therapy was associated with a better effect of protecting liver function and reducing the load of HBV. Further validation studies are needed.
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Affiliation(s)
- Zili Hu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; (Z.H.); (H.Z.); (J.H.); (J.W.); (L.X.); (Y.Z.)
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Huilan Zeng
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; (Z.H.); (H.Z.); (J.H.); (J.W.); (L.X.); (Y.Z.)
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Jingyu Hou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; (Z.H.); (H.Z.); (J.H.); (J.W.); (L.X.); (Y.Z.)
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Juncheng Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; (Z.H.); (H.Z.); (J.H.); (J.W.); (L.X.); (Y.Z.)
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Li Xu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; (Z.H.); (H.Z.); (J.H.); (J.W.); (L.X.); (Y.Z.)
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Yaojun Zhang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; (Z.H.); (H.Z.); (J.H.); (J.W.); (L.X.); (Y.Z.)
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; (Z.H.); (H.Z.); (J.H.); (J.W.); (L.X.); (Y.Z.)
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Correspondence: (M.C.); (Z.Z.); Tel.: +86-20-87-343-117 (M.C.); +86-20-87-343-879 (Z.Z.)
| | - Zhongguo Zhou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; (Z.H.); (H.Z.); (J.H.); (J.W.); (L.X.); (Y.Z.)
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Correspondence: (M.C.); (Z.Z.); Tel.: +86-20-87-343-117 (M.C.); +86-20-87-343-879 (Z.Z.)
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21
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Tenofovir vs. entecavir on prognosis of hepatitis B virus-related hepatocellular carcinoma after curative resection. J Gastroenterol 2022; 57:185-198. [PMID: 35152312 DOI: 10.1007/s00535-022-01855-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 01/20/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are recommended as first-line choices regarding the treatment of chronic hepatits B. The impact of the two antiviral agents on prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative liver resection remains to be explored. We aimed to assess the effect of antiviral therapy with ETV or TDF after curative resection on the prognosis of patients with HBV-related HCC. METHODS A total of 1173 consecutive patients who were treated with ETV or TDF after curative liver resection for HCC were enrolled in the study. HCC recurrence, overall survival, postoperative liver function reserve, and early virologic (VR) and biochemical responses (BR) of patients were compared between the ETV and TDF groups by propensity score matching (PSM) from the date of liver resection for HCC. RESULTS No difference was observed with recurrence-free survival between TDF and ETV in the PSM cohort (hazard ratio [HR], 0.91; 95% confidence interval [CI] 0.70-1.17; P = 0.45). No difference was observed with early VR and BR between TDF and ETV in the PSM cohort. Compared with ETV, TDF therapy was associated with significantly better protection of liver function and higher overall survival rates in the PSM cohort (HR, 0.37; 95% CI 0.20-0.71; P = 0.002). After PSM, 69 (40.8%) patients in the ETV group and 63 (57.3%) patients in the TDF group had single tumor recurrence, while the TDF group had significantly more patients with single tumor recurrence in the PSM cohort (P = 0.007). CONCLUSIONS For patients who underwent curative resection for HBV-related HCC, TDF treatment had a significantly better overall survival and better protection of liver function, but no difference in the incidences of HCC recurrence than ETV treatment.
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22
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Chen Y, Guo D, Li X, Xu C, Zhu Q. Predictors of Spontaneous Rupture of Hepatocellular Carcinoma and Clinical Outcomes Following Hepatectomy. Front Oncol 2022; 12:820867. [PMID: 35155255 PMCID: PMC8828539 DOI: 10.3389/fonc.2022.820867] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 01/03/2022] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVE To explore the independent predictive factors of spontaneous tumor rupture (STR) in patients undergoing curative resection of hepatocellular carcinoma (HCC), and to evaluate the impact of STRHCC on long-term survival after hepatectomy. METHODS The clinicopathological parameters of 106 patients with STRHCC and 201 patients with non-ruptured HCC who underwent hepatectomy from January 2007 to November 2011 at the Eastern Hepatobiliary Surgery Hospital and Zhongnan Hospital of Wuhan University were analyzed using propensity score matching (PSM) and a logistic regression model. RESULTS Factors including hypertension, cirrhosis, total bilirubin (TB), tumor size, and ascites were independent predictors of STR. For all 307 HCC patients, the 1-, 3- and 5-year overall survival (OS) rates were 54.0%, 37.3% and 33.8%, respectively. After PSM, the 1-, 3-, and 5-year OS rates in the ruptured group remained significantly lower at 41.5%, 23.5%, and 17.5% when compared with the non-ruptured group at 70.8%, 47.1%, and 37.6%, respectively, while the 1-, 3-, and 5-year disease-free survival (DFS) rates between the groups did not differ significantly (50.4%, 35.1%, 27.1% vs 55.4%, 38.2%, 27.4%). STRHCC was significantly associated with increased risk of OS, but not of shorter DFS. No significant difference in postoperative morbidity or hospital death was observed between the groups. CONCLUSION Factors including hypertension, liver cirrhosis, higher TB levels, tumor size > 5cm, and ascites are significant predictors of STR. The recurrence rate of patients in the ruptured group was significantly higher than that of patients in the non-ruptured group. STR results in poorer OS but not DFS in patients undergoing curative resection for HCC. STRHCC has no impact on postoperative morbidity and mortality after hepatectomy.
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Affiliation(s)
- Yiran Chen
- Department of Hepatobiliary and Pancreatic Surgery, Hubei Provincial Clinical Medicine Research Center for Minimally Invasive Diagnosis and Treatment of Hepatobiliary and Pancreatic Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Deliang Guo
- Department of Hepatobiliary and Pancreatic Surgery, Hubei Provincial Clinical Medicine Research Center for Minimally Invasive Diagnosis and Treatment of Hepatobiliary and Pancreatic Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xinyi Li
- Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Chang Xu
- Second Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital of Naval Medical University, Shanghai, China
| | - Qian Zhu
- Department of Hepatobiliary and Pancreatic Surgery, Hubei Provincial Clinical Medicine Research Center for Minimally Invasive Diagnosis and Treatment of Hepatobiliary and Pancreatic Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
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23
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Koh JH, Tan DJH, Ong Y, Lim WH, Ng CH, Tay PWL, Yong JN, Muthiah MD, Tan EX, Pang NQ, Kim BK, Syn N, Kow A, Goh BKP, Huang DQ. Liver resection versus liver transplantation for hepatocellular carcinoma within Milan criteria: a meta-analysis of 18,421 patients. Hepatobiliary Surg Nutr 2022; 11:78-93. [PMID: 35284509 DOI: 10.21037/hbsn-21-350] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 11/09/2021] [Indexed: 12/24/2022]
Abstract
Background Outcomes after liver resection (LR) and liver transplantation (LT) for hepatocellular carcinoma (HCC) are heterogenous and may vary by region, over time periods and disease burden. We aimed to compare overall survival (OS) and disease-free survival (DFS) between LT versus LR for HCC within the Milan criteria. Methods Two authors independently searched Medline and Embase databases for studies comparing survival after LT and LR for patients with HCC meeting the Milan criteria. Meta-analyses and metaregression were conducted using random-effects models. Results We screened 2,278 studies and included 35 studies with 18,421 patients. LR was associated with poorer OS [hazard ratio (HR) =1.44; 95% confidence interval (CI): 1.14-1.81; P<0.01] and DFS (HR =2.71; 95% CI: 2.23-3.28; P<0.01) compared to LT, with similar findings among intention-to-treat (ITT) studies. In uninodular disease, OS in LR was comparable to LT (P=0.13) but DFS remained poorer (HR =2.95; 95% CI: 2.30-3.79; P<0.01). By region, LR had poorer OS versus LT in North America and Europe (P≤0.01), but not Asia (P=0.25). LR had inferior survival versus LT in studies completed before 2010 (P=0.01), but not after 2010 (P=0.12). Cohorts that underwent enhanced surveillance had comparable OS after LT and LR (P=0.33), but cohorts undergoing usual surveillance had worse OS after LR (HR =1.95; 95% CI: 1.24-3.07; P<0.01). Conclusions Mortality after LR for HCC is nearly 50% higher compared to LT. Survival between LR and LT were similar in uninodular disease. The risk of recurrence after LR is threefold that of LT.
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Affiliation(s)
- Jin Hean Koh
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Yuki Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Phoebe Wen Lin Tay
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Eunice X Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Ning Qi Pang
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore.,Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, Singapore, Singapore
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Biostatistics and Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
| | - Alfred Kow
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore.,Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, Singapore, Singapore
| | - Brian K P Goh
- Department of Hepato-Pancreato-Biliary and Transplant Surgery, Division of Surgery, Singapore General Hospital, Singapore, Singapore.,Liver Transplant Service, SingHealth Duke-NUS Transplant Centre, Singapore, Singapore
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
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24
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Abstract
Hepatitis B virus (HBV) is a hepatotropic virus and an important human pathogen. There are an estimated 296 million people in the world that are chronically infected by this virus, and many of them will develop severe liver diseases including hepatitis, cirrhosis and hepatocellular carcinoma (HCC). HBV is a small DNA virus that replicates via the reverse transcription pathway. In this review, we summarize the molecular pathways that govern the replication of HBV and its interactions with host cells. We also discuss viral and non-viral factors that are associated with HBV-induced carcinogenesis and pathogenesis, as well as the role of host immune responses in HBV persistence and liver pathogenesis.
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Affiliation(s)
- Yu-Chen Chuang
- Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90089, USA
| | - Kuen-Nan Tsai
- Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90089, USA
| | - Jing-Hsiung James Ou
- Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90089, USA
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25
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Hur MH, Lee JH, Kim JY, Hong JH, Park MK, Cho HJ, Choi NR, Kim J, Kim MA, Nam JY, Lee YB, Cho EJ, Yu SJ, Kim YJ, Lee DH, Lee JM, Hong SK, Yi NJ, Lee KW, Suh KS, Yoon JH. Comparison of Overall Survival between Surgical Resection and Radiofrequency Ablation for Hepatitis B-Related Hepatocellular Carcinoma. Cancers (Basel) 2021; 13:cancers13236009. [PMID: 34885118 PMCID: PMC8657180 DOI: 10.3390/cancers13236009] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 11/25/2021] [Accepted: 11/27/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary The effectiveness of surgical resection and radiofrequency ablation in early hepatocellular carcinoma is still controversial because previous studies show conflicting results. In addition, previous studies did not consider the antiviral treatment-related factors, even though there is now robust evidence that antiviral therapy is crucial for determining the prognosis of patients with chronic hepatitis B-related liver cancer. After adjusting for the antiviral treatment, we demonstrated that radiofrequency ablation may provide comparable overall survival to resection in the treatment of very early or early hepatocellular carcinoma, although recurrence-free survival is marginally shorter than in the resection group. Abstract It remains controversial whether surgical resection, compared to radiofrequency ablation (RFA), improves overall survival (OS) in patients with early hepatocellular carcinoma (HCC). This study aimed to compare OS after RFA with that after resection for HCC. This retrospective study included patients who underwent RFA or surgical resection as initial treatment for hepatitis B virus (HBV)-related HCC at a very early or early stage. A total of 761 patients (RFA, n = 194; resection, n = 567) from Seoul National University Hospital (Seoul, South Korea) and 1277 patients (RFA, n = 352; resection, n = 925) from the Korean Primary Liver Cancer Registry were included in the hospital and nationwide cohorts, respectively. Primary and secondary endpoints were OS and recurrence-free survival (RFS), respectively. Additional analysis was performed when the history of the antiviral treatment and the type of prescribed nucleos(t)ide analogue were confirmed. The rate of complications was compared between the two treatment groups in the hospital cohort. Baseline characteristics were balanced, using inverse probability of treatment weighting (IPTW). In the hospital cohort, the RFA group had a smaller mean tumor size (1.7 vs. 3.9 cm) but a higher proportion of cirrhotic patients than the resection group (85.6% vs. 63.1%) (both p < 0.01). During 81.0 (interquartile range, 62.3–107.1) months of follow-up, there was no difference in OS (adjusted hazard ratio (aHR) = 0.870, 95% confidence interval (CI) = 0.400–1.897, p = 0.73) and RFA was associated with shorter RFS (aHR = 1.562, 95% CI = 1.099–2.219, p = 0.01) after employing IPTW. Antiviral treatment was independently associated with longer OS (aHR = 0.444, 95% CI = 0.251–0.786, p = 0.01) as well as RFS (aHR = 0.544, 95% CI = 0.391–0.757, p < 0.01) in the hospital cohort. In the nationwide cohort, there was no difference in OS (aHR = 0.981, 95% CI = 0.661–1.456, p = 0.92) between the two treatment groups when adjusted for antiviral treatment, which was a negative independent risk factor for mortality (aHR = 0.655, 95% CI = 0.451–0.952, p = 0.03) after IPTW. Among patients treated with tenofovir (n = 96) or entecavir (n = 184) in the hospital cohort, there was no difference in either OS (aHR = 0.522, 95% CI = 0.058–4.724, p = 0.56) or RFS (aHR = 1.116, 95% CI = 0.738–1.688, p = 0.60). The overall incidence of complications was higher in the resection group (26.3%) than in the RFA group (13.9%) (p < 0.01). RFA may provide comparable OS to resection in the treatment of very early or early HCC with a lower rate of complications, although RFS is marginally shorter than in the resection group after adjusting for antiviral treatment. Regardless of the type of NA, antiviral treatment in patients with HBV-related HCC is strongly associated with both OS and RFS.
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Affiliation(s)
- Moon Haeng Hur
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
- Correspondence:
| | - Ju Yeon Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Ji Hoon Hong
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Min Kyung Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Hee Jin Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Na Ryung Choi
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Jihye Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Minseok Albert Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Joon Yeul Nam
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Yun Bin Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (D.H.L.); (J.M.L.)
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (D.H.L.); (J.M.L.)
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (S.K.H.); (N.-J.Y.); (K.-W.L.); (K.-S.S.)
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (S.K.H.); (N.-J.Y.); (K.-W.L.); (K.-S.S.)
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (S.K.H.); (N.-J.Y.); (K.-W.L.); (K.-S.S.)
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (S.K.H.); (N.-J.Y.); (K.-W.L.); (K.-S.S.)
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea; (M.H.H.); (J.Y.K.); (J.H.H.); (M.K.P.); (H.J.C.); (N.R.C.); (J.K.); (M.A.K.); (J.Y.N.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
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Qi W, Shen J, Dai J, Wu Y, Zhang Y, Leng S, Gao F, Ran S, Peng W, Zhang X, Wen T, Li C. Comparison of nucleoside and nucleotide analogs in the recurrence of hepatitis B virus-related hepatocellular carcinoma after surgical resection: A multicenter study. Cancer Med 2021; 10:8421-8431. [PMID: 34643050 PMCID: PMC8633233 DOI: 10.1002/cam4.4348] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/31/2021] [Accepted: 09/07/2021] [Indexed: 02/05/2023] Open
Abstract
Background Antiviral therapy should reduce the recurrence of hepatitis B virus‐related hepatocellular carcinoma (HBV‐related HCC) after surgical resection. However, there is little research on whether various antiviral drugs have different prognostic effects in patients with HBV‐related HCC after curative liver resection. The present study compared the effects of nucleotide analog (NtA) and nucleoside analog (NsA) antiviral therapies after surgical resection on the prognosis of HBV‐related HCC. Methods A total of 1303 patients with HBV‐related HCC who received curative hepatectomy at five institutes between April 2014 and April 2019 were retrospectively enrolled and analyzed. Propensity matching analysis was used to compare the outcomes of HCC patients given NsA versus NtA therapy. Subgroup analysis of patients treated with entecavir (ETV) and tenofovir disoproxil fumarate (TDF) was also performed. Results Among 1303 patients, 759 (58.2%) patients developed recurrence, and 460 (35.3%) patients died. Multivariable analyses revealed that NtA therapy significantly decreased the risk of HCC recurrence (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.51–0.80; p < 0.001) and HCC‐related death (HR, 0.52; 95% CI, 0.36–0.76; p = 0.001) compared to that with NsA therapy. Subgroup analysis showed that TDF treatment was associated with significantly lower rates of HCC recurrence (HR, 0.64; 95% CI, 0.49–0.83; p = 0.001) and death (HR, 0.32; 95% CI, 0.20–0.50; p < 0.001) than ETV treatment. Conclusions Nucleotide analog treatment, but not NsA treatment, significantly reduced the risk of HCC recurrence in patients with HBV‐related HCC and improved overall survival after curative hepatic resection.
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Affiliation(s)
- Weili Qi
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Junyi Shen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Junlong Dai
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Youwei Wu
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Yu Zhang
- Organ Transplantation Center, Sichuan Provincial People's Hospital, Chengdu, Sichuan, China
| | - Shusheng Leng
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Fengwei Gao
- HBPS Diseases Center for Diagnosis and Treatment of Leshan City, People's Hospital of Leshan, Leshan, Sichuan, China
| | - Shun Ran
- Department of Hepatopancreatobiliary Surgery, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Wei Peng
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Xiaoyun Zhang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Tianfu Wen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Chuan Li
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
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Tsai MC, Wang CC, Lee WC, Lin CC, Chang KC, Chen CH, Hung CH, Lin MT, Hsiao CC, Chen CL, Chien RN, Hu TH. Tenofovir Is Superior to Entecavir on Tertiary Prevention for BCLC Stage 0/A Hepatocellular Carcinoma after Curative Resection. Liver Cancer 2021; 11:22-37. [PMID: 35222505 PMCID: PMC8820175 DOI: 10.1159/000518940] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 08/09/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have different effects on hepatocellular carcinoma (HCC) recurrence and death in patients receiving curative hepatectomy for hepatitis B virus (HBV)-related HCC. AIMS The aim of this study was to compare the long-term efficacy of ETV and TDF in HCC recurrence and overall survival (OS) of patients after curative hepatectomy. METHODS From January 2010 to December 2019, 20,572 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 219 consecutive patients treated with ETV (n = 146) or TDF (n = 73) after curative hepatectomy for HBV-related HCC of Barcelona Clinic Liver Cancer stage 0 or A were analyzed by propensity score matching (PSM) (2:1) analysis and competing risk analysis. HCC recurrence and OS of patients were compared between ETV and TDF groups. RESULT After a median follow-up of 52.2 months, 81 patients (37.0%) had HCC recurrence, 33 (15.1%) died, and 5 (2.3%) received liver transplantation. TDF therapy was an independent protective factor for HCC recurrence compared with ETV therapy (HR, 1.687; 95% CI, 1.027-2.770, p = 0.039); however, no difference in the risk of death or liver transplantation. Results were similar in competing risk analysis. We further found that TDF therapy was significantly associated with a lower risk of late recurrence (HR, 4.705; 95% CI, 1.763-12.558, p = 0.002), but not in early recurrence. CONCLUSIONS TDF therapy is associated with a significantly lower risk of HCC recurrence, especially of late recurrence, than ETV therapy among patients who undergo curative hepatectomy for HBV-related early-stage HCC.
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Affiliation(s)
- Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan,Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chih-Che Lin
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Kuo-Chin Chang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Tsung Lin
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chang-Chun Hsiao
- Division of Pulmonary and Critical Care Medicine, Graduate Institute of Clinical Medical Sciences, College of Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung, Taiwan
| | - Chao-Long Chen
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Rong-Nan Chien
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Linko Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan,*Tsung-Hui Hu,
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Huang D, Yang B, Yao Y, Liao M, Zhang Y, Zeng Y, Zhang F, Wang N, Tong G. Autophagic Inhibition of Caveolin-1 by Compound Phyllanthus urinaria L. Activates Ubiquitination and Proteasome Degradation of β-catenin to Suppress Metastasis of Hepatitis B-Associated Hepatocellular Carcinoma. Front Pharmacol 2021; 12:659325. [PMID: 34168559 PMCID: PMC8217966 DOI: 10.3389/fphar.2021.659325] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 05/24/2021] [Indexed: 12/29/2022] Open
Abstract
Compound Phyllanthus urinaria L. (CP) is a traditional Chinese medicine (TCM) formula for cancer treatment in the clinic, particularly during progression of hepatitis B-associated hepatocellular carcinoma (HBV-associated HCC). Nevertheless, its anti-metastatic action and mechanisms are not well elucidated. In this study, CP was found to exert remarkable inhibitory effects on the proliferation, migration and invasion of HBV-associated HCC cells. The following network and biological analyses predicted that CP mainly targeted Caveolin-1 (Cav-1) to induce anti-metastatic effects, and Wnt/β-catenin pathway was one of the core mechanisms of CP action against HBV-associated HCC. Further experimental validation implied that Cav-1 overexpression promoted metastasis of HBV-associated HCC by stabilizing β-catenin, while CP administration induced autophagic degradation of Cav-1, activated the Akt/GSK3β-mediated proteasome degradation of β-catenin via ubiquitination activation, and subsequently attenuated the metastasis-promoting effect of Cav-1. In addition, the anti-cancer and anti-metastatic action of CP was further confirmed by in vivo and ex vivo experiments. It was found that CP inhibited the tumor growth and metastasis of HBV-associated HCC in both mice liver cancer xenograft and zebrafish xenotransplantation models. Taken together, our study not only highlights the novel function of CP formula in suppressing metastasis of HBV-associated HCC, but it also addresses the critical role of Cav-1 in mediating Akt/GSK3β/β-catenin axis to control the late-phase of cancer progression.
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Affiliation(s)
- Danping Huang
- Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Bowen Yang
- The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yaoyao Yao
- The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Mianmian Liao
- The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yu Zhang
- The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yihao Zeng
- The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Fengxue Zhang
- The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Neng Wang
- The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.,Department of Medical Biotechnology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Guangdong Tong
- Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
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The Different Effects of Nucleotide and Nucleoside Analogues on the Prognosis of HBV-Related HCC After Curative Resection. J Gastrointest Surg 2021; 25:1419-1429. [PMID: 32410175 DOI: 10.1007/s11605-020-04633-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Accepted: 04/25/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND Postoperative oral antiviral treatment with nucleoside or nucleotide analogues can suppress viral replication and reduce tumour recurrence for patients with hepatitis b virus-related hepatocellular carcinoma (HBV-related HCC) after curative resection. However, the superior antiviral treatment is still unclear. We conducted this study to investigate the different effects of nucleotide and nucleoside analogues on the prognosis of HBV-related HCC after curative resection. METHODS From February 2007 to February 2016, 487 consecutive patients with newly diagnosed HCC according to the Milan criteria who underwent R0 resection were enrolled according to the inclusion and exclusion criteria. According to their postoperative antiviral treatment, they were divided into the nucleotide group (NtA, n = 111) and the nucleoside group (NsA, n = 376). RESULTS The baseline characteristics, serologic parameters, tumour characteristics, and operative data of the 2 groups were comparable. Nucleotide analogue use significantly decreased HCC recurrence (P = 0.028) and HCC-related death (P = 0.004), with hazard ratios (HRs) of 0.685 (95% CI, 0.484 to 0.971, P = 0.033) and 0.507 (95% CI, 0.310 to 0.830, P = 0.004), respectively, in multivariate Cox analyses. After the study patients were stratified according to three variables, we found that nucleotide analogue use was significantly associated with increased disease-free and overall survival among patients with cirrhosis, HBeAg-negative patients, and patients with positive HBV-DNA. CONCLUSIONS In patients with HBV-related HCC, nucleotide analogues but not nucleoside analogues significantly reduced HCC recurrence and improved overall survival after R0 hepatic resection.
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Jang JW, Yoo SH, Nam HC, Jang BH, Sung Sung PS, Lee W, Kwon JH, Nam SW, Bae SH, Yoon SK, Choi JY. Association of Prophylactic Anti-Hepatitis B Virus Therapy With Improved Long-term Survival in Patients With Hepatocellular Carcinoma Undergoing Transarterial Therapy. Clin Infect Dis 2021; 71:546-555. [PMID: 31504352 DOI: 10.1093/cid/ciz860] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 08/30/2019] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND The effect of prophylactic antiviral therapy (AVT) on survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine whether prophylactic AVT could improve long-term survival in patients undergoing transarterial chemotherapy (TAC). METHODS Between 2002 and 2016, 2860 newly diagnosed HBV-related patients with HCC treated with TAC were screened to analyze 2 groups based on prophylactic use of antivirals. Treatment effects were analyzed using propensity score (PS) matching (1:1) separately for the entire cohort and each subgroup. The primary endpoint was overall survival. RESULTS A total of 1547 patients met the inclusion criteria and 1084 were PS matched for the 2 groups. Median follow-up duration was 16.55 months. In the entire unmatched cohort, patients receiving prophylactic AVT survived significantly longer than those who did not. Among AVT-untreated patients, baseline high viremia and HBV reactivation during treatment were significantly associated with shorter survival. Regarding types of antivirals, survival was significantly longer for patients receiving high-potency antivirals than those receiving low-potency antivirals. Survival differed with antiviral response. In the PS-matched cohort, the prophylactic AVT group survived significantly longer than the nonprophylactic group, irrespective of viral status or tumor stage. Prophylactic AVT remained an independent factor for survival. The association of prophylactic AVT with decreased risk of mortality persisted in patient subgroups after adjusting for baseline risk factors. Sensitivity analyses also confirmed estimated treatment effects. CONCLUSIONS Prophylactic AVT is associated with significantly improved long-term survival among patients undergoing TAC. High-potency antivirals are indicated for this approach.Hepatitis B virus-associated morbidity is a well-known complication during transarterial chemotherapy (TAC). Our large-scale study demonstrated that prophylactic therapy with high-potency antivirals provides a significantly better survival in TAC-treated patients, irrespective of baseline viremia status or tumor stage.
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Affiliation(s)
- Jeong Won Jang
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Sun Hong Yoo
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Hee Chul Nam
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Bo Hyun Jang
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Pil Soo Sung Sung
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Won Lee
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Jung Hyun Kwon
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Soon Woo Nam
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Seung Kew Yoon
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Jong Young Choi
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
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Tertiary Prevention of HCC in Chronic Hepatitis B or C Infected Patients. Cancers (Basel) 2021; 13:cancers13071729. [PMID: 33917345 PMCID: PMC8038691 DOI: 10.3390/cancers13071729] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 03/29/2021] [Accepted: 03/29/2021] [Indexed: 01/27/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) recurrence is the major obstacle concerning patients’ survival. Tertiary prevention by antiviral therapies could reduce HCC recurrence rate in both chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infected patients. In chronic hepatitis B (CHB) patients, nucleos(t)ide analogues (Nuc) provide a more effective HCC tertiary prevention effect than an interferon (IFN)-based regimen. In chronic hepatitis C (CHC) patients, the tertiary prevention effect by direct acting antiviral agents (DAAs) was reported non-inferior to that by IFN-based therapy. Chronic hepatitis C patients left untreated had the worst survival benefit as well as shorted recurrence-free interval than those treated by either type of antiviral regimen. Although the risk of HCC recurrence could only be decreased but not diminished by antiviral therapies due to host and microenvironmental factors beyond virus infection, antiviral therapy helps to preserve and improve liver function which makes multi-modality anticancer treatment feasible to improve survival. Abstract Hepatocellular carcinoma (HCC) ranks as a leading cause of common cancer and cancer-related death. The major etiology of HCC is due to chronic hepatitis virus including HBV and HCV infections. Scheduled HCC surveillance in high risk populations improves the early detection rate and the feasibility of curative treatment. However, high HCC recurrence rate still accounts for the poor prognosis of HCC patients. In this article, we critically review the pathogenesis of viral hepatitis-related hepatocellular carcinoma and the evidence of tertiary prevention efficacy by current available antiviral treatment, and discuss the knowledge gap in viral hepatitis-related HCC tertiary prevention.
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BATTISTELLA S, LYNCH EN, GAMBATO M, ZANETTO A, PELLONE M, SHALABY S, SCIARRONE SS, FERRARESE A, GERMANI G, SENZOLO M, BURRA P, RUSSO FP. Hepatocellular carcinoma risk in patients with HBV-related liver disease receiving antiviral therapy. Minerva Gastroenterol (Torino) 2021; 67:38-49. [DOI: 10.23736/s2724-5985.20.02791-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Choi J, Jo C, Lim YS. Tenofovir Versus Entecavir on Recurrence of Hepatitis B Virus-Related Hepatocellular Carcinoma After Surgical Resection. Hepatology 2021; 73:661-673. [PMID: 32324905 DOI: 10.1002/hep.31289] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Revised: 03/28/2020] [Accepted: 04/10/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Studies have suggested that tenofovir disoproxil fumarate (TDF) treatment is associated with a significantly lower risk of hepatocellular carcinoma (HCC) occurrence when compared with entecavir (ETV) therapy in patients with chronic hepatitis B. We aimed to compare HCC recurrence and survival of patients treated with TDF or ETV after surgical resection for hepatitis B virus (HBV)-related HCC. APPROACH AND RESULTS This historical cohort study included 1,695 consecutive patients treated with ETV (n = 813) or TDF (n = 882) after curative-intent hepatectomy for HBV-related HCC of Barcelona Clinic Liver Cancer stage 0 or A in Korea between 2010 and 2018. HCC recurrence and overall survival of patients were compared between ETV and TDF groups by propensity score-matched and multivariable-adjusted Cox regression analyses from the date of hepatectomy for HCC. The mean age of the study patients was 54.8 years, and 1,294 patients (76.3%) were male. During the median follow-up duration of 37.6 months with continued ETV or TDF therapy, 561 (33.1%) patients developed HCC recurrence, 144 (8.4%) died, and 22 (1.3%) received liver transplant. Compared with ETV, TDF therapy was associated with significantly higher recurrence-free (P = 0.02) and overall survival (P = 0.03) rates by propensity score-matched analysis. By multivariable-adjusted analysis, the TDF group was associated with significantly lower rates of HCC recurrence (hazard ratio [HR], 0.82; 95% confidence interval, 0.68-0.98; P = 0.03), and death or transplantation (HR, 0.62; 95% confidence interval, 0.44-0.88; P = 0.01). TDF therapy was an independent protective factor for both early (<2 years; HR, 0.79; P = 0.03) and late (≥2 years; HR, 0.68; P = 0.03) postoperative HCC recurrence. CONCLUSIONS Among patients who underwent curative hepatectomy for HBV-related HCC, TDF therapy was associated with a significantly lower risk of HCC recurrence and better overall patient survival compared with ETV therapy.
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Affiliation(s)
- Jonggi Choi
- Department of GastroenterologyLiver CenterAsan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea
| | - Chanyoung Jo
- Department of Internal MedicineAsan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea
| | - Young-Suk Lim
- Department of GastroenterologyLiver CenterAsan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea
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Abstract
Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). There are approximately 250 million people in the world that are chronically infected by this virus, resulting in nearly 1 million deaths every year. Many of these patients die from severe liver diseases, including HCC. HBV may induce HCC through the induction of chronic liver inflammation, which can cause oxidative stress and DNA damage. However, many studies also indicated that HBV could induce HCC via the alteration of hepatocellular physiology that may involve genetic and epigenetic changes of the host DNA, the alteration of cellular signaling pathways, and the inhibition of DNA repair mechanisms. This alteration of cellular physiology can lead to the accumulation of DNA damages and the promotion of cell cycles and predispose hepatocytes to oncogenic transformation.
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Affiliation(s)
- Jiyoung Lee
- Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2011 Zonal Avenue, HMR-401, Los Angeles, CA, 90033, USA
| | - Kuen-Nan Tsai
- Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2011 Zonal Avenue, HMR-401, Los Angeles, CA, 90033, USA
| | - Jing-Hsiung James Ou
- Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2011 Zonal Avenue, HMR-401, Los Angeles, CA, 90033, USA.
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He Z, Chen J, Wang J, Xu L, Zhou Z, Chen M, Zhang Y, Shi M. Expression of hepatitis B surface antigen in liver tissues can serve as a predictor of prognosis for hepatitis B virus-related hepatocellular carcinoma patients after liver resection. Eur J Gastroenterol Hepatol 2021; 33:76-82. [PMID: 32049678 PMCID: PMC7704243 DOI: 10.1097/meg.0000000000001698] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 12/19/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND Hepatitis B surface antigen (HBsAg) is a detectable index after hepatitis B virus (HBV) infection, which is a risk factor of hepatocellular carcinoma (HCC). However, few studies have focused on the expression of HBsAg in HCC patients' liver tissues. This study aimed to explore the potential utility of using HBsAg protein expression in normal liver tissues as a prognostic factor for HCC patients who underwent liver resection. STUDY DESIGN The study enrolled 100 HCC patients with seropositivity for HBsAg. The liver tissues were collected, and tissue microarrays were constructed. The expression of HBsAg in liver tissues were measured by immunohistochemistry (IHC). Relevant clinical data and follow-up records were collected for analysis. RESULTS HBsAg expressions was detected in 29 patients (positive group) and was unable to be detected in the remaining 71 patients (negative group). The patients in the positive group had higher HBV DNA levels (P < 0.05) than the patients in the negative group. The overall survival (OS) rate of the positive group was worse than the OS rate of the negative group (P = 0.013). The OS rates after resection at 1 and 2 years in negative group were 90.1% and 85.7%, respectively, while the value in the positive group were 79.3% and 65.5%, respectively. Multivariate analysis showed that HBsAg expression in liver tissues, ascites and alpha-fetoprotein levels were independent factors influencing OS. Similarly, after propensity score matching (PSM), the OS was worse in the positive group than in the negative group, and HBsAg expression could also serve as a predictor for OS (P = 0.039). The OS rates after resection and PSM at 1 and 2 years were 93.2% and 85.9% in the negative group, while the value in the positive group were 79.3% and 65.5%. CONCLUSION As determined according to grouping based on immunohistochemistry staining results for HBsAg, this study indicated that HBsAg expression in liver tissues could predict the OS of HBV-related HCC patients after liver resection.
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Affiliation(s)
- Ziming He
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Jinbin Chen
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Juncheng Wang
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Li Xu
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Zhongguo Zhou
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Minshan Chen
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Yaojun Zhang
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Mude Shi
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center
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Wu CJ, Chau GY, Lee IC, Huo TI, Su CW, Hou MC, Huang YH. Early and late recurrence of surgically resected hepatitis B virus-related hepatocellular carcinoma on nucleos(t)ide analogues therapy. J Formos Med Assoc 2020; 120:1563-1571. [PMID: 33334659 DOI: 10.1016/j.jfma.2020.11.019] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 10/25/2020] [Accepted: 11/23/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/PURPOSE Hepatocellular carcinoma (HCC) is a highly recurrent tumor. Antiviral therapy with nucleos(t)ide analogues (NUCs) may reduce the risk of recurrence in hepatitis B virus (HBV)-related HCC. The risk factors associated with recurrence in HCC patients after surgical resection and with NUCs treatment should be delineated. METHODS Consecutive 339 HBV-related HCC patients receiving surgical resection of HCC with NUCs therapy (including 256 entecavir, 36 tenofovir, and 18 lamivudine) after the surgery were retrospectively reviewed. Factors related to the recurrence-free survival (RFS) and overall survival (OS) were evaluated. RESULTS After a median of 48.5 months of follow-up, 183 (54%) patients developed HCC recurrence, with the 5-year RFS of 42.8% and OS of 79%. Male gender (HR = 1.736, p = 0.037), baseline HBsAg level >200 IU/ml (HR = 1.748, p = 0.008), platelet count ≦100 (109/L) (HR = 1.592, p = 0.023), presence of microscopic vascular invasion (MVI) (HR = 1.499, p = 0.026), safety cut margin of ≦0.5 cm (HR = 1.507, p = 0.013), and Ishak fibrosis score 5-6 (HR = 1.579, p = 0.009) were independent factors associated with RFS in multivariate analysis. While tumor burden, platelet count, MVI, and safety cut margin were factors associated with early recurrence; baseline HBsAg level, and platelet count were independent factors associated with late recurrence. Ishak fibrosis score 5-6, poor differentiation, MVI, diabetes mellitus were factors associated with OS in multivariate analysis. CONCLUSION For HBV-HCC patients on NUCs treatment, tumor factors are associated with early recurrence, while HBsAg level and thrombocytopenia determines late recurrence. For patient with a high baseline HBsAg level, warning of higher risk of recurrence is required even under NUCs treatment.
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Affiliation(s)
- Chi-Jung Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Gar-Yang Chau
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - I-Cheng Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University School of Medicine, 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; Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, 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, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
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Yu Z, Feng H, Zhuo Y, Li M, Zhu X, Huang L, Zhang X, Zhou Z, Zheng C, Jiang Y, Le F, Yu DY, Cheng AS, Sun X, Gao Y. Bufalin inhibits hepatitis B virus-associated hepatocellular carcinoma development through androgen receptor dephosphorylation and cell cycle-related kinase degradation. Cell Oncol (Dordr) 2020; 43:1129-1145. [PMID: 32623699 DOI: 10.1007/s13402-020-00546-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/23/2020] [Indexed: 12/30/2022] Open
Abstract
PURPOSE Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), which has a male predominance, lacks effective therapeutic options. Previously, the cardiac glycoside analogue bufalin has been found to inhibit HBV infection and HCC development. As yet, however, its molecular role in HBV-associated HCC has remained obscure. METHODS Colony formation and soft agar assays, xenograft and orthotopic mouse models and HBV X protein (HBx) transgenic mice with exposure to diethylnitrosamine were used to evaluate the effect of bufalin on HBV-associated HCC growth and tumorigenicity. HBx-induced oncogenic signaling regulated by bufalin was assessed using PCR array, chromatin immunoprecipitation, site-directed mutagenesis, luciferase reporter, transcription and protein expression assays. Synergistic HCC therapeutic effects were examined using combinations of bufalin and sorafenib. RESULTS We found that bufalin exerted a more profound effect on inhibiting the proliferation of HBV-associated HCC cells than of non HBV-associated HCC cells. Bufalin significantly inhibited HBx-induced malignant transfromation in vitro and tumorigenicity in vivo. Androgen receptor (AR) signaling was found to be a target of bufalin resistance to HBV-associated hepatocarcinogenesis. We also found that bufalin induced both AR dephosphorylation and cell cycle-related kinase (CCRK) degradation to inhibit β-catenin/TCF signaling, which subsequently led to cell cycle arrest via cyclin D1 down-regulation and p21 up-regulation, resulting in HCC regression. Furthermore, we found that bufalin reduced > 60% diethylnitrosamine-induced hepatocarcinogenesis in HBx transgenic mice, and improved the sensitivity of refractory HBV-associated HCC cells to sorafenib treatment. CONCLUSION Our results indicate that bufalin acts as a potential anti-HCC therapeutic candidate to block HBx-induced AR/CCRK/β-catenin signaling by targeting AR and CCRK, which may provide a novel strategy for the treatment of HBV-associated HCC.
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Affiliation(s)
- Zhuo Yu
- Liver Disease Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No.528. Zhangheng Road, Pudong New District, Shanghai, People's Republic of China.
| | - Hai Feng
- Department of pharmacology, School of Pharmacy, Harbin Medical University, Harbin, People's Republic of China
| | - Yunhui Zhuo
- Liver Disease Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No.528. Zhangheng Road, Pudong New District, Shanghai, People's Republic of China
| | - Man Li
- Laboratory of Cellular Immunity, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Xiaojun Zhu
- Liver Disease Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No.528. Zhangheng Road, Pudong New District, Shanghai, People's Republic of China
| | - Lingying Huang
- Liver Disease Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No.528. Zhangheng Road, Pudong New District, Shanghai, People's Republic of China
| | - Xin Zhang
- Laboratory of Cellular Immunity, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Zhenhua Zhou
- Laboratory of Cellular Immunity, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Chao Zheng
- Liver Disease Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No.528. Zhangheng Road, Pudong New District, Shanghai, People's Republic of China
| | - Yun Jiang
- Liver Disease Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No.528. Zhangheng Road, Pudong New District, Shanghai, People's Republic of China
| | - Fan Le
- Liver Disease Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No.528. Zhangheng Road, Pudong New District, Shanghai, People's Republic of China
| | - Dae-Yeul Yu
- Disease Model Research Laboratory, Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Republic of Korea
| | - Alfred Szelok Cheng
- School of Biomedical Sciences, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China
| | - Xuehua Sun
- Liver Disease Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No.528. Zhangheng Road, Pudong New District, Shanghai, People's Republic of China.
| | - Yueqiu Gao
- Liver Disease Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No.528. Zhangheng Road, Pudong New District, Shanghai, People's Republic of China. .,Laboratory of Cellular Immunity, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
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Ge Z, Ma J, Qiao B, Wang Y, Zhang H, Gou W. Impact of tenofovir antiviral treatment on survival of chronic hepatitis B related hepatocellular carcinoma after hepatectomy in Chinese individuals from Qingdao municipality. Medicine (Baltimore) 2020; 99:e21454. [PMID: 32769872 PMCID: PMC7593059 DOI: 10.1097/md.0000000000021454] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
The impact of different antiviral regimen on prognosis of chronic hepatitis B (CHB) related hepatocellular carcinoma (HCC) remains to be explored.A total of 479 CHB-related HCC patients after curative liver resection were enrolled receiving tenofovir (TDF, TDF group) or lamivudine, telbivudine, and entecavir (non-TDF group). Both the overall survival and diseases-free survival were analyzed and compared.A total of 242 patients received TDF treatment and 237 patients received other antiviral regimen. Child-Pugh score, serum α-fetoprotein (AFP) level, total bilirubin level, status of hepatitis B e antigen (HBeAg), and cirrhosis were compared between groups. Kaplan-Meier analysis revealed that patients with TDF treatment had significantly longer overall survival than those of patients with other regimen (P = .015). Similarly, compared with patients with non-TDF treatment, disease-free survival time was longer (P = .042) in those with TDF treatment. Multivariate analysis showed that TDF treatment (P = .04), AFP level (P = .03) were significant independent factors associated with overall survival of CHB-related HCC patients. While TDF treatment (P = .04) and serum AFP level (P = .03) were independent factors associated with disease-free survival.Anti-virus treatment with TDF benefits for both overall survival and disease-free survival of CHB-related patients than other Nucleos(t)ide analogues.
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Affiliation(s)
- Zhong Ge
- Department of Hepatobiliary-Pancreatic Surgery
| | - Jian Ma
- Department of Health Care, Qingdao Municipal Hospital, Qingdao University, Qingdao,
| | - Bing Qiao
- 6th Department, Qingdao No. 6 People's Hospital
| | - Yanling Wang
- Dermatological Department, No. 6 People's Hospital, Qingdao, Shandong Province, China
| | | | - Wei Gou
- 6th Department, Qingdao No. 6 People's Hospital
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2019; 20:1042-1113. [PMID: 31270974 PMCID: PMC6609431 DOI: 10.3348/kjr.2019.0140] [Citation(s) in RCA: 191] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 02/24/2019] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Gut Liver 2019; 13:227-299. [PMID: 31060120 PMCID: PMC6529163 DOI: 10.5009/gnl19024] [Citation(s) in RCA: 239] [Impact Index Per Article: 39.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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Precancer antiviral treatment reduces microvascular invasion of early-stage Hepatitis B-related hepatocellular carcinoma. Sci Rep 2019; 9:2220. [PMID: 30778112 PMCID: PMC6379412 DOI: 10.1038/s41598-019-39440-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 01/24/2019] [Indexed: 12/13/2022] Open
Abstract
The impact of antiviral therapy before tumorigenesis on microvascular invasion (MVI) of Chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) is still unknown. In this retrospective cohort study 3,276 HCC patients with early-stage who underwent curative resection were included. We investigated the effect of precancer antiviral therapy on the pathology, especially MVI, of CHB-related HCC. MVI occurrence rates of CHB-related HCC stratified by histopathologic inflammation grades of G1, G2, and G3 were 30.4%, 34.7%, and 38.6%, respectively, compared to 19.8% for CHB-negative HCC. Patients who received standard antiviral treatment showed much lower rates of MVI, higher tumor capsule integrity, less frequent satellite micronodules and lower AFP level compared to the no antiviral group. Moreover, precancer antiviral therapy prolonged the disease-free survival (DFS), which are also proved to be independent indicators of DFS. In addition, we show that antivirals may suppress early progression of HCC primarily by inhibition of HBV viral load, and influencing the expression levels of CK18, GPC3, OPN and pERK. Hence, we demonstrate that precancer antivirals significantly reduce the MVI rate of CHB-related HCC, reduce malignancy of early-stage HCC, and improve HCC prognosis. Thus, this study confirms the importance of antiviral therapy for CHB patients.
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Mai RY, Ye JZ, Long ZR, Shi XM, Bai T, Chen J, Li LQ, Wu GB, Wu FX. Preoperative aspartate aminotransferase-to-platelet-ratio index as a predictor of posthepatectomy liver failure for resectable hepatocellular carcinoma. Cancer Manag Res 2019; 11:1401-1414. [PMID: 30863151 PMCID: PMC6388945 DOI: 10.2147/cmar.s186114] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Purpose This study aimed to investigate the efficacy of preoperative aspartate aminotransferase-to-platelet-ratio index (APRI) score to predict the risk of posthepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) after liver resection, and to compare the discriminatory performance of the APRI with the Child–Pugh score, model for end-stage liver disease (MELD) score, and albumin–bilirubin (ALBI) score. Patients and methods A total of 1,044 consecutive patients with HCC who underwent liver resection were enrolled and studied. Univariate and multivariate analyses were performed to investigate risk factors associated with PHLF. Predictive discrimination of Child–Pugh, MELD, ALBI, and APRI scores for predicting PHLF were assessed according to area under the ROC curve. The cutoff value of the APRI score for predicting PHLF was determined by ROC analysis. APRI scores were stratified by dichotomy to analyze correlations with incidence and grade of PHLF. Results PHLF occurred in 213 (20.4%) patients. Univariate and multivariate analyses revealed that Child–Pugh, MELD, ALBI, and APRI scores were significantly associated with PHLF. Area under the ROC analysis revealed that the APRI score for predicting PHLF was significantly more accurate than Child–Pugh, MELD, or ALBI scores. With an optimal cutoff value of 0.55, the sensitivity and specificity of the APRI score for predicting PHLF were 72.2% and 68.0%, respectively, and the incidence and grade of PHLF in patients with high risk (APRI score >0.55) was significantly higher than in the low-risk cohort (APRI score <0.55). Conclusion The APRI score predicted PHLF in patients with HCC undergoing liver resection more accurately than Child–Pugh, MELD, or ALBI scores.
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Affiliation(s)
- Rong-Yun Mai
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Zhuangzu 530021, China, ;
| | - Jia-Zhou Ye
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Zhuangzu 530021, China, ;
| | - Zhong-Rong Long
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Zhuangzu 530021, China, ;
| | - Xian-Mao Shi
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Zhuangzu 530021, China, ;
| | - Tao Bai
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Zhuangzu 530021, China, ;
| | - Jie Chen
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Zhuangzu 530021, China, ;
| | - Le-Qun Li
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Zhuangzu 530021, China, ;
| | - Guo-Bin Wu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Zhuangzu 530021, China, ;
| | - Fei-Xiang Wu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Zhuangzu 530021, China, ;
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Efficacy of Nucleoside Analogs for Chronic Hepatitis B Virus-Related Hepatocellular Carcinoma After Curative Treatment: A Meta-Analysis. Dig Dis Sci 2018; 63:3207-3219. [PMID: 30140982 DOI: 10.1007/s10620-018-5252-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Accepted: 08/14/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIM The efficacy of nucleoside analogs (NAs) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative treatment remains unclear. The present study aimed to evaluate the efficacy of these agents by conducting a comprehensive meta-analysis of available studies. METHODS We searched several databases including Pubmed, Embase, Cochrane Library, Clinical Trials, and Web of Science, according to PRISMA guidelines. We considered all randomized controlled trials and cohort studies that met the inclusion criteria. Statistical analyses were conducted using Review Manager 5.3 and Stata 14.0. RESULTS Twenty-one studies with 8752 participants were included in the final analysis. The pooled data showed that patients treated with NAs had significantly lower 1- and 3-year HCC recurrence rates (relative risk [RR] 0.76, 95% confidence interval [CI] 0.65-0.90; P = 0.001 and RR 0.79, 95% CI 0.71-0.88; P < 0.001, respectively), but there was no difference in 5-year recurrence rates (RR 0.87, 95% CI 0.74-1.03; P = 0.10). Regarding overall survival (OS), patients treated with NAs had significantly higher 1-, 3-, and 5-year OS rates (RR 1.05, 95% CI 1.02-1.08; P = 0.003; RR 1.25, 95% CI 1.16-1.34; P < 0.001; and RR 1.28, 95% CI 1.18-1.39; P < 0.001, respectively). CONCLUSION NA therapy has the potential to reduce the risk of early recurrence and improve OS in patients with HBV-related HCC after curative treatment, compared with placebo or no treatment. Further research including more homogeneous studies with large sample sizes is required to improve the reliability of these conclusions.
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Beckebaum S, Herzer K, Bauhofer A, Gelson W, De Simone P, de Man R, Engelmann C, Müllhaupt B, Vionnet J, Salizzoni M, Volpes R, Ercolani G, De Carlis L, Angeli P, Burra P, Dufour JF, Rossi M, Cillo U, Neumann U, Fischer L, Niemann G, Toti L, Tisone G. Recurrence of Hepatitis B Infection in Liver Transplant Patients Receiving Long-Term Hepatitis B Immunoglobulin Prophylaxis. Ann Transplant 2018; 23:789-801. [PMID: 30420590 PMCID: PMC6249983 DOI: 10.12659/aot.910176] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Long-term real-world data are relatively sparse regarding recurrence of chronic hepatitis B virus (HBV) infection after liver transplantation using hepatitis B immunoglobulin (HBIg) and nucleos(t)ide analogue (NUC) prophylaxis. MATERIAL AND METHODS Data from 371 adults transplanted for HBV-related disease at 20 European centers and given HBIg for ³12 months ± NUC therapy were analyzed retrospectively. RESULTS HBIg comprised Hepatect® (iv HBIgB; n=299), subcutaneous Zutectra® (sc HBIg, n=236), and other HBIg preparations (n=130); 93.5% received NUC therapy. Mean follow-up was 6.8±3.5 years. The primary efficacy variable, freedom from HBV recurrence, occurred in 95.7% of patients (95% CI [93.1%, 97.5%]). The observed incidence of recurrence was 16/371 (4.3%) (annual rate 0.65%); 5/16 patients with recurrence had discontinued HBIg and 7/16 had anti-HBs <100 IU/l. Excluding these 7 patients, the HBV recurrence rate was 2.4%. The recurrence rate while on HBIg therapy was 1 per 2069 months. In patients who discontinued HBIg, risk of HBV recurrence versus sc HBIg users was increased by 5.2-fold (1 per 1 603 versus 1 per 8379 treatment months). The annual rate of HBV-related hepatocellular carcinoma (HCC) recurrence was 1.7%. CONCLUSIONS These results support the long-term use of HBIg with NUC therapy as an effective management strategy to minimize risk of HBV recurrence and virus-related complications after liver transplantation.
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Affiliation(s)
- Susanne Beckebaum
- Department of Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - Kerstin Herzer
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Artur Bauhofer
- Corporate Medical Affairs and Corporate Clinical Research and Development, Biotest AG, Dreieich, Germany
| | - William Gelson
- Cambridge Liver Unit, Addenbrooke’s Hospital, Cambridge, U.K
| | - Paolo De Simone
- Hepatobiliary Surgery and Liver Transplantation, Chirurgia Epatica e del Trapianto Fegato Pisa, Pisa, Italy
| | - Robert de Man
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Cornelius Engelmann
- Department of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany
| | - Beat Müllhaupt
- Swiss HPB Center and Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
| | - Julien Vionnet
- Transplantation Centre and Service of Gastroenterology and Hepatology, Lausanne, Switzerland
| | - Mauro Salizzoni
- Chirurgia Generale 2U, Centro Trapianto Fegato, AO Città della Salute e della Scienza di Torino, Turin, Italy
| | - Riccardo Volpes
- Hepatology and Gastroenterology Unit, ISMETT-IRCCS, Palermo, Italy
| | - Giorgio Ercolani
- Department of General Surgery, Morgagni-Pierantoni General Hospital, University of Bologna, Bologna, Italy
| | - Luciano De Carlis
- Surgery and Abdominal Transplantation Division, Niguarda Ca’ Granda Hospital, Milan, Italy
| | - Paolo Angeli
- Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy
| | - Jean-François Dufour
- University Clinic for Visceral Surgery and Medicine, Inselspital, Bern, Switzerland
| | - Massimo Rossi
- Department of General Surgery and Organ Transplantation, Umberto I Policlinic, Sapienza University, Rome, Italy
| | - Umberto Cillo
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padova, Italy
| | - Ulf Neumann
- Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Aachen, Germany
| | - Lutz Fischer
- Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Gabriele Niemann
- Corporate Medical Affairs and Corporate Clinical Research and Development, Biotest AG, Dreieich, Germany
| | - Luca Toti
- Transplant Centre, Faculty of Medicine, Azienda Ospedaliera Policlinico Tor Vergata, Rome, Italy
| | - Giuseppe Tisone
- Transplant Centre, Faculty of Medicine, Azienda Ospedaliera Policlinico Tor Vergata, Rome, Italy
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46
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Zhao LY, Huo RR, Xiang X, Torzilli G, Zheng MH, Yang T, Liang XM, Huang X, Tang PL, Xiang BD, Li LQ, You XM, Zhong JH. Hepatic resection for elderly patients with hepatocellular carcinoma: a systematic review of more than 17,000 patients. Expert Rev Gastroenterol Hepatol 2018; 12:1059-1068. [PMID: 30145919 DOI: 10.1080/17474124.2018.1517045] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND With the aging population and increasing incidence of hepatic malignancies in elderly patients, establishing the safety and efficacy of hepatic resection for elderly patients with hepatocellular carcinoma (HCC) is crucial. The present systematic review investigates postoperative morbidity, hospital mortality, median survival time, overall and disease-free survival in elderly patients with undergoing hepatic resection. METHODS Some databases were systematically searched for prospective or retrospective studies to reveal the safety and efficacy of hepatic resection for elderly patients with primary HCC. RESULTS Fifty studies involving 4,169 elderly patients and 13,158 young patients with HCC were included into analyses. Elderly group patients had similar rate of median postoperative morbidity (28.2% vs. 29.6%) but higher mortality (3.0% vs. 1.2%) with young group patients. Moreover, elderly group patients had slightly lower median survival time (55 vs. 58 months), 5-years overall survival (51% vs. 56%) and 5-years disease-free survival (27% vs. 28%) than young group patients. There was an upward trend in 5-years overall and disease-free survival in either elderly or young group. CONCLUSION Though old age may increase the risk of hospital mortality for patients with HCC after hepatic resection, elderly patients can obtain acceptable long-term prognoses from hepatic resection.
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Affiliation(s)
- Ling-Yun Zhao
- a Hepatobiliary Surgery Department , Affiliated Tumor Hospital of Guangxi Medical University , Nanning , China
| | - Rong-Rui Huo
- a Hepatobiliary Surgery Department , Affiliated Tumor Hospital of Guangxi Medical University , Nanning , China
| | - Xiao Xiang
- a Hepatobiliary Surgery Department , Affiliated Tumor Hospital of Guangxi Medical University , Nanning , China
| | - Guido Torzilli
- b Department of Surgery, Division of Hepatobiliary and General Surgery , Humanitas University, Humanitas Research Hospital-IRCCS , Rozzano, Milan , Italy
| | - Ming-Hua Zheng
- c Department of Hepatology , Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
| | - Tian Yang
- d Department of Hepatobiliary Surgery , Eastern Hepatobiliary Surgery Hospital, Second Military Medical University , Shanghai , China
| | - Xin-Min Liang
- e Grade 2016 , Basic medical college of Guangxi Medical University , Nanning , China
| | - Xi Huang
- e Grade 2016 , Basic medical college of Guangxi Medical University , Nanning , China
| | - Pei-Ling Tang
- e Grade 2016 , Basic medical college of Guangxi Medical University , Nanning , China
| | - Bang-De Xiang
- a Hepatobiliary Surgery Department , Affiliated Tumor Hospital of Guangxi Medical University , Nanning , China.,f Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center , Nanning , China
| | - Le-Qun Li
- a Hepatobiliary Surgery Department , Affiliated Tumor Hospital of Guangxi Medical University , Nanning , China.,f Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center , Nanning , China
| | - Xue-Mei You
- a Hepatobiliary Surgery Department , Affiliated Tumor Hospital of Guangxi Medical University , Nanning , China.,f Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center , Nanning , China
| | - Jian-Hong Zhong
- a Hepatobiliary Surgery Department , Affiliated Tumor Hospital of Guangxi Medical University , Nanning , China.,f Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center , Nanning , China
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Akateh C, Pawlik TM, Cloyd JM. Adjuvant antiviral therapy for the prevention of hepatocellular carcinoma recurrence after liver resection: indicated for all patients with chronic hepatitis B? ANNALS OF TRANSLATIONAL MEDICINE 2018; 6:397. [PMID: 30498725 DOI: 10.21037/atm.2018.08.20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Affiliation(s)
- Clifford Akateh
- Department of Surgery, The Ohio State University, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, Columbus, OH, USA
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University, Columbus, OH, USA
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48
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Jiang Y, Tang H, Wang Z, Sun Y, Meng W, Wang G, Li H, Yi S, Wang G, Yang Y, Chen G. Two Nomograms to Select Hepatocellular Carcinoma Patients with Macroscopic Vascular Invasion for Hepatic Resection. J Cancer 2018; 9:3287-3294. [PMID: 30271488 PMCID: PMC6160689 DOI: 10.7150/jca.25899] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Accepted: 07/17/2018] [Indexed: 01/27/2023] Open
Abstract
Background: Hepatocellular carcinoma (HCC) patients with macroscopic vascular invasion (MaVI) have limited lifespans. According to recent studies, surgical treatment may be the most promising option. However, the current staging system does not select patients who will benefit most from hepatic resection. Study design: A total of 123 patients undergoing hepatic resection for HCC with macroscopic vascular invasion (MaVI) between 2010 and 2014 at The Third Affiliated Hospital of Sun Yat-sen University were selected. We developed nomograms for overall survival (OS) and recurrence-free survival (RFS) using a Cox proportional hazards model. We assessed nomogram model performance based on the concordance index (C-index) and a calibration plot. Results: The 1- and 3-year overall survival (OS) rates for all patients were 84% and 71%, respectively. Correspondingly, the 1- and 3-year recurrence-free survival (RFS) rates were 55% and 35%, respectively. In the multivariate Cox model, the extent of vascular invasion, tumour count, fibrinogen, HBV DNA load and serum potassium significantly affected prognosis. The C-index of the two nomograms were 0.80 and 0.69 for OS and RFS respectively. Based on our nomogram, patients predicted to have 1-year and 3-year RFS rates of more than 80% and 56% had actual 1-year and 3-year RFS rates of 81.8% and 57.1%, respectively, including 9.0% and 17.1% of the HCC patients with MaVI in our database. Conclusion: Surgical treatments are a therapeutic option that can provide more survival benefit for HCC patients with MaVI. With the help of our nomograms, selected HCC patients with MaVI can benefit from hepatic resection and have the same survival rate as that for early-stage HCC patients.
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Affiliation(s)
- Yiquan Jiang
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province
| | - Hui Tang
- Key Laboratory of Liver Disease Research of Guangdong Province, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zixian Wang
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China
| | - Yuanjing Sun
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province
| | - Wei Meng
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province
| | - Guoying Wang
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province
| | - Hua Li
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province
| | - Shuhong Yi
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province
| | - Genshu Wang
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province.,Key Laboratory of Liver Disease Research of Guangdong Province, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Guihua Chen
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province.,Key Laboratory of Liver Disease Research of Guangdong Province, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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49
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Shen J, Liu J, Li C, Wen T, Yan L, Yang J. The prognostic significance of serum HBeAg on the recurrence and long-term survival after hepatectomy for hepatocellular carcinoma: A propensity score matching analysis. J Viral Hepat 2018; 25:1057-1065. [PMID: 29660216 DOI: 10.1111/jvh.12911] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 03/01/2018] [Indexed: 02/05/2023]
Abstract
The effects of serum hepatitis B e antigen (HBeAg) on the prognosis of hepatocellular carcinoma (HCC) patients after hepatectomy remain controversial. Our aim was to explore the prognostic significance of serum HBeAg on the prognosis of patients with HCC using a propensity matching model. Between January 2009 and March 2015, 953 patients with HCC who underwent hepatectomy in West China Hospital were analysed. Propensity matching analysis was applied, and survival analysis was performed using the Kaplan-Meier method. Risk factors were identified by the Cox proportional hazards model. All patients with HCC were classified into an HBeAg(-) group (n = 775, 81.3%) or an HBeAg(+) group (n = 178, 18.7%). Patients with positive serum HBeAg had poorer recurrence-free survival and overall survival before and after propensity matching. Similar results were found in patients within the Milan criteria. For patients beyond the Milan criteria, the HBeAg(+) group had poor overall survival before and after propensity matching. In term of recurrence-free survival, there was no statistically significant impact after propensity matching (P = .055), although there was a trend for HBeAg(+) patient to have reduced recurrence-free survival. Positive serum HBeAg, positive HBV-DNA load, largest tumour size, multiple tumours, microvascular invasion and a high serum level of preoperative alpha-fetoprotein were risk factors for recurrence. Our propensity model confirmed that positive serum HBeAg had a negative impact on the recurrence and long-term survival irrespective of tumour stages. HBeAg seroconversion might be beneficial for reducing the rate of recurrence.
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Affiliation(s)
- J Shen
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - J Liu
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China.,Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - C Li
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - T Wen
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - L Yan
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - J Yang
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
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50
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An P, Xu J, Yu Y, Winkler CA. Host and Viral Genetic Variation in HBV-Related Hepatocellular Carcinoma. Front Genet 2018; 9:261. [PMID: 30073017 PMCID: PMC6060371 DOI: 10.3389/fgene.2018.00261] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Accepted: 06/27/2018] [Indexed: 12/15/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the second leading cause of cancer deaths globally. The high prevalence of HCC is due in part to the high prevalence of chronic HBV infection and the high mortality rate is due to the lack of biomarkers for early detection and limited treatment options for late stage HCC. The observed individual variance in development of HCC is attributable to differences in HBV genotype and mutations, host predisposing germline genetic variations, the acquisition of tumor-specific somatic mutations, as well as environmental factors. HBV genotype C and mutations in the preS, basic core promoter (BCP) or HBx regions are associated with an increased risk of HCC. Genome-wide association studies have identified common polymorphisms in KIF1B, HLA-DQ, STAT4, and GRIK1 with altered risk of HBV-related HCC. HBV integration into growth control genes (such as TERT), pro-oncogenic genes, or tumor suppressor genes and the oncogenic activity of truncated HBx promote hepatocarcinogenesis. Somatic mutations in the TERT promoter and classic cancer signaling pathways, including Wnt (CTNNB1), cell cycle regulation (TP53), and epigenetic modification (ARID2 and MLL4) are frequently detected in hepatic tumor tissues. The identification of HBV and host variation associated with tumor initiation and progression has clinical utility for improving early diagnosis and prognosis; whereas the identification of somatic mutations driving tumorigenesis hold promise to inform precision treatment for HCC patients.
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Affiliation(s)
- Ping An
- Basic Research Laboratory, National Cancer Institute, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, United States
| | - Jinghang Xu
- Basic Research Laboratory, National Cancer Institute, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, United States.,Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Peking University, Beijing, China
| | - Yanyan Yu
- Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Peking University, Beijing, China
| | - Cheryl A Winkler
- Basic Research Laboratory, National Cancer Institute, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, United States
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