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1
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Farbod Y, Kankouni H, Moini M, Fung S. Hepatitis B-Induced Hepatocellular Carcinoma: Understanding Viral Carcinogenesis and Disease Management. J Clin Med 2025; 14:2505. [PMID: 40217955 PMCID: PMC11989475 DOI: 10.3390/jcm14072505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 03/30/2025] [Accepted: 04/01/2025] [Indexed: 04/14/2025] Open
Abstract
Hepatitis B virus (HBV) infection is a leading cause of chronic liver disease and liver cancer worldwide. Hepatocellular carcinoma (HCC) remains one of the major causes of cancer-related mortality globally. Effective prevention and management strategies for HBV infection are crucial in reducing liver-related complications, including HCC. HBV plays a distinct role in liver carcinogenesis, and there is growing knowledge about the factors contributing to its oncogenic potential. With advancements in HCC management, special attention must be given to the treatment of HBV infection in patients with HBV-induced HCC. In this review, we summarize current insights into the carcinogenic mechanisms of HBV and discuss the latest approaches to managing HBV-induced HCC.
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Affiliation(s)
- Yasamin Farbod
- Division of Gastroenterology and Hepatology, McGill University, Montreal, QC H3A 0G4, Canada
| | - Husain Kankouni
- Division of Gastroenterology and Hepatology, University of Toronto, Toronto, ON M5G 2C4, Canada
| | - Maryam Moini
- Division of Gastroenterology, McMaster University, Hamilton, ON L8S 2A5, Canada
| | - Scott Fung
- Department of Medicine, University of Toronto, Toronto, ON M5G 2C4, Canada
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2
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Diao YH, Gong FP, Cheng Y. Impact of HIV Infection on Hepatocellular Carcinoma: A Long-Term Prognostic Analysis. J Laparoendosc Adv Surg Tech A 2025; 35:109-117. [PMID: 39976506 DOI: 10.1089/lap.2024.0191] [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] [Indexed: 05/10/2025] Open
Abstract
Purpose: This study aims to explore the influence of human immunodeficiency virus (HIV) infection on the prognosis of patients with hepatocellular carcinoma (HCC). Methods: According to the search strategy, we searched all relevant articles in the three databases (PubMed, Embase, and the Cochrane Library) up to February 18, 2024. All data available for analysis were extracted. Continuous variables were expressed as mean difference (MD) with standard deviation (SD). The categorical variables were expressed as odds ratio (OR) with 95% confidence intervals (CIs). Forest plots were used to illustrate the analysis results, and funnel plots were used to assess publication bias. Results: The study included a total of 4544 subjects. HIV patients were significantly younger compared to those without HIV (MD = -16.13, 95% CI = -17.24 to -15.01, I2 = 91, P < .01), but there were no significant differences in other relevant clinical characteristics between the groups. Survival analysis indicated that HIV patients exhibited a poorer long-term prognosis compared with HIV-negative patients (HR = 0.71, 95% CI = 0.63 to 0.79, I2 = 29%, P < .01). Conclusion: HIV infection, which compromises immune function and liver health, predisposes individuals to earlier onset of HCC and is associated with a poorer prognosis.
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Affiliation(s)
- Yu-Hang Diao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Fa-Ping Gong
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yong Cheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Ramaswamy A, Shukla A, Engineer R, Sundaram S, Srinivas S, Kulkarni S, Patkar S, Baijal S, Kale A, Kapoor A, Mukund A, Choudhari A, Rauthan A, Mathew AS, Panchal R, Bhattacharya K, Patil P, Shetty N, Gala K, Kumar L, Thiruchunapalli D, Kalra N, Sahoo TP, Krishna MV, Lavingia V, Mohanka R, Talwar V, Ostwal V, Bhargava P, Poddar J, Singal A, Goel M. Evaluation and Management of Unresectable Hepatocellular Carcinoma: Multidisciplinary Indian Consensus Statements from a Delphi Panel. South Asian J Cancer 2024. [DOI: 10.1055/s-0044-1788569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/10/2025] Open
Abstract
Background India, like many parts of Asia, likely faces a high burden of hepatocellular carcinoma (HCC), though large-scale data on etiology, presentation, and outcomes are lacking. There appears to be a predominance of unresectable, advanced-stage HCC at presentation in India with variable level of expertise in India to manage these scenarios. This publication summarizes the latest evidence with cognizance of the unique challenges faced in India by treating clinicians.
Methods A multidisciplinary panel of medical oncologists, gastroenterologists, hepatologists, interventional radiologists, and hepatobiliary surgical oncologists held a meeting in June 2022 and reviewed the evidence available for management of HCC. The meeting concentrated on the recognition and management of HCC not amenable to surgical approaches in the Indian context. A literature review of these aspects of management was conducted and consensus statements with level of evidence and grades of recommendation were prepared by individual specialists in each field. Statements were evaluated by the modified Delphi method.
Key Content and Findings The panel comprising 22 experts formulated 40 consensus statements with regard to defining unresectable HCC, optimization of underlying conditions prior to management, rationale use of various liver-directed therapies (LDTs) in unresectable HCC, and systemic therapeutic options in this group of patients.
Conclusion Our consensus statements offer practical, yet evidence-based management guidelines for treating unresectable HCC in the Indian context. There is an emphasis on the crucial need for combining available approaches for LDT, even if less well studied though possibly effective, with standard systemic therapy.
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Affiliation(s)
- Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Akash Shukla
- Department of Gastroenterology, Seth Gordhandas Sunderdas Medical College (GSMC) & King Edward Memorial (KEM) Hospital, Mumbai, Maharashtra, India
- Department of Hepatology, Sir H.N. Reliance Foundation Hospital, Mumbai, Maharashtra, India
| | - Reena Engineer
- Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Sridhar Sundaram
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Sujay Srinivas
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Suyash Kulkarni
- Department of Radiodiagnosis, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Shraddha Patkar
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Sanjay Baijal
- Department of Diagnostic and Interventional Radiology, Medanta Hospital, Gurugram, Haryana, India
| | - Aditya Kale
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Akhil Kapoor
- Department of Medical Oncology, Tata Memorial Hospital (TMH), Homi Bhabha Cancer Hospital (HBCH) and Mahamana Pt Madan Mohan Malaviya Cancer Centre (MPMMCC), Varanasi, Uttar Pradesh, India
| | - Amar Mukund
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Amit Choudhari
- Department of Radio-diagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Amit Rauthan
- Department of Medical Oncology, Manipal Hospital, Bangalore, Karnataka, India
| | - Ashwathy Susan Mathew
- Department of Radiation Oncology, Apollo Proton Cancer Centre, Chennai, Tamil Nadu, India
| | - Rushi Panchal
- Department of Radiation Oncology, MS Patel Cancer Centre, Shree Krishna Hospital, Bhaikaka University, Karamsad-Anand, Gujarat, India
| | - Kausik Bhattacharya
- Department of Radiation Oncology, AIG Hospitals. Hyderabad, Telangana, India
| | - Prachi Patil
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Nitin Shetty
- Department of Radiodiagnosis, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Mumbai, Maharashtra, India
| | - Kunal Gala
- Department of Radio-diagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Lijesh Kumar
- Department of Endovascular and Interventional Radiology, Lisie Hospital, Kochi, Kerala, India
| | - Deepashree Thiruchunapalli
- Department of Interventional Radiology, Dr. Rela Institute and Medical Centre, Chennai, Tamil Nadu, India
| | - Naveen Kalra
- Department of Radio-diagnosis, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Tarini Prasad Sahoo
- Department of Medical Oncology, Silverline Hospital, Bhopal, Madhya Pradesh, India
| | - M Vamshi Krishna
- Department of Medical Oncology and Hematology, Institute of Oncology, AIG Hospital, Hyderabad, Telangana, India
| | - Viraj Lavingia
- Department of Medical Oncology, HCG Cancer Centre, Ahmedabad, Gujarat, India
| | - Ravi Mohanka
- Department of Liver Transplant and HPB Surgery, Sir H.N. Reliance Hospital, Mumbai, Maharashtra, India
| | - Vineet Talwar
- Department of Medical Oncology Rajiv Gandhi Cancer Institute, Delhi, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Prabhat Bhargava
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Jyoti Poddar
- Radiation Oncologist, Therapy Area Medical Expert (Hepatocellular Carcinoma) Roche (India) Pvt Limited
| | - Amit Singal
- Department of Medicine, UT Southwestern Medical Center, Dallas, Texas, United States
| | - Mahesh Goel
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
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Anisetti B, Ahmed AK, Coston T, Gardner L, Majeed U, Reynolds J, Babiker H. Delayed brain metastasis in recurrent hepatocellular carcinoma following liver transplantation: a case report highlighting the predictive value of microvascular invasion. Clin J Gastroenterol 2023; 16:864-870. [PMID: 37532904 DOI: 10.1007/s12328-023-01839-1] [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: 06/15/2023] [Accepted: 07/22/2023] [Indexed: 08/04/2023]
Abstract
Recurrent hepatocellular carcinoma (HCC) poses a significant challenge after liver transplantation, affecting approximately 10-23% of patients with a median onset of 13 months post-transplantation. Extrahepatic involvement, such as lung, bone, adrenal glands, peritoneum, lymph nodes, and central nervous system (CNS), is commonly observed among transplant recipients with HCC recurrence. Notably, vascular invasion (VI), including microvascular invasion (MiVI) and macrovascular invasion (MVI), substantially increase the risk of recurrence by 2.42- and 7.82-fold, respectively. This article presents a unique case of a 72-year-old male patient with a history of HCV-related cirrhosis and HCC who underwent orthotopic liver transplantation (OLT). Six years later, he presented to the emergency department following a fall, which led to the discovery of a pathologic fracture of T7 and an incidental intracranial mass during imaging. Subsequent biopsy confirmed metastatic HCC in the T7 lesion, while magnetic resonance imaging revealed two enhancing brain masses. One mass measured 4.8 cm in the left occipitotemporal lobe, and the other measured 1.7 cm in the right frontal gyrus. Notably, the patient had exhibited MiVI and a mildly elevated alpha-fetoprotein level (AFP) of 7.6 ng/mL at the time of his OLT. This case underscores the predictive value of MiVI in HCC recurrence post-OLT. Accordingly, extended post-transplantation surveillance is crucial for patients with HCC and MiVI. Moreover, this report highlights the uncommon occurrence of delayed brain metastasis following OLT in a patient with HCC.
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Affiliation(s)
- Bhrugun Anisetti
- Department of Hematology and Oncology, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA.
| | - Ahmed K Ahmed
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA
| | - Tucker Coston
- Department of Hematology and Oncology, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA
| | - Lindsay Gardner
- Department of Hematology and Oncology, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA
| | - Umair Majeed
- Department of Hematology and Oncology, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA
| | - Jordan Reynolds
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, USA
| | - Hani Babiker
- Department of Hematology and Oncology, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA
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Gao YX, Ning QQ, Yang PX, Guan YY, Liu PX, Liu ML, Qiao LX, Guo XH, Yang TW, Chen DX. Recent advances in recurrent hepatocellular carcinoma therapy. World J Hepatol 2023; 15:460-476. [PMID: 37206651 PMCID: PMC10190692 DOI: 10.4254/wjh.v15.i4.460] [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: 09/19/2022] [Revised: 12/20/2022] [Accepted: 03/24/2023] [Indexed: 04/20/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, accounting for 75%-85% of cases. Although treatments are given to cure early-stage HCC, up to 50%-70% of individuals may experience a relapse of the illness in the liver after 5 years. Research on the fundamental treatment modalities for recurrent HCC is moving significantly further. The precise selection of individuals for therapy strategies with established survival advantages is crucial to ensuring better outcomes. These strategies aim to minimize substantial morbidity, support good life quality, and enhance survival for patients with recurrent HCC. For individuals with recurring HCC after curative treatment, no approved therapeutic regimen is currently available. A recent study presented novel approaches, like immunotherapy and antiviral medication, to improve the prognosis of patients with recurring HCC with the apparent lack of data to guide the clinical treatment. The data supporting several neoadjuvant and adjuvant therapies for patients with recurring HCC are outlined in this review. We also discuss the potential for future clinical and translational investigations.
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Affiliation(s)
- Yu-Xue Gao
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Qi-Qi Ning
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Peng-Xiang Yang
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Yuan-Yue Guan
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Peng-Xiang Liu
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Meng-Lu Liu
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Lu-Xin Qiao
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Xiang-Hua Guo
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Tong-Wang Yang
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Academician Workstation, Changsha Medical University, Changsha 410219, Hunan Province, China
- Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha 410219, Hunan Province, China
| | - De-Xi Chen
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
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Nevola R, Ruocco R, Criscuolo L, Villani A, Alfano M, Beccia D, Imbriani S, Claar E, Cozzolino D, Sasso FC, Marrone A, Adinolfi LE, Rinaldi L. Predictors of early and late hepatocellular carcinoma recurrence. World J Gastroenterol 2023; 29:1243-1260. [PMID: 36925456 PMCID: PMC10011963 DOI: 10.3748/wjg.v29.i8.1243] [Citation(s) in RCA: 98] [Impact Index Per Article: 49.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 01/06/2023] [Accepted: 01/30/2023] [Indexed: 02/28/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments (liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate (up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as "early" and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden. A recurrence that occurs after 2 years of treatment is defined as "late" and is related to de novo HCC, independent of the primary neoplasm. Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence. Different pathogenesis corresponds to different predictors of the risk of early or late recurrence. An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance. Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens. This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.
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Affiliation(s)
- Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Rachele Ruocco
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Livio Criscuolo
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Angela Villani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Maria Alfano
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Domenico Beccia
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Simona Imbriani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Ernesto Claar
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Domenico Cozzolino
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Luigi Elio Adinolfi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
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Chen YH, Wang CC, Chen YY, Wang JH, Hung CH, Kuo YH. Low-dose nivolumab in advanced hepatocellular carcinoma. BMC Cancer 2022; 22:1153. [PMID: 36348292 DOI: 10.1186/s12885-022-10271-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 11/02/2022] [Indexed: 11/11/2022] Open
Abstract
Abstract
Background
The approved dose of nivolumab is 3 mg/kg or a flat dose of 240 mg for indications. There is no dose-response relationship for nivolumab; therefore, a low-dose regimen may be an option to reduce financial toxicity. This study was designed to investigate the efficacy and safety of low-dose nivolumab in the management of hepatocellular carcinoma (HCC).
Methods
We retrospectively reviewed patients with HCC who received 20 or 100 mg of nivolumab intravenously every 2 weeks. The objective response rate was determined in accordance with the Response Evaluation Criteria in Solid Tumors criteria version 1.1. The Cox regression model and Kaplan–Meier method were used to analyze hazard factors, progression-free survival (PFS), and overall survival (OS). Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Results
In total, 78 patients were enrolled, including 49 with hepatitis B virus (HBV) and 23 with hepatitis C virus (HCV). All patients were staged as Barcelona Clinic Liver Cancer stage C, and 20 patients were classified as having Child–Pugh classification B (7). Nivolumab 20 mg was an independent prognostic factor for better PFS, and albumin-bilirubin grade 1 was the independent prognostic factor for superior OS in the multivariate analyses. Patients with better HBV (HBV DNA < 500 IU/ml) and HCV (HCV RNA undetectable) controls had superior OS. All AEs were grade 1–2 in severity, and all patients tolerated nivolumab without treatment interruption or dose adjustment. Additionally, 31 patients underwent subsequent therapy after nivolumab treatment.
Conclusion
Low-dose nivolumab may be effective with manageable toxicity and can be an alternative option to reduce financial toxicity in patients with advanced HCC who cannot afford the high cost of immune checkpoint inhibitors in real-world practice.
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Tsai HW, Lee YP, Yen CJ, Cheng KH, Huang CJ, Huang W. The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery. Int J Mol Sci 2022; 23:ijms23105376. [PMID: 35628188 PMCID: PMC9140564 DOI: 10.3390/ijms23105376] [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: 04/13/2022] [Revised: 05/09/2022] [Accepted: 05/09/2022] [Indexed: 11/26/2022] Open
Abstract
Chronic hepatitis B (CHB) virus infection is the most important cause of HCC and is also associated with tumor progression. The development of viral biomarkers for HCC prognosis is critical in evaluating relative risks to recurrence in the CHB HCC patients. We report that the large HBV surface protein (LHBS) expression increased in the tumors, implicating that it played a significant role in tumor development. To detect the LHBS in serum and evaluate its association with HCC progression, we developed a sandwich ELISA method for LHBS. The mouse monoclonal antibodies for the pre-S1, pre-S2, and HBS regions were in-house generated and constructed into a chemiluminescent sandwich ELISA system, which allowed sensitive and quantitative measurement of the protein. Using this ELISA assay, we estimated the expression of LHBS in CHB and HCC patients. We found that the serum LHBS level was correlated with the HBS but not the viral titer in serum, indicating that HBV surface proteins’ expression does not mainly depend on viral replication. Moreover, both serum LHBS and HBS levels were lower in the HCC patients than in the CHB. The liver LHBS signals, detected by immunohistochemical staining, showed significant correlations with the serum LHBS and HBS levels. In addition, the more elevated serum LHBS but not HBS level was significantly associated with cirrhosis and worse disease-free and overall survival rates, based on the multivariate analysis. Conclusion: LHBS plays a specific role in tumor progression and is an independent parameter associated with HCC recurrence. Serum LHBS represents a novel noninvasive biomarker for HCC patients with a worse prognosis after surgery.
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Affiliation(s)
- Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; (H.-W.T.); (K.-H.C.)
| | - Yun-Ping Lee
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan;
| | - Chia-Jui Yen
- Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan;
| | - Kuang-Hsiung Cheng
- Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; (H.-W.T.); (K.-H.C.)
| | - Chien-Jung Huang
- Department of Internal Medicine, Taipei City Hospital, Taipei 10341, Taiwan;
| | - Wenya Huang
- Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; (H.-W.T.); (K.-H.C.)
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan;
- Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
- Correspondence: ; Tel.: +886-6-235-3535 (ext. 5766)
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9
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Zhou X, Zhang F, Ao Y, Lu C, Li T, Xu X, Zeng H. Diagnosis experiences from 50 hepatitis B patients in Chongqing, China: a qualitative study. BMC Public Health 2021; 21:2195. [PMID: 34852813 PMCID: PMC8638347 DOI: 10.1186/s12889-021-11929-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 09/28/2021] [Indexed: 11/23/2022] Open
Abstract
Background The aim of this study was to provide recommendations for reducing the impact of hepatitis B infection on patients with chronic hepatitis B by describing their experiences during the diagnosis process. Methods We conducted face-to-face interviews with 50 hepatitis B patients recruited by convenient sampling from an infectious diseases department of a teaching hospital in Chongqing, China from July to August 2019. Thematic analysis framework included interviewees’ social demographic characteristics, diagnosis approach, signs and symptoms before diagnosis, feelings after diagnosis, and doctor’s instructions. Results Most patients first detected hepatitis B through various types of physical examinations when the patients were asymptomatic or had only mild symptoms. Most patients were shocked, scared, or overwhelmed when they were diagnosed with hepatitis B. They were able to remember the doctor’s instructions about maintaining a healthy lifestyle, but not impressed by the doctor’s advice about regular follow-up liver function tests. The lack of regular follow-up has caused irreversible damage to some patients. Conclusions Most patients are passively diagnosed with hepatitis B due to their lack of awareness on active hepatitis B prevention. Patients need professional mental health care to overcome the negative emotions that following the diagnosis. Physicians’ instruction should emphasize the importance of regular follow-up liver function tests in addition to a healthy lifestyle.
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Affiliation(s)
- Xiangxi Zhou
- School of Public Health and Management, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
| | - Fan Zhang
- School of Public Health and Management, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.,Research Center for Medicine and Social Governance in Health, Chongqing Medical University, Chongqing, China.,The Innovation Center for Social Risk Governance in Health, Chongqing Medical University, Chongqing, China
| | - Yongping Ao
- School of Public Health and Management, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
| | - Chunli Lu
- School of Public Health and Management, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
| | - Tingting Li
- Centers for Disease Control and Prevention of Chongqing, Chongqing, China
| | - Xianglong Xu
- Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.,Melbourne Sexual Health Centre, Alfred Health, Melbourne, Australia.,China Australia Joint Research Center for Infectious Diseases, School of Public Health, Xi'an Jiaotong University Health Science Centre, Xi'an, Shaanxi, People's Republic of China
| | - Huan Zeng
- School of Public Health and Management, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China. .,Research Center for Medicine and Social Governance in Health, Chongqing Medical University, Chongqing, China. .,The Innovation Center for Social Risk Governance in Health, Chongqing Medical University, Chongqing, China.
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10
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de Almeida NAA, de Paula VS. Occult Hepatitis B virus (HBV) infection and challenges for hepatitis elimination: A literature review. J Appl Microbiol 2021; 132:1616-1635. [PMID: 34724308 DOI: 10.1111/jam.15351] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 09/08/2021] [Accepted: 10/11/2021] [Indexed: 12/15/2022]
Abstract
Occult hepatitis B infection (OBI) is characterized by the detection of hepatitis B virus (HBV) DNA in serum or liver but negativity for hepatitis B surface antigen. OBI, which is thought to be maintained by host, immunological, viral and/or epigenetic factors, is one of the most challenging clinical features in the study of viral hepatitis. Currently, there is no validated detection test for OBI. It is believed that OBI is widely distributed throughout the world, with a higher prevalence in populations at high-risk HBV, but the detailed worldwide prevalence patterns are unknown. We conducted a survey of recently published studies on OBI rates across all continents. High prevalence rates of OBI are observed in some specific groups, including patients with hepatitis C virus, human immunodeficiency virus co-infection or hepatocellular carcinoma. In 2016, the World Health Organization adopted strategies to eliminate viral hepatitis by 2030, but the difficulties in detecting and treating OBI currently challenge this goal. Subjects with OBI can transmit HBV, and episodes of reactivation can occur. Further studies to understanding the mechanisms that drive the development of OBI are needed and can contribute to efforts at eliminating viral hepatitis.
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11
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Nong W, Ma L, Lan B, Liu N, Yang H, Lao X, Deng Q, Huang Z. Comprehensive Identification of Bridge Genes to Explain the Progression from Chronic Hepatitis B Virus Infection to Hepatocellular Carcinoma. J Inflamm Res 2021; 14:1613-1624. [PMID: 33907440 PMCID: PMC8071210 DOI: 10.2147/jir.s298977] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 03/16/2021] [Indexed: 12/16/2022] Open
Abstract
Background Hepatitis B virus infection co-occurs in 33% of individuals with hepatocellular carcinoma worldwide. However, the molecular link between hepatitis B virus and hepatocellular carcinoma is unknown. Thus, we aimed to elucidate molecular linkages underlying pathogenesis through in-depth data mining analysis. Materials and Methods Differentially expressed genes were identified from patients with chronic hepatitis B virus infection, hepatocellular carcinoma, or both. Gene set enrichment analysis revealed signaling pathways involving differentially expressed genes. Protein-protein interaction networks, protein crosstalk, and enrichment were analyzed to determine whether differentially expressed gene products might serve as a bridge from hepatitis B virus infection to hepatocellular carcinoma pathogenesis. Prognostic potential and transcriptional and post-transcriptional regulators of bridge genes were also examined. Results We identified vital bridge factors in hepatitis B virus infection-associated hepatocellular carcinoma. Differentially expressed genes were clustered into modules based on relative protein function. Signaling pathways associated with cancer, inflammation, immune system, and microenvironment showed significant crosstalk between modules. Thirty-two genes were dysregulated in hepatitis B virus infection-mediated hepatocellular carcinoma. CPEB3, RAB26, SLCO1B1, ST3GAL6 and XK had higher connectivity in the modular network, suggesting significant associations with survival. CDC20 and NUP107 were identified as driver genes as well as markers of poor prognosis. Conclusion Our results suggest that the sustained inflammatory environment created by hepatitis B virus infection is a risk factor for hepatocellular carcinoma. The identification of hepatitis B virus infection-related hepatocellular carcinoma bridge genes provides testable hypotheses about the pathogenesis of hepatocellular carcinoma.
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Affiliation(s)
- Wenwei Nong
- Department of General Surgery, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Liping Ma
- Department of Clinical Laboratory, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Biyang Lan
- Department of General Surgery, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Ning Liu
- Department of General Surgery, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Hongzhi Yang
- Department of General Surgery, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Xiaoxia Lao
- Department of Clinical Laboratory, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Qiaomei Deng
- Department of Clinical Laboratory, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Zhihu Huang
- Department of Clinical Laboratory, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, People's Republic of China
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12
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Bubie A, Zoulim F, Testoni B, Miles B, Posner M, Villanueva A, Losic B. Landscape of oncoviral genotype and co-infection via human papilloma and hepatitis B viral tumor in situ profiling. iScience 2021; 24:102368. [PMID: 33889830 PMCID: PMC8050859 DOI: 10.1016/j.isci.2021.102368] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 03/07/2021] [Accepted: 03/24/2021] [Indexed: 02/06/2023] Open
Abstract
The role of oncoviral genotype and co-infection driving oncogenesis remains unclear. We have developed a scalable, high throughput tool for sensitive and precise oncoviral genotype deconvolution. Using tumor RNA sequencing data, we applied it to 537 virally infected liver, cervical, and head and neck tumors, providing the first comprehensive integrative landscape of tumor-viral gene expression, viral antigen immunogenicity, patient survival, and mutational profiling organized by tumor oncoviral genotype. We find that HBV and HPV genotype and co-infection serve as significant predictors of patient survival and immune activation. Finally, we demonstrate that HPV genotype is more associated with viral oncogene expression than cancer type, implying that expression may be similar across episomal and stochastic integration-based infections. While oncoviral infections are known risk factors for oncogenesis, viral genotype and co-infection are shown to strongly associate with disease progression, patient survival, mutational signatures, and putative tumor neoantigen immunogenicity, facilitating novel clinical associations with infections.
ViralMine parses oncoviral genotypes and co-infection from in situ tumor data Oncoviral genotyping of TCGA CESC, HNSC, and LIHC cohorts Tumor fitness, immunogenicity, and mutational signatures associate with oncoviral genotype
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Affiliation(s)
- Adrian Bubie
- Departments of Genetics and Genomic Sciences, New York, NY 10029, USA
| | - Fabien Zoulim
- INSERM, U1052, Cancer Research Center of Lyon (CRCL), Lyon, 69008, France
| | - Barbara Testoni
- INSERM, U1052, Cancer Research Center of Lyon (CRCL), Lyon, 69008, France
| | - Brett Miles
- Department of Otolaryngology Head and Neck Surgery, New York, NY 10029, USA
| | - Marshall Posner
- Division of Hematology Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Augusto Villanueva
- Departments of Genetics and Genomic Sciences, New York, NY 10029, USA.,Division of Liver Diseases, Division of Hematology/Oncology, Department of Medicine, Graduate School of Biomedical Sciences, Tisch Cancer Institute, Diabetes, Obesity, and Metabolism Institute, New York, NY 10029, USA
| | - Bojan Losic
- Departments of Genetics and Genomic Sciences, New York, NY 10029, USA.,Division of Liver Diseases, Division of Hematology/Oncology, Department of Medicine, Graduate School of Biomedical Sciences, Tisch Cancer Institute, Diabetes, Obesity, and Metabolism Institute, New York, NY 10029, USA
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13
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Talla C, Uchenna Itanyi I, Tsuyuki K, Stadnick N, Grace Ogidi A, Oluwaseun Olakunde B, Patel D, Okpanachi Oko J, Aarons G, Ariel Onoka C, Edozie Ezeanolue E. Hepatitis B infection and risk factors among pregnant women and their male partners in the Baby Shower Programme in Nigeria: a cross-sectional study. Trop Med Int Health 2021; 26:316-326. [PMID: 33247862 PMCID: PMC7925376 DOI: 10.1111/tmi.13531] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To determine the population prevalence and determinants of hepatitis B (Hep B) status, and status discordance, among pregnant women and their male partners in Nigeria. METHODS Cross-sectional study assessing the seroprevalence of Hep B virus in a cohort of 16 920 pregnant women and their male partners in northcentral Nigeria. Rapid HBsAg antibody test was used for Hep B diagnosis. Demographic, socio-economic and behavioural information was collected through interviewer-administered questionnaires and evaluated as determinants of Hep B status and couple status discordance using logistic regression. RESULTS Of 16 920 participants who had a Hep B test result, 6750 couples and 1316 discordant couples were identified. The prevalence of Hep B among all participants was 10.9%, with lower prevalence among pregnant women (10.2%) than their male partners (11.9%), P < 0.001. The prevalence of Hep B sero-discordance among couples was 19.5% (1316/6750). Younger age, prior Hep B testing and a prior positive Hep B test increased the odds of Hep B infection while being a woman decreased the odds of Hep B among all participants, and among couples. Furthermore, polygamy (adjusted odds ratio [AOR]: 1.49, 95% confidence interval [CI]: 1.19-1.87), prior Hep B testing (AOR: 2.38, 95% CI: 1.14-4.97) and a prior positive Hep B test result were significant determinants of status discordance among the participating couples. CONCLUSION The prevalence of Hep B among pregnant women and their male partners in northcentral Nigeria is high. A large-scale intervention is required to reduce Hep B prevalence in this setting.
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Affiliation(s)
- Carol Talla
- Caritas Nigeria, Abuja, Federal Capital Territory, Nigeria
| | - Ijeoma Uchenna Itanyi
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
- Department of Community Medicine, University of Nigeria Nsukka, Enugu, Nigeria
| | - Kiyomi Tsuyuki
- Division of Infectious Diseases & Global Public Health, Department of Medicine, University of California, San Diego, USA
| | - Nicole Stadnick
- Department of Psychiatry, University of California, San Diego, USA
- UC San Diego Dissemination and Implementation Science Center, USA
| | - Amaka Grace Ogidi
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
| | - Babayemi Oluwaseun Olakunde
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
- National Agency for the Control of AIDS, Abuja, Nigeria
| | | | | | - Gregory Aarons
- Department of Psychiatry, University of California, San Diego, USA
- UC San Diego Dissemination and Implementation Science Center, USA
| | - Chima Ariel Onoka
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
- Department of Community Medicine, University of Nigeria Nsukka, Enugu, Nigeria
| | - Echezona Edozie Ezeanolue
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
- Healthy Sunrise Foundation, USA
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14
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A Meta-Analysis on the Rate of Hepatocellular Carcinoma Recurrence after Liver Transplant and Associations to Etiology, Alpha-Fetoprotein, Income and Ethnicity. J Clin Med 2021; 10:jcm10020238. [PMID: 33440759 PMCID: PMC7828059 DOI: 10.3390/jcm10020238] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 12/16/2020] [Accepted: 01/06/2021] [Indexed: 02/08/2023] Open
Abstract
Hepatocellular carcinoma (HCC) recurrence after liver transplant is associated with a poor prognosis and significantly increases morbidity and mortality among liver transplant patients. Therefore, this meta-analysis aims to evaluate the overall prevalence of HCC recurrence following liver transplant. Medline and Embase databases were searched, and a meta-analysis of proportions was conducted. Observational studies reporting the prevalence of recurrent hepatocellular carcinoma (HCC) after liver transplant were included, with the analysis being stratified by adherence to Milan criteria, ethnicity, socio-economic status, alpha fetoprotein (AFP) levels, living donor vs. deceased donor, and the underlying aetiology of the liver disease. A meta-regression on the date of the study completion was also performed. Of a total 40,495 patients, 3888 developed an HCC recurrence. The overall prevalence of recurrent HCC was 13% (CI: 0.12-0.15). Patients beyond the Milan criteria (MC) were more likely to recur than patients within MC. Asian populations had the greatest prevalence of HCC recurrence (19%; CI: 0.15-0.24) when compared to Western (12%; CI: 0.11-0.13) and Latin American populations (11%; CI: 0.09-0.14). The prevalence of recurrent HCC was the highest in patients infected with hepatitis B virus (HBV) (18%; CI: 0.11-0.27) compared to other aetiologies. A higher AFP also resulted in an increased recurrence. This highlights interesting differences based on ethnicity, income, and aetiology, and further studies are needed to determine the reasons for the disparity.
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15
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Okeke E, Mark Davwar P, Mullen B, Duguru M, Agbaji O, Sagay A, Murphy R, Hawkins C. The impact of HIV on hepatocellular cancer survival in Nigeria. Trop Med Int Health 2020; 26:335-342. [PMID: 33244817 DOI: 10.1111/tmi.13532] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV-infected individuals. We compared host and tumour characteristics between HIV-infected and HIV-uninfected Nigerians with HCC and examined the impact of HIV on survival. METHODS This prospective observational study was conducted at Jos University Teaching Hospital in Jos, Nigeria, among adults (>18 years) with HCC enrolled between September 2015 and September 2017 and followed until April 2019. Demographics, tumour characteristics and survival were compared between HCC subjects with and without HIV. RESULTS 101 (10 HIV-infected and 91 HIV-uninfected) subjects were enrolled [male 72%; median age 48 (IQR 35-60)]. 60% HIV-infected subjects were receiving ART; 90% had CD4 counts ≥ 200/mm3 at HCC diagnosis, and 20% had HIV RNA levels < 20 copies/mL. 57.4% were infected with chronic HBV (HBsAg+). The duration of symptoms was shorter in HIV-infected vs. HIV-uninfected subjects [93 (IQR 54-132) vs. 155 (93-248] days; p = 0.02]. At the end of follow-up, 99 of 101 (98.0%) subjects were confirmed to have died: 9 of 10 (90.0%) HIV-infected and 90 of 91 (98.9%) HIV-uninfected. The probability of survival at three months was 22% and 47% in HIV-infected and HIV-uninfected subjects, respectively (P = 0.02). Median time to death was significantly shorter in HIV-infected vs. HIV-uninfected subjects [24 days (IQR 16-88) vs. 85 days (IQR 34-178), respectively (P = 0.03)]. CONCLUSIONS High early mortality was observed in this cohort of Nigerian adults with HCC. HIV infection was associated with a faster clinical presentation and shorter survival. More aggressive HCC surveillance may be warranted in HIV-infected subjects, particularly if they are co-infected with chronic HBV.
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Affiliation(s)
- E Okeke
- Department of Medicine, University of Jos and Jos University Teaching Hospital, Jos, Nigeria
| | - P Mark Davwar
- Department of Medicine, University of Jos and Jos University Teaching Hospital, Jos, Nigeria
| | - B Mullen
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - M Duguru
- Department of Medicine, University of Jos and Jos University Teaching Hospital, Jos, Nigeria
| | - O Agbaji
- Department of Medicine, University of Jos and Jos University Teaching Hospital, Jos, Nigeria
| | - A Sagay
- Department of Obstetrics and Gynecology, University of Jos and Jos University Teaching Hospital, Jos, Nigeria
| | - R Murphy
- Department of Medicine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - C Hawkins
- Department of Medicine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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16
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Seid AS, Anugwom CM, Wondifraw Z, Braimoh GA, Bane A, Debes JD. Single center analysis of therapy and outcomes of hepatocellular carcinoma in Sub-Saharan Africa. Expert Rev Gastroenterol Hepatol 2020; 14:1007-1011. [PMID: 32730120 PMCID: PMC7544626 DOI: 10.1080/17474124.2020.1802246] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE To evaluate the characteristics and response to therapy for HCC in sub-Saharan Africa. PATIENTS AND METHODS We retrospectively evaluated demographic, clinical and outcome variables of HCC in a referral clinic in Ethiopia from 2016 to 2018. Survival assessment was performed using the Mann-Whitney test. Associations between categorical variables was assessed using Pearson Chi-square test. RESULTS We report 46 HCC cases with a median age of 54 years (IQR 45-62) and 50% female. Viral hepatitis was the most common underlying etiology, with 41% of subjects infected with hepatitis B virus (HBV) and 45% with hepatitis C. The median MELD was 12 (IQR 8-17), we found no association between survival and a MELD score </> 15, regardless of underlying disease (pr=0.61, p>0.05). 31% of individuals underwent supportive treatment with a median survival of 27 days (IQR 19-181), 18% used Sorafenib (median survival of 94 days, IQR 24-121), and trans-arterial chemoembolization (TACE) was utilized in 16% (median survival of 352 days, IQR 30-436). HBV cases were diagnosed younger (31% before the age of 40) and those on Tenofovir had a longer median survival than those off Tenofovir (121 vs 34 days). CONCLUSION Our study found that antiviral treatment of HBV infection was associated with longer survival in HCC. Furthermore, Sorafenib seemed beneficial in patients that used this modality and NLR was a good prognostic factor.
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Affiliation(s)
- Amir Sultan Seid
- Addis Ababa University, College of Health Sciences, Ethiopia,Corresponding Author: Jose D. Debes, Address: University of Minnesota, 420 Delaware Street, S.E; MMC 810, Minneapolis, MN 55455, Phone: 612 625 6353
| | - Chimaobi M. Anugwom
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, United States,Corresponding Author: Jose D. Debes, Address: University of Minnesota, 420 Delaware Street, S.E; MMC 810, Minneapolis, MN 55455, Phone: 612 625 6353
| | | | | | - Abate Bane
- Addis Ababa University, College of Health Sciences, Ethiopia,Hennepin Healthcare, Minneapolis, Minnesota, United States
| | - Jose D. Debes
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, United States,Hennepin Healthcare, Minneapolis, Minnesota, United States,Division of Infectious Diseases, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States,Corresponding Author: Jose D. Debes, Address: University of Minnesota, 420 Delaware Street, S.E; MMC 810, Minneapolis, MN 55455, Phone: 612 625 6353
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17
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Ogawa E, Yeo YH, Dang N, Le MH, Jeong D, Tran S, Henry L, Cheung R, Nguyen MH. Diagnosis Rates of Chronic Hepatitis B in Privately Insured Patients in the United States. JAMA Netw Open 2020; 3:e201844. [PMID: 32271388 PMCID: PMC7146097 DOI: 10.1001/jamanetworkopen.2020.1844] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
IMPORTANCE To achieve the World Health Organization goal of viral hepatitis elimination by 2030, it is important to estimate current rates of chronic hepatitis B (CHB) diagnosis and treatment. OBJECTIVE To provide an accurate accounting of the number of patients with CHB aged 6 years or older who have not yet been diagnosed in the United States. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study used the commercial US Truven Health MarketScan Database (138 634 154 privately insured individuals in January 2007 to December 2014) to identify patients with CHB diagnosis and the National Health and Nutrition Examination Survey to estimate the actual number of privately insured persons with CHB. Based on sex and age distribution derived from the US Census Bureau, we calculated the total population with CHB and the proportion of those who remained undiagnosed among the 198 073 302 privately insured individuals. Next, we identified diagnosed CHB patients who received 1 or more prescription for CHB medications to calculate the treatment rate for those with severe disease states, such as cirrhosis and hepatocellular carcinoma, that would warrant treatment. Analyses were performed from October 2017 to January 2020. MAIN OUTCOMES AND MEASURES The rate and number of patients with CHB who remained undiagnosed and treatment rates for patients with CHB who have cirrhosis or hepatocellular carcinoma. RESULTS Among the 198 073 302 privately insured individuals (48.55% male; 15.52% aged 6-17 years; 84.48% aged ≥18 years), there were 511 029 (95% CI, 317 733-704 325) individuals with CHB, but only 95 075 of these had been diagnosed, yielding a diagnosis rate of only 18.60% (95% CI, 13.50%-29.92%), meaning that 81.40% (95% CI, 70.08%-86.50%) were undiagnosed. The treatment rates were 34.79% (95% CI, 33.31%-36.27%) for those with cirrhosis and 48.64% (95% CI, 45.59%-51.69%) for those with hepatocellular carcinoma. CONCLUSIONS AND RELEVANCE In this study, only approximately 1 in 5 privately insured patients with CHB had been diagnosed. Only one-third of patients with CHB who had cirrhosis and one-half who had hepatocellular carcinoma received antiviral therapy. Further efforts are needed to improve the current situation of poor connection to care for patients with CHB, especially for those with advanced liver disease.
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Affiliation(s)
- Eiichi Ogawa
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California
| | - Nolan Dang
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California
| | - Michael H. Le
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California
| | - Donghak Jeong
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California
| | - Sally Tran
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California
| | - Linda Henry
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California
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18
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Sirilert S, Khamrin P, Kumthip K, Malasao R, Maneekarn N, Tongsong T. Placental infection of hepatitis B virus among Thai pregnant women: Clinical risk factors and its association with fetal infection. Prenat Diagn 2019; 40:380-386. [PMID: 31856333 DOI: 10.1002/pd.5628] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 10/08/2019] [Accepted: 10/25/2019] [Indexed: 12/20/2022]
Abstract
OBJECTIVES To identify the risk factors of placental and fetal infections among HBsAg-positive women. METHODS A prospective cohort study involving HBsAg-positive pregnant women was conducted. Maternal risk factors, including serum HBeAg status, anti-HBcIgM, and HBV-DNA levels, were determined. Placental infection was identified by PCR and confirmed by DNA sequencing. Fetal infection was defined as a positive umbilical cord blood HBV-DNA at birth. RESULTS A total of 96 HBsAg-positive women were enrolled in the study. The prevalence of placental infection was high (44 of 96; 45.8%) among HBsAg-positive women. The major risk factors for placental infection were high maternal viral load and the presence of HBeAg. Fetal infection was detected in one quarter of HBsAg-positive women (25 of 95; 25.3%). The risk of fetal infection was strongly associated with placental infection (78.3%), high maternal viral load, and the presence of HBeAg. There was no significant difference in perinatal outcomes between the groups with and without placental infection. Data on rates of chronic HBV infection in infants after fetal infection were not available. CONCLUSION A significant association between maternal measures of viral replication and placental and fetal infection was demonstrated. These findings suggest that transplacental infection prior to birth may be a mechanism contributing to the higher rates of newborn prophylaxis failure in women with a high viral load.
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Affiliation(s)
- Sirinart Sirilert
- Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Pattara Khamrin
- Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Kattareeya Kumthip
- Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Rungnapa Malasao
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Niwat Maneekarn
- Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Theera Tongsong
- Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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19
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Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check. Front Med 2019; 14:273-283. [PMID: 31863306 DOI: 10.1007/s11684-019-0728-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Accepted: 10/12/2019] [Indexed: 02/06/2023]
Abstract
In terms of global cancer-related deaths, hepatocellular carcinoma (HCC) has the fourth highest mortality rate. Up until 2017, treatment of advanced HCC was largely limited to sorafenib, an oral tyrosine kinase inhibitor, with little to no success in the development of alternative treatment options. However, in the past two years, there has been an unprecedented increase in both the number and type of treatment options available for HCC. As of 2019, the US FDA has approved four oral tyrosine kinase inhibitors, two immune checkpoint inhibitors, and one anti-angiogenesis antibody for the treatment of HCC. Even with this new variety, systemic treatment of advanced HCC remains largely unsatisfactory, and the median survival rate stands at approximately one year. The expected breakthrough of using immune checkpoint inhibitors in advanced HCC did not materialize in 2019. The use of immune checkpoint inhibitors in conjunction with oral tyrosine kinase inhibitors or anti-angiogenesis medications is the current clinical research trend, the results of which are eagerly anticipated. Despite limited progress in survival, HCC research is currently experiencing a period of growth and innovation, and there is hope for significant advances in the treatment of advanced HCC as the field continues to develop.
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20
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Huang XB, He YG, Zheng L, Feng H, Li YM, Li HY, Yang FX, Li J. Identification of hepatitis B virus and liver cancer bridge molecules based on functional module network. World J Gastroenterol 2019; 25:4921-4932. [PMID: 31543683 PMCID: PMC6737318 DOI: 10.3748/wjg.v25.i33.4921] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 06/29/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The potential role of chronic inflammation in the development of cancer has been widely recognized. However, there has been little research fully and thoroughly exploring the molecular link between hepatitis B virus (HBV) and hepatocellular carcinoma (HCC). AIM To elucidate the molecular links between HBV and HCC through analyzing the molecular processes of HBV-HCC using a multidimensional approach. METHODS First, maladjusted genes shared between HBV and HCC were identified by disease-related differentially expressed genes. Second, the protein-protein interaction network based on dysfunctional genes identified a series of dysfunctional modules and significant crosstalk between modules based on the hypergeometric test. In addition, key regulators were detected by pivot analysis. Finally, targeted drugs that have regulatory effects on diseases were predicted by modular methods and drug target information. RESULTS The study found that 67 genes continued to increase in the HBV-HCC process. Moreover, 366 overlapping genes in the module network participated in multiple functional blocks. It could be presumed that these genes and their interactions play an important role in the relationship between inflammation and cancer. Correspondingly, significant crosstalk constructed a module level bridge for HBV-HCC molecular processes. On the other hand, a series of non-coding RNAs and transcription factors that have potential pivot regulatory effects on HBV and HCC were identified. Among them, some of the regulators also had persistent disorders in the process of HBV-HCC including microRNA-192, microRNA-215, and microRNA-874, and early growth response 2, FOS, and Kruppel-like factor 4. Therefore, the study concluded that these pivots are the key bridge molecules outside the module. Last but not least, a variety of drugs that may have some potential pharmacological or toxic side effects on HBV-induced HCC were predicted, but their mechanisms still need to be further explored. CONCLUSION The results suggest that the persistent inflammatory environment of HBV can be utilized as an important risk factor to induce the occurrence of HCC, which is supported by molecular evidence.
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Affiliation(s)
- Xiao-Bing Huang
- Department of Hepatobiliary Surgery, Second Hospital Affiliated to Third Military Medical University of Xinqiao Hospital, Chongqing 400037, China
| | - Yong-Gang He
- Department of Hepatobiliary Surgery, Second Hospital Affiliated to Third Military Medical University of Xinqiao Hospital, Chongqing 400037, China
| | - Lu Zheng
- Department of Hepatobiliary Surgery, Second Hospital Affiliated to Third Military Medical University of Xinqiao Hospital, Chongqing 400037, China
| | - Huan Feng
- Division of Nursing, Second Hospital Affiliated to Third Military Medical University, Xinqiao Hospital, Chongqing 400037, China
| | - Yu-Ming Li
- Department of Hepatobiliary Surgery, Second Hospital Affiliated to Third Military Medical University of Xinqiao Hospital, Chongqing 400037, China
| | - Hong-Yan Li
- Department of Hepatobiliary Surgery, Second Hospital Affiliated to Third Military Medical University of Xinqiao Hospital, Chongqing 400037, China
| | - Feng-Xia Yang
- Department of Hepatobiliary Surgery, Second Hospital Affiliated to Third Military Medical University of Xinqiao Hospital, Chongqing 400037, China
| | - Jing Li
- Department of Hepatobiliary Surgery, Second Hospital Affiliated to Third Military Medical University of Xinqiao Hospital, Chongqing 400037, China
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Shi J, Han X, Wang J, Han G, Zhao M, Duan X, Mi L, Li N, Yin X, Shi H, Li C, Gao J, Xu J, Yin F. Matrine prevents the early development of hepatocellular carcinoma like lesions in rat liver. Exp Ther Med 2019; 18:2583-2591. [PMID: 31555367 PMCID: PMC6755378 DOI: 10.3892/etm.2019.7875] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2019] [Accepted: 07/05/2019] [Indexed: 12/19/2022] Open
Abstract
Matrine (C15H24N2O) is an alkaloid extracted from the Chinese herb Sophora flavescens that has anti-fibrotic and anti-cancer properties. The aim of the present study was to determine the chemopreventive effect of matrine on the development of primary hepatocellular carcinoma (HCC) and its possible association with the suppression of the Notch signaling pathway. The rats were randomly divided into four groups: Control, model, low-dose matrine and high-dose matrine groups. The model was established by combining a partial hepatectomy with diethylnitrosamine (DEN) + 2-acetylaminofluorene (2-AAF). Low- and high-dose matrine groups received intragastric administration of matrine (0.25 and 2.5 g/l of matrine, respectively). DEN + 2-AAF injections and hepatectomy were not performed in the control group. All rats were sacrificed 2, 4 and 7 weeks after hepatectomy. HCC-like histopathological lesions were detected using hematoxylin and eosin staining. The expression levels of α-1-fetoprotein (AFP), albumin (ALB), Notch1 and Hes1 were analyzed using immunohistochemistry. Hepatic lobule structure loss, liver tissue necrosis and inflammatory cell infiltration, and edema degeneration were observed in the model group. By contrast, hepatocyte cord structure was restored and hepatocyte edema degeneration was significantly reduced after 7 weeks of treatment with matrine. In addition, compared with the model group, matrine reduced the expression of AFP, increased the expression of ALB and reduced the expression of Notch1 and Hes1 (only for high-dose matrine; all P<0.05). The findings suggested that matrine could prevent the early development of HCC-like lesions in a rat model, possibly by modulating Notch pathway activation.
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Affiliation(s)
- Jianfei Shi
- Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China
| | - Xin Han
- Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China
| | - Jinfeng Wang
- Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China
| | - Guangjie Han
- Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China
| | - Man Zhao
- Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China
| | - Xiaoling Duan
- Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China
| | - Lili Mi
- Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China
| | - Ning Li
- Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China
| | - Xiaolei Yin
- Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China
| | - Huacun Shi
- Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China
| | - Cuizhen Li
- Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China
| | - Jintan Gao
- Department of Tuberculosis, Hebei Chest Hospital, Shijiazhuang, Hebei 050041, P.R. China
| | - Jinsheng Xu
- Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China
| | - Fei Yin
- Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China
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Entecavir-loaded poly (lactic-co-glycolic acid) microspheres for long-term therapy of chronic hepatitis-B: Preparation and in vitro and in vivo evaluation. Int J Pharm 2019; 560:27-34. [PMID: 30711615 DOI: 10.1016/j.ijpharm.2019.01.052] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 01/07/2019] [Accepted: 01/23/2019] [Indexed: 12/21/2022]
Abstract
To avoid severe exacerbations in the load of hepatitis B virus (HBV) as a consequence of discontinuous use of anti-HBV drugs, entecavir (ETV), the first-line anti-HBV drug, was primally formulated as extended-release poly (lactic-co-glycolic acid) microspheres in the present study. Because ETV is slightly soluble in water and in some other organic solvents used for microsphere preparation, methods for solid-microencapsulation were employed to fabricate the ETV microspheres. The optimized microspheres were evaluated for their morphology, particle size, drug loading, in vitro drug release, and in vivo pharmacokinetics in rats. The optimized formulation was found to have a mean particle size of 86 µm and drug loading of 13%. Differential scanning calorimetry and powder X-ray diffraction indicated that ETV existed in crystal, amorphous, and molecular states in the microspheres. In vitro and in vivo release revealed that the dissolution of ETV dominated the release process. The morphology of the microspheres and changes in the morphology during in vitro release were assessed by scanning electron microscopy. The novel ETV-MS described in this study should have great potential for clinical use as an alternative treatment against HBV.
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