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Cornberg M, Sandmann L, Jaroszewicz J, Kennedy P, Lampertico P, Lemoine M, Lens S, Testoni B, Lai-Hung Wong G, Russo FP. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2025:S0168-8278(25)00174-6. [PMID: 40348683 DOI: 10.1016/j.jhep.2025.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Accepted: 03/20/2025] [Indexed: 05/14/2025]
Abstract
The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.
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Wei X, Guo Z, Zhang T, Liang J. A New Risk Score Based on Lipid Indicators for Patients with Advanced Hepatocellular Carcinoma. J Hepatocell Carcinoma 2025; 12:107-121. [PMID: 39867263 PMCID: PMC11762032 DOI: 10.2147/jhc.s505028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 01/04/2025] [Indexed: 01/28/2025] Open
Abstract
Background The prognosis is extremely troubling in advanced hepatocellular carcinoma (HCC). Prognostic scores have been developed. Yet, the positive predictive values might appear inadequate. This retrospective study aimed to develop a quick and efficient risk score to assess prognosis and clinical response. Methods A total of 391 hCC patients were enrolled and were divided into training and validation groups between 2015 and 2024. Patients were separated into high-risk and low-risk groups using X-tile software. Using the COX proportional risk model analysis method, we then created a risk score and examined them using Kaplan-Meier, time-dependent receiver operating characteristics (ROC) curve, and nomogram analysis. Results In predicting overall survival (OS), free fatty acid/high-density lipoprotein cholesterol (FFHL), tumor size, and BCLC stage were independent prognostic variables. A new risk score was developed just above and used as a prognostic factor (p < 0.001 in the training and validation groups) and had a high time-dependent ROC for progress-free survival (PFS) (area under the curve [AUC] 0.688-0.789 in the training group; AUC 0.592-0.741 in the validation group) and OS (AUC 0.812-0.918 in the training group; AUC 0.692-0.981 in the validation group). In comparison to the best overall response (BOR), the score offered a more accurate evaluation of durable clinical benefit (DCB) (p < 0.001 in the training and validation group; p = 0.061 vs 0.001 in the training and validation group). Conclusion A new score based on lipid markers is a useful tool for evaluating prognosis and distinguishing patients with DCB.
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Affiliation(s)
- Xing Wei
- Department of Medical Oncology, Peking University International Hospital, Beijing, People’s Republic of China
| | - Ziwei Guo
- Department of Medicine, Double Crane Runchuang Technology (Beijing) Co., Ltd, Beijing, People’s Republic of China
| | - Tingting Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, People’s Republic of China
| | - Jun Liang
- Department of Medical Oncology, Peking University International Hospital, Beijing, People’s Republic of China
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Bruni A, Castellana C, Dajti E, Barbara G, Marasco G, Maida M, Serviddio G, Facciorusso A. Epidemiological, diagnostic, therapeutic and prognostic impact of hepatitis B and D virus infection on hepatocellular carcinoma: A review of the literature. Virology 2024; 600:110273. [PMID: 39454228 DOI: 10.1016/j.virol.2024.110273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 10/17/2024] [Accepted: 10/21/2024] [Indexed: 10/28/2024]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) accounts for >90% of primary liver cancer cases, and chronic infections with hepatitis B virus (HBV) and hepatitis D virus (HDV) are major contributors. METHODS A comprehensive literature review was conducted using the MEDLINE (PubMed) database, focusing on studies related to HBV, HDV, and HCC. RESULTS HBV contributes to HCC through mechanisms like viral integration into the host genome, chronic inflammation, and immune modulation, leading to genomic instability and altered cell signaling. HDV exacerbates HBV-induced liver damage, accelerating fibrosis and cirrhosis, and significantly increasing HCC risk. Antiviral therapies and vaccinations have majorly reduced the burden of HBV-related HCC, but HDV remains challenging to treat due to limited therapeutic options. Emerging treatments like Bulevirtide showed promising results. CONCLUSION This review highlights the critical impact of HBV and HDV co-infections on HCC development, emphasizing the need for more effective therapeutic strategies. While advances in antiviral therapies have reduced the incidence of HBV-related HCC, the high burden of HDV-related complications persists. Future research should focus on improving treatments for HDV and understanding its unique contribution to HCC pathogenesis.
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Affiliation(s)
- Angelo Bruni
- Department of Medical and Surgical Sciences, Università di Bologna, Bologna, Italy
| | - Chiara Castellana
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Elton Dajti
- Department of Medical and Surgical Sciences, Università di Bologna, Bologna, Italy; Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giovanni Barbara
- Department of Medical and Surgical Sciences, Università di Bologna, Bologna, Italy; Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences, Università di Bologna, Bologna, Italy; Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Marcello Maida
- Department of Medicine and Surgery, University of Enna 'Kore', Enna, Italy; Gastroenterology Unit, Umberto I Hospital, Enna, Italy
| | - Gaetano Serviddio
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Antonio Facciorusso
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
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Chung YE. Deep learning assisted biomarker development in patients with chronic hepatitis B: Editorial on "Prognostic role of computed tomography analysis using deep learning algorithm in patients with chronic hepatitis B viral infection". Clin Mol Hepatol 2024; 30:669-672. [PMID: 39038960 PMCID: PMC11540355 DOI: 10.3350/cmh.2024.0563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Accepted: 07/20/2024] [Indexed: 07/24/2024] Open
Affiliation(s)
- Yong Eun Chung
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Bera C, Hamdan-Perez N, Patel K. Non-Invasive Assessment of Liver Fibrosis in Hepatitis B Patients. J Clin Med 2024; 13:1046. [PMID: 38398358 PMCID: PMC10889471 DOI: 10.3390/jcm13041046] [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: 01/08/2024] [Revised: 02/02/2024] [Accepted: 02/08/2024] [Indexed: 02/25/2024] Open
Abstract
The aim of this review is to provide updated information on the clinical use of non-invasive serum and imaging-based tests for fibrosis assessment in chronic hepatitis B (CHB) virus infection. In recent years, non-invasive tests (NIT) have been increasingly used to determine eligibility for treatment. Liver biopsy is still considered the gold standard for assessing inflammatory activity and fibrosis staging, but it is an invasive procedure with inherent limitations. Simple serum markers such as APRI and FIB-4 are limited by indeterminate results but remain useful initial tests for fibrosis severity if imaging elastography is not available. Point-of-care US-based elastography techniques, such as vibration-controlled transient elastography or 2D shear wave elastography, are increasingly available and have better accuracy than simple serum tests for advanced fibrosis or cirrhosis, although stiffness cut-offs are variable based on E-antigen status and inflammatory activity. Current NITs have poor diagnostic performance for following changes in fibrosis with antiviral therapy. However, NITs may have greater clinical utility for determining prognosis in patients with CHB that have advanced disease, especially for the development of hepatocellular carcinoma and/or liver decompensation. Algorithms combining serum and imaging NITs appear promising for advanced fibrosis and prognostic risk stratification.
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Affiliation(s)
- Chinmay Bera
- Division of Gastroenterology, University Health Network Toronto, Toronto General Hospital, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada; (N.H.-P.)
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Campbell C, Wang T, Gillespie I, Barnes E, Matthews PC. Analysis of primary care electronic health record data of people living with hepatitis B virus: infection and hepatocellular carcinoma risk associated with socio-economic deprivation. Public Health 2024; 226:215-227. [PMID: 38091810 PMCID: PMC7615551 DOI: 10.1016/j.puhe.2023.10.036] [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: 04/24/2023] [Revised: 08/28/2023] [Accepted: 10/18/2023] [Indexed: 01/15/2024]
Abstract
OBJECTIVES We set out to characterise chronic hepatitis B (CHB) in the primary care population in England and investigate risk factors for progression to hepatocellular carcinoma (HCC). STUDY DESIGN Retrospective cohort study. METHODS We identified 8039 individuals with CHB in individuals aged ≥18 years between 1999 and 2019 in the English primary care database QResearch. HCC risk factors were investigated using Cox proportional hazards modelling. RESULTS Most of those with a record of CHB were males (60%) of non-White ethnicity (>70%), and a high proportion were in the most deprived Townsend deprivation quintile (44%). Among 7029 individuals with longitudinal data, 161 HCC cases occurred. Increased HCC hazards were significantly associated with male sex (adjusted hazards ratio [aHR] 3.17, 95% confidence interval [95% CI] 1.92-5.23), in the fifth deprivation quintile as compared to the third quintile (aHR 1.69, 95% CI 1.01-2.84), with older age (for age groups 56-65 and ≥66 years, compared to 26-35 years, aHRs 2.82 [95% CI 1.45-5.46] and 3.76 [95% CI 1.79-7.9], respectively), Caribbean ethnicity (aHR 3.32, 95% CI 1.43-7.71, compared to White ethnicity), ascites (aHR 3.15, 95% CI 1.30-7.67), cirrhosis (aHR 6.55, 95% CI 4.57-9.38) and peptic ulcer disease (aHR 2.26, 95% CI 1.45-3.51). CONCLUSIONS Targeting interventions and HCC surveillance at vulnerable groups is essential to improve CHB outcomes and to support progress towards international goals for the elimination of hepatitis infection as a public health threat.
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Affiliation(s)
- C Campbell
- Nuffield Department of Medicine, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
| | - T Wang
- Nuffield Department of Medicine, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
| | | | - E Barnes
- NIHR Oxford Biomedical Research Centre, Oxford, UK; Department of Hepatology, Oxford University Hospitals, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK
| | - P C Matthews
- NIHR Oxford Biomedical Research Centre, Oxford, UK; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Division of Infection and Immunity, University College London, Gower Street, London WC1E 6BT, UK; Department of Infectious Diseases, University College London Hospital, Euston Road, London NW1 2BU, UK.
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Hao X, Fan R, Zeng HM, Hou JL. Hepatocellular Carcinoma Risk Scores from Modeling to Real Clinical Practice in Areas Highly Endemic for Hepatitis B Infection. J Clin Transl Hepatol 2023; 11:1508-1519. [PMID: 38161501 PMCID: PMC10752803 DOI: 10.14218/jcth.2023.00087] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 05/04/2023] [Accepted: 06/02/2023] [Indexed: 01/03/2024] Open
Abstract
Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and represents a global health challenge. Liver cancer ranks third in cancer-related mortality with 830,000 deaths and sixth in incidence with 906,000 new cases annually worldwide. HCC most commonly occurs in patients with underlying liver disease, especially chronic hepatitis B virus (HBV) infection in highly endemic areas. Predicting HCC risk based on scoring models for patients with chronic liver disease is a simple, effective strategy for identifying and stratifying patients to improve the early diagnosis rate and prognosis of HCC. We examined 23 HCC risk scores published worldwide in CHB patients with (n=10) or without (n=13) antiviral treatment. We also described the characteristics of the risk score's predictive performance and application status. In the future, higher predictive accuracy could be achieved by combining novel technologies and machine learning algorithms to develop and update HCC risk score models and integrated early warning and diagnosis systems for HCC in hospitals and communities.
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Affiliation(s)
- Xin Hao
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, China
| | - Rong Fan
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, China
| | - Hong-Mei Zeng
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jin-Lin Hou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, China
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Huang DQ, Singal AG, Kanwal F, Lampertico P, Buti M, Sirlin CB, Nguyen MH, Loomba R. Hepatocellular carcinoma surveillance - utilization, barriers and the impact of changing aetiology. Nat Rev Gastroenterol Hepatol 2023; 20:797-809. [PMID: 37537332 DOI: 10.1038/s41575-023-00818-8] [Citation(s) in RCA: 71] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/30/2023] [Indexed: 08/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Surveillance for HCC is critical for early detection and treatment, but fewer than one-quarter of individuals at risk of HCC undergo surveillance. Multiple failures across the screening process contribute to the underutilization of surveillance, including limited disease awareness among patients and health-care providers, knowledge gaps, and difficulty recognizing patients who are at risk. Non-alcoholic fatty liver disease and alcohol-associated liver disease are the fastest-rising causes of HCC-related death worldwide and are associated with unique barriers to surveillance. In particular, more than one-third of patients with HCC related to non-alcoholic fatty liver disease do not have cirrhosis and therefore lack a routine indication for HCC surveillance on the basis of current practice guidelines. Semi-annual abdominal ultrasound with measurement of α-fetoprotein levels is recommended for HCC surveillance, but the sensitivity of this approach for early HCC is limited, especially for patients with cirrhosis or obesity. In this Review, we discuss the current status of HCC surveillance and the remaining challenges, including the changing aetiology of liver disease. We also discuss strategies to improve the utilization and quality of surveillance for HCC.
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Affiliation(s)
- Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore.
| | - Amit G Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Fasiha Kanwal
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Pietro Lampertico
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
- CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Maria Buti
- Liver Unit, Department of Internal Medicine, Hospital Universitari Valle d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBER-EHD del Instituto Carlos III, Barcelona, Spain
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, UCSD School of Medicine, San Diego, CA, USA
| | - Mindie H Nguyen
- Department of Epidemiology and Population Health, Stanford University Medical Center, Stanford University, Palo Alto, CA, USA
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford University, Palo Alto, CA, USA
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, CA, USA
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, San Diego, CA, USA
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Hui S, Bell S, Le S, Dev A. Hepatocellular carcinoma surveillance in Australia: current and future perspectives. Med J Aust 2023; 219:432-438. [PMID: 37803907 DOI: 10.5694/mja2.52124] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 09/04/2023] [Indexed: 10/08/2023]
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and is increasing in incidence in Australia. For most people with cirrhosis and chronic hepatitis B, HCC screening and surveillance is recommended with 6-monthly ultrasound. However, most patients with HCC are still diagnosed outside of surveillance with incurable disease. While HCC surveillance almost certainly reduces cancer-related mortality, the potential harms of surveillance are incompletely understood. Surveillance uptake remains suboptimal in many contexts, and stems from a combination of patient, clinician and system level barriers. Improved case-finding strategies may be required to identify high risk individuals in need of surveillance, as cirrhosis and viral hepatitis are often asymptomatic. HCC prediction models and novel surveillance tools such as biomarker panels, computed tomography and magnetic resonance imaging may have a future role in personalised HCC surveillance. Analyses suggest surveillance may be cost-effective, but Australian data remain limited. A centralised HCC surveillance program may ultimately have a role in delivering improved and more equitable care.
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Affiliation(s)
- Samuel Hui
- School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, VIC
| | - Sally Bell
- School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, VIC
| | - Suong Le
- School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, VIC
| | - Anouk Dev
- School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, VIC
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Spearman CW, Andersson MI, Bright B, Davwar PM, Desalegn H, Guingane AN, Johannessen A, Kabagambe K, Lemoine M, Matthews PC, Ndow G, Riches N, Shimakawa Y, Sombié R, Stockdale AJ, Taljaard JJ, Vinikoor MJ, Wandeler G, Okeke E, Sonderup M. A new approach to prevent, diagnose, and treat hepatitis B in Africa. BMC GLOBAL AND PUBLIC HEALTH 2023; 1:24. [PMID: 38798823 PMCID: PMC11116268 DOI: 10.1186/s44263-023-00026-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 10/02/2023] [Indexed: 05/29/2024]
Abstract
There are 82 million people living with hepatitis B (PLWHB) in the World Health Organization Africa region, where it is the main cause of liver disease. Effective vaccines have been available for over 40 years, yet there are 990,000 new infections annually, due to limited implementation of hepatitis B birth dose vaccination and antenatal tenofovir prophylaxis for highly viraemic women, which could eliminate mother-to-child transmission. Despite effective and cheap antiviral treatment which can suppress hepatitis B virus replication and reduce the risk of hepatocellular carcinoma (HCC), < 2% of PLWHB are diagnosed, and only 0.1% are treated. As a result, PLWHB are frequently diagnosed only when they have already developed decompensated cirrhosis and late-stage HCC, and consequently 80,000 hepatitis B-associated deaths occur each year. Major barriers include complex treatment guidelines which were derived from high-income settings, lack of affordable diagnostics, lack or insufficient domestic funding for hepatitis care, and limited healthcare infrastructure. Current treatment criteria may overlook patients at risk of cirrhosis and HCC. Therefore, expanded and simplified treatment criteria are needed. We advocate for decentralized community treatment programmes, adapted for low-resource and rural settings with limited laboratory infrastructure. We propose a strategy of treat-all except patients fulfilling criteria that suggest low risk of disease progression. Expanded treatment represents a financial challenge requiring concerted action from policy makers, industry, and international donor agencies. It is crucial to accelerate hepatitis B elimination plans, integrate hepatitis B care into existing healthcare programmes, and prioritize longitudinal and implementation research to improve care for PLWHB.
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Affiliation(s)
- C. Wendy Spearman
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Monique I. Andersson
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Radcliffe Department of Medicine, University of Oxford, Oxford, UK
- Division of Medical Virology, University of Stellenbosch, Stellenbosch, South Africa
| | - Bisi Bright
- LiveWell Initiative, Yesuf Abiodun Street, Victoria Island, Lagos, Nigeria
- Women in Hepatitis Africa, Womens Wellness Center for Hepatitis, Isale Ajoke, Iwaya-Makoko, Lagos State, Nigeria
| | - Pantong M. Davwar
- Department of Internal Medicine, Jos Univeristy Teaching Hospital, Jos, Nigeria
| | - Hailemichael Desalegn
- Department of Internal Medicine, St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Alice Nanelin Guingane
- Hepato-Gastroenterology Department, Bogodogo University Hospital Center, Ouagadougou, Burkina Faso
| | - Asgeir Johannessen
- Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Kenneth Kabagambe
- The National Organisation for People Living With Hepatitis B, Kampala, Uganda
| | - Maud Lemoine
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Imperial College London, London, UK
- Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Atlantic Boulevard, Fajara, The Gambia
| | - Philippa C. Matthews
- The Francis Crick Institute, 1 Midland Road, London, NW1 1AT UK
- Division of Infection and Immunity, University College London, Gower Street, London, WC1E 6BT UK
- Department of Infectious Diseases, University College London Hospital, Euston Road, London, NW1 2BU UK
| | - Gibril Ndow
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Imperial College London, London, UK
- Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Atlantic Boulevard, Fajara, The Gambia
| | - Nicholas Riches
- Department of Clinical Sciences and International Public Health, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Yusuke Shimakawa
- Institut Pasteur, Université Paris Cité, Unité d’Épidémiologie Des Maladies Émergentes, Paris, France
| | - Roger Sombié
- Service d’hépato-Gastroentérologie, CHU Yalgado OUÉDRAOGO, Université Joseph KI-ZERBO, Ouagadougou, Burkina Faso
| | - Alexander J. Stockdale
- Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
- Department of Clinical Infection, Microbiology and Immunity, University of Liverpool, Liverpool, UK
| | - Jantjie J. Taljaard
- Division of Infectious Diseases, Department of Medicine, Tygerberg Hospital and Stellenbosch University, Cape Town, South Africa
| | - Michael J. Vinikoor
- School of Medicine, University of Alabama at Birmingham, Birmingham, AL USA
- Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
- School of Medicine, University of Zambia, Lusaka, Zambia
| | - Gilles Wandeler
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Edith Okeke
- Department of Medicine, Jos University Teaching Hospital, Jos, Nigeria
| | - Mark Sonderup
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - on behalf of the Hepatitis B in Africa Collaborative Network (HEPSANET)
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Radcliffe Department of Medicine, University of Oxford, Oxford, UK
- Division of Medical Virology, University of Stellenbosch, Stellenbosch, South Africa
- LiveWell Initiative, Yesuf Abiodun Street, Victoria Island, Lagos, Nigeria
- Women in Hepatitis Africa, Womens Wellness Center for Hepatitis, Isale Ajoke, Iwaya-Makoko, Lagos State, Nigeria
- Department of Internal Medicine, Jos Univeristy Teaching Hospital, Jos, Nigeria
- Department of Internal Medicine, St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia
- Hepato-Gastroenterology Department, Bogodogo University Hospital Center, Ouagadougou, Burkina Faso
- Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- The National Organisation for People Living With Hepatitis B, Kampala, Uganda
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Imperial College London, London, UK
- Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Atlantic Boulevard, Fajara, The Gambia
- The Francis Crick Institute, 1 Midland Road, London, NW1 1AT UK
- Division of Infection and Immunity, University College London, Gower Street, London, WC1E 6BT UK
- Department of Infectious Diseases, University College London Hospital, Euston Road, London, NW1 2BU UK
- Department of Clinical Sciences and International Public Health, Liverpool School of Tropical Medicine, Liverpool, UK
- Institut Pasteur, Université Paris Cité, Unité d’Épidémiologie Des Maladies Émergentes, Paris, France
- Service d’hépato-Gastroentérologie, CHU Yalgado OUÉDRAOGO, Université Joseph KI-ZERBO, Ouagadougou, Burkina Faso
- Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
- Department of Clinical Infection, Microbiology and Immunity, University of Liverpool, Liverpool, UK
- Division of Infectious Diseases, Department of Medicine, Tygerberg Hospital and Stellenbosch University, Cape Town, South Africa
- School of Medicine, University of Alabama at Birmingham, Birmingham, AL USA
- Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
- School of Medicine, University of Zambia, Lusaka, Zambia
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
- Department of Medicine, Jos University Teaching Hospital, Jos, Nigeria
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Wang J, Wang K, Chen C, Xiong Y, Guo C, Wang C, Yang W, Fu Y, Su M, Li S, Ji D. Survival analysis and development of a prognostic nomogram for patients with hepatitis B virus-associated hepatocellular carcinoma. Heliyon 2023; 9:e20850. [PMID: 37867830 PMCID: PMC10587491 DOI: 10.1016/j.heliyon.2023.e20850] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 10/06/2023] [Accepted: 10/09/2023] [Indexed: 10/24/2023] Open
Abstract
Background and aims Hepatitis B virus (HBV) is a common cause of hepatocellular carcinoma (HCC) in China, and this study aimed to identify high-risk factors for overall survival and develop a nomogram prediction model. Methods In the present retrospective cohort study, patients with HBV-associated HCC diagnosed from January 2009 to December 2018 were enrolled. Their clinical characteristics and time-to-event information were retrieved from electronic medical records. The zero time was the date of HCC diagnosis, and the endpoint was death or liver transplantation. Multivariable COX proportional hazard regression was used to screen independent risk factors for overall survival; then a nomogram model was developed to predict the survival probability of HCC patients. Results A total of 1723 patients were enrolled, with 82.7 % male and a median age of 54.0 years. During a median follow-up time of 41.3 months, 672 cases (39.0 %) died. Age ≥60 years (HR = 1.209), Male (HR = 1.293), ALB <35 g/L (HR = 1.491), AST ≥80 U/L (HR = 1.818); AFP 20-400 ng/mL (HR = 2.284), AFP ≥400 ng/mL (HR = 2.746); LSM 9-22 kPa (HR = 2.266), LSM ≥22 kPa (HR = 4.326); BCLC stage B/C (HR = 4.079) and BCLC stage D (HR = 16.830) were the independent high-risk factors associated with HCC survival. A prognostic nomogram with a consistency index of 0.842 (95 % CI: 0.827-0.858) was developed. The calibration curve for long-term survival rate fitted well. Conclusions This study identified independent risk factors affecting the survival of patients with HBV-associated HCC and constructed a predictive nomogram model, which can individually predict the overall survival and has good clinical application value.
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Affiliation(s)
- Jianjun Wang
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Kexin Wang
- 307 Clinical Medical College of PLA, Anhui Medical University, Beijing, 100071, China
| | - Chun Chen
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Yuting Xiong
- 307 Clinical Medical College of PLA, Anhui Medical University, Beijing, 100071, China
| | - Chang Guo
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Chunyan Wang
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Wucai Yang
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Yiming Fu
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Min Su
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Shuyao Li
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Dong Ji
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
- 307 Clinical Medical College of PLA, Anhui Medical University, Beijing, 100071, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
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Dilokthornsakul P, Sawangjit R, Tangkijvanich P, Chayanupatkul M, Sriuttha P, Permsuwan U. Risk prediction algorithms in guiding antiviral therapy initiation among patients with chronic hepatitis B in Thailand: an economic evaluation and budget impact analysis. Expert Rev Pharmacoecon Outcomes Res 2023; 23:951-958. [PMID: 37381798 DOI: 10.1080/14737167.2023.2231636] [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: 04/22/2023] [Accepted: 06/19/2023] [Indexed: 06/30/2023]
Abstract
OBJECTIVE Several risk prediction algorithms have been developed to guide antiviral therapy initiation among patients with chronic hepatitis B (CHB). This study assessed the cost-effectiveness and budget impact of three risk prediction algorithms among patients with CHB in Thailand. METHODS A decision tree with a Markov model was constructed. Three risk prediction algorithms were compared with current practices including HePAA, TREAT-B and REACH-B. PubMed was searched from its inception to December 2022 to identify inputs. Tenofovir alafenamide and best supportive care were selected for antiviral-eligible patients, and incremental cost-effectiveness ratios per quality-adjusted life year (QALY) were calculated. RESULTS Our base case analysis showed that HePAA and REACH-B could provide better QALY (0.098 for HePAA and 0.921 for REACH-B) with decreased total healthcare costs (-10909 THB for HePAA and -8,637 THB for REACH-B). TREAT-B provided worse QALY (-0.144) with increased total healthcare costs (10,435 THB). The budget impacts for HePAA and REACH-B were 387 million THB and 3,653 million THB, respectively. CONCLUSION HePAA and REACH-B algorithms are cost-effective in guiding antiviral therapy initiation. REACH-B is the most cost-effective option, but has a high budget impact. Policymakers should consider both cost-effectiveness and budget impact findings when deciding which algorithm should be implemented.
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Affiliation(s)
- Piyameth Dilokthornsakul
- Center of Medical and Health Technology Assessment (CM-HTA), Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
- Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
| | - Ratree Sawangjit
- Clinical Trial and Evidence-Based Synthesis Research Unit, Department of Clinical Pharmacy, Faculty of Pharmacy, Mahasarakham University, Mahasarakham, Thailand
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Maneerat Chayanupatkul
- Center of Excellence in Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pajaree Sriuttha
- Center of Medical and Health Technology Assessment (CM-HTA), Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
- Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
| | - Unchalee Permsuwan
- Center of Medical and Health Technology Assessment (CM-HTA), Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
- Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
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13
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Wu Z(E, Xu D, Hu PJH, Huang TS. A hierarchical multilabel graph attention network method to predict the deterioration paths of chronic hepatitis B patients. J Am Med Inform Assoc 2023; 30:846-858. [PMID: 36794643 PMCID: PMC10114116 DOI: 10.1093/jamia/ocad008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 12/26/2022] [Accepted: 01/25/2023] [Indexed: 02/17/2023] Open
Abstract
OBJECTIVE Estimating the deterioration paths of chronic hepatitis B (CHB) patients is critical for physicians' decisions and patient management. A novel, hierarchical multilabel graph attention-based method aims to predict patient deterioration paths more effectively. Applied to a CHB patient data set, it offers strong predictive utilities and clinical value. MATERIALS AND METHODS The proposed method incorporates patients' responses to medications, diagnosis event sequences, and outcome dependencies to estimate deterioration paths. From the electronic health records maintained by a major healthcare organization in Taiwan, we collect clinical data about 177 959 patients diagnosed with hepatitis B virus infection. We use this sample to evaluate the proposed method's predictive efficacy relative to 9 existing methods, as measured by precision, recall, F-measure, and area under the curve (AUC). RESULTS We use 20% of the sample as holdouts to test each method's prediction performance. The results indicate that our method consistently and significantly outperforms all benchmark methods. It attains the highest AUC, with a 4.8% improvement over the best-performing benchmark, as well as 20.9% and 11.4% improvements in precision and F-measures, respectively. The comparative results demonstrate that our method is more effective for predicting CHB patients' deterioration paths than existing predictive methods. DISCUSSION AND CONCLUSION The proposed method underscores the value of patient-medication interactions, temporal sequential patterns of distinct diagnosis, and patient outcome dependencies for capturing dynamics that underpin patient deterioration over time. Its efficacious estimates grant physicians a more holistic view of patient progressions and can enhance their clinical decision-making and patient management.
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Affiliation(s)
- Zejian (Eric) Wu
- Department of Operations and Information Systems, David Eccles School of Business, University of Utah, Salt Lake City, Utah, USA
| | - Da Xu
- Department of Information Systems, College of Business, California State University Long Beach, Long Beach, California, USA
| | - Paul Jen-Hwa Hu
- Department of Operations and Information Systems, David Eccles School of Business, University of Utah, Salt Lake City, Utah, USA
| | - Ting-Shuo Huang
- Department of General Surgery, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan
- Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan City, Taiwan
- Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan
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Kang CK, Brennan PN, Dillon JF. How to Effectively Monitor Aging Patients with Chronic Hepatitis B: A Review. Clin Interv Aging 2022; 17:1811-1820. [PMID: 36532948 PMCID: PMC9748119 DOI: 10.2147/cia.s366255] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 11/17/2022] [Indexed: 05/11/2024] Open
Abstract
Hepatitis B virus (HBV) infection is a major global public health challenge associated with significant morbidity and mortality. Due to worldwide population aging, HBV infection in the elderly will become increasingly prevalent. Effective universal vaccination programs exist but these are largely targeted towards the younger population. Therefore, the elderly population remains at risk of higher disease burden. New diagnoses of HBV infection in the elderly are usually asymptomatic chronic infections which increases their risk of developing cirrhosis, hepatocellular carcinoma, and liver disease-related mortality, especially if left untreated. Physiological changes and the increasing prevalence of multimorbidity associated with aging also potentially worsen outcomes in elderly patients with chronic HBV infection. Therefore, this cohort of patients should be monitored closely and effectively. Current international clinical practice guidelines unfortunately do not provide hard treatment endpoints specific to elderly patients with chronic HBV infection. Management of these patients is complex and requires an individualized approach. Multiple factors such as physiological changes, comorbidities, compliance, treatment tolerability and efficacy, burden of treatment, and realistic treatment goals need to be considered. Shared decision-making between patient and clinician is essential to ensure that the final decision for or against treatment aligns with the patient's values and preferences. This review article aims to summarize the monitoring and management of chronic HBV infection in the aging population.
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Affiliation(s)
- Chan Keat Kang
- Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
| | - Paul N Brennan
- Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
| | - John F Dillon
- Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
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15
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Spearman CW, Dusheiko G, Jonas E, Abdo A, Afihene M, Cunha L, Desalegn H, Kassianides C, Katsidzira L, Kramvis A, Lam P, Lesi OA, Micah EA, Musabeyezu E, Ndow G, Nnabuchi CV, Ocama P, Okeke E, Rwegasha J, Shewaye AB, Some FF, Tzeuton C, Sonderup MW. Hepatocellular carcinoma: measures to improve the outlook in sub-Saharan Africa. Lancet Gastroenterol Hepatol 2022; 7:1036-1048. [PMID: 35810766 DOI: 10.1016/s2468-1253(22)00041-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 01/26/2022] [Accepted: 02/02/2022] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma is a leading public health concern in sub-Saharan Africa, and it is most prevalent in young adults (median 45 years [IQR 35-57]). Overall, outcomes are poor, with a median survival of 2·5 months after presentation. Major risk factors for hepatocellular carcinoma are hepatitis B virus (HBV), hepatitis C virus, aflatoxin B1 exposure, and alcohol consumption, with metabolic dysfunction-associated fatty liver disease slowly emerging as a risk factor over the past few years. Crucially, these risk factors are preventable and manageable with effective implementation of the HBV birth-dose vaccination, treatment of chronic viral hepatitis, provision of harm reduction services, and by decreasing aflatoxin B1 exposure and harmful alcohol consumption. Primary prevention is central to the management of hepatocellular carcinoma, especially in poorly resourced environments. Effective screening and surveillance programmes with recall policies need to be implemented, because detection and curative management of hepatocellular carcinoma is possible if it is detected at an early stage, even in countries with minimal resources, with appropriate upskilling of medical personnel. The establishment of centres of excellence with advanced diagnostic and therapeutic capabilities within countries should improve hepatocellular carcinoma outcomes and assist in driving the implementation of much needed systematic data systems focused on hepatocellular carcinoma to establish the accurate burden in sub-Saharan Africa. Such data would support the public health importance of hepatocellular carcinoma and provide a strong basis for advocacy, programme development, resource allocation, and monitoring of progress in reducing mortality.
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Affiliation(s)
- C Wendy Spearman
- Division of Hepatology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
| | - Geoffrey Dusheiko
- University College London Medical School, London, UK; Kings College Hospital, London, UK
| | - Eduard Jonas
- Surgical Gastroenterology Unit, Division of General Surgery, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Abdelmounem Abdo
- National Centre for Gastrointestinal and Liver Disease, Ibn Sina Hospital, Alamarat, Khartoum, Sudan
| | - Mary Afihene
- Department of Medicine, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Lina Cunha
- Gastroenterology Unit, Maputo Private Hospital, Maputo, Mozambique
| | - Hailemichael Desalegn
- Department of Internal Medicine, St Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Chris Kassianides
- Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Leolin Katsidzira
- Internal Medicine Unit, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe
| | - Anna Kramvis
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa
| | | | - Olufunmilayo A Lesi
- Gastroenterology and Hepatology Unit, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Eileen A Micah
- Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | | | - Gibril Ndow
- Disease Control and Elimination Theme, MRC Unit The Gambia at the London School of Tropical Medicine, London, UK; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Chidi V Nnabuchi
- Asokoro District Hospital, Nile University Teaching Hospital, Abuja, Nigeria
| | - Ponsiano Ocama
- School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Edith Okeke
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, College of Health Sciences, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
| | - John Rwegasha
- Gastroenterology Training Centre, Department of Internal Medicine, Muhimbili National Hospital, Dar Es Salaam, Tanzania
| | - Abate B Shewaye
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Fatuma F Some
- Department of Medicine, School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya
| | - Christian Tzeuton
- Faculty of Medicine and Pharmaceutical Sciences of Douala, University of Douala, Douala, Cameroon
| | - Mark W Sonderup
- Division of Hepatology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
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16
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Bollerup S, Engsig F, Hallager S, Mocroft A, Roege BT, Christensen PB, Laursen AL, Krarup H, Clausen MR, Thielsen P, Madsen LG, Noerregaard L, Barfod TS, Balslev U, Tarp B, Hansen JB, Mygind LH, Gerstoft J, Weis N. Incidence of Hepatocellular Carcinoma and Decompensated Liver Cirrhosis and Prognostic Accuracy of the PAGE-B HCC Risk Score in a Low Endemic Hepatitis B Virus Infected Population. J Hepatocell Carcinoma 2022; 9:1093-1104. [PMID: 36281336 PMCID: PMC9587738 DOI: 10.2147/jhc.s372571] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 08/22/2022] [Indexed: 11/21/2022] Open
Abstract
Purpose We aimed to determine incidence of hepatocellular carcinoma (HCC) and decompensated liver cirrhosis in persons with chronic hepatitis B virus (HBV) infection in Denmark stratified by disease phase, liver cirrhosis, and treatment status at baseline. Additionally, we aimed to assess the prognostic value of the PAGE-B HCC risk score in a mainly non-cirrhotic population. Patients and Methods In this register-based cohort study, we included all individuals over the age of 18, with chronic HBV infection first registered between 2002 and 2016 in at least one of three nationwide registers. The study population was followed until HCC, decompensated liver cirrhosis, death, emigration, or December 31, 2017, which ever came first. Results Among 6016 individuals included in the study, 10 individuals with and 23 without baseline liver cirrhosis developed HCC during a median follow up of 7.3 years (range 0.0-15.5). This corresponded to five-year cumulative incidences of 7.1% (95% confidence interval (CI) 2.0-12.3) and 0.2% (95% CI 0.1-0.4) in persons with and without baseline liver cirrhosis. The five-year cumulative incidence of decompensated liver cirrhosis was 0.7% (95% CI 0.5-1.0). Among 2038 evaluated for liver events stratified by disease phase, incidence of HCC was low in all who were non-cirrhotic and untreated for HBV at baseline. PAGE-B score was evaluated in 1529 persons. The 5-year cumulative incidence of HCC was 0, 0.8 (95% CI 0.5-1.8), and 8.7 (95% CI 1.0-16.4) in persons scoring <10, 10-17 and >17, respectively (c-statistic 0.91 (95% CI 0.84-0.98)). Conclusion We found low incidence of HCC and decompensated liver cirrhosis in persons with chronic HBV infection in Denmark. Moreover, the PAGE-B score showed good accuracy for five-year risk of developing HCC in the population with chronic HBV infection in Denmark.
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Affiliation(s)
- Signe Bollerup
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
| | - Frederik Engsig
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
| | - Sofie Hallager
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
| | - Amanda Mocroft
- Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London, England,Centre of Excellence for Health, Immunity and Infections (CHIP) and PERSIMUNE, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Birgit T Roege
- Department of Internal Medicine, Kolding Hospital, Kolding, Denmark
| | - Peer B Christensen
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark,Clinical Institute, University of Southern Denmark, Odense, Denmark
| | - Alex L Laursen
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
| | - Henrik Krarup
- Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark,Department of Medical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Mette R Clausen
- Department of Medical Gastroenterology and Hepatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Peter Thielsen
- Department of Gastroenterology, Herlev Hospital, Herlev, Denmark
| | - Lone G Madsen
- Department of Medical Gastroenterology, Zealand University Hospital, Koege, Denmark,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Lars Noerregaard
- Department of Lung- and Infectious Diseases, North Zealand Hospital, Hilleroed, Denmark
| | - Toke S Barfod
- Department of Internal Medicine and Infectious Diseases, Zealand University Hospital, Roskilde, Denmark
| | - Ulla Balslev
- Department of Infectious Diseases, Herlev Hospital, Herlev, Denmark
| | - Britta Tarp
- Diagnostic Centre, University Research Clinic for Innovative Patient Pathways, Silkeborg Regional Hospital, Silkeborg, Denmark
| | - Jesper B Hansen
- Department of Medical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Lone H Mygind
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
| | - Jan Gerstoft
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark,Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Nina Weis
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark,Correspondence: Nina Weis, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark, Tel: +45 38623514, Email
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17
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Ferreira da Silva AC, Cunha-Silva M, Sevá-Pereira T, Mazo DF. Evaluation of the Hepatocellular Carcinoma Predictive Scores PAGE-B and mPAGE-B among Brazilian Patients with Chronic Hepatitis B Virus Infection. Viruses 2022; 14:v14091968. [PMID: 36146774 PMCID: PMC9503912 DOI: 10.3390/v14091968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/28/2022] [Accepted: 09/02/2022] [Indexed: 11/29/2022] Open
Abstract
Hepatitis B virus (HBV) is intrinsically oncogenic and related to hepatocellular carcinoma (HCC). Predictive scores of HCC have been developed but have been poorly studied in admixed populations. Therefore, we aimed to evaluate the performance of PAGE-B and mPAGE-B scores for HCC prediction in HBV Brazilian patients and factors related to HCC occurrence. This is a retrospective study that evaluated patients followed at a tertiary university center. A total of 224 patients were included, with a median follow-up period of 9 years. The mean age at HBV diagnosis was 38.71 ± 14.19 years, predominantly males (66.1%). The cumulative incidence of HCC at 3, 5, and 7 years was 0.993%, 2.70%, and 5.25%, respectively, being related in the univariate logistic regression analysis to male sex (p = 0.0461), older age (p = 0.0001), cirrhosis at HBV diagnosis (p < 0.0001), and higher values of PAGE-B and mPAGE-B scores (p = 0.0002 and p < 0.0001, respectively). Older age, male sex, and cirrhosis at HBV diagnosis were independently associated with HCC occurrence. The AUROCs of PAGE-B and mPAGE-B were 0.7906 and 0.7904, respectively, with no differences between them (p = 0.9767). In conclusion, both PAGE-B and mPAGE-B showed a correct prediction of HCC above 70% in this cohort.
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Affiliation(s)
- Ana Caroline Ferreira da Silva
- Division of Gastroenterology (Gastrocentro), Department of Internal Medicine, School of Medical Sciences of University of Campinas (UNICAMP), Campinas 13083-878, SP, Brazil
| | - Marlone Cunha-Silva
- Division of Gastroenterology (Gastrocentro), Department of Internal Medicine, School of Medical Sciences of University of Campinas (UNICAMP), Campinas 13083-878, SP, Brazil
| | - Tiago Sevá-Pereira
- Division of Gastroenterology (Gastrocentro), Department of Internal Medicine, School of Medical Sciences of University of Campinas (UNICAMP), Campinas 13083-878, SP, Brazil
| | - Daniel F. Mazo
- Division of Gastroenterology (Gastrocentro), Department of Internal Medicine, School of Medical Sciences of University of Campinas (UNICAMP), Campinas 13083-878, SP, Brazil
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine (FMUSP), Sao Paulo 05403-900, SP, Brazil
- Correspondence:
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Comparative Performance of 14 HCC Prediction Models in CHB: A Dynamic Validation at Serial On-Treatment Timepoints. Am J Gastroenterol 2022; 117:1444-1453. [PMID: 35973147 DOI: 10.14309/ajg.0000000000001865] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 05/27/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION To assess comparative performance of 14 hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B (CHB) patients using on-treatment values at different timepoints. METHODS Based on a nationwide prospective cohort of 986 treatment-naive CHB patients undergoing entecavir therapy with every 26-week follow-up, 14 HCC risk scores were calculated using on-treatment values at week 26, 52, 78, and 104, respectively. Model performance predicting 3-year HCC was assessed using time-dependent area under the receiver operating characteristic curve (AUC) and calibration index. Model cutoffs were validated through common diagnostic accuracy measures. RESULTS During median 4.7-year follow-up, 56 (7.5%) developed HCC. Discrimination using on-treatment values within first 2 years was generally acceptable for most models (AUCs ranging from 0.68 to 0.81), except for REACH-B, NGM-HCC, and PAGE-B, although AUCs slightly decreased from week 26 to 104. Of these, REAL-B, CAMD, GAG-HCC, AASL-HCC, LSM-HCC, mPAGE-B, and mREACH-BII showed highest discrimination with AUCs ranging from 0.76 to 0.81, 0.72 to 0.76, 0.70 to 0.76, and 0.71 to 0.74 when reassessment at week 26, 52, 78, and 104, respectively. With reassessment within first 2 years, both REAL-B and CAMD calibrated well (Brier score ranging from 0.037 to 0.052). Of 9 models reporting cutoffs, REAL-B, AASL-HCC, and mPAGE-B using on-treatment values could identify 30%-40% of patients as low risk with minimal HCC incidence in the low-risk group (0.40% [REAL-B]-1.56% [mPAGE-B]). DISCUSSION In this undergoing antiviral treatment CHB cohort, most HCC prediction models performed well even using on-treatment values during first 2 years, particularly REAL-B, AASL-HCC, CAMD, and mPAGE-B model.
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19
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Risk prediction models for hepatocellular carcinoma in chronic hepatitis B patients on antiviral therapy: A meta-analysis. Clin Res Hepatol Gastroenterol 2022; 46:101930. [PMID: 35460902 DOI: 10.1016/j.clinre.2022.101930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 04/11/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS The risk prediction of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is a challenge especially in the era of antiviral therapy. The aim of this meta-analysis was to comprehensively evaluate the performance of existing HCC prediction scores in HCC prediction on antivirals. METHODS We searched PubMed, Web of Science and Cochrane Library for relevant prospective studies from the inception to August 24, 2021. The areas under the receiver operating characteristics (AUROCs) and their relevant 95% confidence intervals (CIs) of the risk prediction models were calculated. RESULTS Nine eligible articles with 21561 patients (HCC developed in 947patients, 4.39%; mean follow-up duration: 5 years) and 14 predictive risk scores were included. The pooled AUROC of all included scores for 3-year and 5-year prediction of HCC was 0.72 (95%CI 0.68-0.76) and 0.80 (95%CI 0.76-0.83), with the corresponding sensitivity of 0.84 (95% CI 0.71-0.92) and 0.91(95% CI 0.86-0.95) and specificity of 0.46 (95% CI 0.30-0.63) and 0.48 (95% CI 0.37-0.59), respectively. All the 14 prediction models, as a whole, performed well in different populations, whether they include factor cirrhotic status or not; while those integrated viral load were less accurate (sensitivity 0.78, specificity of 0.57). CONCLUSIONS In patients with CHB on antivirals, the scores included in our meta-analysis have been proven to be useful for mid-long term HCC prediction. Viral load seems not useful, whereas cirrhosis and its objective surrogates remain the predominant components. These models are expected to translate clinical benefits if used in complementarity with regular HCC surveillance.
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Anstee QM, Castera L, Loomba R. Impact of non-invasive biomarkers on hepatology practice: Past, present and future. J Hepatol 2022; 76:1362-1378. [PMID: 35589256 DOI: 10.1016/j.jhep.2022.03.026] [Citation(s) in RCA: 127] [Impact Index Per Article: 42.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 03/28/2022] [Indexed: 12/11/2022]
Abstract
Over the last two decades, there have been tremendous advances in the non-invasive diagnosis and risk stratification of chronic liver diseases (CLDs). Non-invasive approaches are based on the quantification of biomarkers in serum samples or on the measurement of liver stiffness, using either ultrasound- or magnetic resonance-based elastography techniques. The fibrosis-4 index (non-patented) and enhanced liver fibrosis test (patented) are the most widely adopted serum markers, whereas vibration-controlled transient elastography is the most widely adopted elastography technique. In this review, we discuss the role of non-invasive tests in the current era, as well as their accuracy and how their use in clinical practice has changed the practice of hepatology, including identification of early cirrhosis in patients with risk factors for CLD, diagnosis of portal hypertension, establishing prognosis in compensated cirrhosis, guiding antiviral treatment, and screening for fibrosis and cirrhosis in primary care.
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Affiliation(s)
- Quentin M Anstee
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Newcastle NIHR Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
| | - Laurent Castera
- Université de Paris, UMR1149 (CRI), Inserm, F-75018 Paris, France; Service d'Hépatologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Beaujon, F-92110 Clichy-la-Garenne, France.
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, United States; Herbert Wertheim School of Public Health, University of California at San Diego, La Jolla, CA, United States.
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21
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Duberg A, Lybeck C, Fält A, Montgomery S, Aleman S. Chronic hepatitis B virus infection and the risk of hepatocellular carcinoma by age and country of origin in people living in Sweden: A national register study. Hepatol Commun 2022; 6:2418-2430. [PMID: 35503810 PMCID: PMC9426385 DOI: 10.1002/hep4.1974] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 04/04/2022] [Accepted: 04/10/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), and surveillance is recommended for patients without cirrhosis when risk exceeds an incidence rate (IR) of 0.2%. Populations in Asia and sub-Saharan Africa have been associated with HCC at younger ages, but the risk after immigration to Western countries should be investigated. The aim of this study was to study HCC by age and country of origin in people with chronic HBV infection in Sweden. Through national registers, residents with chronic HBV diagnosis (1990-2015) were identified with information on country of origin, immigration/emigration, death, coinfections, antiviral therapy, and HCC. Observation time started at HBV diagnosis, and IR and hazard ratios for HCC were calculated by sex, age, and region of origin. Among 16,410 individuals (47% women), the origin and observation time (person years) were as follows: Western Europe, 2316 (25,415); Eastern Europe, 2349 (26,237); Middle East/North Africa, 4402 (47,320); sub-Saharan Africa, 3677 (30,565); Asia, 3537 (35,358); and other, 129 (1277). There were 232 individuals with HCC (82% in men). The IR increased with age and exceeded 0.2% for Asian men from age group 40-49 years (IR, 0.63; 95% confidence interval, 0.39-1.00), for men of other origins from age group 50-59 years, and for women aged ≥60 years originating from Eastern Europe, Asia, and Middle East/North Africa. After exclusion of patients with cirrhosis or HBV treatment, the IR still exceeded 0.2% in Asian men aged 40-49 years. This study demonstrates that HBV-infected men of Asian origin should be recommended HCC surveillance at younger ages, but there is a need for further studies of HCC incidence in African-born men without cirrhosis living in the Western world.
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Affiliation(s)
- Ann‐Sofi Duberg
- Department of Infectious DiseasesSchool of Medical SciencesFaculty of Medicine and HealthÖrebro UniversityÖrebroSweden
| | - Charlotte Lybeck
- Department of Infectious DiseasesSchool of Medical SciencesFaculty of Medicine and HealthÖrebro UniversityÖrebroSweden
| | - Anna Fält
- Clinical Epidemiology and BiostatisticsSchool of Medical SciencesÖrebro UniversityÖrebroSweden
| | - Scott Montgomery
- Clinical Epidemiology and BiostatisticsSchool of Medical SciencesÖrebro UniversityÖrebroSweden,Clinical Epidemiology DivisionKarolinska InstitutetStockholmSweden,Department of Epidemiology and Public HealthUniversity College LondonLondonUK
| | - Soo Aleman
- Department of Infectious DiseasesKarolinska University HospitalStockholmSweden,Department of Medicine HuddingeKarolinska InstitutetStockholmSweden
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22
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Papatheodoridi M, Su TH, Hadziyannis E, Liao CH, Orfanidou Α, Yang HC, Zachou K, Liu CJ, Kourikou A, Gatselis N, Manolakopoulos S, Dalekos G, Kao JH, Hadziyannis S, Papatheodoridis GV. Hepatocellular carcinoma after treatment cessation in non-cirrhotic HBeAg-negative chronic hepatitis B: A multicentre cohort study. Liver Int 2022; 42:541-550. [PMID: 34890120 DOI: 10.1111/liv.15128] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 12/06/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Scarce data exist on the effect of nucleos(t)ide analogue (NA) discontinuation on hepatocellular carcinoma (HCC) risk in HBeAg-negative chronic hepatitis B (CHBe-). Therefore, we assessed whether HCC risk is increased in non-cirrhotic CHBe- patients who discontinue compared to those remaining on NAs. METHODS This cohort study included 650 consecutive non-cirrhotic Caucasian or Asian patients with CHBe- without a history of HCC who discontinued NAs after a median of 5 or 3 years (cases, n = 325; Caucasians: 143, Asians: 182) or remained on NA therapy beyond 5 or 3 years respectively (controls, n = 325; Caucasians: 223, Asians: 102). Propensity score (PS) 1:1 matching was applied to adjust for patients' origin, age and sex. RESULTS During a median follow-up of 44 months, HCC developed in 7/325 cases and 9/325 controls or 7/245 PS-matched cases and 7/245 PS-matched controls with 5-year cumulative HCC incidence of 5.1% and 4.9% respectively (log-rank, P = .836). No difference in 5-year HCC risk was observed between cases and controls of Caucasian (3.0% vs 4.8%; log-rank, P = .510) or Asian origin (1.3% vs 2.2%; log-rank, P = .873). In both cases and controls, HCC incidence was independently associated with age and PAGE-B score. In cases alone, HCC development after NA discontinuation was associated only with pretreatment platelet counts and PAGE-B score, but not with any type of relapse or HBsAg loss. CONCLUSIONS Our findings suggest that discontinuation of effective long-term NA therapy in non-cirrhotic CHBe- patients are not associated with increased HCC risk, which is not affected by post-NA relapses and/or HBsAg loss.
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Affiliation(s)
- Margarita Papatheodoridi
- Department of Gastroenterology, National and Kapodistrian University of Athens School of Health Sciences, General Hospital of Athens "Laiko", Athens, Greece
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Emilia Hadziyannis
- 2nd Department of Internal Medicine, National and Kapodistrian University of Athens School of Health Sciences, General Hospital of Athens "Hippokratio", Athens, Greece
| | - Chun-Hsun Liao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Αfroditi Orfanidou
- Department of Gastroenterology, National and Kapodistrian University of Athens School of Health Sciences, General Hospital of Athens "Laiko", Athens, Greece
| | - Hung-Chi Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Kalliopi Zachou
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Anastasia Kourikou
- 2nd Department of Internal Medicine, National and Kapodistrian University of Athens School of Health Sciences, General Hospital of Athens "Hippokratio", Athens, Greece
| | - Nikolaos Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Spilios Manolakopoulos
- Department of Gastroenterology, National and Kapodistrian University of Athens School of Health Sciences, General Hospital of Athens "Laiko", Athens, Greece.,2nd Department of Internal Medicine, National and Kapodistrian University of Athens School of Health Sciences, General Hospital of Athens "Hippokratio", Athens, Greece
| | - George Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Stephanos Hadziyannis
- 2nd Department of Internal Medicine, National and Kapodistrian University of Athens School of Health Sciences, General Hospital of Athens "Hippokratio", Athens, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, National and Kapodistrian University of Athens School of Health Sciences, General Hospital of Athens "Laiko", Athens, Greece
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23
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Kubota N, Fujiwara N, Hoshida Y. Liver cancer risk-predictive molecular biomarkers specific to clinico-epidemiological contexts. Adv Cancer Res 2022; 156:1-37. [PMID: 35961696 PMCID: PMC7616039 DOI: 10.1016/bs.acr.2022.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Hepatocellular carcinoma (HCC) risk prediction is increasingly important because of the low annual HCC incidence in patients with the rapidly emerging non-alcoholic fatty liver disease or cured HCV infection. To date, numerous clinical HCC risk biomarkers and scores have been reported in literature. However, heterogeneity in clinico-epidemiological context, e.g., liver disease etiology, patient race/ethnicity, regional environmental exposure, and lifestyle-related factors, obscure their real clinical utility and applicability. Proper characterization of these factors will help refine HCC risk prediction according to certain clinical context/scenarios and contribute to improved early HCC detection. Molecular factors underlying the clinical heterogeneity encompass various features in host genetics, hepatic and systemic molecular dysregulations, and cross-organ interactions, which may serve as clinical-context-specific biomarkers and/or therapeutic targets. Toward the goal to enable individual-risk-based HCC screening by incorporating the HCC risk biomarkers/scores, their assessment in patient with well-defined clinical context/scenario is critical to gauge their real value and to maximize benefit of the tailored patient management for substantial improvement of the poor HCC prognosis.
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Affiliation(s)
- Naoto Kubota
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Naoto Fujiwara
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yujin Hoshida
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States.
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24
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Shiha G, Mikhail NNH, Soliman R, Hassan A, Eslam M. Predictive performance and clinical utility of HCC risk scores in chronic hepatitis C: a comparative study. Hepatol Int 2022; 16:159-170. [PMID: 35034266 DOI: 10.1007/s12072-021-10284-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 12/06/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Many HCC risk prediction scores were developed to guide HCC risk stratification and identify CHC patients who either need intensified surveillance or may not require screening. There is a need to compare different scores and their predictive performance in clinical practice. We aim to compare the newest HCC risk scores evaluating their discriminative ability, and clinical utility in a large cohort of CHC patients. PATIENTS AND METHODS The performance of the scores was evaluated in 3075 CHC patients who achieved SVR following DAAs using Log rank, Harrell's c statistic, also tested for HCC-risk stratification and negative predictive values. RESULTS HCC developed in 212 patients within 5 years follow-up. Twelve HCC risk scores were identified and displayed significant Log rank (p ≤ 0.05) except Alonso-Lopez TE-HCC, and Chun scores (p = 0.374, p = 0.053, respectively). Analysis of the remaining ten scores revealed that ADRES, GES pre-post treatment, GES algorithm and Watanabe (post-treatment) scores including dynamics of AFP, were clinically applicable and demonstrated good statistical performance; Log rank analysis < 0.001, Harrell's C statistic (0.66-0.83) and high negative predictive values (94.38-97.65%). In these three scores, the 5 years cumulative IR in low risk groups be very low (0.54-1.6), so screening could be avoided safely in these patients. CONCLUSION ADRES, GES (pre- and post-treatment), GES algorithm and Watanabe (post-treatment) scores seem to offer acceptable HCC-risk predictability and clinical utility in CHC patients. The dynamics of AFP as a component of these scores may explain their high performance when compared to other scores.
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Affiliation(s)
- Gamal Shiha
- Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, Mansoura, Egypt.
- Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
| | - Nabiel N H Mikhail
- Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, Mansoura, Egypt
- Biostatistics and Cancer Epidemiology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Reham Soliman
- Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, Mansoura, Egypt
- Tropical Medicine Department, Faculty of Medicine, Port Said University, Port Said, Egypt
| | - Ayman Hassan
- Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, Mansoura, Egypt
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
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25
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Dunn R, Wetten A, McPherson S, Donnelly MC. Viral hepatitis in 2021: The challenges remaining and how we should tackle them. World J Gastroenterol 2022; 28:76-95. [PMID: 35125820 PMCID: PMC8793011 DOI: 10.3748/wjg.v28.i1.76] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 06/26/2021] [Accepted: 12/22/2021] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis results in 1.4 million deaths annually. The World Health Organization (WHO) set an ambitious target to eliminate viral hepatitis by 2030, but significant challenges remain. These include inequalities in access to healthcare, reaching at risk populations and providing access to screening and effective treatment. Stigma around viral hepatitis persists and must be addressed. The WHO goal of global elimination by 2030 is a worthy aim, but remains ambitious and the coronavirus 2019 pandemic undoubtedly has set back progress. This review article will focus on hepatitis A to E, highlighting problems that have been resolved in the field over the past decade, those that remain to be resolved and suggest directions for future problem solving and research.
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Affiliation(s)
- Rebecca Dunn
- Gastroenterology, University Hospital of North Tees, Stockton on Tees TS198PE, United Kingdom
| | - Aaron Wetten
- Liver Unit, Freeman Hospital, Newcastle NE77DN, United Kingdom
- Translational and Clinical Research Institute, Newcastle University, Newcastle NE17RU, United Kingdom
| | - Stuart McPherson
- Liver Unit, Freeman Hospital, Newcastle NE77DN, United Kingdom
- Translational and Clinical Research Institute, Newcastle University, Newcastle NE17RU, United Kingdom
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26
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Wu S, Zeng N, Sun F, Zhou J, Wu X, Sun Y, Wang B, Zhan S, Kong Y, Jia J, You H, Yang HI. Hepatocellular Carcinoma Prediction Models in Chronic Hepatitis B: A Systematic Review of 14 Models and External Validation. Clin Gastroenterol Hepatol 2021; 19:2499-2513. [PMID: 33667678 DOI: 10.1016/j.cgh.2021.02.040] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 02/25/2021] [Accepted: 02/26/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The aim of our study was to characterize the performance of hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B (CHB) patients through meta-analysis followed by external validation. METHODS We performed a systematic review and meta-analysis of current literature, followed by external validation in independent multi-center cohort with 986 patients with CHB undergoing entecavir treatment (median follow-up: 4.7 years). Model performance to predict HCC within 3, 5, 7, and 10 years was assessed using area under receiver operating characteristic curve (AUROC) and calibration index. Subgroup analysis were conducted by treatment status, cirrhotic, race and baseline alanine aminotransferase. RESULTS We identified 14 models with 123,885 patients (5,452 HCC cases), with REACH-B, CU-HCC, GAG-HCC, PAGE-B and mPAGE-B models being broadly externally validated. Discrimination was generally acceptable for all models, with pooled AUC ranging from 0.70 (95% CI, 0.63-0.76 for REACH-B) to 0.83 (95% CI, 0.78-0.87 for REAL-B) for 3-year, 0.68 (95% CI, 0.64-0.73 for REACH-B) to 0.81 (95% CI, 0.77-0.85 for REAL-B) for 5-year and 0.70 (95% CI, 0.58-0.80 for PAGE-B) to 0.81 (95% CI, 0.78-0.84 for REAL-B and 0.77-0.86 for AASL-HCC) for 10-year prediction. However, calibration performance was poorly reported in most studies. In external validation cohort, REAL-B showed highest discrimination with 0.76 (95% CI, 0.69-0.83) and 0.75 (95% CI, 0.70-0.81) for 3 and 5-year prediction. The REAL-B model was also well calibrated in the external validation cohort (3-year Brier score 0.066). Results were consistent in subgroup analyses. CONCLUSIONS In a systematic review of available HCC models, the REAL-B model exhibited best discrimination and calibration.
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Affiliation(s)
- Shanshan Wu
- National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Na Zeng
- National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Feng Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, Mainland China
| | - Jialing Zhou
- Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Xiaoning Wu
- Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Yameng Sun
- Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Bingqiong Wang
- Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Siyan Zhan
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, Mainland China
| | - Yuanyuan Kong
- National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Jidong Jia
- National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China; Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Hong You
- National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China; Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China.
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Buti M, Riveiro-Barciela M, Esteban R. Treatment of Chronic Hepatitis B Virus with Oral Anti-Viral Therapy. Clin Liver Dis 2021; 25:725-740. [PMID: 34593150 DOI: 10.1016/j.cld.2021.06.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Nucleoside analogues are the drugs most commonly used in the treatment of chronic hepatitis B. They act by inhibiting viral replication and have minimal impact on HBsAg loss. Nucleoside analogues are indicated in patients with chronic hepatitis, cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and in those with extrahepatic manifestations. Real-world experience has been ongoing for more than 10 years, and the efficacy and safety results obtained are similar to those reported in clinical trials. Prolonged use is needed to maintain suppression of viral replication, prevent the development of liver cirrhosis and decompensated cirrhosis, and to decrease the risk of hepatocellular carcinoma.
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Affiliation(s)
- Maria Buti
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, General Hospital, 5th floor, Barcelona 08035, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
| | - Mar Riveiro-Barciela
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, General Hospital, 5th floor, Barcelona 08035, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Rafael Esteban
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, General Hospital, 5th floor, Barcelona 08035, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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28
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Demirtas CO, Brunetto MR. Surveillance for hepatocellular carcinoma in chronic viral hepatitis: Is it time to personalize it? World J Gastroenterol 2021; 27:5536-5554. [PMID: 34588750 PMCID: PMC8433616 DOI: 10.3748/wjg.v27.i33.5536] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 04/28/2021] [Accepted: 08/02/2021] [Indexed: 02/06/2023] Open
Abstract
Surveillance with abdominal ultrasound with or without alpha-fetoprotein is recommended by clinical practice guidelines for patients who are considered to be at risk of developing hepatocellular carcinoma (HCC), including those with cirrhosis, advanced fibrosis and special subgroups of chronic hepatitis B (CHB). Application of the standard surveillance strategy to all patients with chronic liver disease (CLD) with or without cirrhosis imposes major sustainability and economic burdens on healthcare systems. Thus, a number of HCC risk scores were constructed, mainly from Asian cohorts, to stratify the HCC prediction in patients with CHB. Similarly, even if less than for CHB, a few scoring systems were developed for chronic hepatitis C patients or cirrhotic patients with CLD of different etiologies. Recently, a few newsworthy HCC-risk algorithms were developed for patients with cirrhosis using the combination of serologic HCC markers and clinical parameters. Overall, the HCC risk stratification appears at hand by several validated multiple score systems, but their optimal performance is obtained only in populations who show highly homogenous clinic-pathologic, epidemiologic, etiologic and therapeutic characteristics and this limitation poses a major drawback to their sustainable use in clinical practice. A better understanding of the dynamic process driving the progression from CLD to HCC derived from studies based on molecular approaches and genetics, epigenetics and liquid biopsy will enable the identification of new biomarkers to define the individual risk of HCC in the near future, with the possibility to achieve a real and cost/effective personalization of surveillance.
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Affiliation(s)
- Coskun Ozer Demirtas
- Department of Gastroenterology and Hepatology, Marmara University, School of Medicine, Istanbul 34854, Turkey
| | - Maurizia Rossana Brunetto
- Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa 56125, Italy
- Hepatology Unit, University Hospital of Pisa, Pisa 56125, Italy
- Biostructure and Bio-imaging Institute, National Research Council of Italy, Naples 56125, Italy
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29
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Berzigotti A, Tsochatzis E, Boursier J, Castera L, Cazzagon N, Friedrich-Rust M, Petta S, Thiele M. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update. J Hepatol 2021; 75:659-689. [PMID: 34166721 DOI: 10.1016/j.jhep.2021.05.025] [Citation(s) in RCA: 998] [Impact Index Per Article: 249.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 05/28/2021] [Indexed: 02/07/2023]
Abstract
Non-invasive tests are increasingly being used to improve the diagnosis and prognostication of chronic liver diseases across aetiologies. Herein, we provide the latest update to the EASL Clinical Practice Guidelines on the use of non-invasive tests for the evaluation of liver disease severity and prognosis, focusing on the topics for which relevant evidence has been published in the last 5 years.
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Li B, Zhao Y, Cai W, Ming A, Li H. Validation and update of a multivariable prediction model for the identification and management of patients at risk for hepatocellular carcinoma. Clin Proteomics 2021; 18:21. [PMID: 34412596 PMCID: PMC8374120 DOI: 10.1186/s12014-021-09326-w] [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: 06/07/2021] [Accepted: 08/08/2021] [Indexed: 02/07/2023] Open
Abstract
Background A hepatocellular carcinoma (HCC) prediction model (ASAP), including age, sex, and the biomarkers alpha-fetoprotein and prothrombin induced by vitamin K absence-II, showed potential clinical value in the early detection of HCC. We validated and updated the model in a real-world cohort and promoted its transferability to daily clinical practice. Methods This retrospective cohort analysis included 1012 of the 2479 eligible patients aged 35 years or older undergoing surveillance for HCC. The data were extracted from the electronic medical records. Biomarker values within the test-to-diagnosis interval were used to validate the ASAP model. Due to its unsatisfactory calibration, three logistic regression models were constructed to recalibrate and update the model. Their discrimination, calibration, and clinical utility were compared. The performance statistics of the final updated model at several risk thresholds are presented. The outcomes of 855 non-HCC patients were further assessed during a median of 10.2 months of follow-up. Statistical analyses were performed using packages in R software. Results The ASAP model had superior discriminative performance in the validation cohort [C-statistic = 0.982, (95% confidence interval 0.972–0.992)] but significantly overestimated the risk of HCC (intercept − 3.243 and slope 1.192 in the calibration plot), reducing its clinical usefulness. Recalibration-in-the-large, which exhibited performance comparable to that of the refitted model revision, led to the retention of the excellent discrimination and substantial improvements in the calibration and clinical utility, achieving a sensitivity of 100% at the median prediction probability of the absence of HCC (1.3%). The probability threshold of 1.3% and the incidence of HCC in the cohort (15.5%) were used to stratify the patients into low-, medium-, and high-risk groups. The cumulative HCC incidences in the non-HCC patients significantly differed among the risk groups (log-rank test, p-value < 0.001). The 3-month, 6-month and 18-month cumulative incidences in the low-risk group were 0.6%, 0.9% and 0.9%, respectively. Conclusions The ASAP model is an accurate tool for HCC risk estimation that requires recalibration before use in a new region because calibration varies with clinical environments. Additionally, rational risk stratification and risk-based management decision-making, e.g., 3-month follow-up recommendations for targeted individuals, helped improve HCC surveillance, which warrants assessment in larger cohorts. Supplementary Information The online version contains supplementary material available at 10.1186/s12014-021-09326-w.
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Affiliation(s)
- Bo Li
- Clinical Laboratory, Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Youyun Zhao
- Clinical Laboratory, Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Wangxi Cai
- Clinical Laboratory, Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Anping Ming
- Clinical Laboratory, Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Hanmin Li
- Institute of Hepatology, Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China. .,Theory and Application Research of Liver and Kidney in Traditional Chinese Medicine, Hubei Provincial Key Laboratory, Cell Molecular Biology Laboratory, Level 3 Laboratory of Traditional Chinese Medicine Research, State Administration of Traditional Chinese Medicine, 4 Huayuanshan, Yanzhi Road, Liangdao Street, Wuchang District, Hubei, 430061, Wuhan, China.
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Gui H, Huang Y, Zhao G, Chen L, Cai W, Wang H, Guo Q, Xie Q. External Validation of aMAP Hepatocellular Carcinoma Risk Score in Patients With Chronic Hepatitis B-Related Cirrhosis Receiving ETV or TDF Therapy. Front Med (Lausanne) 2021; 8:677920. [PMID: 34422855 PMCID: PMC8371628 DOI: 10.3389/fmed.2021.677920] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 07/12/2021] [Indexed: 12/16/2022] Open
Abstract
Background and Aim: A prediction model of hepatocellular carcinoma (HCC) risk in patients with chronic liver diseases, based on age, male sex, albumin-bilirubin, and platelets (aMAP), has been previously reported. We validated the aMAP score and compared its performance to those of other risk scores in an independent at-risk cohort. Methods: Treatment-naïve patients with chronic hepatitis B-related compensated cirrhosis who received entecavir or tenofovir monotherapy for at least 12 months were enrolled in this study. The performances of the aMAP and other HCC risk scores were assessed using Harrell's c-index, and predefined cut-off values were evaluated using survival analysis. Results: Of the 1,042 patients, 131 (12.6%) developed HCC during a median follow-up of 41 months. The aMAP score provided the highest Harrell's c-index (0.724), followed by CAMD (0.719), mPAGE-B (0.719), and PAGE-B (0.695). The 5-year cumulative HCC probabilities were 2.9% for patients with a low aMAP score (<50), 11.2% for patients with an intermediate aMAP score (50-60), and 27.9% for patients with a high aMAP score (>60). Using both aMAP and mPAGE-B, 11.6% of patients were identified as low risk with a negative predictive value of 98.2% for not developing HCC within 5 years. Patients with aMAP >60 and diabetes exhibited an extremely high risk of HCC, with a cumulative incidence of 49.3% at 5 years. The predictive performance of aMAP with a reassessment at 1 year after the initiation of antiviral therapy outperformed the predictive performance of aMAP at enrollment. Conclusions: The aMAP score accurately predicted the risk of HCC in at-risk patients with compensated cirrhosis undergoing antiviral therapy. A combination of the aMAP score and diabetes status could further stratify the risk of HCC.
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Affiliation(s)
| | | | | | | | | | | | - Qing Guo
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Mehta N, Parikh ND, Kelley RK, Hameed B, Singal AG. Surveillance and Monitoring of Hepatocellular Carcinoma During the COVID-19 Pandemic. Clin Gastroenterol Hepatol 2021; 19:1520-1530. [PMID: 32652308 PMCID: PMC7342037 DOI: 10.1016/j.cgh.2020.06.072] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 06/23/2020] [Accepted: 06/25/2020] [Indexed: 01/27/2023]
Abstract
The Coronavirus disease 2019 (COVID-19) pandemic is expected to have a long-lasting impact on the approach to care for patients at risk for and with hepatocellular carcinoma (HCC) due to the risks from potential exposure and resource reallocation. The goal of this document is to provide recommendations on HCC surveillance and monitoring, including strategies to limit unnecessary exposure while continuing to provide high-quality care for patients. Publications and guidelines pertaining to the management of HCC during COVID-19 were reviewed for recommendations related to surveillance and monitoring practices, and any available guidance was referenced to support the authors' recommendations when applicable. Existing HCC risk stratification models should be utilized to prioritize imaging resources to those patients at highest risk of incident HCC and recurrence following therapy though surveillance can likely continue as before in settings where COVID-19 prevalence is low and adequate protections are in place. Waitlisted patients who will benefit from urgent LT should be prioritized for surveillance whereas it would be reasonable to extend surveillance interval by a short period in HCC patients with lower risk tumor features and those more than 2 years since their last treatment. For patients eligible for systemic therapy, the treatment regimen should be dictated by the risk of COVID-19 associated with route of administration, monitoring and treatment of adverse events, within the context of relative treatment efficacy.
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Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California.
| | - Neehar D. Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - R. Katie Kelley
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California
| | - Bilal Hameed
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California
| | - Amit G. Singal
- Division of Digestive and Liver Disease, UT Southwestern Medical Center, Dallas, Texas
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33
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Cornberg M, Sandmann L, Protzer U, Niederau C, Tacke F, Berg T, Glebe D, Jilg W, Wedemeyer H, Wirth S, Höner Zu Siederdissen C, Lynen-Jansen P, van Leeuwen P, Petersen J. S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) zur Prophylaxe, Diagnostik und Therapie der Hepatitis-B-Virusinfektion – (AWMF-Register-Nr. 021-11). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:691-776. [PMID: 34255317 DOI: 10.1055/a-1498-2512] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Markus Cornberg
- Deutsches Zentrum für Infektionsforschung (DZIF), Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover; Centre for individualised infection Medicine (CiiM), Hannover.,Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Lisa Sandmann
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Ulrike Protzer
- Institut für Virologie, Technische Universität München/Helmholtz Zentrum München, München
| | | | - Frank Tacke
- Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Charité Universitätsmedizin Berlin, Berlin
| | - Thomas Berg
- Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig, Leipzig
| | - Dieter Glebe
- Institut für Medizinische Virologie, Nationales Referenzzentrum für Hepatitis-B-Viren und Hepatitis-D-Viren, Justus-Liebig-Universität Gießen, Gießen
| | - Wolfgang Jilg
- Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensberg, Regensburg
| | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Stefan Wirth
- Zentrum für Kinder- und Jugendmedizin, Helios Universitätsklinikum Wuppertal, Wuppertal
| | | | - Petra Lynen-Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin
| | - Pia van Leeuwen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin
| | - Jörg Petersen
- IFI Institut für Interdisziplinäre Medizin an der Asklepios Klinik St. Georg, Hamburg
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Kamalapirat T, Yingcharoen K, Ungtrakul T, Soonklang K, Dechma J, Chunnuan P, Kusuman P, Pothijaroen C, Tawpa J, Cheirsilpa K, Auewarakul C. Assessing risk scores for predicting hepatocellular carcinoma in Thai patients with chronic hepatitis B. J Viral Hepat 2021; 28:1034-1041. [PMID: 33880807 DOI: 10.1111/jvh.13517] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 03/16/2021] [Accepted: 04/04/2021] [Indexed: 12/12/2022]
Abstract
Chronic hepatitis B (CHB) infection-associated hepatocellular carcinoma (HCC) is a major health problem in Asian countries. Several HCC risk prediction models have been developed using either treated or untreated CHB patients. However, there is limited validation of these risk scores in a treated and untreated mixed CHB patient cohort. This study analysed and validated HCC risk scores among 2208 CHB patients who enrolled in the HCC surveillance programme in Thailand during July 2010. The baseline clinical and radiologic data of these CHB patients were applied to calculate various HCC risk scores. There were 20 patients (0.9%) with HCC development at the 5.9-year follow-up. The areas under the receiver operating characteristic curves (AUROCs) predicting HCC risk at 5 years were 0.80 (0.68-0.91), 0.73 (0.60-0.85), 0.79 (0.67-0.91), 0.70 (0.58-0.82), 0.72 (0.59-0.85), 0.76 (0.63-0.87) and 0.77 (0.64-0.89) for the GAG-HCC, CU-HCC, REACH-B, PAGE-B, mPAGE-B, CAMD and AASL scores, respectively. The overall HCC risk scores were accurate and comparable. However, the subgroup analysis revealed better HCC-risk-predictive performance in the treated patients, while performance was less helpful in those not fulfilling criteria for antiviral therapy. Clinicians should be aware of these data when using the HCC risk score in untreated CHB patients.
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Affiliation(s)
- Thanachote Kamalapirat
- Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Kesinee Yingcharoen
- Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Teerapat Ungtrakul
- Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Kamonwan Soonklang
- Data Management Unit, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Jiraporn Dechma
- Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Pitchayachuda Chunnuan
- Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Pattama Kusuman
- Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Charinthip Pothijaroen
- Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Jantarika Tawpa
- Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Kunsuda Cheirsilpa
- Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Chirayu Auewarakul
- Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
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Wang Y, Wang M, Li H, Chen K, Zeng H, Bi X, Zhu Z, Jiao Y, Wang Y, Zhu J, Zhao H, Liu X, Dai C, Fan C, Zhao C, Guo D, Zhao H, Zhou J, Wang D, Wu Z, Zhao X, Cui W, Zhang X, Cai J, Chen W, Qu C. A male-ABCD algorithm for hepatocellular carcinoma risk prediction in HBsAg carriers. Chin J Cancer Res 2021; 33:352-363. [PMID: 34321832 PMCID: PMC8286891 DOI: 10.21147/j.issn.1000-9604.2021.03.07] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 04/28/2021] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVE Hepatocellular carcinoma (HCC) development among hepatitis B surface antigen (HBsAg) carriers shows gender disparity, influenced by underlying liver diseases that display variations in laboratory tests. We aimed to construct a risk-stratified HCC prediction model for HBsAg-positive male adults. METHODS HBsAg-positive males of 35-69 years old (N=6,153) were included from a multi-center population-based liver cancer screening study. Randomly, three centers were set as training, the other three centers as validation. Within 2 years since initiation, we administrated at least two rounds of HCC screening using B-ultrasonography and α-fetoprotein (AFP). We used logistic regression models to determine potential risk factors, built and examined the operating characteristics of a point-based algorithm for HCC risk prediction. RESULTS With 2 years of follow-up, 302 HCC cases were diagnosed. A male-ABCD algorithm was constructed including participant's age, blood levels of GGT (γ-glutamyl-transpeptidase), counts of platelets, white cells, concentration of DCP (des-γ-carboxy-prothrombin) and AFP, with scores ranging from 0 to 18.3. The area under receiver operating characteristic was 0.91 (0.90-0.93), larger than existing models. At 1.5 points of risk score, 26.10% of the participants in training cohort and 14.94% in validation cohort were recognized at low risk, with sensitivity of identifying HCC remained 100%. At 2.5 points, 46.51% of the participants in training cohort and 33.68% in validation cohort were recognized at low risk with 99.06% and 97.78% of sensitivity, respectively. At 4.5 points, only 20.86% of participants in training cohort and 23.73% in validation cohort were recognized at high risk, with positive prediction value of 22.85% and 12.35%, respectively. CONCLUSIONS Male-ABCD algorithm identified individual's risk for HCC occurrence within short term for their HCC precision surveillance.
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Affiliation(s)
- Yuting Wang
- State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Minjie Wang
- Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - He Li
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Kun Chen
- State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hongmei Zeng
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xinyu Bi
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zheng Zhu
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yuchen Jiao
- State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yong Wang
- Department of Ultrasonography, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jian Zhu
- Qidong Liver Cancer Institute & Qidong People’s Hospital, Qidong 226200, China
| | - Hui Zhao
- Lingbi Center for Disease Control and Prevention, Suzhou 234200, China
| | - Xiang Liu
- Mengcheng Center for Disease Control and Prevention, Bozhou 233500, China
| | - Chunyun Dai
- Sheyang Center for Disease Control and Prevention, Yancheng 224300, China
| | - Chunsun Fan
- Qidong Liver Cancer Institute & Qidong People’s Hospital, Qidong 226200, China
| | - Can Zhao
- Shenqiu County Center for Disease Control and Prevention, Zhoukou 411624, China
| | - Deyin Guo
- Dancheng Center for Disease Control and Prevention, Zhoukou 477150, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jianguo Zhou
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dongmei Wang
- State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zhiyuan Wu
- State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xinming Zhao
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wei Cui
- Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
- Department of Nutrition, T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wanqing Chen
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Chunfeng Qu
- State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Papatheodoridis GV, Dalekos GN, Idilman R, Sypsa V, Van Boemmel F, Buti M, Calleja JL, Goulis J, Manolakopoulos S, Loglio A, Papatheodoridi M, Gatselis N, Veelken R, Lopez-Gomez M, Hansen BE, Savvidou S, Kourikou A, Vlachogiannakos J, Galanis K, Yurdaydin C, Esteban R, Janssen HL, Berg T, Lampertico P. Predictive performance of newer Asian hepatocellular carcinoma risk scores in treated Caucasians with chronic hepatitis B. JHEP Rep 2021; 3:100290. [PMID: 34041470 PMCID: PMC8144729 DOI: 10.1016/j.jhepr.2021.100290] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/23/2021] [Accepted: 03/25/2021] [Indexed: 12/22/2022] Open
Abstract
Background & Aims Recently, several risk scores for prediction of hepatocellular carcinoma (HCC) were developed in cohorts of treated Asian patients with chronic hepatitis B (CHB), but they have not been assessed in non-Asian patients. We evaluated the predictability and comparative utility of our PAGE-B and recent Asian HCC risk scores in nucleos(t)ide analogue (NA)-treated adult Caucasian patients with CHB, with or without well-documented compensated cirrhosis but not previous diagnosis of HCC. Methods We included 1,951 patients treated with entecavir/tenofovir and followed up for a median of 7.6 years. The c-statistic was used to estimate the predictability of PAGE-B, HCC-Rescue, CAMD, mPAGE-B, and AASL score for HCC development within 5 or 10 years. The low- and high-risk group cut-offs were used for estimation of negative (NPV) and positive predictive values (PPV), respectively. Results HCC developed in 103/1,951 (5.3%) patients during the first 5 years and in another 39/1,428 (2.7%) patients between years 5 and 10. The 3-, 5-, and 10-year cumulative HCC rates were 3.3%, 5.9%, and 9.6%, respectively. All scores offered good 5- and 10-year HCC prediction (c-statistic: 0.78–0.82). NPVs were always >99% (99.3–100%), whereas PPV ranged between 13% and 24%. Conclusions In NA-treated Caucasian patients with CHB including compensated cirrhosis, HCC risk scores developed in NA-treated Asian patients offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. PAGE-B and mPAGE-B scores are simpler in clinical practice, as they do not require an accurate diagnosis of cirrhosis, but the addition of albumin in mPAGE-B score does not seem to offer an advantage in patients with well compensated liver disease. Lay summary Several risk scores for prediction of hepatocellular carcinoma (HCC) were recently developed in cohorts of treated Asian patients with chronic hepatitis B (CHB). In Caucasian patients with CHB treated with oral antivirals, newer Asian HCC risk scores offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. For clinical practice, PAGE-B and mPAGE-B scores are simpler, as they do not require an accurate diagnosis of cirrhosis.
In treated Caucasian patients with chronic hepatitis B, newer Asian hepatocellular carcinoma risk scores offer good 5- and 10-year predictability, similar to that of PAGE-B. PAGE-B and mPAGE-B scores are simpler in clinical practice, as they do not require an accurate diagnosis of cirrhosis. The addition of albumin in mPAGE-B does not seem to offer an advantage in patients with well-compensated liver disease.
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Key Words
- ALT, alanine aminotransferase
- AUROC, area under receiver operating characteristic
- CHB, chronic hepatitis B
- Cirrhosis
- ETV, entecavir
- Entecavir
- HCC, hepatocellular carcinoma
- HR, hazard ratio
- NA, nucleos(t)ide analogue
- NPV, negative predictive value
- PPV, positive predictive value
- Prediction
- TDF, tenofovir disoproxil fumarate
- Tenofovir
- ULN, upper limit of normal
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Affiliation(s)
- George V. Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens, Greece
- Corresponding author. Address: Department of Gastroenterology, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital of Athens, 17 Agiou Thoma Street, 11527 Athens, Greece. Tel: +30-2132061115, Fax: +30-2107462601
| | - George N. Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Ramazan Idilman
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Vana Sypsa
- Department of Hygiene, Epidemiology & Medical Statistics, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Florian Van Boemmel
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Maria Buti
- Hospital General Universitario Vall Hebron and Ciberehd, Barcelona, Spain
| | | | - John Goulis
- 4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece
| | - Spilios Manolakopoulos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens, Greece
- 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Hippokratio”, Athens, Greece
| | - Alessandro Loglio
- Division of Gastroenterology and Hepatology, CRC “A. M. and A. Migliavacca” Center for Liver Disease, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Margarita Papatheodoridi
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens, Greece
| | - Nikolaos Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Rhea Veelken
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | | | - Bettina E. Hansen
- Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands
- Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada
| | - Savvoula Savvidou
- 4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece
| | - Anastasia Kourikou
- 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Hippokratio”, Athens, Greece
| | - John Vlachogiannakos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens, Greece
| | - Kostas Galanis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Cihan Yurdaydin
- Department of Gastroenterology & Hepatology, Koc University Medical School, Istanbul, Turkey
| | - Rafael Esteban
- Hospital General Universitario Vall Hebron and Ciberehd, Barcelona, Spain
| | - Harry L.A. Janssen
- Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, CRC “A. M. and A. Migliavacca” Center for Liver Disease, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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37
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Brancaccio G, Salpini R, Piermatteo L, Surdo M, Fini V, Colagrossi L, Cantone M, Battisti A, Oda Y, Di Carlo D, Ceccherini-Silberstein F, Perno CF, Gaeta GB, Svicher V. An Increase in the Levels of Middle Surface Antigen Characterizes Patients Developing HBV-Driven Liver Cancer Despite Prolonged Virological Suppression. Microorganisms 2021; 9:752. [PMID: 33918474 PMCID: PMC8065957 DOI: 10.3390/microorganisms9040752] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 03/25/2021] [Accepted: 04/01/2021] [Indexed: 01/05/2023] Open
Abstract
Hepatitis B virus (HBV) contains three surface glycoproteins-Large-HBs (L-HBs), Middle-HBs (M-HBs), and Small-HBs (S-HBs), known to contribute to HBV-driven pro-oncogenic properties. Here, we examined the kinetics of HBs-isoforms in virologically-suppressed patients who developed or did not develop hepatocellular carcinoma (HCC). This study enrolled 30 chronically HBV-infected cirrhotic patients under fully-suppressive anti-HBV treatment. Among them, 13 patients developed HCC. Serum samples were collected at enrolment (T0) and at HCC diagnosis or at the last control for non-HCC patients (median (range) follow-up: 38 (12-48) months). Ad-hoc ELISAs were designed to quantify L-HBs, M-HBs and S-HBs (Beacle). At T0, median (IQR) levels of S-HBs, M-HBs and L-HBs were 3140 (457-6995), 220 (31-433) and 0.2 (0-1.7) ng/mL. No significant differences in the fraction of the three HBs-isoforms were noticed between patients who developed or did not develop HCC at T0. On treatment, S-HBs showed a >25% decline or remained stable in a similar proportion of HCC and non-HCC patients (58.3% of HCC- vs. 47.1% of non-HCC patients, p = 0.6; 25% of HCC vs. 29.4% of non-HCC, p = 0.8, respectively). Conversely, M-HBs showed a >25% increase in a higher proportion of HCC compared to non-HCC patients (50% vs. 11.8%, p = 0.02), in line with M-HBs pro-oncogenic role reported in in vitro studies. No difference in L-HBs kinetics was observed in HCC and non-HCC patients. In conclusion, an increase in M-HBs levels characterizes a significant fraction of HCC-patients while under prolonged HBV suppression and stable/reduced total-HBs. The role of M-HBs kinetics in identifying patients at higher HCC risk deserves further investigation.
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Affiliation(s)
| | - Romina Salpini
- Department of Experimental Medicine, Tor Vergata University, 00133 Rome, Italy; (R.S.); (L.P.); (A.B.); (F.C.-S.)
| | - Lorenzo Piermatteo
- Department of Experimental Medicine, Tor Vergata University, 00133 Rome, Italy; (R.S.); (L.P.); (A.B.); (F.C.-S.)
| | - Matteo Surdo
- Molecular Genetics Laboratory, Eurofins Genoma, 00138 Rome, Italy; (M.S.); (V.F.)
| | - Vanessa Fini
- Molecular Genetics Laboratory, Eurofins Genoma, 00138 Rome, Italy; (M.S.); (V.F.)
| | - Luna Colagrossi
- Department of Diagnostic Medicine and Laboratory, Bambin Gesù Children’s Hospital, 00165 Rome, Italy; (L.C.); (C.F.P.)
| | - Marco Cantone
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania “Luigi Vanvitelli”, 81100 Naples, Italy; (M.C.); (G.B.G.)
| | - Arianna Battisti
- Department of Experimental Medicine, Tor Vergata University, 00133 Rome, Italy; (R.S.); (L.P.); (A.B.); (F.C.-S.)
| | | | - Domenico Di Carlo
- Paediatric Clinical Research Center “Romeo and Enrica Invernizzi”, University of Milan, 26900 Milan, Italy;
| | | | - Carlo Federico Perno
- Department of Diagnostic Medicine and Laboratory, Bambin Gesù Children’s Hospital, 00165 Rome, Italy; (L.C.); (C.F.P.)
| | - Giovanni Battista Gaeta
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania “Luigi Vanvitelli”, 81100 Naples, Italy; (M.C.); (G.B.G.)
| | - Valentina Svicher
- Department of Experimental Medicine, Tor Vergata University, 00133 Rome, Italy; (R.S.); (L.P.); (A.B.); (F.C.-S.)
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38
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Sangiovanni A, Colombo M. Surveillance for hepatocellular carcinoma in patients with advanced liver fibrosis. Saudi J Gastroenterol 2021; 27:64-72. [PMID: 33723094 PMCID: PMC8183361 DOI: 10.4103/sjg.sjg_636_20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Surveillance is the only pragmatic approach to improve treatment of hepatocellular carcinoma (HCC) owing to the fact that it allows detection of the tumor at an early and better curable stage. International liver societies recommend surveillance with biannual abdominal ultrasound (US) for patients with cirrhosis of any etiology because of their high risk of developing HCC. This strategy is considered cost-effective, as surveillance requires an articulated and costly set of interventions, including linkage to care of patients with an early detected tumor. However, as transition to HCC is increasingly being observed in noncirrhotic patients, the majority of which does not reach the threshold of cost effectiveness for screening. The European and Japanese liver societies elected to confine recommendations for HCC screening to noncirrhotic patients with advanced fibrosis due to hepatitis C or hepatitis B only. These latter recommendations, however, are challenged by the increasing number of patients with viral hepatitis in whom HCC risk has been attenuated but not eradicated by successful antiviral therapy. In this set of patients, entry criteria of surveillance need to be refined in the light of the suboptimal diagnostic accuracy of non invasive tests that are employed to identify the ideal candidates for surveillance.
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Affiliation(s)
- Angelo Sangiovanni
- IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC “A. M. and A. Migliavacca” Center for Liver Disease, Milan, Italy
| | - Massimo Colombo
- Liver Center, IRCCS San Raffaele Hospital, Milan, Italy,Address for correspondence: Prof. Massimo Colombo, Liver Center, IRCCS, Ospedale San Raffaele Hospital, Via Olgettina, 60 Milan, Italy. E-mail:
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39
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Papatheodoridi A, Chatzigeorgiou A, Chrysavgis L, Lembessis P, Loglio A, Facchetti F, Cholongitas E, Koutsilieris M, Lampertico P, Papatheodoridis G. Circulating cell-free DNA species affect the risk of hepatocellular carcinoma in treated chronic hepatitis B patients. J Viral Hepat 2021; 28:464-474. [PMID: 33260272 DOI: 10.1111/jvh.13446] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 11/16/2020] [Indexed: 01/08/2023]
Abstract
Hepatocellular carcinoma (HCC) may still develop in chronic hepatitis B (CHB) patients even under effective long-term oral antiviral therapy, but its pathogenesis in the setting of long-standing inhibition of viral replication has not been completely elucidated. We investigated whether species of circulating cell-free DNA (cfDNA) may be involved in the process of hepatocarcinogenesis in treated CHB patients. Serum samples were obtained from HBeAg-negative CHB patients with (HCC cases, n = 37) or without HCC development during the first 5 years of oral antiviral therapy (controls, n = 74). HCC cases and controls were matched 1:2 for age, sex and platelets. Determination of different circulating cfDNA species (before HCC diagnosis in HCC cases) including total cfDNA quantity, levels of Alu repeat DNA and RNase P coding DNA, copies of mitochondrial DNA and levels of 5-methyl-2'-deoxycytidine as an indicator of DNA methylation was performed. HCC cases compared with controls had higher median levels of Alu247 (123 vs 69 genomic equivalent, p = .042) and RNase P coding DNA (68 vs 15 genomic equivalent, p < .001). In contrast, median cfDNA concentration, Alu115 levels, Alu247/Alu115 ratio as an index of DNA integrity and mitochondrial DNA copies did not differ significantly between HCC cases and controls. Receiver operating characteristic curve analysis showed that levels RNase P coding DNA offered good prediction of subsequent HCC development (c-statistic: 0.80, p < .001). In conclusion, serum levels of RNase P coding DNA are increased years before HCC diagnosis and could be potentially helpful in the prediction of the HCC risk in treated HBeAg-negative CHB patients.
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Affiliation(s)
- Alkistis Papatheodoridi
- Department of Physiology, Medical School of National and Kapodistrian University of Athens, Athens, Greece
- Department of Clinical Therapeutics, 'Alexandra' General Hospital of Athens, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Antonios Chatzigeorgiou
- Department of Physiology, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Lampros Chrysavgis
- Department of Physiology, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Panagiotis Lembessis
- Department of Physiology, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Alessandro Loglio
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC 'A. M. and A. Migliavacca' Center for Liver Disease, Milan, Italy
| | - Floriana Facchetti
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC 'A. M. and A. Migliavacca' Center for Liver Disease, Milan, Italy
| | - Evangelos Cholongitas
- 1st Department of Internal Medicine, General Hospital of Athens 'Laiko', Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Michael Koutsilieris
- Department of Physiology, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Pietro Lampertico
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC 'A. M. and A. Migliavacca' Center for Liver Disease, Milan, Italy
| | - George Papatheodoridis
- Department of Gastroenterology, General Hospital of Athens 'Laiko', Medical School of National and Kapodistrian University of Athens, Athens, Greece
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40
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Sinharay R, Grant AJ, Rivett L, Blackwell R, Mells G, Gelson W. Assessing efficacy of hepatocellular carcinoma prediction scores to prioritise hepatitis B surveillance in the COVID-19 era. GASTROHEP 2021; 3:80-87. [PMID: 33821150 PMCID: PMC8014760 DOI: 10.1002/ygh2.443] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 01/25/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE An estimated 250 million people worldwide are chronically infected with hepatitis B virus (HBV), the leading cause of hepatocellular carcinoma (HCC) globally. The novel Sars-cov2 virus continues to spread at an alarming rate, and with guidance at the onset of the pandemic recommending the deferral of HCC surveillance, the implications on liver cancer care are now emerging and highlight the urgent need for reorganisation of services. METHODS We analysed how five HCC risk prediction scores could aid stratification of patients with chronic HBV. We calculated scores using parameters measured from 3 years prior (where available, n = 17) and at the time of HCC diagnosis in all adult patients with chronic HBV diagnosed with HCC (n = 46), and controls (n = 100). We compared the number of patients requiring cancer surveillance according to each score and regional surveillance guidance. RESULTS The aMAP score had the highest discriminatory performance in HCC risk prediction at 3 years (area under receiver-operating characteristic curve (auROC) of 0.824), followed by the mREACH B score (auROC of 0.719), and mPAGE B score (auROC of 0.742). However, only the mREACH B score had a negative predictive value (NPV) >99%. Applying the mREACH B score to our HBV cohort identified 11 patients requiring HCC surveillance, compared with 62 under current guidelines. CONCLUSION The use of HCC risk prediction scores could streamline the surveillance of patients with chronic HBV at a time of extremely limited resources. Overall, the mREACH B score had both a strong discriminatory performance and a high NPV, thus safely identifying low risk patients not requiring surveillance.
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Affiliation(s)
- Ricky Sinharay
- Department of PathologyUniversity of CambridgeCambridgeUK
- Cambridge Liver UnitCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | | | - Lucy Rivett
- Department of Infectious DiseasesCambridge University NHS Hospitals Foundation TrustCambridgeUK
- Clinical Microbiology and Public Health LaboratoryPublic Health EnglandCambridgeUK
| | - Rebecca Blackwell
- Cambridge Liver UnitCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | - George Mells
- Cambridge Liver UnitCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | - William Gelson
- Cambridge Liver UnitCambridge University Hospitals NHS Foundation TrustCambridgeUK
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41
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Kim SU, Chon YE, Seo YS, Lee HW, Lee HA, Kim MN, Min IK, Park JY, Kim DY, Ahn SH, Tak WY, Kim BK, Park SY. A multi-centre study of trends in hepatitis B virus-related hepatocellular carcinoma risk over time during long-term entecavir therapy. J Viral Hepat 2020; 27:1352-1358. [PMID: 32852880 DOI: 10.1111/jvh.13384] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/22/2020] [Accepted: 06/28/2020] [Indexed: 12/13/2022]
Abstract
The risk of developing hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is reduced by antiviral therapy. Here, we evaluated the chronological trends in HCC development risk starting in 2007, when entecavir reimbursement was first initiated in South Korea. Treatment-naïve patients with chronic hepatitis B (CHB) receiving entecavir 0.5 mg/d were stratified into three groups according to entecavir start time: early (2007-2010), middle (2011-2012) and late (2013-2014) cohorts Among 2442 patients, cumulative probabilities of developing HCC after 1, 3 and 5 years were, respectively, 1.7%, 5.1%, and 8.2% (early cohort; n = 672); 1.5%, 5.1% and 8.9% (middle cohort; n = 757); and 1.2%, 5.3% and 10.6% (late cohort; n = 1013; P > .05 between each pair). Older age, male, positive hepatitis B e antigen, liver cirrhosis, Child-Pugh class B (vs A) and lower platelet count significantly predicted HCC development in univariate analysis (P < .001), whereas entecavir start time (early vs middle vs late cohorts) did not affect the risk of HCC development (P = .457). A multivariate analysis revealed that older age (adjusted hazard ratio [aHR]=1.041), male gender (aHR = 2.069), liver cirrhosis (aHR = 3.771) and Child-Pugh class B (vs A, aHR = 1.548) were independently associated with an increased risk of HCC development, whereas higher platelet count was independently associated with a reduced risk of HCC development (aHR = 0.993; all P < .05). In conclusion, the risk of developing HCC among patients receiving entecavir in South Korea has been stable since 2007. To establish more effective HCC surveillance programs, further studies regarding the carcinogenic roles of nonviral factors are required.
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Affiliation(s)
- Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Yong Eun Chon
- Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Mi Na Kim
- Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Korea
| | - In Kyung Min
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu, Korea
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42
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Kao JH, Hu TH, Jia J, Kurosaki M, Lim YS, Lin HC, Sinn DH, Tanaka Y, Wai-Sun Wong V, Yuen MF. East Asia expert opinion on treatment initiation for chronic hepatitis B. Aliment Pharmacol Ther 2020; 52:1540-1550. [PMID: 32951256 DOI: 10.1111/apt.16097] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 07/27/2020] [Accepted: 09/03/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Globally, chronic hepatitis B (CHB) is a major public health concern. Timely and effective management can prevent disease progression to cirrhosis and reduce the risk of hepatocellular carcinoma (HCC). Currently, there is no consensus on the clinical management of CHB in East Asia. AIM To establish an East Asia expert opinion on treatment initiation for CHB based on alanine aminotransferase (ALT) level, hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level, cirrhosis and HCC risk scores. METHODS A meeting was held online with a panel of 10 experts from East Asia to discuss ALT, HBV DNA, cirrhosis and HCC risk scores. Indications for CHB treatment in the latest international guidelines were reviewed. Consensus was summarised to provide recommendations on the initiation of treatment for CHB. RESULTS Anti-viral therapy is recommended for CHB patients with (a) HBV DNA ≥ 2000 IU/mL and ALT ≥ 1× upper limit of normal (ULN); (b) HBV DNA ≥ 2000 IU/mL, ALT < 1× ULN and ≥ F2 fibrosis and/or ≥ A2 necroinflammation occurs; (c) cirrhosis and detectable HBV DNA; or (d) HBV DNA ≥ 2000 IU/mL, ALT < 1× ULN and a family history of cirrhosis or HCC, extrahepatic manifestations or age > 40 years. Patients with cirrhosis and/or HCC should be treated regardless of ALT levels if HBV DNA level is detectable. Initiating anti-viral therapy or close monitoring at 3-month intervals is recommended for CHB patients with at least two HCC risk factors. CONCLUSIONS These expert recommendations will contribute to a new standard of daily clinical practice in East Asia.
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43
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Yip TCF, Liang LY, Wong GLH. Assessment of HCC Risk in Patients with Chronic HBV (REACH, PAGE-B, and Beyond). CURRENT HEPATOLOGY REPORTS 2020; 19:285-292. [DOI: 10.1007/s11901-020-00526-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
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44
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Reply to: "Clinical relevance of dynamic risk assessment for developing hepatocellular carcinoma during prolonged antiviral therapy". J Hepatol 2020; 73:223-224. [PMID: 32229038 DOI: 10.1016/j.jhep.2020.03.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 03/08/2020] [Indexed: 12/04/2022]
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45
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Kim GA, Lim YS. Editorial: hepatitis B DNA thresholds and risk of hepatocellular carcinoma: different number patterns in HBeAg-positive versus HBeAg-negative patients. Authors' reply. Aliment Pharmacol Ther 2020; 51:1440-1441. [PMID: 32445524 DOI: 10.1111/apt.15794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Gi-Ae Kim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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46
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Da Fonseca LG, Forner A. Adherence and quality are key for a beneficial HCC surveillance. Liver Int 2020; 40:751-753. [PMID: 32255572 DOI: 10.1111/liv.14421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 02/23/2020] [Indexed: 02/13/2023]
Affiliation(s)
- Leonardo G Da Fonseca
- Clinical Oncology, Instituto do Cancer do Estado de Sao Paulo, University of Sao Paulo, Sao Paulo, Brazil
| | - Alejandro Forner
- Liver Unit, Barcelona Clinic Liver Cancer (BCLC) group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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