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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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Wong LL, Hromalik LR, Hernandez BY, Acoba JD, Kwee SA. The Changing Pathogenesis of Liver Cancer in Hawaii over Three Decades. Cancer Epidemiol Biomarkers Prev 2025; 34:527-533. [PMID: 39869025 PMCID: PMC11968224 DOI: 10.1158/1055-9965.epi-24-1399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 11/13/2024] [Accepted: 01/21/2025] [Indexed: 01/28/2025] Open
Abstract
BACKGROUND Worldwide trends support the increasing contribution of hepatic steatosis to the incidence of hepatocellular carcinoma (HCC). This study investigates if similar changes are seen in Hawaii, where the incidence of HCC is higher than in most of the United States. METHODS This is a retrospective study of 1,651 patients diagnosed with HCC (1991-2023) that includes 60% to 70% of HCC cases in Hawaii. We evaluated changes in patient demographics, risk factors, and disease etiology over the past three decades. RESULTS From 1991 to 2023, there were significant increases in the proportion of HCC cases attributable to metabolic dysfunction-associated steatotic liver disease (MASLD), coinciding with an increase in the prevalence of metabolic risk factors including obesity, diabetes, hyperlipidemia, and hypertension. Cases with a history of smoking also increased through 2020. Conversely, HCC cases presenting with cirrhosis alone decreased. Hepatitis C virus (HCV)-associated cases increased through 2015 and then tapered, whereas Hepatitis B virus (HBV)-associated cases decreased through 2020. There was no significant change in the proportion of alcohol-associated cases. CONCLUSIONS Although HBV continues to be a major contributor to HCC in Hawaii, HCV-related HCC cases have tapered, whereas metabolic risk factors for HCC and cases attributable to MASLD have increased over time, paralleling overall trends observed in the United States. Efforts are needed to manage these metabolic factors to address the burden of HCC. IMPACT Although Hawaii continues to have a large burden of viral hepatitis-related HCC, metabolic factors and MASLD have affected the pathogenesis of liver cancer in Hawaii over the past three decades.
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Affiliation(s)
- Linda L. Wong
- Department of Surgery, University of Hawaii, John A. Burns School of Medicine
- University of Hawaii, Cancer Center
| | - Larry R. Hromalik
- Department of Surgery, University of Hawaii, John A. Burns School of Medicine
| | | | - Jared D. Acoba
- University of Hawaii, Cancer Center
- Department of Medicine, University of Hawaii, John A Burns School of Medicine
| | - Sandi A. Kwee
- University of Hawaii, Cancer Center
- PET Imaging, Queens Medical Center
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Gujarathi R, Klein JA, Liao CY, Pillai A. The Changing Demographics and Epidemiology of Hepatocellular Carcinoma. Clin Liver Dis 2025; 29:1-15. [PMID: 39608950 DOI: 10.1016/j.cld.2024.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2024]
Abstract
The epidemiology of hepatocellular carcinoma (HCC) has shifted significantly in the last 2 decades with non-viral etiologies such as metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease on the rise. Key factors include the global obesity epidemic and the resurgence of alcohol use disorder, both of which were exacerbated by the coronavirus disease 2019 pandemic. While these non-viral etiologies of HCC are becoming the leading cause in developed countries, the potential impact of immigration patterns on Hepatitis B virus epidemiology cannot be ignored. The risk of HCC remains significant in individuals with cirrhosis and viral hepatitis after curative treatments.
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Affiliation(s)
- Rushabh Gujarathi
- Department of Internal Medicine, University of Chicago, Chicago, IL, USA
| | - Jeremy A Klein
- Department of Internal Medicine, University of Chicago, Chicago, IL, USA
| | - Chih-Yi Liao
- Department of Internal Medicine, University of Chicago, Chicago, IL, USA
| | - Anjana Pillai
- Department of Internal Medicine, University of Chicago, Chicago, IL, USA.
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Hwang SY, Danpanichkul P, Agopian V, Mehta N, Parikh ND, Abou-Alfa GK, Singal AG, Yang JD. Hepatocellular carcinoma: updates on epidemiology, surveillance, diagnosis and treatment. Clin Mol Hepatol 2025; 31:S228-S254. [PMID: 39722614 PMCID: PMC11925437 DOI: 10.3350/cmh.2024.0824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 11/08/2024] [Accepted: 12/20/2024] [Indexed: 12/28/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a major global burden, ranking as the third leading cause of cancer-related mortality. HCC due to chronic hepatitis B virus (HBV) or C virus (HCV) infection has decreased due to universal vaccination for HBV and effective antiviral therapy for both HBV and HCV, but HCC related to metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease is increasing. Biannual liver ultrasonography and serum α-fetoprotein are the primary surveillance tools for early HCC detection among high-risk patients (e.g., cirrhosis, chronic HBV). Alternative surveillance tools such as blood-based biomarker panels and abbreviated magnetic resonance imaging (MRI) are being investigated. Multiphasic computed tomography or MRI is the standard for HCC diagnosis, but histological confirmation should be considered, especially when inconclusive findings are seen on cross-sectional imaging. Staging and treatment decisions are complex and should be made in multidisciplinary settings, incorporating multiple factors including tumor burden, degree of liver dysfunction, patient performance status, available expertise, and patient preferences. Early-stage HCC is best treated with curative options such as resection, ablation, or transplantation. For intermediate-stage disease, locoregional therapies are primarily recommended although systemic therapies may be preferred for patients with large intrahepatic tumor burden. In advanced-stage disease, immune checkpoint inhibitor-based therapy is the preferred treatment regimen. In this review article, we discuss the recent global epidemiology, risk factors, and HCC care continuum encompassing surveillance, diagnosis, staging, and treatments.
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Affiliation(s)
- Soo Young Hwang
- Department of Internal Medicine, University of Maryland Medical Center, Midtown Campus, Baltimore, Maryland, USA
| | - Pojsakorn Danpanichkul
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Vatche Agopian
- Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
| | - Neehar D. Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Ghassan K. Abou-Alfa
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
- Department of Medicine, Weill Medical College at Cornell University, New York, USA
- Trinity College Dublin, Dublin, Ireland
| | - Amit G. Singal
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
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Shafiq AM, Taha NA, Zaky AH, Mohammed AH, Omran OM, Abozaid L, Ahmed HHT, Ameen MG. Prognostic significance of the tumor budding and tumor-infiltrating lymphocytes in survival of hepatocellular carcinoma patients. Int J Health Sci (Qassim) 2024; 18:10-19. [PMID: 39502429 PMCID: PMC11533185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2024] Open
Abstract
Objective In spite of great advance in the management of hepatocellular carcinoma (HCC), the prognostic factors are still obviously not understood. The role of tumor budding (TB) and tumor-infiltrating lymphocytes (TILs) in HCC as pathological parameters affecting prognosis stands principally unknown. Methods Seventy-four surgical resection pathology specimens of HCC patients were used. Assessment of TB and TILs were performed using hematoxylin-eosin-stained slides. Follow-up data were collected over a 5-year period to determine disease-free survival rates, overall survival (OS) rates, and how they related to TB, TILs, and other clinicopathological factors. Results There was a significant statistical association between high-grade TB and lymphovascular embolization (LVE), tumor necrosis, and grade of HCC with P = 0.003, 0.036, and 0.017, respectively. The positive TILs group showed a statistically significant correlation with histological grade, LVE, and serum alpha-fetoprotein (AFP) level with P = 0.002, 0.006, and 0.043, respectively. Multivariate analysis using the Cox proportional hazard model revealed that TILs are not an independent pathological factor for disease-free and OS, although TB is an independent pathological factor for both. Conclusions In all HCC patients, TB was seen, and there was a significant link between the grade of the HCC and the presence of tumor necrosis, LVE, and high-grade TB. The majority (92%) of HCC patients had TILs, and there was a strong relationship between the histological grade, LVE, and serum AFP level. While TILs show variation of the immunologic reaction to the tumor, TB tends to suggest a hostile biologic nature and a bad prognosis.
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Affiliation(s)
- Ahmed Mahran Shafiq
- Department of Medical Oncology and Hematological Malignancies, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Noura Ali Taha
- Department of Medical Oncology and Hematological Malignancies, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Amen Hamdy Zaky
- Department of Medical Oncology and Hematological Malignancies, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Abdallah Hedia Mohammed
- Department of Medical Oncology and Hematological Malignancies, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Ola M. Omran
- Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
- Department of Pathology, College of Medicine, Qassim University, Buraidah, Qassim Region, Saudi Arabia
| | - Lobaina Abozaid
- Department of Pathology, College of Medicine, Qassim University, Buraidah, Qassim Region, Saudi Arabia
| | - Hagir H. T. Ahmed
- Department of Pathology, College of Medicine, Qassim University, Buraidah, Qassim Region, Saudi Arabia
| | - Mahmoud Gamal Ameen
- Department of Oncologic Pathology, South Egypt Cancer Institute, Assiut University, Assiut Egypt
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Danpanichkul P, Aboona MB, Sukphutanan B, Kongarin S, Duangsonk K, Ng CH, Muthiah MD, Huang DQ, Seko Y, Díaz LA, Arab JP, Yang JD, Chen VL, Kim D, Noureddin M, Liangpunsakul S, Wijarnpreecha K. Incidence of liver cancer in young adults according to the Global Burden of Disease database 2019. Hepatology 2024; 80:828-843. [PMID: 38598364 DOI: 10.1097/hep.0000000000000872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 02/19/2024] [Indexed: 04/12/2024]
Abstract
BACKGROUND AND AIMS The worldwide burden of cancer is increasing in younger populations. However, the epidemiology of primary liver cancer remains understudied in young adults compared to other cancer forms. APPROACH AND RESULTS This study analyzed data from the Global Burden of Disease study between 2010 and 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years associated with primary liver cancer in the young (15-49 y), stratified by region, nation, sociodemographic index, and sex. The study found a global estimate of 78,299 primary liver cancer cases, 60,602 deaths, and 2.90 million disability-adjusted life years in the young population. The Western Pacific region exhibited the highest burden in 2019, showing the most significant increase compared to other regions between 2010 and 2019. More than half of the countries worldwide have undergone an increase in primary liver cancer incidence rates in young adults. Around 12.51% of deaths due to primary liver cancer occur in young individuals. Throughout the study period, there was a significant decline in primary liver cancer mortality due to most etiologies, except for metabolic dysfunction-associated steatotic liver disease-attributable primary liver cancer (annual percentage change + 0.87%, 95% CI: 0.70%-1.05%) and alcohol-attributable primary liver cancer (annual percentage change + 0.21%, 95% CI: 0.01%-0.42%). The limitations of the Global Burden of Disease database include reliance on the quality of primary data and possible underestimation of alcohol consumption. CONCLUSIONS Over the past decade, there has been a marked increase in the burden of primary liver cancer, especially that originating from steatotic liver disease. This trend calls for the development of urgent and comprehensive strategies to mitigate this rising burden globally.
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Affiliation(s)
- Pojsakorn Danpanichkul
- Immunology Unit, Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Majd B Aboona
- Department of Internal Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | | | | | - Kwanjit Duangsonk
- Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Cheng Han Ng
- Department of Medicine, Division of Gastroenterology and Hepatology, National University Health System, Singapore
- Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine, Kurume, Japan
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Daniel Q Huang
- Department of Medicine, Division of Gastroenterology and Hepatology, National University Health System, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- MASLD Research Center, Division of Gastroenterology, University of California, San Diego, La Jolla, California, USA
| | - Yuya Seko
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, Japan
| | - Luis Antonio Díaz
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
- Observatorio Multicéntrico de Enfermedades Gastrointestinales, OMEGA, Santiago, Chile
| | - Juan Pablo Arab
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Vincent L Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - Mazen Noureddin
- Houston Research Institute and Houston Methodist Hospital, Houston, Texas, USA
| | - Suthat Liangpunsakul
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, USA
| | - Karn Wijarnpreecha
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Phoenix, Arizona, USA
- Department of Internal Medicine, Banner University Medical Center, Phoenix, Arizona, USA
- BIO5 Institute, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, USA
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Mak LY. Disease modifiers and novel markers in hepatitis B virus-related hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2024; 24:145-154. [PMID: 39099070 PMCID: PMC11449577 DOI: 10.17998/jlc.2024.08.03] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 07/25/2024] [Accepted: 08/03/2024] [Indexed: 08/06/2024]
Abstract
Chronic hepatitis B (CHB) infection is responsible for 40% of the global burden of hepatocellular carcinoma (HCC) with a high case fatality rate. The risk of HCC differs among CHB subjects owing to differences in host and viral factors. Modifiable risk factors include viral load, use of antiviral therapy, co-infection with other hepatotropic viruses, concomitant metabolic dysfunctionassociated steatotic liver disease or diabetes mellitus, environmental exposure, and medication use. Detecting HCC at early stage improves survival, and current practice recommends HCC surveillance among individuals with cirrhosis, family history of HCC, or above an age cut-off. Ultrasonography with or without serum alpha feto-protein (AFP) every 6 months is widely accepted strategy for HCC surveillance. Novel tumor-specific markers, when combined with AFP, improve diagnostic accuracy than AFP alone to detect HCC at an early stage. To predict the risk of HCC, a number of clinical risk scores have been developed but none of them are clinically implemented nor endorsed by clinical practice guidelines. Biomarkers that reflect viral transcriptional activity and degree of liver fibrosis can potentially stratify the risk of HCC, especially among subjects who are already on antiviral therapy. Ongoing exploration of these novel biomarkers is required to confirm their performance characteristics, replicability and practicability.
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Affiliation(s)
- Lung-Yi Mak
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Liver Research, The Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
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Akbulut Z, Aru B, Aydın F, Yanıkkaya Demirel G. Immune checkpoint inhibitors in the treatment of hepatocellular carcinoma. Front Immunol 2024; 15:1379622. [PMID: 38638433 PMCID: PMC11024234 DOI: 10.3389/fimmu.2024.1379622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 03/18/2024] [Indexed: 04/20/2024] Open
Abstract
Despite advances in cancer treatment, hepatocellular carcinoma (HCC), the most common form of liver cancer, remains a major public health problem worldwide. The immune microenvironment plays a critical role in regulating tumor progression and resistance to therapy, and in HCC, the tumor microenvironment (TME) is characterized by an abundance of immunosuppressive cells and signals that facilitate immune evasion and metastasis. Recently, anti-cancer immunotherapies, therapeutic interventions designed to modulate the immune system to recognize and eliminate cancer, have become an important cornerstone of cancer therapy. Immunotherapy has demonstrated the ability to improve survival and provide durable cancer control in certain groups of HCC patients, while reducing adverse side effects. These findings represent a significant step toward improving cancer treatment outcomes. As demonstrated in clinical trials, the administration of immune checkpoint inhibitors (ICIs), particularly in combination with anti-angiogenic agents and tyrosine kinase inhibitors, has prolonged survival in a subset of patients with HCC, providing an alternative for patients who progress on first-line therapy. In this review, we aimed to provide an overview of HCC and the role of the immune system in its development, and to summarize the findings of clinical trials involving ICIs, either as monotherapies or in combination with other agents in the treatment of the disease. Challenges and considerations regarding the administration of ICIs in the treatment of HCC are also outlined.
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Affiliation(s)
- Zeynep Akbulut
- Cancer and Stem Cell Research Center, Maltepe University, Istanbul, Türkiye
- Department of Medical Biology and Genetics, Faculty of Medicine, Maltepe University, Istanbul, Türkiye
| | - Başak Aru
- Department of Immunology, Faculty of Medicine, Yeditepe University, Istanbul, Türkiye
| | - Furkan Aydın
- Department of Immunology, Faculty of Medicine, Yeditepe University, Istanbul, Türkiye
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Patmore LA, van Eekhout KMA, Buti M, Koc ÖM, Agarwal K, de Knegt RJ, Janssen HLA, van der Valk M, Lieveld FI, Hansen BE, Kramer M, de Bruijne J, Claassen MAA, Smit C, de Man RA, Takkenberg B, Carey I, Sonneveld MJ. Hepatocellular carcinoma risk in sub-Saharan African and Afro-Surinamese individuals with chronic hepatitis B living in Europe. J Hepatol 2024; 80:243-250. [PMID: 37898348 DOI: 10.1016/j.jhep.2023.10.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 09/20/2023] [Accepted: 10/16/2023] [Indexed: 10/30/2023]
Abstract
BACKGROUND & AIMS Sub-Saharan African (SSA) ethnicity has been associated with a higher risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis B in cross-sectional studies. However, the incidence of HCC and performance of HCC risk scores in this population are unknown. METHODS We conducted an international multicenter retrospective cohort study of all consecutive HBV-monoinfected individuals of SSA or Afro-Surinamese (AS) ethnicity managed at sites in the Netherlands, the United Kingdom and Spain. We assessed the 5- and 10-year cumulative incidences of HCC in the overall study population, among different clinically relevant subgroups and across (m)PAGE-B subgroups. Next, we explored the different risk factors for HCC. RESULTS During a median follow-up of 8 years, we analyzed 1,473 individuals of whom 34 developed HCC. The 5- and 10-year cumulative incidences of HCC were 1% and 2.4%. The 10-year cumulative incidence of HCC was 0.7% among individuals without advanced fibrosis at baseline, compared to 12.1% among individuals with advanced fibrosis (p <0.001). Higher age (adjusted hazard ratio [aHR] 1.05), lower platelet count (aHR 0.98), lower albumin level (aHR 0.90) and higher HBV DNA log10 (aHR 1.21) were significantly associated with HCC development. The 10-year cumulative incidence of HCC was 0.5% among individuals with a low PAGE-B score, compared to 2.9% in the intermediate- and 15.9% in the high-risk groups (p <0.001). CONCLUSIONS In this unique international multicenter cohort of SSA and AS individuals with chronic hepatitis B, we observed 5- and 10-year cumulative HCC risks of 1% and 2.4%, respectively. The risk of HCC was negligible for individuals without advanced fibrosis at baseline, and among individuals with low baseline (m)PAGE-B scores. These findings can be used to guide HCC surveillance strategies. IMPACT AND IMPLICATIONS Sub-Saharan African ethnicity has been associated with a higher risk of hepatocellular carcinoma among individuals with chronic hepatitis B. In this international multicenter cohort study of sub-Saharan African and Afro-Surinamese individuals living with chronic hepatitis B in Europe, we observed 5- and 10-year cumulative incidences of hepatocellular carcinoma of 1% and 2.4%, respectively. The risk was negligible among individuals without advanced fibrosis and a low baseline (m)PAGE-B score. These findings can be used to guide HCC surveillance strategies in this population.
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Affiliation(s)
- Lesley A Patmore
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
| | - Kirsi M A van Eekhout
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Maria Buti
- Liver Unit, Hospital University Valle d'Hebron, Barcelona, Spain
| | - Özgur M Koc
- Department of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Kosh Agarwal
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Rob J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Harry L A Janssen
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Marc van der Valk
- Amsterdam University Medical Centers, University of Amsterdam, Department of Infectious Disease, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands; Hiv Monitoring Foundation, Amsterdam, The Netherlands
| | - Faydra I Lieveld
- Department of Gastroenterology and Hepatology, Utrecht UMC, Utrecht, The Netherlands; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Bettina E Hansen
- Deperatment of Epidemiology & Biostatistics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; IHPME, University of Toronto & Toronto Centre for Liver disease, UHN, Toronto, Canada
| | - Matthijs Kramer
- Department of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Joep de Bruijne
- Department of Gastroenterology and Hepatology, Utrecht UMC, Utrecht, The Netherlands
| | - Mark A A Claassen
- Department of Internal Medicine and Infectious Diseases, Rijnstate Hospital, Arnhem, The Netherlands
| | - Colette Smit
- Hiv Monitoring Foundation, Amsterdam, The Netherlands
| | - Rob A de Man
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Bart Takkenberg
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Ivana Carey
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Milan J Sonneveld
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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Decharatanachart P, Pan-ngum W, Peeraphatdit T, Tanpowpong N, Tangkijvanich P, Treeprasertsuk S, Rerknimitr R, Chaiteerakij R. Cost-Utility Analysis of Non-Contrast Abbreviated Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance in Cirrhosis. Gut Liver 2024; 18:135-146. [PMID: 37560799 PMCID: PMC10791494 DOI: 10.5009/gnl230089] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 05/01/2023] [Accepted: 05/23/2023] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND/AIMS Ultrasonography has a low sensitivity for detecting early-stage hepatocellular carcinoma (HCC) in cirrhotic patients. Non-contrast abbreviated magnetic resonance imaging (aMRI) demonstrated a comparable performance to that of magnetic resonance imaging without the risk of contrast media exposure and at a lower cost than that of full diagnostic MRI. We aimed to investigate the cost-effectiveness of non-contrast aMRI for HCC surveillance in cirrhotic patients, using ultrasonography with alpha-fetoprotein (AFP) as a reference. METHODS Cost-utility analysis was performed using a Markov model in Thailand and the United States. Incremental cost-effectiveness ratios were calculated using the total costs and quality-adjusted life years (QALYs) gained in each strategy. Surveillance protocols were considered cost-effective based on a willingness-to-pay value of $4,665 (160,000 Thai Baht) in Thailand and $50,000 in the United States. RESULTS aMRI was cost-effective in both countries with incremental cost-effectiveness ratios of $3,667/QALY in Thailand and $37,062/QALY in the United States. Patient-level microsimulations showed consistent findings that aMRI was cost-effective in both countries. By probabilistic sensitivity analysis, aMRI was found to be more cost-effective than combined ultrasonography and AFP with a probability of 0.77 in Thailand and 0.98 in the United States. By sensitivity analyses, annual HCC incidence was revealed as the most influential factor affecting cost-effectiveness. The cost-effectiveness of aMRI increased in settings with a higher HCC incidence. At a higher HCC incidence, aMRI would remain cost-effective at a higher aMRI-to-ultrasonography with AFP cost ratio. CONCLUSIONS Compared to ultrasonography with AFP, non-contrast aMRI is a cost-effective strategy for HCC surveillance and may be useful for such surveillance in cirrhotic patients, especially in those with high HCC risks.
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Affiliation(s)
| | - Wirichada Pan-ngum
- Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Thoetchai Peeraphatdit
- Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Natthaporn Tanpowpong
- Department of Radiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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11
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Singal AG, Llovet JM, Yarchoan M, Mehta N, Heimbach JK, Dawson LA, Jou JH, Kulik LM, Agopian VG, Marrero JA, Mendiratta-Lala M, Brown DB, Rilling WS, Goyal L, Wei AC, Taddei TH. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology 2023; 78:1922-1965. [PMID: 37199193 PMCID: PMC10663390 DOI: 10.1097/hep.0000000000000466] [Citation(s) in RCA: 646] [Impact Index Per Article: 323.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 05/01/2023] [Indexed: 05/19/2023]
Affiliation(s)
- Amit G. Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Josep M. Llovet
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York, USA
- Translational Research in Hepatic Oncology, Liver Unit, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic, University of Barcelona, Catalonia, Spain
- Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain
| | - Mark Yarchoan
- Department of Medical Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA
| | - Neil Mehta
- University of California, San Francisco, San Francisco, California, USA
| | | | - Laura A. Dawson
- Radiation Medicine Program/University Health Network, Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - Janice H. Jou
- Division of Gastroenterology and Hepatology, Oregon Health and Science University, Portland, Oregon, USA
| | - Laura M. Kulik
- Northwestern Medical Faculty Foundation, Chicago, Illinois, USA
| | - Vatche G. Agopian
- The Dumont–University of California, Los Angeles, Transplant Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA
| | - Jorge A. Marrero
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Mishal Mendiratta-Lala
- Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan, USA
| | - Daniel B. Brown
- Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - William S. Rilling
- Division of Interventional Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Lipika Goyal
- Department of Medicine, Stanford School of Medicine, Palo Alto, California, USA
| | - Alice C. Wei
- Memorial Sloan Kettering Cancer Center, New York City, New York, USA
| | - Tamar H. Taddei
- Department of Medicine (Digestive Diseases), Yale School of Medicine, New Haven, CT, USA
- Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA
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12
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Roldan GA, Blomker J, Aby ES. Hepatocellular Carcinoma from a Hepatologist's Perspective. Semin Intervent Radiol 2023; 40:524-535. [PMID: 38274218 PMCID: PMC10807972 DOI: 10.1055/s-0043-1777846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2024]
Abstract
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, represents a growing health challenge worldwide. The incidence of HCC is rising, which, in turn, has led to a corresponding increase in the associated number of deaths. HCC will become the third leading cause of cancer-related deaths in the United States by 2030. HCC usually develops in the setting of chronic liver disease. Individuals at increased risk of HCC are recommended to undergo surveillance with ultrasound every 6 months along with serum α-fetoprotein testing. Computed tomography (CT) and magnetic resonance imaging (MRI) are considered alternatives based on specific patient factors. Lesions suspicious for HCC are recommended to undergo a diagnostic testing, which includes contrast-enhanced multiphase CT or MRI and liver biopsy when findings are indeterminate. The Barcelona Clinic Liver Cancer prognosis and treatment strategy is the most used assessment for patients with HCC ( Fig. 2 ). Curative therapies include resection, liver transplantation, and ablation. Locoregional therapies, such as transarterial chemoembolization and radioembolization, can be used for patients with intermediate-stage HCC. For patients with advanced-stage HCC, systemic therapy is often used. This review aims to provide an overview of HCC from a hepatologist's perspective, including epidemiology, screening, surveillance, diagnosis, and management.
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Affiliation(s)
- Giovanni A. Roldan
- Department of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, Minnesota
| | - Jacquelin Blomker
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota
| | - Elizabeth S. Aby
- Department of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, Minnesota
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13
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Taha NA, Shafiq AM, Mohammed AH, Zaky AH, Omran OM, Ameen MG. FOS-Like Antigen 1 Expression Was Associated With Survival of Hepatocellular Carcinoma Patients. World J Oncol 2023; 14:285-299. [PMID: 37560339 PMCID: PMC10409557 DOI: 10.14740/wjon1608] [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: 05/01/2023] [Accepted: 06/10/2023] [Indexed: 08/11/2023] Open
Abstract
Background Early diagnosis and proper management of hepatocellular carcinoma (HCC) improve patient prognosis. Several studies attempted to discover new genes to understand the pathogenesis and identify the prognostic and predictive factors in HCC patients, to improve patient's overall survival (OS) and maintain their physical and social activity. The transcription factor FOS-like antigen 1 (FOSL1) acts as one of the important prognostic factors in different tumors, and its overexpression correlates with tumors' progression and worse patient survival. However, its expression and molecular mechanisms underlying its dysregulation in human HCC remain poorly understood. Our study was conducted to evaluate the expression of FOSL1 in HCC tissues and its relationship with various clinicopathological parameters besides OS. Methods This study is a retrospective cohort study conducted among 113 patients with a proven diagnosis of HCC, who underwent tumor resection and received treatment at South Egypt Cancer Institute. Immunohistochemistry for FOSL1 expression and survival curves were conducted followed by statistical analysis. Results HCC occurred at older age group and affected males more than females. There was a statistically significant correlation between combined cytoplasmic and nuclear expression of FOSL1 and worse prognosis in HCC patients. There was a statistically significant correlation of FOSL1 expression with histological grade, lymphovascular embolization, and tumor budding where high expression indicated potential deterioration of HCC patients. There was statistically significant correlation between tumor size, tumor grade and FOSL1 expression with the cumulative OS. Conclusions Combined cytoplasmic and nuclear FOSL1 expression has significant prognostic association with HCC and diagnostic importance, as it can identify cirrhosis and premalignant lesions that can progress to HCC. Furthermore, Kaplan-Meier survival analysis found that overexpressed FOSL1 was correlated with poor OS.
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Affiliation(s)
- Noura Ali Taha
- Department of Medical Oncology and Hematological Malignancies, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Ahmed Mahran Shafiq
- Department of Medical Oncology and Hematological Malignancies, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Abdallah Hedia Mohammed
- Department of Medical Oncology and Hematological Malignancies, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Amen Hamdy Zaky
- Department of Medical Oncology and Hematological Malignancies, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Ola M. Omran
- Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
- Department of Pathology, College of Medicine, Qassim University, KSA
| | - Mahmoud Gamal Ameen
- Department of Oncologic Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
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14
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Zhou K, Song Z, Rostomian N, Dodge JL, Stern MC, Setiawan VW, Terrault NA, Cockburn MG, Liu L. Association of nativity with survival among adults with hepatocellular carcinoma. J Natl Cancer Inst 2023; 115:861-869. [PMID: 37160726 PMCID: PMC10323898 DOI: 10.1093/jnci/djad067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 02/13/2023] [Accepted: 04/13/2023] [Indexed: 05/11/2023] Open
Abstract
INTRODUCTION Immigrants comprise a considerable proportion of those diagnosed with hepatocellular carcinoma (HCC) in the United States. Nativity or birthplace affects incidence and risk factors for HCC, but little is known about its influence on survival after diagnosis. METHODS We identified 51 533 adults with HCC with available birthplace in the California Cancer Registry between 1988 and 2017. HCC cases were categorized as foreign born or US born and stratified by mutually exclusive race and ethnicity groups. Primary outcome was all-cause mortality. Race and ethnicity-specific Cox regression propensity score-weighted models evaluated the relationship between nativity and death as well as region of birth among foreign-born patients. RESULTS A total of 40% of all HCC cases were foreign born, and 92.2%, 45.2%, 9.1%, and 5.8% of Asian/Pacific Islander (API), Hispanic, White, and Black patients were foreign born, respectively. Five-year survival rates were higher in foreign-born patients compared with US-born patients: 12.9% vs 9.6% for White patients, 11.7% vs 9.8% for Hispanic patients, 12.8% vs 8.1% for Black patients, and 16.4% vs 12.4% for API patients. Nativity was associated with survival, with better survival in foreign-born patients: White patients: hazard ratio (HR) = 0.86 (95% confidence interval [CI] = 0.81 to 0.90), Hispanic patients: HR = 0.90 (95% CI = 0.86 to 0.93), Black patients: HR = 0.89 (95% CI = 0.76 to 1.05), and API patients: HR = 0.94 (95% CI = 0.88 to 1.00). Among foreign-born patients, lower mortality was observed in those from Central and South America compared with Mexico for Hispanic patients, East Asia compared with Southeast Asia for API patients, and East Europe and Greater Middle East compared with West/South/North Europe for White patients. CONCLUSION Foreign-born patients with HCC have better survival than US-born patients. Further investigation into the mechanisms of this survival disparity by nativity is needed.
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Affiliation(s)
- Kali Zhou
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Ziwei Song
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | | | - Jennifer L Dodge
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Mariana C Stern
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - V Wendy Setiawan
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Norah A Terrault
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Myles G Cockburn
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Lihua Liu
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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15
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Devarbhavi H, Asrani SK, Arab JP, Nartey YA, Pose E, Kamath PS. Global burden of Liver Disease: 2023 Update. J Hepatol 2023:S0168-8278(23)00194-0. [PMID: 36990226 DOI: 10.1016/j.jhep.2023.03.017] [Citation(s) in RCA: 708] [Impact Index Per Article: 354.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 03/06/2023] [Accepted: 03/09/2023] [Indexed: 03/31/2023]
Abstract
Liver disease accounts for 2 million deaths and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately 2/3 of all liver related deaths occur in men. Deaths are largely attributable to complications of cirrhosis and hepatocellular carcinoma, with acute hepatitis accounting for a smaller proportion of deaths. The most common causes of cirrhosis worldwide are related to viral hepatitis, alcohol, and nonalcoholic fatty liver disease (NAFLD). Hepatotropic viruses are the etiological factor in most cases of acute hepatitis, but drug-induced liver injury increasingly accounts for a significant proportion of cases. This iteration of the global burden of liver disease is an update of the 2019 version and focuses mainly on areas where significant new information is available like alcohol-associated liver disease, NAFLD, viral hepatitis, and HCC. We also devote a separate section to the burden of liver disease in Africa, an area of the world typically neglected in such documents.
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Affiliation(s)
- Harshad Devarbhavi
- Department of Gastroenterology and Hepatology, St. John's Medical College Hospital, Bangalore, India
| | - Sumeet K Asrani
- Baylor University Medical Center, Baylor Scott and White, Dallas, TX, United States.
| | - Juan Pablo Arab
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada; Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Yvonne Ayerki Nartey
- Department of Internal Medicine, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Elisa Pose
- Liver Unit, Hospital Clinic of Barcelona. Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
| | - Patrick S Kamath
- Mayo Clinic College of Medicine and Science, Rochester, MN, United States
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16
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Surial B, Ramírez Mena A, Roumet M, Limacher A, Smit C, Leleux O, Mocroft A, van der Valk M, Bonnet F, Peters L, Rockstroh JK, Günthard HF, Berzigotti A, Rauch A, Wandeler G. External validation of the PAGE-B score for HCC risk prediction in people living with HIV/HBV coinfection. J Hepatol 2023; 78:947-957. [PMID: 36690280 DOI: 10.1016/j.jhep.2022.12.029] [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: 10/06/2022] [Revised: 12/21/2022] [Accepted: 12/23/2022] [Indexed: 01/22/2023]
Abstract
BACKGROUND & AIMS HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection. METHODS We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves. RESULTS In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was <10 in 26.5%, 10-17 in 57.7%, and ≥18 in 15.7% of patients. Within a median follow-up of 9.6 years, HCC occurred in 68 individuals (2.58/1,000 patient-years, 95% CI 2.03-3.27). The regression slope of the prognostic index for developing HCC within 15 years was 0.93 (95% CI 0.61-1.25), and the pooled c-index was 0.77 (range 0.73-0.80), both indicating good model discrimination. The cumulative incidence of HCC was lower in our study compared to the derivation study. A PAGE-B cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. Restricting efforts to individuals with a PAGE-B of ≥10 would spare unnecessary HCC screening in 27% of individuals. CONCLUSIONS For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening. IMPACT AND IMPLICATIONS Chronic HBV infection is the most important cause of hepatocellular carcinoma (HCC) among people living with HIV. Valid risk prediction may enable better targeting of HCC screening efforts to high-risk individuals. We aimed to validate PAGE-B, a risk prediction tool that is based on age, sex, and platelets, in 2,963 individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy. In the present study, PAGE-B showed good discrimination, adequate calibration, and a cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. These results indicate that PAGE-B is a simple and valid risk prediction tool to determine the need for HCC screening among people living with HIV and HBV.
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Affiliation(s)
- Bernard Surial
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
| | - Adrià Ramírez Mena
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland; Graduate School of Health Sciences, University of Bern, Bern, Switzerland
| | | | | | - Colette Smit
- Stichting Hiv Monitoring, Amsterdam, the Netherlands
| | - Olivier Leleux
- University of Bordeaux, INSERM, Institut Bergonié, BPH, U1219, CIC-EC 1401, F-33000, Bordeaux, France
| | - Amanda Mocroft
- CHIP, Rigshospitalet, Copenhagen, Denmark; Centre for Clinical Research Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, UK
| | - Marc van der Valk
- Stichting Hiv Monitoring, Amsterdam, the Netherlands; Department of Infectious Diseases, Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Fabrice Bonnet
- University of Bordeaux, INSERM, Institut Bergonié, BPH, U1219, CIC-EC 1401, F-33000, Bordeaux, France; CHU Bordeaux, Hôpital Saint-André, Service de Médecine Interne et Maladies Infectieuses, Bordeaux, France
| | | | | | - Huldrych F Günthard
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland; Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Annalisa Berzigotti
- Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Andri Rauch
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Gilles Wandeler
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
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17
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Su CC, Chen BS, Chen HH, Sung WW, Wang CC, Tsai MC. Improved Trends in the Mortality-to-Incidence Ratios for Liver Cancer in Countries with High Development Index and Health Expenditures. Healthcare (Basel) 2023; 11:159. [PMID: 36673528 PMCID: PMC9859532 DOI: 10.3390/healthcare11020159] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 12/26/2022] [Accepted: 12/29/2022] [Indexed: 01/06/2023] Open
Abstract
Primary liver cancer is one of the leading causes of death globally. Liver cancer has a unique geographical distribution, as its etiologies include chronic viral infections and aging. We hypothesize that the human development index (HDI), current health expenditure (CHE) per capita, and CHE-to-gross domestic product ratio (CHE/GDP) influence the incidence, mortality, and mortality-to-incidence ratios (MIRs) of liver cancer worldwide. Data were obtained from the Global Cancer Observatory (GLOBOCAN) database and the World Health Organization. MIRs and the changes in MIR over time (δMIR) were used to evaluate the correlation of expenditures on healthcare and the HDI disparities via Spearman's rank correlation coefficient. The crude incidence and mortality were significantly associated with HDI, CHE per capita, and CHE/GDP. Specifically, there were significant associations between δMIR and HDI, as well as between δMIR and CHE per capita. However, there were no significant associations between δMIR and CHE/GDP. Evidently, a favorable liver cancer δMIR was not associated with CHE/GDP, although it had a significant association with HDI and CHE per capita. These results are worthy of the attention of public health systems in correlation to improved outcomes in liver cancer.
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Affiliation(s)
- Chang-Cheng Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
| | - Brian-Shiian Chen
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
| | - Hsin-Hung Chen
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
| | - Wen-Wei Sung
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Department of Urology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Chi-Chih Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
| | - Ming-Chang Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
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18
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Mohamed EA, Giama NH, Abdalla AO, Shaleh HM, Oseini AM, Ali HA, Ahmed F, Taha W, Ahmed Mohammed H, Cvinar J, Waaeys IA, Ali H, Allotey LK, Ali AO, Mohamed SA, Harmsen WS, Ahmmad EM, Bajwa NA, Afgarshe MD, Shire AM, Balls-Berry JE, Roberts LR. High prevalence of chronic viral hepatitis B and C in Minnesota Somalis contributes to rising hepatocellular carcinoma incidence. World J Gastroenterol 2022; 28:5217-5229. [PMID: 36188718 PMCID: PMC9516675 DOI: 10.3748/wjg.v28.i35.5217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 03/28/2022] [Accepted: 08/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are known risk factors for liver disease, cirrhosis and hepatocellular carcinoma (HCC). There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC. We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota. AIM To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program. METHODS We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community advisory boards, community clinics and local mosques between November 2010 and December 2015 (data was analyzed in 2020). Serum was tested for hepatitis B surface antigen, hepatitis B core antibody, hepatitis B surface antibody and anti-HCV antibody. RESULTS Of 779 participants, 15.4% tested positive for chronic HBV infection, 50.2% for prior exposure to HBV and 7.6% for chronic HCV infection. Calculated age-adjusted frequencies in males and females for chronic HBV were 12.5% and 11.6%; for prior exposure to HBV were 44.8% and 41.3%; and for chronic HCV were 6.7% and 5.7%, respectively. Seven participants developed incident HCC during follow up. CONCLUSION Chronic HBV and HCV are major risk factors for liver disease and HCC among Somali immigrants, with prevalence of both infections substantially higher than in the general United States population. Community-based screening is essential for identifying and providing health education and linkage to care for diagnosed patients.
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Affiliation(s)
- Essa A Mohamed
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
- Center for Clinical and Translational Science, Mayo Clinic, Rochester, MN 55905, United States
| | - Nasra H Giama
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
- School of Nursing, University of Minnesota, Minneapolis, MN 55455, United States
| | - Abubaker O Abdalla
- Division of Digestive Diseases, Emory School of Medicine, Atlanta, GA 30322, United States
| | - Hassan M Shaleh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, United States
| | - Abdul M Oseini
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Hamdi A Ali
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Fowsiyo Ahmed
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Wesam Taha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
- Department of Internal Medicine, NewYork-Presbyterian Queens, Flushing, NY 11355, United States
| | - Hager Ahmed Mohammed
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
- Department of Pediatrics, University of Nevada Las Vegas, Las Vegas, NV 89154, United States
| | - Jessica Cvinar
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Ibrahim A Waaeys
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, United States
| | - Hawa Ali
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Loretta K Allotey
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Abdiwahab O Ali
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, United States
| | - Safra A Mohamed
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, United States
| | - William S Harmsen
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, United States
| | - Eimad M Ahmmad
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Numra A Bajwa
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Mohamud D Afgarshe
- Department of Medicine, Gargar Urgent Care and Clinic, Minneapolis, MN 55406, United States
| | - Abdirashid M Shire
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
- Office of the Director, Shire Scientific, Minneapolis, MN 55405, United States
| | - Joyce E Balls-Berry
- Center for Clinical and Translational Science, Mayo Clinic, Rochester, MN 55905, United States
- Department of Neurology, Washington University School of Medicine in St Louis, St Louis, MO 63130, United States
- Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, MO 63130, United States
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
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19
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Sweed D, Sweed E, Moaz I, Mosbeh A, Fayed Y, Elhamed SMA, Sweed E, Macshut M, Abdelsattar S, Kilany S, Saied SA, Badr R, Abdallah MS, Ehsan N. The clinicopathological and prognostic factors of hepatocellular carcinoma: a 10-year tertiary center experience in Egypt. World J Surg Oncol 2022; 20:298. [PMID: 36117166 PMCID: PMC9484175 DOI: 10.1186/s12957-022-02764-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 09/06/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) remains a major health problem despite the emergence of several preventive and therapeutic modalities. HCC has heterogeneous and wide morpho-molecular patterns, resulting in unique clinical and prognostic criteria. Therefore, we aimed to study the clinical and pathological criteria of HCC to update the morpho-molecular classifications and provide a guide to the diagnosis of this disease. METHODS Five hundred thirty pathologically analyzed HCC cases were included in this study. The clinical and survival data of these cases were collected. RESULTS Hepatitis C virus is still the dominant cause of HCC in Egypt. Post-direct-acting antiviral agent HCC showed an aggressive course compared to interferon-related HCC. Old age, male gender, elevated alpha-fetoprotein level, tumor size, and background liver were important prognostic parameters. Special HCC variants have characteristic clinical, laboratory, radiological, prognostic, and survival data. Tumor-infiltrating lymphocytes rather than neutrophil-rich HCC have an excellent prognosis. CONCLUSIONS HCC is a heterogenous tumor with diverse clinical, pathological, and prognostic parameters. Incorporating the clinicopathological profile per specific subtype is essential in the treatment decision of patients with HCC. TRIAL REGISTRATION This was a retrospective study that included 530 HCC cases eligible for analysis. The cases were obtained from the archives of the Pathology Department, during the period between January 2010 and December 2019. Clinical and survival data were collected from the patients' medical records after approval by the institutional review board (IRB No. 246/2021) of Liver National Institute, Menoufia University. The research followed the guidelines outlined in the Declaration of Helsinki and registered on ClinicalTrials.gov (NCT05047146).
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Affiliation(s)
- Dina Sweed
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Enas Sweed
- Radiology Department, Faculty of Medicine, Benha University, Benha, Egypt
| | - Inas Moaz
- Epidemiology, and Preventive Medicine Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Asmaa Mosbeh
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Yahya Fayed
- Hepatopancreatobiliary Surgery Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Sara Mohamed Abd Elhamed
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Eman Sweed
- Clinical Pharmacology Department, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Mahmoud Macshut
- Hepatopancreatobiliary Surgery Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Shimaa Abdelsattar
- Clinical Biochemistry and Molecular Diagnostics Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Shimaa Kilany
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Sara A. Saied
- Clinical Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Reda Badr
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Mahmoud S. Abdallah
- Clinical Pharmacy, Faculty of Pharmacy, University of Sadat City, Sadat City, Menoufia Egypt
| | - Nermine Ehsan
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
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20
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Papageorge MV, de Geus SWL, Woods AP, Ng SC, Lee S, McAneny D, Tseng JF, Kenzik KM, Sachs TE. Surveillance Patterns for Hepatocellular Carcinoma among Screening-Eligible Patients in the Medicare Population. Ann Surg Oncol 2022; 29:8424-8431. [PMID: 36057903 DOI: 10.1245/s10434-022-12360-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 07/14/2022] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Routine screening plays a critical role in the diagnosis of hepatocellular carcinoma (HCC), but not all patients undergo consistent surveillance. This study aims to evaluate surveillance patterns and their association with diagnosis stage and survival among Medicare patients at risk for HCC. PATIENTS AND METHODS Patients with HCC and guideline-based screening eligibility who underwent imaging with ultrasound or abdominal magnetic resonance imaging (MRI) in the 2 years prior to diagnosis were identified from SEER-Medicare (2008-2015). Three surveillance cohorts were created: diagnostic (imaging only within 3 months prior), intermittent (imaging only once within 2 years prior, excluding diagnostic), and routine (at least two imaging encounters within 2 years prior, excluding diagnostic). Multivariable logistic regression was used to predict early-stage diagnosis (stage I-II), and 5-year survival was evaluated using the accelerated failure time method with Weibull distribution. RESULTS Among 2261 eligible patients, 26.1% were classified as diagnostic, 15.8% as intermittent, and 58.1% as routine surveillance. The median age was 74 years (IQR 70-78 years). The majority of patients had a preexisting cirrhosis diagnosis (81.5%). Routine and intermittent, compared with diagnostic, surveillance were predictive of early-stage disease (routine: OR 2.05, 95% CI 1.64-2.56; intermittent: OR 1.43, 95% CI 1.07-1.90). Patients who underwent routine surveillance had significantly lower risk of mortality (HR 0.84, 95% CI 0.75-0.94) compared with the diagnostic group. CONCLUSIONS A large proportion of screening-eligible patients do not undergo routine surveillance, which is associated with late-stage diagnosis and higher risk of mortality. These findings demonstrate the impact of timely and consistent healthcare access and can guide interventions for promoting surveillance among these patients.
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Affiliation(s)
- Marianna V Papageorge
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA
| | - Susanna W L de Geus
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA
| | - Alison P Woods
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA.,Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sing Chau Ng
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA
| | | | - David McAneny
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA
| | - Jennifer F Tseng
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA
| | - Kelly M Kenzik
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA
| | - Teviah E Sachs
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA.
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21
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Duberg A, Lybeck C, Fält A, Montgomery S, Aleman S. Reply. Hepatol Commun 2022; 6:3593-3594. [PMID: 36017781 PMCID: PMC9701469 DOI: 10.1002/hep4.2083] [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: 07/06/2022] [Accepted: 08/01/2022] [Indexed: 12/14/2022] Open
Affiliation(s)
- Ann‐Sofi Duberg
- Department of Infectious Diseases, School of Medical Sciences, Faculty of Medicine and HealthÖrebro UniversityOrebroSweden
| | - Charlotte Lybeck
- Department of Infectious Diseases, School of Medical Sciences, Faculty of Medicine and HealthÖrebro UniversityOrebroSweden
| | - Anna Fält
- Clinical Epidemiology and Biostatistics, School of Medical SciencesÖrebro UniversityOrebroSweden
| | - Scott Montgomery
- Clinical Epidemiology and Biostatistics, School of Medical SciencesÖrebro UniversityOrebroSweden,Clinical Epidemiology DivisionKarolinska InstitutetStockholmSweden,Department of Epidemiology and Public HealthUniversity College LondonLondonUnited Kingdom
| | - Soo Aleman
- Department of Infectious DiseasesKarolinska University HospitalStockholmSweden,Department of Medicine HuddingeKarolinska InstitutetStockholmSweden
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22
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Zunica ERM, Heintz EC, Axelrod CL, Kirwan JP. Obesity Management in the Primary Prevention of Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:cancers14164051. [PMID: 36011044 PMCID: PMC9406638 DOI: 10.3390/cancers14164051] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 08/16/2022] [Accepted: 08/20/2022] [Indexed: 11/16/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent primary hepatic malignancy and a leading cause of cancer-related death globally. HCC is associated with an indolent clinical presentation, resulting in frequent advanced stage diagnoses where surgical resection or transplant therapies are not an option and medical therapies are largely ineffective at improving survival. As such, there is a critical need to identify and enhance primary prevention strategies to mitigate HCC-related morbidity and mortality. Obesity is an independent risk factor for the onset and progression of HCC. Furthermore, obesity is a leading cause of nonalcoholic steatohepatitis (NASH), the fasting growing etiological factor of HCC. Herein, we review evolving clinical and mechanistic associations between obesity and hepatocarcinogenesis with an emphasis on the therapeutic efficacy of prevailing lifestyle/behavioral, medical, and surgical treatment strategies for weight reduction and NASH reversal.
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Affiliation(s)
| | | | | | - John P. Kirwan
- Correspondence: (C.L.A.); (J.P.K.); Tel.: +1-225-763-2513 (J.P.K.)
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23
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Walker PF, Settgast AM, DeSilva MB. Cancer Screening in Refugees and Immigrants: A Global Perspective. Am J Trop Med Hyg 2022; 106:tpmd210692. [PMID: 35533696 PMCID: PMC9209943 DOI: 10.4269/ajtmh.21-0692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 02/09/2022] [Indexed: 12/24/2022] Open
Abstract
Clinicians in the United States are trained to screen for cancer based on patient age, gender, family history, and environmental risk factors such as smoking. These cancers generally include, breast, cervical, colon, lung, and prostate cancers. We know that refugees and other immigrants to the United States experience dramatic disparities in cancer screening. Additionally, many immigrants experience elevated risks from infection-attributable cancers due to their country or region of origin. U.S.- based clinicians may not routinely consider these unique risk factors. Although this article focuses on refugees, it is also intended to guide clinicians caring for other foreign-born immigrant groups living in the United States (hereafter referred to as "immigrants"). The document contains two sections: 1) special considerations for U.S. Preventive Services Task Force guidelines cancer screening recommendations in immigrants and 2) cancer risks and screening recommendation unique to certain immigrant groups. Disparities in cancer screening and prevalence are often greater for specific immigrant groups than for broader racial or ethnic groups (e.g., Black, Asian, Hispanic) into which they may fit. Disaggregation of data by language or country of origin is useful to identify such disparities and to design intervention opportunities within specific communities that are culturally distinct and/or who have different environmental exposures. Unique cancer risks and disparities in screening support a nuanced approach to cancer screening for immigrant and refugee populations, which is the focus of this narrative review.
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Affiliation(s)
- Patricia F. Walker
- HealthPartners Institute, Bloomington, Minnesota
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota
- HealthPartners Travel and Tropical Medicine Center, St. Paul, Minnesota
| | - Ann M. Settgast
- HealthPartners Institute, Bloomington, Minnesota
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota
- HealthPartners Center for International Health, St. Paul, Minnesota
- HealthPartners Travel and Tropical Medicine Center, St. Paul, Minnesota
| | - Malini B. DeSilva
- HealthPartners Institute, Bloomington, Minnesota
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota
- HealthPartners Travel and Tropical Medicine Center, St. Paul, Minnesota
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24
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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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25
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Ezzat R, Eltabbakh M, El Kassas M. Unique situation of hepatocellular carcinoma in Egypt: A review of epidemiology and control measures. World J Gastrointest Oncol 2021; 13:1919-1938. [PMID: 35070033 PMCID: PMC8713321 DOI: 10.4251/wjgo.v13.i12.1919] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/17/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common primary malignancy worldwide, and the third most common cause of death among cancers worldwide. HCC occurs in several pre-existing conditions, including hepatitis C, hepatitis B virus, and non-alcoholic cirrhosis. Egypt used to be the country with the heaviest hepatitis C virus (HCV) burden. The relationship between HCV and HCC is an important research area. In Egypt, HCC is a significant public health problem. A possible cause for the increasing rates of detection of HCC in Egypt is the mass screening program that was carried by the government for detecting and treating HCV. A multidisciplinary approach is now widely applied to HCC management in health centers all over Egypt. Different treatment modalities are available in Egypt, with success rates comparable to global rates. The Egyptian health authorities have made the elimination of HCV from Egypt a special priority, and this approach should lead to a decrease in number of HCC cases in the near future. In this article we review the current situation of HCC in Egypt, including epidemiological aspects, relevant risk factors for HCC development, strategies, and efforts established by health authorities for the screening and prevention of both HCV and HCC in Egypt. We highlight the different modalities for HCC treatment.
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Affiliation(s)
- Reem Ezzat
- Internal Medicine Department, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Mohamed Eltabbakh
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
| | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo 11795, Cairo, Egypt
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26
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Jayakrishnan T, Aulakh S, Baksh M, Nguyen K, Ailawadhi M, Samreen A, Parrondo R, Sher T, Roy V, Manochakian R, Paulus A, Chanan-Khan A, Ailawadhi S. Landmark Cancer Clinical Trials and Real-World Patient Populations: Examining Race and Age Reporting. Cancers (Basel) 2021; 13:5770. [PMID: 34830924 PMCID: PMC8616211 DOI: 10.3390/cancers13225770] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 10/25/2021] [Accepted: 11/12/2021] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Concern exists that the clinical trial populations differ from respective cancer populations in terms of their age distribution affecting the generalizability of the results, especially in underrepresented minorities. We hypothesized that the clinical trials that do not report race are likely to suffer from a higher degree of age disparity. METHODS Food and Drug Administration (FDA) drug approvals from July 2007 to June 2019 were reviewed to identify oncology approvals, and trials with age details were selected. The outcomes studied were the weighted mean difference in age between the clinical trial population and real-world population for various cancers, the prevalence of race reporting and association of age and race reporting with each other. RESULTS Of the 261 trials, race was reported in 223 (85.4%) of the trials, while 38 trials (14.6%) had no mention of race. Race reporting improved minimally over time: 29 (85.3%) in 2007-2010 vs. 49 (80.3%) in 2011-2014 vs. 145 (85.4%) during the period 2015-2019 (p-value = 0.41). Age discrepancy between the clinical trial population and the real-world population was higher for studies that did not report race (mean difference -8.8 years (95% CI -12.6 to -5.0 years)) vs. studies that did report it (mean difference -5.1 years, (95% CI -6.4 to -3.7 years), p-value = 0.04). CONCLUSION The study demonstrates that a significant number of clinical trials leading to cancer drug approvals suffer from racial and age disparity when compared to real-world populations, and that the two factors may be interrelated. We recommend continued efforts to recruit diverse populations.
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Affiliation(s)
- Thejus Jayakrishnan
- Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland, OH 44106, USA;
| | - Sonikpreet Aulakh
- Departments of Internal Medicine and Neurosciences, West Virginia University, Morgantown, WV 26506, USA;
| | - Mizba Baksh
- Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL 100151, USA; (M.B.); (M.A.); (A.S.); (R.P.); (T.S.); (V.R.); (R.M.); (A.C.-K.)
| | - Kianna Nguyen
- Mayo Clinic Alix School of Medicine, Rochester, MN 55905, USA;
| | - Meghna Ailawadhi
- Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL 100151, USA; (M.B.); (M.A.); (A.S.); (R.P.); (T.S.); (V.R.); (R.M.); (A.C.-K.)
| | - Ayesha Samreen
- Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL 100151, USA; (M.B.); (M.A.); (A.S.); (R.P.); (T.S.); (V.R.); (R.M.); (A.C.-K.)
| | - Ricardo Parrondo
- Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL 100151, USA; (M.B.); (M.A.); (A.S.); (R.P.); (T.S.); (V.R.); (R.M.); (A.C.-K.)
| | - Taimur Sher
- Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL 100151, USA; (M.B.); (M.A.); (A.S.); (R.P.); (T.S.); (V.R.); (R.M.); (A.C.-K.)
| | - Vivek Roy
- Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL 100151, USA; (M.B.); (M.A.); (A.S.); (R.P.); (T.S.); (V.R.); (R.M.); (A.C.-K.)
| | - Rami Manochakian
- Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL 100151, USA; (M.B.); (M.A.); (A.S.); (R.P.); (T.S.); (V.R.); (R.M.); (A.C.-K.)
| | - Aneel Paulus
- Division of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA;
| | - Asher Chanan-Khan
- Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL 100151, USA; (M.B.); (M.A.); (A.S.); (R.P.); (T.S.); (V.R.); (R.M.); (A.C.-K.)
- Division of Hematology-Oncology, St. Vincent’s Cancer Center, Jacksonville, FL 32224, USA
| | - Sikander Ailawadhi
- Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL 100151, USA; (M.B.); (M.A.); (A.S.); (R.P.); (T.S.); (V.R.); (R.M.); (A.C.-K.)
- Division of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA;
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27
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Konyn P, Ahmed A, Kim D. Current epidemiology in hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2021; 15:1295-1307. [PMID: 34624198 DOI: 10.1080/17474124.2021.1991792] [Citation(s) in RCA: 154] [Impact Index Per Article: 38.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 10/07/2021] [Indexed: 01/27/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third-leading cause of cancer-related mortality in the world. AREAS COVERED This review will discuss risk factors, demographic differences, global trends, and the economic burden of HCC. Viral hepatitis, particularly hepatitis B virus (HBV) infection, is the most common underlying liver disease leading to HCC in those with cirrhosis. Other important risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, metabolic syndrome, etc. With the introduction of direct-acting antiviral agents for hepatitis C virus infection, routine vaccination against HBV, and increasing support for robust public screening programs, the incidence rates for HCC due to viral hepatitis is falling in many countries. Meanwhile, the prevalence of obesity and metabolic syndrome are on the rise, as is NAFLD-related HCC incidence. Asia and Africa have the highest incidence rates of HCC. In multiethnic countries, racial and ethnic minorities experience disparities in HCC incidence as well as mortality, representing an essential area for improvement in terms of healthcare inequity. EXPERT OPINION Interventions to minimize the global burden of HCC aim to reduce rates of the most common risk factors and implement effective treatment of underlying etiology and comprehensive screening programs for HCC.
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Affiliation(s)
- Peter Konyn
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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28
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Kronenfeld JP, Goel N. An Analysis of Individual and Contextual-Level Disparities in Screening, Treatment, and Outcomes for Hepatocellular Carcinoma. J Hepatocell Carcinoma 2021; 8:1209-1219. [PMID: 34611524 PMCID: PMC8487287 DOI: 10.2147/jhc.s284430] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 09/02/2021] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and affects patients of all genders, races, ethnicities, and socioeconomic status. While the causes of HCC are numerous, the primary etiology is cirrhosis from alcohol and non-alcoholic fatty liver disease in the United States and from infectious agents such as Hepatitis B and Hepatitis C in the developing world. In patients at-risk for developing HCC, screening is recommended with ultrasound imaging and alpha fetoprotein laboratory tests. In socioeconomically vulnerable patients, however, individual-level barriers (eg, insurance status) and contextual-level disparities (eg, health facilities) may not be readily available, thus limiting screening. Additional challenges faced by racial/ethnic minorities can further challenge the spectrum of HCC care and lead to inadequate screening, delayed diagnosis, and unequal access to treatment. Efforts to improve these multilevel factors that lead to screening and treatment disparities are critical to overcoming challenges. Providing health insurance to those without access, improving societal challenges that confine patients to a lower socioeconomic status, and reducing challenges to seeking healthcare can decrease the morbidity and mortality of these patients. Additionally, engaging with communities and allowing them to collaborate in their own healthcare can also help to attenuate these inequities. Through collaborative multidisciplinary change, we can make progress in tackling disparities in vulnerable populations to achieve health equity
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Affiliation(s)
- Joshua P Kronenfeld
- Division of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Neha Goel
- Division of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
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29
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Kedar Mukthinuthalapati VVP, Sewram V, Ndlovu N, Kimani S, Abdelaziz AO, Chiao EY, Abou-Alfa GK. Hepatocellular Carcinoma in Sub-Saharan Africa. JCO Glob Oncol 2021; 7:756-766. [PMID: 34043413 PMCID: PMC8457845 DOI: 10.1200/go.20.00425] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
More than 80% of global hepatocellular carcinoma (HCC) patients are estimated to occur in sub-Saharan Africa (SSA) and Eastern Asia. The most common risk factor of HCC in SSA is chronic hepatitis B virus (HBV) infection, with the incidence highest in West Africa. HBV is highly endemic in SSA and is perpetuated by incomplete adherence to birth dose immunization, lack of longitudinal follow-up care, and impaired access to antiviral therapy. HBV may directly cause HCC through somatic genetic alterations or indirectly through altered liver function and liver cirrhosis. Other risk factors of HCC in SSA include aflatoxins and, to a lesser extent, African iron overload. HIV plus HBV co-infection increases the risk of developing HCC and is increasingly becoming more common because of improving the survival of patients with HIV infection. Compared with the rest of the world, patients with HCC in SSA have the lowest survival. This is partly due to the late presentation of HCC with advanced symptomatic disease as a result of underdeveloped surveillance practices. Moreover, access to care and resource limitations further limit outcomes for the patients who receive a diagnosis in SSA. There is a need for multipronged strategies to decrease the incidence of HCC and improve its outcomes in SSA.
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Affiliation(s)
| | - Vikash Sewram
- Department of Global Health, Faculty of Medicine and Health Sciences, African Cancer Institute, Stellenbosch University, Cape Town, South Africa
| | - Ntokozo Ndlovu
- University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
| | - Stephen Kimani
- The University of North Carolina at Chapel Hill, Chapel Hill, NC
| | | | | | - Ghassan K Abou-Alfa
- Memorial Sloan Kettering Cancer Center, New York, NY.,Weill Medical College at Cornell University, New York, NY
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Taye BW, Clark PJ, Hartel G, Powell EE, Valery PC. Remoteness of residence predicts tumor stage, receipt of treatment, and mortality in patients with hepatocellular carcinoma. JGH OPEN 2021; 5:754-762. [PMID: 34263069 PMCID: PMC8264246 DOI: 10.1002/jgh3.12580] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 05/14/2021] [Accepted: 05/18/2021] [Indexed: 12/26/2022]
Abstract
Background and Aim Surveillance and early detection and curative treatment of hepatocellular carcinoma (HCC) are the mainstay of improving survival for patients, but there are several barriers to achieving this goal. We reported the impact of remoteness of residence on receipt of treatment, tumor stage, and survival in patients with HCC in Queensland. Methods We conducted a retrospective cohort study of 1651 HCC patients (147 migrants) from 1 January 2007 to 31 December 2016. We used Wilcoxon rank‐sum test to compare the median age at the time of diagnosis and Bayesian Weibull accelerated failure time regression to identify independent predictors of time to death. Results The median survival time after HCC diagnosis was 9.0 months (interquartile range 2.0–24.0). Metropolitan residence (P = 0.02), non‐English language (P < 0.001), foreign country of origin (P < 0.001), and HBV etiology (P < 0.001) were significantly associated with receiving surgical resection for HCC treatment. The strongest predictors of time to death were undifferentiated tumor at presentation (time ratio [TR] = 0.30, 95% credible interval (CrI) 0.23–0.39), age ≥70 years (TR = 0.42, 95% CrI 0.34–0.53), living in remote areas (TR = 0.67, 95% CrI 0.55–0.80), and presence of ≥1 comorbidity (TR = 0.69 95% CrI 0.54–0.90). All the other covariates adjusted, including country of birth (TR = 0.76, 95% CrI 0.49–1.06), did not predict survival time. Conclusions Patients living in rural and remote areas had late stage clinical presentation and poor survival. Remoteness of residence may limit access to HCC surveillance in at‐risk patients such as those with cirrhosis, and timely curative treatment to improve survival in these patients.
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Affiliation(s)
- Belaynew W Taye
- Faculty of Medicine University of Queensland Brisbane Queensland Australia.,Cancer and Chronic Disease Epidemiology Group QIMR Berghofer Medical Research Institute Brisbane Queensland Australia.,Mater Research Institute University of Queensland Brisbane Queensland Australia
| | - Paul J Clark
- Faculty of Medicine University of Queensland Brisbane Queensland Australia.,Mater Research Institute University of Queensland Brisbane Queensland Australia.,Department of Gastroenterology and Hepatology Mater Hospitals Brisbane Brisbane Queensland Australia.,Department of Gastroenterology and Hepatology Princess Alexandra Hospital Brisbane Queensland Australia
| | - Gunter Hartel
- Cancer and Chronic Disease Epidemiology Group QIMR Berghofer Medical Research Institute Brisbane Queensland Australia
| | - Elizabeth E Powell
- Department of Gastroenterology and Hepatology Princess Alexandra Hospital Brisbane Queensland Australia
| | - Patricia C Valery
- Faculty of Medicine University of Queensland Brisbane Queensland Australia.,Cancer and Chronic Disease Epidemiology Group QIMR Berghofer Medical Research Institute Brisbane Queensland Australia
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31
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Lok AS, Perrillo R, Lalama CM, Fried MW, Belle SH, Ghany MG, Khalili M, Fontana RJ, Sterling RK, Terrault N, Feld JJ, Di Bisceglie AM, Lau DT, Hassan M, Janssen HL, Roberts LR, Lisker‐Melman M, Wong DK, Juan J, Yim C, Patel K, Lee WM, Murakami CS, Do S, Han SB, Tran TT, Cooper SL, Tsai N, Younoszai B, Muir A, Evon D, Darling JM, Carithers RC, Kowdley KV, Wang CC, Luketic VA, Jake Liang T, Hoofnagle JH, Doo E, Chang K, Park J, Wahed A, King WC, Kleiner D. Low Incidence of Adverse Outcomes in Adults With Chronic Hepatitis B Virus Infection in the Era of Antiviral Therapy. Hepatology 2021; 73:2124-2140. [PMID: 32936969 PMCID: PMC8546406 DOI: 10.1002/hep.31554] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 07/28/2020] [Accepted: 08/19/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Outcomes of persons with chronic hepatitis B virus (HBV) infection in the era of antiviral therapy (AVT) are not well characterized. We determined the incidence and factors associated with clinical outcomes in a multiethnic, North American cohort of adults with chronic HBV infection, who were not on AVT at enrollment. APPROACH AND RESULTS Adults with chronic HBV infection, not receiving AVT, and without a history of decompensation, HCC, or liver transplantation (LT), were prospectively followed. Participants with known human immunodeficiency virus (HIV), hepatitis C virus, or hepatitis D virus (HDV) coinfection were excluded. During follow-up, treatment could be initiated per standard of care. Clinical outcomes included: incident cirrhosis, decompensation, HCC, OLT, and HBV-related death. Among 1,418 participants analyzed, 51.5% were women, median age was 41.1 years, 75% were Asian, 10% White, 13% Black, 24% HBeAg(+), and 1.5% cirrhosis at baseline. During the study, 274 started treatment, 83 had an alanine aminotransferase flare, 118 of 330 initially HBeAg(+) became HBeAg(-), and 90 of 1,329 became HBsAg(-). After 6,641 person-years follow-up, 8 participants (4 of 21 with baseline cirrhosis) had 12 clinical outcomes (2 decompensation, 5 HCC, 2 OLT, and 3 HBV-related deaths) and 19 of 1,397 had incident cirrhosis. Twenty-one of 26 participants had first outcome before treatment, none had become HBsAg(-), whereas 5/9 HBeAg(+) had become HBeAg(-) at time of first outcome. Cumulative percentage of clinical outcomes was 16% at year 4 in participants with baseline cirrhosis and 2% (including incident cirrhosis) at year 7 in those without. CONCLUSIONS Incidence of adverse outcomes was low in this closely monitored, large cohort of North American adults with predominantly inactive, chronic HBV without cirrhosis. Our data highlight the benefits of HBsAg loss and the importance of early diagnosis and treatment to prevent cirrhosis and other complications of chronic HBV infection.
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Affiliation(s)
- Anna S. Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Robert Perrillo
- Hepatology Division, Baylor Scott and White Medical Center, Dallas, TX
| | | | - Michael W. Fried
- UNC Liver Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Steven H. Belle
- Epidemiology and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA
| | | | - Mandana Khalili
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, CA
| | - Robert J. Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Richard K. Sterling
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA
| | - Norah Terrault
- Division of Gastrointestinal and Liver Diseases, Keck Medicine of University of Southern California, Los Angeles, CA
| | - Jordan J. Feld
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Adrian M. Di Bisceglie
- Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO
| | - Daryl T.Y. Lau
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
| | - Mohamed Hassan
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolois, MN
| | - Harry L.A. Janssen
- Toronto Centre for Liver Disease, University of Toronto, Toronto, ON, Canada
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32
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Damiris K, Abbad H, Pyrsopoulos N. Cellular based treatment modalities for unresectable hepatocellular carcinoma. World J Clin Oncol 2021; 12:290-308. [PMID: 34131562 PMCID: PMC8173328 DOI: 10.5306/wjco.v12.i5.290] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/19/2021] [Accepted: 04/28/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is unfortunately associated with an overall poor prognosis and high mortality. Early and intermediate stages of HCC allow for treatment with surgical resection, ablation and even liver transplantation, however disease progression warrants conventional systemic therapy. For years treatment options were limited to molecular-targeting medications, of which sorafenib remains the standard of care. The recent development and success of immune checkpoint inhibitors has proven to be a breakthrough in the treatment of HCC, but there is an urgent need for the development of further novel therapeutic treatments that prolong overall survival and minimize recurrence. Current investigation is focused on adoptive cell therapy including chimeric antigen receptor-T cells (CAR-T cells), T cell receptor (TCR) engineered T cells, dendritic cells, natural killer cells, and tumor infiltrating lymphocyte cells, which have shown remarkable success in the treatment of hematological and solid tumor malignancies. In this review we briefly introduce readers to the currently approved systemic treatment options and present clinical and experimental evidence of HCC immunotherapeutic treatments that will hopefully one day allow for revolutionary change in the treatment modalities used for unresectable HCC. We also provide an up-to-date compilation of ongoing clinical trials investigating CAR-T cells, TCR engineered T cells, cancer vaccines and oncolytic viruses, while discussing strategies that can help overcome commonly faced challenges when utilizing cellular based treatments.
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Affiliation(s)
- Konstantinos Damiris
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Hamza Abbad
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Department of Medicine, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
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33
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Kapacee ZA, McNamara MG, de Liguori Carino N, Lamarca A, Valle JW, Hubner RA. Systemic therapies in advanced hepatocellular carcinoma: How do older patients fare? Eur J Surg Oncol 2021; 47:583-590. [DOI: 10.1016/j.ejso.2020.03.210] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 03/19/2020] [Indexed: 01/15/2023] Open
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34
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Cargill Z, Brown SE, Dusheiko G, Agarwal K. Risk stratification in chronic hepatitis B patients for hepatocellular carcinoma surveillance: management in migrant sub-Saharan African populations. Gut 2021; 70:629-630. [PMID: 32606207 DOI: 10.1136/gutjnl-2020-322181] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 06/15/2020] [Accepted: 06/15/2020] [Indexed: 01/22/2023]
Affiliation(s)
- Zillah Cargill
- Institute of Liver Studies, King's College Hospital Liver Unit, London, UK
| | - Sarah E Brown
- Institute of Liver Studies, King's College Hospital Liver Unit, London, UK
| | - Geoff Dusheiko
- Institute of Liver Studies, King's College Hospital Liver Unit, London, UK.,UCL Division of Medicine, London, UK
| | - Kosh Agarwal
- Institute of Liver Studies, King's College Hospital Liver Unit, London, UK
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35
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Arora SP, Liposits G, Caird S, Dunne RF, Moffat GT, Okonji D, Rodriquenz MG, Dua D, Dotan E. Hepatocellular carcinoma in older adults: A comprehensive review by Young International Society of Geriatric Oncology. J Geriatr Oncol 2019; 11:557-565. [PMID: 31704038 DOI: 10.1016/j.jgo.2019.10.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Revised: 09/12/2019] [Accepted: 10/03/2019] [Indexed: 02/08/2023]
Abstract
Given the prevalence and the rising incidence of hepatocellular carcinoma (HCC) in older adults worldwide, there is an urgent need to improve our understanding of the implications of treatment modalities in this population. The care of older patients with HCC is challenging due to the lack of evidence-based recommendations in this population. The current treatment approach for older patients relies on extrapolation of data from clinical trials conducted mostly in younger patients or fit older adults. Further, in the last few years, the arsenal of systemic treatments has increased with currently seven FDA-approved therapies available for patients with advanced HCC. Therefore, understanding how to apply current data to this unique and diverse patient population is necessary. This review will aim to shed light on the approach to older adults with HCC through an assessment of available data in the literature.
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Affiliation(s)
- Sukeshi Patel Arora
- Mays Cancer Center, University of Texas Health San Antonio, Leader in Gastrointestinal Malignancies, 7979 Wurzbach Rd, 78229 San Antonio, TX, USA.
| | | | - Susan Caird
- Gold Coast University Hospital, Southport, Australia, Griffith University, School of Medicine, Australia
| | - Richard F Dunne
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA
| | | | - David Okonji
- Wellington Blood and Cancer Centre, Wellington Regional Hospital, Wellington, New Zealand
| | | | | | - Efrat Dotan
- Fox Chase Cancer Center, Philadelphia, PA, USA
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36
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Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 2019; 16:589-604. [PMID: 31439937 PMCID: PMC6813818 DOI: 10.1038/s41575-019-0186-y] [Citation(s) in RCA: 2792] [Impact Index Per Article: 465.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/04/2019] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Risk factors for HCC include chronic hepatitis B and hepatitis C, alcohol addiction, metabolic liver disease (particularly nonalcoholic fatty liver disease) and exposure to dietary toxins such as aflatoxins and aristolochic acid. All these risk factors are potentially preventable, highlighting the considerable potential of risk prevention for decreasing the global burden of HCC. HCC surveillance and early detection increase the chance of potentially curative treatment; however, HCC surveillance is substantially underutilized, even in countries with sufficient medical resources. Early-stage HCC can be treated curatively by local ablation, surgical resection or liver transplantation. Treatment selection depends on tumour characteristics, the severity of underlying liver dysfunction, age, other medical comorbidities, and available medical resources and local expertise. Catheter-based locoregional treatment is used in patients with intermediate-stage cancer. Kinase and immune checkpoint inhibitors have been shown to be effective treatment options in patients with advanced-stage HCC. Together, rational deployment of prevention, attainment of global goals for viral hepatitis eradication, and improvements in HCC surveillance and therapy hold promise for achieving a substantial reduction in the worldwide HCC burden within the next few decades.
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Affiliation(s)
- Ju Dong Yang
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Pierre Hainaut
- Tumor Molecular Biology and Biomarkers Group, Institute for Advanced Biosciences, Inserm U 1209 CNRS UMR5309, Université Grenoble Alpes, Grenoble, France
| | - Gregory J Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Amina Amadou
- Tumor Molecular Biology and Biomarkers Group, Institute for Advanced Biosciences, Inserm U 1209 CNRS UMR5309, Université Grenoble Alpes, Grenoble, France
| | - Amelie Plymoth
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
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37
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Liu S, Du Y, Ma H, Liang Q, Zhu X, Tian J. Preclinical comparison of regorafenib and sorafenib efficacy for hepatocellular carcinoma using multimodality molecular imaging. Cancer Lett 2019; 453:74-83. [PMID: 30928380 DOI: 10.1016/j.canlet.2019.03.037] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2018] [Revised: 01/31/2019] [Accepted: 03/22/2019] [Indexed: 12/19/2022]
Abstract
Sorafenib has been used as a clinical targeted therapy for hepatocellular carcinoma (HCC) for more than a decade. In 2017, regorafenib was approved for HCC treatment and has since been reported to prolong the survival of advanced HCC patients after treatment failure with sorafenib. However, there has been no direct systematic comparison of the therapeutic effects of regorafenib and sorafenib against HCC. In this study, we comprehensively compared the therapeutic effects of sorafenib and regorafenib against HCC in vitro and in vivo using multimodality molecular imaging, which can show molecular and cellular differences at early stages. The side effects of sorafenib and regorafenib were also systematically evaluated. The data showed that compared with sorafenib treatment, regorafenib exerted stronger antitumor and antiangiogenic effects and significantly increased the survival rate of HCC mice. Sorafenib but not regorafenib treatment caused body weight loss and liver and kidney dysfunction, while regorafenib but not sorafenib treatment caused hypertension. Our study may provide an experimental basis for the guidance of clinical HCC targeted treatment with regorafenib and sorafenib.
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Affiliation(s)
- Shengnan Liu
- Sino-Dutch Biomedical and Information Engineering School, Northeastern University, Shenyang, Liaoning, China; CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
| | - Yang Du
- CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100080, China
| | - He Ma
- Sino-Dutch Biomedical and Information Engineering School, Northeastern University, Shenyang, Liaoning, China.
| | - Qian Liang
- CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100080, China
| | - Xu Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Therapy, Peking University School of Oncology, NO.52 Fucheng Road, Haidian District, Beijing, 100142, China.
| | - Jie Tian
- CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100080, China; Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine, Beihang University, Beijing, 100191, China; Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China.
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38
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Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. J Hepatol 2019; 70:151-171. [PMID: 30266282 DOI: 10.1016/j.jhep.2018.09.014] [Citation(s) in RCA: 2221] [Impact Index Per Article: 370.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 09/10/2018] [Accepted: 09/17/2018] [Indexed: 02/06/2023]
Abstract
Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma. Cirrhosis is currently the 11th most common cause of death globally and liver cancer is the 16th leading cause of death; combined, they account for 3.5% of all deaths worldwide. Cirrhosis is within the top 20 causes of disability-adjusted life years and years of life lost, accounting for 1.6% and 2.1% of the worldwide burden. About 2 billion people consume alcohol worldwide and upwards of 75 million are diagnosed with alcohol-use disorders and are at risk of alcohol-associated liver disease. Approximately 2 billion adults are obese or overweight and over 400 million have diabetes; both of which are risk factors for non-alcoholic fatty liver disease and hepatocellular carcinoma. The global prevalence of viral hepatitis remains high, while drug-induced liver injury continues to increase as a major cause of acute hepatitis. Liver transplantation is the second most common solid organ transplantation, yet less than 10% of global transplantation needs are met at current rates. Though these numbers are sobering, they highlight an important opportunity to improve public health given that most causes of liver diseases are preventable.
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Affiliation(s)
| | | | - John Eaton
- Mayo Clinic College of Medicine, Rochester, MN, USA
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39
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Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma's (HCC) epidemiology and prognosis differs among regions across the globe, largely because of environmental factors and underlying liver disease. Little is known about the changes led by immigration and the effect on HCC outcome. We aimed to understand the effect of immigration on HCC. PATIENTS AND METHODS A retrospective cohort study of patients diagnosed with HCC was carried out in a tertiary center in the USA between 2005 and 2016. We characterized individuals as US born or having immigrated there after being born elsewhere. Variables related to clinical presentation, surveillance, therapy, and survival were evaluated. RESULTS A total of 232 HCC cases were included, 169 US born (73%) and 63 immigrants (27%). Both groups were diagnosed with HCC at similar ages (60 vs. 62 years, P=0.13). Hepatitis C was the most common underlying liver disease in the US-born population compared with the immigrant population (83 vs. 52%, P<0.001), whereas hepatitis B was more common in the latter (4 vs. 29%, P<0.001). Interestingly, hepatitis B virus-related HCC was diagnosed at similar ages in US-born and immigrant individuals (59 and 57 years). At the time of diagnosis, both populations had similar tumor sizes, rates of metastasis, and diagnosis during surveillance. One-year survival was similar in both groups (65 vs. 63%). CONCLUSION Immigrants that develop HCC have different underlying liver disease than those born in the USA, but similar HCC characteristics and outcomes, even when including hepatitis B virus-related HCCs. Our study, albeit small, suggests that changes in the environment by immigration leads to clinical adaptation of HCC.
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40
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Kovacovicova K, Skolnaja M, Heinmaa M, Mistrik M, Pata P, Pata I, Bartek J, Vinciguerra M. Senolytic Cocktail Dasatinib+Quercetin (D+Q) Does Not Enhance the Efficacy of Senescence-Inducing Chemotherapy in Liver Cancer. Front Oncol 2018; 8:459. [PMID: 30425964 PMCID: PMC6218402 DOI: 10.3389/fonc.2018.00459] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 10/01/2018] [Indexed: 12/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, which develops in the context of fibrosis and cirrhosis caused by chronic inflammation, in turn due to non-alcoholic fatty liver disease (NAFLD), alcohol consumption and/or hepatitis viral infection. An increased number of senescent cells are associated with age-related tissue degeneration during NAFLD-induced HCC, or during chemotherapeutic treatment. Senolytic agents target selectively senescent cells. A combination of the senolytic drugs dasatinib and quercetin (D+Q) reduced hepatic lipid accumulation and alleviated age-associated physical dysfunction in mice. However, whether D+Q can impact the treatment of HCC, at the end-stage of the NAFLD inflammatory spectrum, is unknown. Here, using two well-established HCC cell lines (HepG2, Huh-7), we demonstrate that the maximal cytostatic doses for D and/or Q (1 + 1 μM) lacked efficacy in removing doxorubicin-induced β-gal-positive senescent cells. Moreover, D+Q did not affect doxorubicin-dependent induction of flattened morphology, activation of p16, expression of SASP-associated genes or formation of γH2AX foci. We then investigated the antitumor efficacy of doxorubicin, D+Q, or the combination, in xenograft studies conducted with HCC cells inoculated in athymic nude mice. Doxorubicin reduced tumor growth by 30% compared to control mice, while D+Q was ineffective in synergizing with doxorubicin and in clearing doxorubicin-induced HCC senescent cells. Unexpectedly, D+Q alone appeared to have acute pro-tumorigenic effects in control mice. While our data need to be confirmed in animal models that fully recapitulate NAFLD, we demonstrate that these compounds are ineffective, alone or in synergy with senescence-inducing chemotherapy, against experimental HCC.
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Affiliation(s)
| | - Marianna Skolnaja
- Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia.,IVEX Lab, Tallinn, Estonia
| | - Mihkel Heinmaa
- Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia
| | - Martin Mistrik
- Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University, Olomouc, Czechia
| | - Pille Pata
- Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia.,IVEX Lab, Tallinn, Estonia
| | | | - Jiri Bartek
- Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University, Olomouc, Czechia.,Genome Integrity Unit, Danish Cancer Society Research Center, Copenhagen, Denmark.,Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Solna, Sweden
| | - Manlio Vinciguerra
- International Clinical Research Center (FNUSA-ICRC), Brno, Czechia.,Division of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
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41
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Kennedy K, Graham SM, Arora N, Shuhart MC, Kim HN. Hepatocellular carcinoma among US and non-US-born patients with chronic hepatitis B: Risk factors and age at diagnosis. PLoS One 2018; 13:e0204031. [PMID: 30252863 PMCID: PMC6155504 DOI: 10.1371/journal.pone.0204031] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 08/31/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Risk factors for hepatocellular carcinoma (HCC) have not been well characterized among African immigrants with chronic hepatitis B virus (HBV) infection. We conducted a case-control study to identify demographic and clinical factors associated with HCC among a diverse cohort of patients with chronic HBV infection seen in a large academic health setting. METHODS We identified a total of 278 patients with HCC and chronic HBV seen at two medical centers in a 14-year span from January 2002 to December 2015. These cases were age- and sex-matched in a 1:3 ratio with 823 non-cancer control subjects with chronic HBV. Conditional logistic regression was used to estimate the odds of HCC by race, with black race stratified by African-born status, after adjusting for diabetes, HIV or HCV coinfection, alcohol misuse and cirrhosis. RESULTS Of the 278 HCC cases, 67% were 60 years of age or older, 78% were male, 87% had cirrhosis and 72% were Asian. HIV infection was present in 6% of cases. Only 7% (19 of 278) of HCC cases were black, of whom 14 were African immigrants. The median age at HCC diagnosis was 44 years in Africans. Notably, nearly all (93%) of the African-born patients with HCC were diagnosed at an age younger than 60 years compared with 52% of Asian cases (P<0.001). The main factors independently associated with greater odds of HCC overall were Asian race (adjusted odds ratio [aOR] 3.3, 95% confidence interval [CI] 1.9-5.5) and cirrhosis (aOR 19.7, 95% CI 12.2-31.8). CONCLUSION African immigrants accounted for a small proportion of HBV-associated HCC cases overall compared with Asians but appeared to have greater likelihood of early-onset HCC. Optimal strategies for HCC prevention in these key subroups with chronic HBV warrant further study.
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Affiliation(s)
- Kaitlyn Kennedy
- Department of Global Health, School of Medicine, University of Washington, Seattle, Washington, United States of America
| | - Susan M. Graham
- Department of Global Health, School of Medicine, University of Washington, Seattle, Washington, United States of America
- Department of Medicine, Division of Allergy & Infectious Diseases, University of Washington, Seattle, Washington, United States of America
| | - Nayan Arora
- Department of Medicine, Divison of Nephrology, University of Washington, Seattle, Washington, United States of America
| | - Margaret C. Shuhart
- Department of Medicine, Division of Gastroenterology, University of Washington, Seattle, Washington, United States of America
| | - H. Nina Kim
- Department of Global Health, School of Medicine, University of Washington, Seattle, Washington, United States of America
- Department of Medicine, Division of Allergy & Infectious Diseases, University of Washington, Seattle, Washington, United States of America
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VoPham T, Weaver MD, Vetter C, Hart JE, Tamimi RM, Laden F, Bertrand KA. Circadian Misalignment and Hepatocellular Carcinoma Incidence in the United States. Cancer Epidemiol Biomarkers Prev 2018; 27:719-727. [PMID: 29636342 DOI: 10.1158/1055-9965.epi-17-1052] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Revised: 01/31/2018] [Accepted: 04/05/2018] [Indexed: 12/29/2022] Open
Abstract
Background: Circadian misalignment may increase the risk of developing hepatocellular carcinoma (HCC). The aim of this study was to examine the association between distance from time zone meridian, a proxy for circadian misalignment, and HCC risk in the United States adjusting for known HCC risk factors.Methods: Surveillance, Epidemiology, and End Results (SEER) provided information on 56,347 HCC cases diagnosed between 2000 and 2014 from 16 population-based cancer registries in the United States. Distance from time zone meridian was estimated using the location of each SEER county's Center of Population in a geographic information system. Poisson regression with robust variance estimation was used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between distance from time zone meridian and HCC risk adjusting for individual-level age at diagnosis, sex, race/ethnicity, year of diagnosis, SEER registry, and county-level prevalence of health conditions, lifestyle factors, shift work occupation, socioeconomic status, and demographic and environmental factors.Results: A 5-degree increase in longitude moving east to west within a time zone was associated with a statistically significant increased risk for HCC (IRR, 1.07; 95% CI, 1.01-1.14, P = 0.03). A statistically significant positive association was observed among those <65 years old, while no association was observed among individuals ≥65 years old (Pfor interaction < 0.01).Conclusions: Circadian misalignment from residing in the western region of a time zone may impact hepatocarcinogenesis.Impact: Circadian misalignment may be an independent risk factor for HCC. Cancer Epidemiol Biomarkers Prev; 27(7); 719-27. ©2018 AACR.
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Affiliation(s)
- Trang VoPham
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. .,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Matthew D Weaver
- Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts.,Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts
| | - Céline Vetter
- Department of Integrative Physiology, University of Colorado, Boulder, Boulder, Colorado.,Broad Institute of Harvard and MIT, Cambridge, Massachusetts
| | - Jaime E Hart
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.,Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Rulla M Tamimi
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Francine Laden
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.,Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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Early age at diagnosis of hepatocellular carcinoma in sub-Saharan Africa – Authors' reply. Lancet Gastroenterol Hepatol 2017; 2:394. [DOI: 10.1016/s2468-1253(17)30107-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Accepted: 03/28/2017] [Indexed: 11/18/2022]
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Medhanie GA, Fedewa SA, Adissu H, DeSantis CE, Siegel RL, Jemal A. Cancer incidence profile in sub-Saharan African-born blacks in the United States: Similarities and differences with US-born non-Hispanic blacks. Cancer 2017; 123:3116-3124. [PMID: 28407201 DOI: 10.1002/cncr.30701] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Revised: 02/28/2017] [Accepted: 03/07/2017] [Indexed: 01/22/2023]
Abstract
BACKGROUND Sub-Saharan African-born blacks (ABs) are one of the fastest-growing populations in the United States. However, to the authors' knowledge, data regarding the cancer burden in this group are lacking, which would inform targeted cancer prevention and control. METHODS The authors calculated age-standardized proportional incidence ratios (PIRs) comparing the frequency of the top 15 cancers in ABs with that of US-born non-Hispanic blacks (USBs) by sex and region of birth using incidence data for 2000 through 2012 from the Surveillance, Epidemiology, and End Results (SEER 17) program. RESULTS Compared with USBs, ABs had significantly higher PIRs of infection-related cancers (liver, stomach, and Kaposi sarcoma), blood cancers (leukemia and non-Hodgkin lymphoma), prostate cancer, and thyroid cancers (females only). For example, the PIR for Kaposi sarcoma in AB versus USB women was 12.06 (95% confidence interval [95% CI], 5.23-18.90). In contrast, ABs had lower PIRs for smoking-related and colorectal cancers (eg, for lung cancer among men, the PIR was 0.30 [95% CI, 0.27-0.34]). Furthermore, cancer occurrence in ABs versus USBs varied by region of birth. For example, the higher PIRs for liver cancer noted among male ABs (PIR, 3.57; 95% CI, 1.79-5.35) and for thyroid cancer in female ABs (PIR, 3.03; 95% CI, 2.03-4.02) were confined to Eastern African-born blacks, whereas the higher PIR for prostate cancer (PIR, 1.90; 95% CI, 1.78, 2.02) was confined to Western African-born blacks. CONCLUSIONS The cancer incidence profile of ABs is different from that of USBs and varies by region of birth, suggesting differences in environmental, cultural, social, and genetic factors. The findings of the current study could stimulate etiologic research and help to inform targeted interventions. Cancer 2017;123:3116-24. © 2017 American Cancer Society.
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Affiliation(s)
- Genet A Medhanie
- Food Animal and Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, Ohio
| | - Stacey A Fedewa
- Surveillance and Health Services Research Program, American Cancer Society, Atlanta, Georgia
| | | | - Carol E DeSantis
- Surveillance and Health Services Research Program, American Cancer Society, Atlanta, Georgia
| | - Rebecca L Siegel
- Surveillance and Health Services Research Program, American Cancer Society, Atlanta, Georgia
| | - Ahmedin Jemal
- Surveillance and Health Services Research Program, American Cancer Society, Atlanta, Georgia
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