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Kondili LA, Lazarus JV, Jepsen P, Murray F, Schattenberg JM, Korenjak M, Craxì L, Buti M. Inequities in primary liver cancer in Europe: The state of play. J Hepatol 2024; 80:645-660. [PMID: 38237866 DOI: 10.1016/j.jhep.2023.12.031] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 12/01/2023] [Accepted: 12/11/2023] [Indexed: 02/12/2024]
Abstract
Given the increasing burden of liver cancer in Europe, it is crucial to investigate how social determinants of health (SDoH) affect liver cancer risk factors and access to care in order to improve health outcomes equitably. This paper summarises the available evidence on the differential distribution of liver cancer risk factors, incidence, and health outcomes in the European Economic Area and the United Kingdom from an SDoH perspective. Vulnerable and marginalised populations have low socio-economic and educational levels and are the most affected by liver cancer risk factors. Reasons for this include varied access to hepatitis B virus vaccination and limited access to viral hepatitis B and C screening, harm reduction, and treatment. Additionally, alcohol-related liver disease remains highly prevalent among individuals with low education, insecure employment, economic instability, migrants, and deprived populations. Moreover, significant variation exists across Europe in the proportion of adults with steatotic liver disease, overweight/obesity, and diabetes, based on geographical area, gender, socio-economic and educational background, and density of ultra-processed food outlets. Inequities in cirrhosis mortality rates have been reported, with the highest death rates among individuals living in socio-economically disadvantaged areas and those with lower educational levels. Furthermore, insufficient healthcare access for key populations with primary liver cancer is influenced by complex healthcare systems, stigmatisation, discrimination, low education, language barriers, and fear of disclosure. These challenges contribute to inequities in liver cancer care pathways. Future studies are needed to explore the different SDoH-interlinked effects on liver cancer incidence and outcomes in European countries. The ultimate goal is to develop evidence-based multilevel public health interventions that reduce the SDoH impact in precipitating and perpetuating the disproportionate burden of liver cancer in specific populations.
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Affiliation(s)
- Loreta A Kondili
- National Centre for Global Health, Istituto Superiore di Sanità, Rome, Italy, UniCamillus International Medical University, Rome, Italy
| | - Jeffrey V Lazarus
- CUNY Graduate School of Public Health and Health Policy (CUNY SPH), New York, NY, USA; Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Peter Jepsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Frank Murray
- Beaumont Private Clinic, Beaumont, Dublin 9, Ireland
| | - Jörn M Schattenberg
- Department of Internal Medicine II, Saarland University Medical Center, Homburg and Saarland University, Saarbrücken, Germany
| | | | - Lucia Craxì
- Department of Biomedicine, Neuroscience, and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Maria Buti
- Liver Unit, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
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Stroffolini T, Stroffolini G. A Historical Overview on the Role of Hepatitis B and C Viruses as Aetiological Factors for Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:cancers15082388. [PMID: 37190317 DOI: 10.3390/cancers15082388] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/14/2023] [Accepted: 04/19/2023] [Indexed: 05/17/2023] Open
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the leading cause of hepatocellular carcinoma (HCC) worldwide. Currently, HBV-related HCC predominates in Sub-Saharan Africa and South-East-Asia, while HCV-related HCC predominates in northern Africa and in the western world. Liver cirrhosis is the underlying condition in most HBV cases and in nearly all HCV cases. Several cofactors, viral and non-viral, play a role in the progression toward HCC: dual HBV/HCV infection, HDV, HIV, alcohol intake, smoking, diabetes mellitus, obesity, and NAFLD/NASH. HBV vaccine is effective in preventing both infection and HCC; antiviral drugs may suppress HBV replication and eradicate HCV infection, halting progression to HCC. Inequalities exist between high- and low-income countries with respect to vaccine availability and access to antivirals. These factors represent barriers to the control of HCC incidence. Lack of an effective vaccine against HCV is also a serious barrier to HCV elimination and HCC prevention. The most crucial steps and knowledge that have arisen over time on the association between the two major hepatotropic viruses and HCC are discussed in this historical review.
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Affiliation(s)
- Tommaso Stroffolini
- Department of Tropical and Infectious Diseases, Policlinico Umberto I, 00161 Rome, Italy
| | - Giacomo Stroffolini
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Via Don A. Sempreboni, 5, Negrar, 37024 Verona, Italy
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A Systematic Review of the Current Hepatitis B Viral Infection and Hepatocellular Carcinoma Situation in Mediterranean Countries. BIOMED RESEARCH INTERNATIONAL 2020; 2020:7027169. [PMID: 32626758 PMCID: PMC7305551 DOI: 10.1155/2020/7027169] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 02/04/2020] [Accepted: 02/22/2020] [Indexed: 12/13/2022]
Abstract
Viral hepatitis B is a global public health problem affecting nearly two billion subjects; 3.3% of whom are from the WHO (World Health Organization) Eastern Mediterranean Region (EMRO). It induces both acute and chronic hepatic disorders with subsequent liver cirrhosis and hepatocellular carcinoma (HCC) in a considerable percentage of patients based on the age of exposure. In this review, hepatitis B virus (HBV) and HCC prevalence, distribution and prevalence of different genotypes, and male/female infection frequencies in relation to the vaccination status in the Mediterranean countries were reported. Study Design. This systematic review describes the prevalence of hepatitis B infection, genotype distribution of hepatitis B virus, and prevalence and incidence of hepatocellular carcinoma in Mediterranean countries belonging to three different continents: Southern Europe (Spain, France, Italy, Croatia, and Greece), North Africa (Morocco, Algeria, Tunisia, Libya, and Egypt), and the Near East region (Syria, Lebanon, Turkey, Israel, and Palestine). We tried to collect new data from electronic databases: PubMed, ScienceDirect, ResearchGate, Google Scholar, and public health reports between 1980 and 2019. For each publication, we recorded reference, publication year, study characteristics (date, locations, sample size, and study population), and participant characteristics (population group, year, age, and sex). No language limitation was imposed, and articles or reports from non-peer-reviewed sources were not considered for this analysis. The main keywords were HBV prevalence, hepatitis B infection, HBV genotype, and HCC. Inclusion and Exclusion Criteria. Healthy population-based studies included the following sample populations: (i) voluntary blood donors, (ii) pregnant women, (iii) community studies, (iv) hemodialysis patients, (v) hospitalized patients, (vi) healthcare workers, (vii) sex workers, (viii) drug abusers, and (ix) prisoners. We excluded studies from the following special groups who were assumed to be at a special high risk: patients from sexually transmitted disease clinics and thalassemia clinics and professional or paid blood donors.
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Giannitrapani L, Zerbo M, Amodeo S, Pipitone E, Galia M, Li Cavoli TV, Minissale MG, Licata A, Schiavone C, Brancatelli G, Montalto G, Soresi M. The Changing Epidemiology of Hepatocellular Carcinoma : Experience of a Single Center. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5309307. [PMID: 32185209 PMCID: PMC7063180 DOI: 10.1155/2020/5309307] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 01/27/2020] [Indexed: 02/08/2023]
Abstract
AIMS To analyze the main etiological factors and some clinical features of patients with hepatocellular carcinoma (HCC) at diagnosis and to compare them with those we described ten years ago. Materials and Methods. We compared two groups of patients with HCC, Group 1 consisting of 132 patients (82 M, 50 F) diagnosed in the 2003-2008 period and Group 2 including 119 patients (82 M, 37 F) diagnosed in the 2013-2018 period. For all patients, age, sex, viral markers, alcohol consumption, serum alpha-fetoprotein (AFP) levels, and the main liver function parameters were recorded. The diagnosis of HCC was based on AASLD, EASL guidelines. The staging was classified according to the "Barcelona Clinic Liver Cancer staging system" (BCLC). RESULTS Mean age was 69.0 ± 8 years in Group 1 and 71.0 ± 9 in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (. CONCLUSIONS This study shows that over the last decade a number of features of patients with HCC in our region have changed, particularly age at onset, etiological factors, and staging of HCC.
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Affiliation(s)
- Lydia Giannitrapani
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Maddalena Zerbo
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Simona Amodeo
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Elisa Pipitone
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Massimo Galia
- Department of Biomedicine, Neuroscience and Advanced Diagnostic (Bi. N. D.) Section of Radiological Sciences, University of Palermo, Palermo, Italy
| | - Tancredi Vincenzo Li Cavoli
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Maria Giovanna Minissale
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Anna Licata
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Cosima Schiavone
- Unit of Internistic Ultrasound, Department of Medicine and Science of Aging, G. D'Annunzio University, Chieti, Italy
| | - Giuseppe Brancatelli
- Department of Biomedicine, Neuroscience and Advanced Diagnostic (Bi. N. D.) Section of Radiological Sciences, University of Palermo, Palermo, Italy
| | - Giuseppe Montalto
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Maurizio Soresi
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
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Sagnelli E, Macera M, Russo A, Coppola N, Sagnelli C. Epidemiological and etiological variations in hepatocellular carcinoma. Infection 2020; 48:7-17. [PMID: 31347138 DOI: 10.1007/s15010-019-01345-y] [Citation(s) in RCA: 142] [Impact Index Per Article: 28.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer and a leading cause of cancer-related deaths worldwide. The major risk factors for HCC development are chronic liver disease and cirrhosis due to hepatitis B virus (HBV) and/or hepatitis C virus (HCV), alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), steatohepatitis, intake of aflatoxin-contaminated food, diabetes, and obesity. RESULTS In Western countries, the number of NASH-related HCC cases is increasing, that of HBV- or HCV-related cases is declining due to the wide application of HBV universal vaccination and the introduction of effective therapies against HBV and HCV infections, and that of alcohol-related cases remaining substantially unchanged. Nevertheless, the burden of HCC is expected to increase worldwide in the next few decades, due to the population growth and aging expected in coming years. Overall, the abovementioned changes and future variations in lifestyle and in the impact of environmental factors in Western countries and a decreasing exposure to dietary aflatoxins and improved socio-economic conditions in developing countries will create new HCC epidemiology in the next few decades. CONCLUSION A substantial further reduction in cases of HCC requires a wider application of universal HBV vaccination and effective treatment of HBV- and HCV-related chronic hepatitis and cirrhosis, more effective campaigns to favor correct dietary habits and reduce alcohol consumption and the intensification of studies on HCC pathogenesis for future optimized prevention strategies.
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Affiliation(s)
- Evangelista Sagnelli
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy.
| | - Margherita Macera
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy
| | - Antonio Russo
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy
| | - Nicola Coppola
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy
| | - Caterina Sagnelli
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy
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Yushchuk ND, Sleptsova SS, Malov SI, Bilukina IF, Semenov SI, Stepanenko LA, Ogarkov OB, Savilov ED, Malov IV. [Assessment of external risk factors of hepatocellular cancer development and markers of genetic predisposition to its development in the ethnic group of yakut - men]. TERAPEVT ARKH 2020; 92:56-61. [PMID: 32598664 DOI: 10.26442/00403660.2020.01.000505] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Indexed: 01/10/2023]
Abstract
AIM To establish the main external and genetically determined risk factors for the development of hepatocellular cancer in the ethnic group of male Yakuts living in the Republic of Sakha (Yakutia) [RS (Y)] in the epidemiologically unfavorable conditions of the incidence of viral hepatitis. MATERIALS AND METHODS A total of 97 male Yakuts were examined, including 44 people diagnosed with hepatocellular cancer and 53 people diagnosed with chronic viral hepatitis. HCC risk factors were identified by analyzing medical records and questioning patients. In the experimental and control groups, genetic studies of single nucleotide polymorphisms of genes mapped on the X-chromosome and involved in the activation of antiviral immunity along the TLR7 signaling pathway were performed. RESULTS AND DISCUSSION In 100% of patients with hepatocellular cancer, infection with hepatitis B, C, D viruses or co - infection with these agents was detected. Every fourth patient with HCC in the RS (Y) was infected with hepatitis D. The course of hepatocellular cancer associated with HDV was characterized by rapid progression of liver cirrhosis, development of portal hypertension, bleeding from varicose veins of the stomach and esophagus (36.4%) and edematous ascitic syndrome (63.6%). In addition to viral agents, additional risk factors for liver cancer were identified, such as alcohol abuse, overweight, diabetes mellitus, and smoking. Among the studied variation sites of genes localized on the X-chromosome and encoding the reaction of innate antiviral immunity, no genetic marker was found with a sufficient degree of confidence determining the likelihood of hepatocellular cancer developing. CONCLUSIONS The high incidence of hepatocellular carcinoma of the male population in the RS (Y) is due to the widespread prevalence of parenteral viral hepatitis, especially viral hepatitis D. Due to the introduction of mass vaccination of the population against hepatitis B in the Russian Federation in the foreseeable future in the RS (Y) we should see a decrease in the proportion of hepatocellular cancer associated with hepatitis B and D viruses, and therefore the focus should be on the treatment and prevention of hepatitis C virus and non - infectious risk factors.
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Affiliation(s)
- N D Yushchuk
- A.I. Evdokimov Moscow State University of Medicine and Dentistry
| | - S S Sleptsova
- M.K. Ammosov North-Eastern Federal University, Medical Institute
| | - S I Malov
- Irkutsk State Medical University.,Irkutsk State Medical Academy of Continuing Education
| | - I F Bilukina
- M.K. Ammosov North-Eastern Federal University, Medical Institute
| | - S I Semenov
- M.K. Ammosov North-Eastern Federal University, Medical Institute
| | | | - O B Ogarkov
- Irkutsk State Medical Academy of Continuing Education.,Scientific Center of Family Health and Human Reproduction
| | - E D Savilov
- Irkutsk State Medical Academy of Continuing Education.,Scientific Center of Family Health and Human Reproduction
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Sagnelli C, Sagnelli E. Towards the worldwide eradication of hepatitis B virus infection: A combination of prophylactic and therapeutic factors. World J Clin Infect Dis 2019; 9:11-22. [DOI: 10.5495/wjcid.v9.i2.11] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 07/10/2019] [Accepted: 07/17/2019] [Indexed: 02/06/2023] Open
Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80131, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80131, Italy
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Sagnelli C, Pisaturo M, Calò F, Martini S, Sagnelli E, Coppola N. Reactivation of hepatitis B virus infection in patients with hemo-lymphoproliferative diseases, and its prevention. World J Gastroenterol 2019; 25:3299-3312. [PMID: 31341357 PMCID: PMC6639550 DOI: 10.3748/wjg.v25.i26.3299] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Revised: 05/10/2019] [Accepted: 05/18/2019] [Indexed: 02/06/2023] Open
Abstract
Reactivation of hepatitis B virus (HBV) replication is characterized by increased HBV-DNA serum values of about 1 log or by HBV DNA turning positive if previously undetectable in serum, possibly associated with liver damage and seldom life-threatening. Due to HBV reactivation, hepatitis B surface antigen (HBsAg)-negative/anti-HBc-positive subjects may revert to HBsAg-positive. In patients with hemo-lymphoproliferative disease, the frequency of HBV reactivation depends on the type of lymphoproliferative disorder, the individual's HBV serological status and the potency and duration of immunosuppression. In particular, it occurs in 10%-50% of the HBsAg-positive and in 2%-25% of the HBsAg- negative/anti-HBc-positive, the highest incidences being registered in patients receiving rituximab-based therapy. HBV reactivation can be prevented by accurate screening of patients at risk and by a pharmacological prophylaxis with anti-HBV nucleo(t)sides starting 2-3 wk before the beginning of immunosuppressive treatment and covering the entire period of administration of immunosuppressive drugs and a long subsequent period, the duration of which depends substantially on the degree of immunodepression achieved. Patients with significant HBV replication before immunosuppressive therapy should receive anti-HBV nucleo(t)sides as a long-term (may be life-long) treatment. This review article is mainly directed to doctors engaged every day in the treatment of patients with onco-lymphoproliferative diseases, so that they can broaden their knowledge on HBV infection and on its reactivation induced by the drugs with high immunosuppressive potential that they use in the care of their patients.
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Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Federica Calò
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Salvatore Martini
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
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