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Simão M, Gonçalves C. Hepatitis C Virus Infection in Europe. Pathogens 2024; 13:841. [PMID: 39452713 PMCID: PMC11510056 DOI: 10.3390/pathogens13100841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 09/24/2024] [Accepted: 09/27/2024] [Indexed: 10/26/2024] Open
Abstract
The Hepatitis C Virus (HCV) is a significant public health challenge in European countries. Historically, healthcare-related procedures were the primary source of HCV infection in Europe. However, with the implementation of blood safety programs, injection drug use has become the main transmission route. The infection's distribution and genotype prevalence vary widely across the continent. Even with the availability of highly effective direct-acting antiviral (DAA) therapies, HCV infection is far from being controlled. A significant proportion of patients remain undiagnosed, contributing to the ongoing transmission of the virus. Additionally, several barriers hinder the widespread use of DAAs, including high treatment costs, stigma, poor linkage to care, and considerable geographical variations in prevalence and transmission routes. The World Health Organization has set ambitious targets to reduce liver-related deaths, decrease new viral hepatitis infections, and ensure that 90% of infected individuals are diagnosed by 2030. However, most European countries face challenges, highlighting the need for screening programs, funding mechanisms, and public health strategies to effectively control HCV infection in Europe.
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Affiliation(s)
| | - Cristina Gonçalves
- Pediatric Gastrenterology and Hepatology Unit, Pediatric Hospital Dona Estefânia, ULS S. José, 1169-045 Lisbon, Portugal
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Phyo Z, Ko K, Ouoba S, Sugiyama A, Mirzaev UK, Akuffo GA, Chhoung C, Akita T, Tanaka J. Intermediate hepatitis C virus (HCV) endemicity and its genotype distribution in Myanmar: A systematic review and meta-analysis. PLoS One 2024; 19:e0307872. [PMID: 39298388 PMCID: PMC11412534 DOI: 10.1371/journal.pone.0307872] [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: 03/14/2024] [Accepted: 07/14/2024] [Indexed: 09/21/2024] Open
Abstract
BACKGROUND Comprehensive details on Hepatitis C virus (HCV) infection in Myanmar are lacking. This study determined the prevalence of HCV antibodies and ribonucleic acid (RNA) and the distribution of HCV genotypes across different populations in Myanmar from 1990 to 2023. MATERIAL AND METHODS A systematic search in PubMed, Web of Science, Scopus, and local journals identified studies reporting on HCV antibodies, RNA, and genotypes, excluding clinical research related to liver disease prognosis. Screening and data extraction was done by two authors and study populations were categorized into low-risk, high-risk, liver disease patients, and refugees outside the country. The pooled prevalence was performed by Dersimonian and Laird method using the R program. The publication bias was shown by funnel plot, the Egger test was used to assess the symmetry of the plot, and the heterogeneity was examined by the Cochran Q test and I2 index. RESULTS Out of 135 reports screened for eligibility, 35 reports comprising 51 studies were included in which 33 studies provided data on HCV seroprevalence in 685,403 individuals, 8 studies reported HCV RNA prevalence in 25,018 individuals, and 10 studies examined HCV genotypes in 1,845 individuals. The pooled seroprevalence of HCV among low-risk, high-risk, liver disease patients and refugees were 2.18%, 37.07%, 33.84%, and 2.52% respectively. HCV RNA-positive rates in these groups were 1.40%, 5.25%, 24.96%, and 0.84% respectively. Seroprevalence studies showed publication bias (Egger test, p = 0.0001), while RNA studies did not (Egger test, p = 0.8392). HCV genotype 3 was predominant in all sub-groups in Myanmar. CONCLUSION Our study shows Myanmar has intermediate HCV endemicity with lowest HCV prevalence of 2.18% in low-risk groups and highest prevalence of 37.07% in high- risk groups. However, the findings highlight the need for further epidemiological studies to understand actual disease burden and implement effective countermeasures to achieve the WHO's goal of HCV elimination by 2030.
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Affiliation(s)
- Zayar Phyo
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
| | - Ko Ko
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
| | - Serge Ouoba
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Science de la Santé (IRSS), Nanoro, Burkina Faso
| | - Aya Sugiyama
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
| | - Ulugbek Khudayberdievich Mirzaev
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
- Department of Hepatology, Scientific Research Institute of Virology, Tashkent, Uzbekistan
| | - Golda Ataa Akuffo
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
| | - Chanroth Chhoung
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
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Mascarenhas A, Serrazina J, Bronze S, Cortez-Pinto H, Presa J, Barreira A, Carrola P, Vara-Luiz F, Rosu-Pires A, Martins PL, Prata R, Revés J, Bravo C, Nascimento C, Gouveia C, Franco AR, Lima P, O’Neill C, Mendes RR, Simão IR, Santos IC, Gonçalves AR, Barreiro P, Mendo R, Barosa R, Figueiredo P, Chagas C, On behalf of “Hepatologia em Rede”. Prediction of Hepatocellular Carcinoma in a Portuguese Population after Hepatitis C Cure: Comparative Accuracy of Noninvasive Tests (Transient Elastography, FIB-4, and aMAP). GE - PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024:1-13. [DOI: 10.1159/000540700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
<b><i>Introduction:</i></b> Chronic infection with hepatitis C virus (HCV) causes 25% of hepatocellular carcinoma (HCC) cases worldwide, a major cause of morbimortality even after sustained virologic response (SVR). Universal screening to all patients with advanced liver fibrosis is currently recommended. A risk-based strategy could improve the detection rate of early HCC and diminish the surveillance burden. Although several risk prediction models exist, exclusion of a subgroup of patients from surveillance has not yet been recommended. The objective of this study was the comparison of the predictive accuracy of transient elastography, FIB-4, and aMAP for HCC in HCV patients after SVR in Portugal. <b><i>Methods:</i></b> This was a multicentric retrospective study including patients with HCV after SVR. Comparative, univariate, multivariate, area under the ROC (receiver-operating characteristic) curve (AUC), and Youden’s J-statistic analysis were performed. <b><i>Results:</i></b> HCC incidence was 4.2% (1.3/100 patient-years) after a median follow-up of 31 months with inclusion of 337 patients. All patients had a liver stiffness measurement (LSM) before SVR (considered the baseline), but only 148 (43.9%) had a transient elastography after SVR. FIB-4 and aMAP post-SVR were calculated in all patients. Multiple parameters positively correlated with HCC, but only age and baseline transient elastography remained as independent predictors in the multivariate analysis. The optimal cutoffs for prediction of HCC were baseline transient elastography 13.7 kPa, post-SVR transient elastography 16.5 and 15.8 kPa (first and last measurements, respectively), FIB-4 1.6, and aMAP 58. Baseline transient elastography revealed a fair accuracy in predicting HCC (AUC 0.776, <i>p</i> < 0.001), with the cutoff of 13.7 kPa presenting a sensitivity of 85% and a specificity of 69%. Regarding patients who were F3–4 at baseline (<i>n</i> = 162), almost one-third had a baseline LSM ≤13.7 kPa (<i>n</i> = 51, 31.5%), an FIB-4 ≤1.6 (<i>n</i> = 50, 30.9%), and an aMAP score ≤58 (<i>n</i> = 48, 29.6%), and these cutoffs presented an NPV of 98%, 94%, and 96%, respectively, when considering HCC development. <b><i>Conclusion:</i></b> Transient elastography (FibroScan) before SVR was a fair predictor of HCC, being more accurate than FIB-4 and aMAP. Transient elastography values ≤13.7 kPa at baseline, FIB-4 ≤1.6 and aMAP ≤58 were the cutoffs considered of low risk for HCC in a Portuguese cohort of HCV patients after SVR with advanced fibrosis. aMAP score is a risk-based surveillance tool that could improve the current HCC screening strategy, but further validation is needed.
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Pewkliang Y, Thongsri P, Suthivanich P, Thongbaiphet N, Keatkla J, Pasomsub E, Anurathapan U, Borwornpinyo S, Wongkajornsilp A, Hongeng S, Sa-Ngiamsuntorn K. Immortalized hepatocyte-like cells: A competent hepatocyte model for studying clinical HCV isolate infection. PLoS One 2024; 19:e0303265. [PMID: 38739590 PMCID: PMC11090328 DOI: 10.1371/journal.pone.0303265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 04/23/2024] [Indexed: 05/16/2024] Open
Abstract
More than 58 million individuals worldwide are inflicted with chronic HCV. The disease carries a high risk of end stage liver disease, i.e., cirrhosis and hepatocellular carcinoma. Although direct-acting antiviral agents (DAAs) have revolutionized therapy, the emergence of drug-resistant strains has become a growing concern. Conventional cellular models, Huh7 and its derivatives were very permissive to only HCVcc (JFH-1), but not HCV clinical isolates. The lack of suitable host cells had hindered comprehensive research on patient-derived HCV. Here, we established a novel hepatocyte model for HCV culture to host clinically pan-genotype HCV strains. The immortalized hepatocyte-like cell line (imHC) derived from human mesenchymal stem cell carries HCV receptors and essential host factors. The imHC outperformed Huh7 as a host for HCV (JFH-1) and sustained the entire HCV life cycle of pan-genotypic clinical isolates. We analyzed the alteration of host markers (i.e., hepatic markers, cellular innate immune response, and cell apoptosis) in response to HCV infection. The imHC model uncovered the underlying mechanisms governing the action of IFN-α and the activation of sofosbuvir. The insights from HCV-cell culture model hold promise for understanding disease pathogenesis and novel anti-HCV development.
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Affiliation(s)
- Yongyut Pewkliang
- Faculty of Medicine Ramathibodi Hospital, Program in Translational Medicine, Mahidol University, Rama VI Road, Rajathevi, Bangkok, Thailand
| | - Piyanoot Thongsri
- Faculty of Medicine Ramathibodi Hospital, Program in Translational Medicine, Mahidol University, Rama VI Road, Rajathevi, Bangkok, Thailand
| | - Phichaya Suthivanich
- Faculty of Science, Excellent Center for Drug Discovery, Mahidol University, Rama VI Road, Rajathevi, Bangkok, Thailand
| | - Nipa Thongbaiphet
- Faculty of Medicine Ramathibodi Hospital, Department of Pathology, Virology Laboratory, Mahidol University, Rajathevi, Bangkok, Thailand
| | - Jiraporn Keatkla
- Faculty of Medicine Ramathibodi Hospital, Department of Pathology, Virology Laboratory, Mahidol University, Rajathevi, Bangkok, Thailand
| | - Ekawat Pasomsub
- Faculty of Medicine Ramathibodi Hospital, Department of Pathology, Virology Laboratory, Mahidol University, Rajathevi, Bangkok, Thailand
| | - Usanarat Anurathapan
- Faculty of Medicine Ramathibodi Hospital, Department of Pediatrics, Mahidol University, Rajathevi, Bangkok, Thailand
| | - Suparerk Borwornpinyo
- Faculty of Science, Excellent Center for Drug Discovery, Mahidol University, Rama VI Road, Rajathevi, Bangkok, Thailand
- Faculty of Science, Department of Biotechnology, Mahidol University, Rajathevi, Bangkok, Thailand
| | - Adisak Wongkajornsilp
- Faculty of Medicine Siriraj Hospital, Department of Pharmacology, Mahidol University, Bangkok, Thailand
| | - Suradej Hongeng
- Faculty of Medicine Ramathibodi Hospital, Department of Pediatrics, Mahidol University, Rajathevi, Bangkok, Thailand
| | - Khanit Sa-Ngiamsuntorn
- Faculty of Pharmacy, Department of Biochemistry, Mahidol University, Rajathevi, Bangkok, Thailand
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Capasso M, Cossiga V, Guarino M, Ranieri L, Morisco F. The Role of Hepatitis Viruses as Drivers of Hepatocancerogenesis. Cancers (Basel) 2024; 16:1505. [PMID: 38672587 PMCID: PMC11048534 DOI: 10.3390/cancers16081505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 04/08/2024] [Accepted: 04/12/2024] [Indexed: 04/28/2024] Open
Abstract
Recently, metabolic associated steatotic liver disease (MASLD) became the leading cause of chronic liver disease worldwide and one of the most frequent causes of hepatocellular carcinoma (HCC). Nonetheless, in this epidemiological trend, viral hepatitis remains the major driver in hepatic carcinogenesis. Globally, hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma, with an overall attributable risk of approximately 40%, followed by hepatitis C virus (HCV), which accounts for 28-30% of cases, with significant geographic variations between the Eastern and Western world. Considering all the etiologies, HCC risk increases proportionally with the progression of liver disease, but the risk is consistently higher in patients with viral triggers. This evidence indicates that both direct (due to the oncogenic properties of the viruses) and indirect (through the mechanisms of chronic inflammation that lead to cirrhosis) mechanisms are involved, alongside the presence of co-factors contributing to liver damage (smoking, alcohol, and metabolic factors) that synergistically enhance the oncogenic process. The aim of this review is to analyze the oncogenic role of hepatitis viruses in the liver, evaluating epidemiological changes and direct and indirect viral mechanisms that lead to liver cancer.
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Affiliation(s)
| | - Valentina Cossiga
- Diseases of the Liver and Biliary System Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy; (M.C.); (M.G.); (L.R.); (F.M.)
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Pinazo-Bandera JM, Aranda J, García-García AM, Alcántara R, Ortega-Alonso A, Del Campo-Herrera E, Clavijo E, García-Escaño MD, Ruiz Ruiz JJ, Morales-Herrera M, Valle-López V, Martín-Alarcón R, Viciana I, Jiménez JB, Fernández-García F, Toro-Ortiz JP, Sánchez-Yáñez E, Álvarez-Álvarez I, Andrade RJ, Robles-Díaz M, García-Cortés M. Hepatitis C virus point-of-care microelimination approach in a vulnerable population in the South of Spain. Gastroenterol Rep (Oxf) 2024; 12:goad077. [PMID: 38264764 PMCID: PMC10805342 DOI: 10.1093/gastro/goad077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 12/05/2023] [Accepted: 12/19/2023] [Indexed: 01/25/2024] Open
Abstract
Background Since the introduction of direct-acting antivirals, thousands of chronic hepatitis C patients have been successfully treated. However, vulnerable populations have a higher prevalence of hepatitis C virus (HCV) infection and face barriers that impede their access to antivirals. We carried out an HCV microelimination program focused on vulnerable population groups in Malaga. Methods People in drug addiction treatment centers and homeless shelters in Malaga who participated in the program between October 2020 and October 2021 were included. After providing participants with educational information on HCV, a dry drop test (DDT) was used to collect blood for subsequent screening for HCV infection. The participants who were diagnosed with HCV infection were scheduled for comprehensive healthcare assessments, including blood tests, ultrasonography, elastography, and the prescription of antivirals, all conducted in a single hospital visit. Sustained viral response (SVR) was analysed 12 weeks after end of treatment. Results Of the 417 persons invited to participate, 271 (65%) agreed to participate in the program. These participants were screened for HCV infection and 28 of them were diagnosed with HCV infection (10%). These hepatitis C-infected patients had a mean age of 53 ± 9 years; 86% were males and 93% were or had been drug users. Among 23 patients with HCV infection, HCV genotype 1a predominated (74%). Medical exams showed that 19% (4/21) had advanced fibrosis (F3-4), and 5% (1/21) had portal hypertension. Finally, 23 infected patients received treatment with glecaprevir/pibrentasvir or sofosbuvir/velpatasvir and SVR was confirmed in 22 patients (96%). Conclusions Drug users and homeless people have a higher prevalence of HCV infection than the general population. The microelimination program with educational activity and screening tools achieved a high participation rate, easy healthcare access, and a high rate of SVR despite the SARS-CoV-2 pandemic.
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Affiliation(s)
- José María Pinazo-Bandera
- Gastroenterology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
- Biomedic Research Network in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
| | - Jesús Aranda
- Gastroenterology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
| | - Alberto Manuel García-García
- Gastroenterology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
| | - Ramiro Alcántara
- Gastroenterology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
| | - Aida Ortega-Alonso
- Gastroenterology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
- Biomedic Research Network in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
| | - Enrique Del Campo-Herrera
- Gastroenterology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
| | - Encarnación Clavijo
- Microbiology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
| | - M Dolores García-Escaño
- Gastroenterology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
| | - Juan Jesús Ruiz Ruiz
- Provincial Center for Drug Addiction, Provincial Council of Málaga, Málaga, Spain
| | | | | | | | - Isabel Viciana
- Microbiology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
| | | | - Felix Fernández-García
- Gastroenterology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
| | - Juan Pedro Toro-Ortiz
- Gastroenterology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
| | - Elena Sánchez-Yáñez
- Farmacy Department, Virgen de la Victoria University Hospital, Málaga, Spain
| | - Ismael Álvarez-Álvarez
- Gastroenterology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
- Biomedic Research Network in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
| | - Raúl J Andrade
- Gastroenterology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
- Biomedic Research Network in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
| | - Mercedes Robles-Díaz
- Gastroenterology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
- Biomedic Research Network in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
| | - Miren García-Cortés
- Gastroenterology Department, Málaga Biomedicine Research Institute-IBIMA BIONAND Platform, Virgen de la Victoria University Hospital, University of Málaga, Málaga, Spain
- Biomedic Research Network in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
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Pizzato M, di Maso M, Collatuzzo G, Pelucchi C, Turati F, Negri E, La Vecchia C, Boffetta P, Alicandro G. Cancer mortality associated with low education in Italy. J Public Health (Oxf) 2023; 45:822-828. [PMID: 37681283 DOI: 10.1093/pubmed/fdad164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 07/25/2023] [Accepted: 08/15/2023] [Indexed: 09/09/2023] Open
Abstract
BACKGROUND This study provides a nationwide representative quantification of the impact of educational inequalities on cancer mortality in Italy. METHODS The study is based on prevalence data and mortality rate ratios according to levels of education obtained from the Italian 2011 census cohort, including >35 million individuals aged 30-74. We estimated the population attributable fraction (PAF) and the number of cancer deaths associated with low education (below university degree) in Italy by sex. RESULTS PAFs for low levels of education were 29.1% among men and 13.3% among women, corresponding to 22,271 cancer deaths associated with low education in men and 7456 in women in 2019. PAFs by cancer site in men were: 53.0% for upper aerodigestive tract (UADT), 44.6% for liver, 41.3% for stomach, 41.3% for lung, 37.0% for bladder, 18.5% for colorectal, 9.8% for prostate and 9.1% for pancreatic cancers. PAFs in women were: 44.5% for cervical, 36.1% for UADT, 34.9% for stomach and 13.9% for colorectal cancers. The cancer sites with the highest number of deaths associated with low education were lung among men (7902/22,271, 35.5%) and colorectum among women (780/7456, 10.5%). CONCLUSIONS About a quarter of cancer deaths in 2019 in Italy may be prevented by reducing the socioeconomic determinants that contribute to educational disparities in cancer mortality.
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Affiliation(s)
- Margherita Pizzato
- Department of Clinical Sciences and Community Health, University of Milan, 20133 Milano, Italy
| | - Matteo di Maso
- Department of Clinical Sciences and Community Health, University of Milan, 20133 Milano, Italy
| | - Giulia Collatuzzo
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Claudio Pelucchi
- Department of Clinical Sciences and Community Health, University of Milan, 20133 Milano, Italy
| | - Federica Turati
- Department of Clinical Sciences and Community Health, University of Milan, 20133 Milano, Italy
| | - Eva Negri
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, University of Milan, 20133 Milano, Italy
| | - Paolo Boffetta
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
- Stony Brook Cancer Center, Stony Brook University, 11794 Stony Brook, NY, USA
| | - Gianfranco Alicandro
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milano, Italy
- Cystic Fibrosis Centre, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy
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Mansoor M, de Glanville WA, Alam R, Aslam K, Ahmed M, Isaakidis P, Pasha A. Prevalence and risk factors for hepatitis C virus infection in an informal settlement in Karachi, Pakistan. PLOS GLOBAL PUBLIC HEALTH 2023; 3:e0002076. [PMID: 37729129 PMCID: PMC10511086 DOI: 10.1371/journal.pgph.0002076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 08/24/2023] [Indexed: 09/22/2023]
Abstract
The burden of hepatitis C virus (HCV) infection in Pakistan is amongst the highest in the world. People living in slums are likely to be at high risk of infection. Here, we describe the results of a cross-sectional survey conducted in March 2022 that aimed to quantify the prevalence of HCV infection in Machar Colony, one of the largest and oldest slum settlements in Karachi. Risk factors for HCV seropositivity were identified using multi-level logistic regression. We recruited 1,303 individuals in a random selection of 441 households from Machar Colony. The survey-adjusted HCV-seroprevalence was 13.5% (95% Confidence Interval (CI) 11.1-15.8) and survey-adjusted viraemic prevalence was 4.1% (95% CI 3.1-5.4) with a viraemic ratio of 32% (95% CI 24.3-40.5). Of 162 seropositive people, 71 (44%) reported receiving previous treatment for chronic hepatitis C. The odds of HCV seropositivity were found to increase with each additional reported therapeutic injection in the past 12 months (OR = 1.07 (95% Credible Interval (CrI) 1.00-1.13)). We found weaker evidence for a positive association between HCV seropositivity and a reported history of receiving a blood transfusion (OR = 1.72 (95% CrI 0.90-3.21)). The seroprevalence was more than double the previously reported seroprevalence in Sindh Province. The overall proportion of seropositive people that were viraemic was lower than expected. This may reflect the long-term impacts of a non-governmental clinic providing free of cost and easily accessible hepatitis C diagnosis and treatment to the population since 2015. Reuse of needles and syringes is likely to be an important driver of HCV transmission in this setting. Future public health interventions should address the expected risks associated with iatrogenic HCV transmission in this community.
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Affiliation(s)
- Munazza Mansoor
- Interactive Research and Development (IRD), Karachi, Pakistan
| | | | - Ridwa Alam
- Interactive Research and Development (IRD), Karachi, Pakistan
| | - Khawar Aslam
- Médecins Sans Frontières (MSF), Brussels, Belgium
| | | | - Petros Isaakidis
- Southern Africa Medical Unit, Médecins Sans Frontières, Cape Town, South Africa
| | - Aneeta Pasha
- Interactive Research and Development (IRD), Karachi, Pakistan
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Aaron A, Zhong H, Hiebert L, Zhuo Y, Adee M, Paraschiv A, Stratulat S, Ward JW, Chhatwal J. Hepatitis C Elimination in Moldova Is Feasible and Cost-Saving: A Modeling Study. J Infect Dis 2023; 228:S189-S197. [PMID: 37703345 DOI: 10.1093/infdis/jiad138] [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: 09/15/2023] Open
Abstract
BACKGROUND Moldova, an upper-middle-income country in Eastern Europe, is facing a high burden of hepatitis C virus (HCV). Our objective was to assist the National Agency of Public Health of Moldova in planning to achieve the World Health Organization's HCV elimination goals by 2030. METHODS This study adapted a previously developed microsimulation model to simulate the HCV epidemic in Moldova from 2004 to 2050. Model outcomes included temporal trends in HCV infection, prevalence, mortality, and total cost of care, including screening and treatment. We evaluated scenarios that could eliminate HCV by 2030. RESULTS Multiple strategies could lead to HCV elimination in Moldova by 2030. A realistic scenario of a 20% annual screening and 80% treatment rate would require 2.75 million individuals to be screened and 65 000 treated by 2030. Compared to 2015, this program will reduce HCV incidence by 98% and HCV-related deaths by 72% in 2030. Between 2022 and 2030, this strategy would cost $17.5 million for HCV screening and treatment. However, by 2050, the health system would save >$85 million compared to no investment in elimination efforts. CONCLUSIONS HCV elimination in Moldova is feasible and can be cost saving, but requires resources to scale HCV screening and treatment.
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Affiliation(s)
- Alec Aaron
- Massachusetts General Hospital Institute for Technology Assessment, Boston, Massachusetts
| | - Huaiyang Zhong
- Massachusetts General Hospital Institute for Technology Assessment, Boston, Massachusetts
- Department of Radiology, Harvard Medical School, Boston, Massachusetts
- Grado Department of Industrial and Systems Engineering, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Lindsey Hiebert
- Coalition for Global Hepatitis Elimination, Task Force for Global Health, Decatur, Georgia
| | - Yueran Zhuo
- College of Business, Mississippi State University, Mississippi State, Mississippi
| | - Madeline Adee
- School of Public Health, University of California, Berkeley, California
| | - Angela Paraschiv
- Department of Preventive Medicine, Epidemiology Discipline, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Moldova
| | - Silvia Stratulat
- Department of Epidemiological Surveillance of HIV Infection and Viral Hepatitis, National Agency for Public Health, Chisinau, Moldova
| | - John W Ward
- Coalition for Global Hepatitis Elimination, Task Force for Global Health, Decatur, Georgia
| | - Jagpreet Chhatwal
- Massachusetts General Hospital Institute for Technology Assessment, Boston, Massachusetts
- Department of Radiology, Harvard Medical School, Boston, Massachusetts
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10
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Isakov V, Nikityuk D. Elimination of HCV in Russia: Barriers and Perspective. Viruses 2022; 14:790. [PMID: 35458520 PMCID: PMC9024583 DOI: 10.3390/v14040790] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 03/29/2022] [Accepted: 04/07/2022] [Indexed: 01/13/2023] Open
Abstract
Hepatitis C virus (HCV) is highly prevalent in Russia, representing the largest pool of hepatitis C patients in Europe. Effective treatment regimens with direct-acting antivirals can achieve HCV cure in all patients; therefore, in 2016 the World Health Organization proposed eliminating hepatitis C as a public health threat by 2030. However, only a small number of countries are on track to meet the WHO's hepatitis C elimination targets by 2030 due to many barriers in healthcare systems. This review focuses on a discussion about the epidemiology of HCV in Russia, the economic burden of HCV-related diseases, and treatment access with particular reference to the barriers for the elimination of HCV.
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Affiliation(s)
- Vasily Isakov
- Federal Research Centre of Nutrition, Biotechnology and Food Safety, Department of Gastroenterology & Hepatology, 109240 Moscow, Russia;
- I. M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Dmitry Nikityuk
- Federal Research Centre of Nutrition, Biotechnology and Food Safety, Department of Gastroenterology & Hepatology, 109240 Moscow, Russia;
- I. M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia
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11
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Mentzer AJ, Brenner N, Allen N, Littlejohns TJ, Chong AY, Cortes A, Almond R, Hill M, Sheard S, McVean G, Collins R, Hill AVS, Waterboer T. Identification of host-pathogen-disease relationships using a scalable multiplex serology platform in UK Biobank. Nat Commun 2022; 13:1818. [PMID: 35383168 PMCID: PMC8983701 DOI: 10.1038/s41467-022-29307-3] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 03/04/2022] [Indexed: 12/12/2022] Open
Abstract
Certain infectious agents are recognised causes of cancer and other chronic diseases. To understand the pathological mechanisms underlying such relationships, here we design a Multiplex Serology platform to measure quantitative antibody responses against 45 antigens from 20 infectious agents including human herpes, hepatitis, polyoma, papilloma, and retroviruses, as well as Chlamydia trachomatis, Helicobacter pylori and Toxoplasma gondii, then assayed a random subset of 9695 UK Biobank participants. We find seroprevalence estimates consistent with those expected from prior literature and confirm multiple associations of antibody responses with sociodemographic characteristics (e.g., lifetime sexual partners with C. trachomatis), HLA genetic variants (rs6927022 with Epstein-Barr virus (EBV) EBNA1 antibodies) and disease outcomes (human papillomavirus-16 seropositivity with cervical intraepithelial neoplasia, and EBV responses with multiple sclerosis). Our accessible dataset is one of the largest incorporating diverse infectious agents in a prospective UK cohort offering opportunities to improve our understanding of host-pathogen-disease relationships with significant clinical and public health implications.
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Affiliation(s)
- Alexander J Mentzer
- The Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
| | - Nicole Brenner
- Division of Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Naomi Allen
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
- UK Biobank, Stockport, UK
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Thomas J Littlejohns
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Amanda Y Chong
- The Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
| | - Adrian Cortes
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
| | | | - Michael Hill
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
- MRC-Population Health Research Unit, University of Oxford, Oxford, UK
| | | | - Gil McVean
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
| | - Rory Collins
- UK Biobank, Stockport, UK
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Adrian V S Hill
- The Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
- The Jenner Institute, University of Oxford, Oxford, UK
| | - Tim Waterboer
- Division of Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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12
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Beliy PA, Dudina KR, Znoyko OO, Markova TN, Morozova IA, Blokhina NP, Nurmukhametova EA, Yushchuk ND. Prevalence of chronic HCV infection in patients with type 2 diabetes mellitus in Russia. DIABETES MELLITUS 2022; 25:4-13. [DOI: 10.14341/dm12847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
BACKGROUND: The poor outcomes of chronic hepatitis C (CHC) and type 2 diabetes determine the socio-economic significance of the combined pathology since they lead to premature death. The proportion of patients with type 2 diabetes with markers of viral hepatitis (VH) in the Russian Federation is not known, which does not allow us to estimate the burden for the state of this medical problem.OBJECTIVE: Assessment of the prevalence of concomitant pathology, HCV infection and type 2 diabetes, as well as the proportion of severe liver damage in its structure, according to the analysis of the primary medical records of four Moscow hospitals.MATERIALS AND METHODS: A retrospective analysis of the medical records of patients with HCV infection and diabetes mellitus, who admitted at different periods to four hospitals in Moscow, was carried out, as well as a total examination for the presence of anti-HCV in the blood of all patients with diabetes who were admitted within a certain period to the endocrinology department of a multidisciplinary hospital. Additionally, to determine the proportion of patients with liver cirrhosis (LC), an additional examination of patients with this combined pathology was carried out in accordance with the standards for the diagnosis of hepatitis C.RESULTS: In total, according to data from 4 hospitals in Moscow, over a certain period, 2% (105/5298) of diabetes patients with anti-HCV in their blood were identified. Sex ratio for men: women = 54 (51%): 51 (49%). Patients aged 50–69 years prevailed — 70% (74/105). Seroprevalence of HCV in cohorts of patients with type 2 diabetes according to the analysis in 3 health facilities: 0.9% (20/2196), 1.9% (8/432), 1.9% (28/1500). A significant drawback was revealed that did not allow assessing the true seroprevalence of HCV: not all patients were hospitalized with the results of a VH test, and not all of them were assigned an examination for VH markers if it was not performed before hospitalization. The proportion of type 2 diabetes patients with anti-HCV in the blood according to the results of total screening (3.7%; 16/432) became comparable to the proportion of type 2 diabetes patients among patients with CHC admitted to an infectious hospital (4.2%; 49 / 1170). The proportion of patients with LC according to the analysis of the medical records of the infectious hospital is 65% (32/49), in the group of endocrinological patients with additional examination it is 18% (13/71).CONCLUSION: For the first time in the Russian Federation, data were obtained on the prevalence of HCV infection in combination with type 2 diabetes. The results of the study indicate the need to develop effective screening programs to detect active HCV infection in the group of patients with diabetes, as well as patients among them with severe hepatic fibrosis for the timely conduct of highly effective antiviral therapy, which will prevent poor outcomes in a separate perspective.
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Affiliation(s)
- P. A. Beliy
- A.I. Evdokimov Moscow State University of Medicine and Dentistry
| | - K. R. Dudina
- A.I. Evdokimov Moscow State University of Medicine and Dentistry
| | - O. O. Znoyko
- A.I. Evdokimov Moscow State University of Medicine and Dentistry
| | | | | | | | | | - N. D. Yushchuk
- A.I. Evdokimov Moscow State University of Medicine and Dentistry
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13
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Baliashvili D, Averhoff F, Kasradze A, Salyer SJ, Kuchukhidze G, Gamkrelidze A, Imnadze P, Alkhazashvili M, Chanturia G, Chitadze N, Sukhiashvili R, Blanton C, Drobeniuc J, Morgan J, Hagan LM. Risk factors and genotype distribution of hepatitis C virus in Georgia: A nationwide population-based survey. PLoS One 2022; 17:e0262935. [PMID: 35061841 PMCID: PMC8782338 DOI: 10.1371/journal.pone.0262935] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 01/08/2022] [Indexed: 12/02/2022] Open
Abstract
In preparation for the National Hepatitis C Elimination Program in the country of Georgia, a nationwide household-based hepatitis C virus (HCV) seroprevalence survey was conducted in 2015. Data were used to estimate HCV genotype distribution and better understand potential sex-specific risk factors that contribute to HCV transmission. HCV genotype distribution by sex and reported risk factors were calculated. We used explanatory logistic regression models stratified by sex to identify behavioral and healthcare-related risk factors for HCV seropositivity, and predictive logistic regression models to identify additional variables that could help predict the presence of infection. Factors associated with HCV seropositivity in explanatory models included, among males, history of injection drug use (IDU) (aOR = 22.4, 95% CI = 12.7, 39.8) and receiving a blood transfusion (aOR = 3.6, 95% CI = 1.4, 8.8), and among females, history of receiving a blood transfusion (aOR = 4.0, 95% CI 2.1, 7.7), kidney dialysis (aOR = 7.3 95% CI 1.5, 35.3) and surgery (aOR = 1.9, 95% CI 1.1, 3.2). The male-specific predictive model additionally identified age, urban residence, and history of incarceration as factors predictive of seropositivity and were used to create a male-specific exposure index (Area under the curve [AUC] = 0.84). The female-specific predictive model had insufficient discriminatory performance to support creating an exposure index (AUC = 0.61). The most prevalent HCV genotype (GT) nationally was GT1b (40.5%), followed by GT3 (34.7%) and GT2 (23.6%). Risk factors for HCV seropositivity and distribution of HCV genotypes in Georgia vary substantially by sex. The HCV exposure index developed for males could be used to inform targeted testing programs.
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Affiliation(s)
- Davit Baliashvili
- National Center for Disease Control and Public Health, Tbilisi, Georgia
- Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia, United States of America
- * E-mail: ,
| | - Francisco Averhoff
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Ana Kasradze
- National Center for Disease Control and Public Health, Tbilisi, Georgia
| | - Stephanie J. Salyer
- Division of Global Health Protection, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | | | | | - Paata Imnadze
- National Center for Disease Control and Public Health, Tbilisi, Georgia
| | | | - Gvantsa Chanturia
- National Center for Disease Control and Public Health, Tbilisi, Georgia
| | | | | | - Curtis Blanton
- Division of Global Health Protection, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Jan Drobeniuc
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Juliette Morgan
- Division of Global Health Protection, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
- Global Disease Detection – South Caucasus Regional Center, Centers for Disease Control and Prevention, Tbilisi, Georgia
| | - Liesl M. Hagan
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
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14
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Datfar T, Doulberis M, Papaefthymiou A, Hines IN, Manzini G. Viral Hepatitis and Hepatocellular Carcinoma: State of the Art. Pathogens 2021; 10:pathogens10111366. [PMID: 34832522 PMCID: PMC8619105 DOI: 10.3390/pathogens10111366] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 09/26/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis is one of the main causes leading to hepatocellular carcinoma (HCC). The continued rise in incidence of HCC suggests additional factors following infection may be involved. This review examines recent studies investigating the molecular mechanisms of chronic hepatitis and its association with hepatocarcinogenesis. Hepatitis B virus patients with genotype C display an aggressive disease course leading to HCC more than other genotypes. Furthermore, hepatitis B excretory antigen (HBeAg) seems to be a more sensitive predictive tumor marker exhibiting a six-fold higher relative risk in patients with positive HBsAg and HBeAg than those with HBsAg only. Single or combined mutations of viral genome can predict HCC development in up to 80% of patients. Several mutations in HBx-gene are related with higher HCC incidence. Overexpression of the core protein in HCV leads to hepatocellular lipid accumulation associated with oncogenesis. Reduced number and decreased functionality of natural killer cells in chronic HCV individuals dysregulate their surveillance function in tumor and viral cells resulting in HCC. Furthermore, high T-cell immunoglobulin and mucin 3 levels supress CD8+ T-cells, which lead to immunological dysregulation. Hepatitis D promotes HCC development indirectly via modifications to innate immunity, epigenetic alterations and production of reactive oxygen species with the LHDAg being the most highly associated with HCC development. Summarizing the results, HBV and HCV infection represent the most associated forms of viral hepatitis causing HCC. Further studies are warranted to further improve the prediction of high-risk patients and development of targeted therapeutics preventing the transition from hepatic inflammation–fibrosis to cancer.
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Affiliation(s)
- Toofan Datfar
- Department of General and Visceral Surgery, Hospital of Aarau, 5001 Aarau, Switzerland;
- Correspondence: ; Tel.: +41-76-4930834
| | - Michael Doulberis
- Department of Gastroenterology and Hepatology, Hospital of Aarau, 5001 Aarau, Switzerland;
| | | | - Ian N. Hines
- Department of Nutrition Science, East Carolina University, Greenville, NC 27858, USA;
| | - Giulia Manzini
- Department of General and Visceral Surgery, Hospital of Aarau, 5001 Aarau, Switzerland;
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15
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Craviotto V, Furfaro F, Loy L, Zilli A, Peyrin-Biroulet L, Fiorino G, Danese S, Allocca M. Viral infections in inflammatory bowel disease: Tips and tricks for correct management. World J Gastroenterol 2021; 27:4276-4297. [PMID: 34366605 PMCID: PMC8316900 DOI: 10.3748/wjg.v27.i27.4276] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/01/2021] [Accepted: 05/15/2021] [Indexed: 02/06/2023] Open
Abstract
Over the past decades, the treatment of inflammatory bowel diseases (IBD) has become more targeted, anticipating the use of immune-modifying therapies at an earlier stage. This top-down approach has been correlated with favorable short and long-term outcomes, but it has also brought with it concerns regarding potential infectious complications. This large IBD population treated with immune-modifying therapies, especially if combined, has an increased risk of severe infections, including opportunistic infections that are sustained by viral, bacterial, parasitic, and fungal agents. Viral infections have emerged as a focal safety concern in patients with IBD, representing a challenge for the clinician: they are often difficult to diagnose and are associated with significant morbidity and mortality. The first step is to improve effective preventive strategies, such as applying vaccination protocols, adopt adequate prophylaxis and educate patients about potential risk factors. Since viral infections in immunosuppressed patients may present atypical signs and symptoms, the challenges for the gastroenterologist are to suspect, recognize and diagnose such complications. Appropriate treatment of common viral infections allows us to minimize their impact on disease outcomes and patients’ lives. This practical review supports this standard of care to improve knowledge in this subject area.
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Affiliation(s)
- Vincenzo Craviotto
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
| | - Federica Furfaro
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
| | - Laura Loy
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
| | - Alessandra Zilli
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
| | - Laurent Peyrin-Biroulet
- Department of Hepato-Gastroenterology and Inserm U954, University Hospital of Nancy, Lorraine University, Nancy 54511, France
| | - Gionata Fiorino
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milano, Italy
| | - Silvio Danese
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milano, Italy
| | - Mariangela Allocca
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milano, Italy
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16
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Baesi K, Velayati AA, Ashtiani MF, Fakhredini K, Banifazl M, Larijani MS, Basimi P, Ramezani A. Prevalence of Naturally Occurring Resistance Associated Substitutions in NS3/4A Protease Inhibitors in Iranian HCV/HIV Infected Patients. Curr HIV Res 2021; 19:391-397. [PMID: 34238162 DOI: 10.2174/1566523221666210707142838] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 04/03/2021] [Accepted: 04/21/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) acts in host as a complicated mixture of related variants with the potency to genetically escape host immune responses. Direct acting antivirals (DAAs) have been approved for HCV treatment with shorter duration, better cure rates and lower side effects. However, naturally occurring resistance associated substitutions(RASs) make some obstacles to this antiviral therapy success. OBJECTIVE In this study, we aimed at determination of the naturally occurring NS3/4A RASs in HCV/human immunodeficiency virus (HIV)infected patients. METHODS A total of 120 DAA-naïve HCV-HIV co-infected patients were included. HCV NS3/4Agenome region was amplified with PCR and mutation analysis was performed by Sanger sequencing technique. The amino acid sequence diversity of the region wasanalyzed using geno2pheno HCV. RESULTS Phylogenetic analysis showed that 73 cases were infected by 3a and 47 subjects by subtype1a. The overall RASs among studied subjects wereobserved in 6 (5%) individuals from 120 studied cases who were infected with HCV 1a. V36M/L,Q80L,S122G/L,R155T/G,A156S,D168Y/N and S174A/N/T mutations were detected in this study. CONCLUSION Although the prevalence of RASs was totally low in this study, the presence of several cases of double and triple mutants among this population suggests prior evaluation of protease inhibitors related mutations before initiation of standard treatment and also investigation on a large population could be of high value.
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Affiliation(s)
- Kazem Baesi
- Hepatitis & AIDS Dept., Pasteur Institute of Iran, Tehran, Iran
| | - Ali Akbar Velayati
- Masih Daneshvari Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
| | | | - Kamal Fakhredini
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Banifazl
- Iranian Society for Support of Patients with Infectious Disease, Tehran, Iran
| | | | - Parya Basimi
- Hepatitis & AIDS Dept., Pasteur Institute of Iran, Tehran, Iran
| | - Amitis Ramezani
- Clinical Research Dept., Pasteur Institute of Iran, Tehran, Iran
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17
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Isakov V, Tsyrkunov V, Nikityuk D. Is elimination of hepatitis C virus realistic by 2030: Eastern Europe. Liver Int 2021; 41 Suppl 1:50-55. [PMID: 34155800 DOI: 10.1111/liv.14836] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 02/22/2021] [Indexed: 01/06/2023]
Abstract
The WHO elimination goals (diagnosis of 90% of the cases of hepatitis C virus (HCV), treatment coverage in 80% and a 65% reduction in deaths from HCV) are set to be reached by 2030. Although these elimination programmes are extremely important in the Eastern European countries (Russia, Ukraine, Belarus and Moldova) with a high prevalence of HCV, limited economic resources prevent their development and implementation. Regardless of the decrease in the incidence HCV in all Eastern European countries, low diagnosis and treatment access, especially in high-risk populations, will not allow to achieve HCV elimination or even to control the infection by 2030.
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Affiliation(s)
- Vasily Isakov
- Department of Gastroenterology & Hepatology, Federal Research Centre of Nutrition, Biotechnology and Food Safety, Moscow, Russia
| | | | - Dmitry Nikityuk
- Department of Gastroenterology & Hepatology, Federal Research Centre of Nutrition, Biotechnology and Food Safety, Moscow, Russia
- I.M.Sechenov First Moscow State Medical University
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18
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Taconet L, Seifner A, Baylis SA, Chudy M, Kreβ J, Mathys E, Wirz M, Buchheit KH, Behr-Gross ME. Detection of hepatitis C virus and parvovirus B19 in human plasma pools by nucleic-acid amplification techniques - Trends in results of EDQM proficiency testing studies from 2004 to 2018. Biologicals 2021; 71:9-19. [PMID: 34006447 DOI: 10.1016/j.biologicals.2021.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 04/07/2021] [Accepted: 04/15/2021] [Indexed: 11/29/2022] Open
Abstract
The European Directorate for the Quality of Medicines & HealthCare (EDQM) has run proficiency testing schemes on the detection of viral contaminants in human plasma pools by nucleic-acid amplification techniques since 1999 for hepatitis C virus and since 2004 for parvovirus B19. A retrospective analysis was performed to assess their impact and identify trends and progress in the results obtained by participating laboratories over a 15-year span, from 2004 to 2018. The results demonstrate that overall performance improved over that time, especially among the regular participants. Participation in these proficiency testing schemes is therefore recommended for all interested control laboratories. This analysis also shows that hepatitis C virus detection now seems well established compared to that of parvovirus B19, which still appears more challenging.
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Affiliation(s)
- Laure Taconet
- European Directorate for the Quality of Medicines and HealthCare, 7 Allée Kastner, CS 30026, F-67081, Strasbourg, France.
| | - Alexandra Seifner
- European Directorate for the Quality of Medicines and HealthCare, 7 Allée Kastner, CS 30026, F-67081, Strasbourg, France
| | | | | | | | - Esther Mathys
- Institut Scientifique de Santé Publique, Bruxelles, Belgium
| | - Maria Wirz
- Istituto Superiore di Sanità, Rome, Italy
| | - Karl-Heinz Buchheit
- European Directorate for the Quality of Medicines and HealthCare, 7 Allée Kastner, CS 30026, F-67081, Strasbourg, France
| | - Marie-Emmanuelle Behr-Gross
- European Directorate for the Quality of Medicines and HealthCare, 7 Allée Kastner, CS 30026, F-67081, Strasbourg, France
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19
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Mandoh SS, Ayman K, Elbardakheny A, Raaft H, Ibrahim AA, Alshaikh RA, Mansour FR. A cross sectional study of the risk factors of hepatitis C infection in North Egypt. Virusdisease 2021; 32:22-28. [PMID: 33969153 DOI: 10.1007/s13337-020-00639-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 10/27/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C is a viral infection that has been declared as a global health problem by the World Health Organization. Egypt has the highest prevalence of hepatitis C virus (HCV) which results in a high morbidity and mortality from chronic liver disease, cirrhosis, and even hepatocellular carcinoma. Cities have lower rates of infection than rural areas. Studies about the abnormally high prevalence of HCV in Egypt ascribed that to the governmental campaign to treat Schistosoma. However, these treatment campaigns have stopped more than 35 years ago, which means that some other modes of transmission must have been involved. The objective of this work is to study the main reasons of HCV prevalence in the Egyptian Delta valley. A questionnaire-based study was conducted by members of the HCV Fighters project. Responses were collected from 949 volunteers (451 HCV patients and 498 healthy volunteers as control). The data were analyzed using SPSS version 19.0. The two-sample proportion test was used for statistical comparison between groups. The most probable risk factors of HCV transmission in Egypt included regular visits to dental clinics (55.2%), previous surgical operations (54.4%), former blood transfusion (52%), intrafamilial HCV infection (45.9%) and history of bilharzial infection (44.3%). Increasing public awareness about modes of transmission and risk factors of HCV infection is a must, especially within family members of HCV patients. Strict commitment to proper medical care precautions by health care practitioners is required.
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Affiliation(s)
- Soad S Mandoh
- HCV Fighters, Faculty of Pharmacy, Tanta University, Tanta, 31111 Egypt
| | - Kholoud Ayman
- HCV Fighters, Faculty of Pharmacy, Tanta University, Tanta, 31111 Egypt
| | | | - Hala Raaft
- HCV Fighters, Faculty of Pharmacy, Tanta University, Tanta, 31111 Egypt
| | - Ahmed A Ibrahim
- HCV Fighters, Faculty of Pharmacy, Tanta University, Tanta, 31111 Egypt
| | - Rasha Alsaeed Alshaikh
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, 31111 Egypt
| | - Fotouh R Mansour
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Tanta University, Tanta, 31111 Egypt
- Pharmaceutical Services Center, Faculty of Pharmacy, Tanta University, El-Geish Street, The Medical Campus, Tanta, 31111 Egypt
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HCV Genotype Distribution of Patients with Chronic Hepatitis C in Istanbul. MEDICAL BULLETIN OF SISLI ETFAL HOSPITAL 2021; 55:86-92. [PMID: 33935541 PMCID: PMC8085459 DOI: 10.14744/semb.2020.66990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 12/06/2020] [Indexed: 11/20/2022]
Abstract
Objectives: Hepatitis C virus (HCV), which has no protective vaccine, is a common cause of chronic hepatitis, which is a severe public health threat. There are differences in nucleotide and amino acid sequences in different regions of the HCV genome. As a result of these differences, HCV has been shown to have at least seven major genotypes and many subtypes. In Turkey, the prevalence of genotype 1 is between 51.7% and 97.1%, the highest rate among all genotypes, while subtype 1b is the genotype with the highest rate. It is important to detect mixed genotype infection reliably as it causes treatment failure. This study aims to reveal the distribution of the HCV genotypes in our hospital in Istanbul over the years and to contribute to the epidemiological data of Turkey. Methods: For this purpose, 385 patient samples sent to Sisli Hamidiye Etfal Training and Research Hospital, Clinical Microbiology Laboratory for HCV genotype determination between January 2016 and June 2019 were evaluated retrospectively. Anti-HCV was screened by enzyme immunoassay and confirmation was performed by Line immunoassay. HCV genotyping assays targeting highly conserved 5’UTR and most variable region NS5B regions were used. Results: The most common genotype was genotype 1 (81.3%) with 313 cases and subtypes 1a and 1b were detected at the rates of 10.9% and 67.8%, respectively. In addition, genotype 3, 2, 4, 5 were detected at the rates of 8.8%, 3.4%, 2.9%, 0.8%, respectively and mixed genotype was found in 2.9% of cases. Although genotype 5 is seen in South Africa, it is found in the Middle East region, albeit at a low rate. In our study, it was observed that genotype 5 was detected in different years from patients of Syrian origin. Conclusion: In this study, genotype 1 was the most common genotype with a rate of 81.3% and subtype 1b was 67.8%, in accordance with the literature. However, genotypes 3, 2, 4 and 5 were also present at low rates. It is important to monitor these rare genotypes since some of them are dominant in surrounding countries. In addition, 2.9% of HCV mixed genotype was detected and this should be considered concerning management of HCV infection.
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Iossa D, Vitrone M, Gagliardi M, Falco E, Ragone E, Zampino R, Durante-Mangoni E. Anthropometric parameters and liver histology influence lipid metabolic changes in HCV chronic hepatitis on direct-acting antiviral treatment. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:35. [PMID: 33553328 PMCID: PMC7859777 DOI: 10.21037/atm-20-669] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background Hepatitis C virus (HCV) infection affects lipid metabolism. We investigated the impact of direct-acting antiviral (DAA) treatment on lipid metabolism in chronic hepatitis C (CHC), with a focus on the effects of anthropometric parameters and liver histology. We also analyzed the dynamics of metabolic indexes used to estimate cardiovascular risk. Methods In 49 patients with CHC treated with DAAs, lipid metabolic changes, anthropometric parameters, liver histology and cardiovascular risk indexes, including triglyceride to HDL ratio (Tr/HDL), fatty liver index (FLI) and visceral adiposity index (VAI) were evaluated at baseline (BL), end of treatment (EOT) and 12 [sustained virological response (SVR) 12] and 24 (SVR24) weeks after EOT. Results SVR occurred in 96% of cases. Total and LDL cholesterol and ApoB levels increased significantly between BL and EOT (P<0.001, <0.001 and 0.05, respectively) and remained stable thereafter. Total and LDL cholesterol significantly increased only in patients with higher BL waist circumference (P<0.01 and 0.009), fibrosis (P=0.002 and 0.005) and steatosis (P=0.043 and 0.033, respectively). HDL cholesterol significantly rose at SVR24. However, cardiovascular risk indexes (Tr/HDL ratio, FLI and VAI) did not significantly change during DAA treatment and follow up. Conclusions Patients with HCV eradication after DAA treatment develop a pro-atherogenic lipid pattern, which varies according to anthropometric parameters and liver histology. However, no increase of cardiovascular risk indexes occurs in the short-term. Total and LDL cholesterol should be monitored long-term in CHC patients cured from infection.
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Affiliation(s)
- Domenico Iossa
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Martina Vitrone
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Massimo Gagliardi
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Erasmo Falco
- Units of Infectious & Transplant Medicine AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Enrico Ragone
- Units of Infectious & Transplant Medicine AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Rosa Zampino
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy.,Units of Infectious & Transplant Medicine AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Emanuele Durante-Mangoni
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy.,Units of Infectious & Transplant Medicine AORN dei Colli, Monaldi Hospital, Naples, Italy
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Wiessing L, Giraudon I, Duffell E, Veldhuijzen I, Zimmermann R, Hope V. Epidemiology of Hepatitis C Virus: People Who Inject Drugs and Other Key Populations. HEPATITIS C: EPIDEMIOLOGY, PREVENTION AND ELIMINATION 2021:109-149. [DOI: 10.1007/978-3-030-64649-3_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Sikander M, Malik S, Rodriguez A, Yallapu MM, Narula AS, Satapathy SK, Dhevan V, Chauhan SC, Jaggi M. Role of Nutraceuticals in COVID-19 Mediated Liver Dysfunction. Molecules 2020; 25:5905. [PMID: 33322162 PMCID: PMC7764432 DOI: 10.3390/molecules25245905] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 12/05/2020] [Accepted: 12/09/2020] [Indexed: 01/08/2023] Open
Abstract
COVID-19 is known as one of the deadliest pandemics of the century. The rapid spread of this deadly virus at incredible speed has stunned the planet and poses a challenge to global scientific and medical communities. Patients with COVID-19 are at an increased risk of co-morbidities associated with liver dysfunction and injury. Moreover, hepatotoxicity induced by antiviral therapy is gaining importance and is an area of great concern. Currently, alternatives therapies are being sought to mitigate hepatic damage, and there has been growing interest in the research on bioactive phytochemical agents (nutraceuticals) due to their versatility in health benefits reported in various epidemiological studies. Therefore, this review provides information and summarizes the juncture of antiviral, immunomodulatory, and hepatoprotective nutraceuticals that can be useful during the management of COVID-19.
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Affiliation(s)
- Mohammed Sikander
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (M.S.); (S.M.); (A.R.); (M.M.Y.); (S.C.C.)
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Shabnam Malik
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (M.S.); (S.M.); (A.R.); (M.M.Y.); (S.C.C.)
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Anyssa Rodriguez
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (M.S.); (S.M.); (A.R.); (M.M.Y.); (S.C.C.)
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Murali M. Yallapu
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (M.S.); (S.M.); (A.R.); (M.M.Y.); (S.C.C.)
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Acharan S. Narula
- Narula Research, LLC, 107 Boulder Bluff, Chapel Hill, NC 27516, USA;
| | - Sanjaya K. Satapathy
- Division of Hepatology, Department of Internal Medicine, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Barbara and Zucker School of Medicine, Northwell Health, Manhasset, NY 11030, USA;
| | - Vijian Dhevan
- Department of Surgery, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA;
| | - Subhash C. Chauhan
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (M.S.); (S.M.); (A.R.); (M.M.Y.); (S.C.C.)
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Meena Jaggi
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (M.S.); (S.M.); (A.R.); (M.M.Y.); (S.C.C.)
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
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Clinical, Epidemiological, and Geospatial Characteristics of Patients Infected with Hepatitis C Virus Treated with Second-Generation Direct-Action Antivirals in a Reference Center in a Mesoregion of São Paulo State, Brazil. Microorganisms 2020; 8:microorganisms8101575. [PMID: 33066136 PMCID: PMC7601958 DOI: 10.3390/microorganisms8101575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/02/2020] [Accepted: 10/09/2020] [Indexed: 11/17/2022] Open
Abstract
Hepatitis virus infection is a major public health problem worldwide. Currently, Brazil has almost 700,000 cases. The Brazilian Unified Health System (SUS) provides therapeutic regimens for people infected with hepatitis C virus (HCV). We determined the clinical, laboratory, epidemiologic, and geospatial characteristics of patients infected with HCV treated with second-generation direct-action antivirals (DAAs) in a hospital reference center in São Paulo state, Brazil, using data from file records. A map was constructed using a geographic information system. From 2015 to 2018, 197 individuals received second-generation DAAs (mean age, 57.68 ± 1.36 years; interquartile range, 56.22–59.14 years; 58.9% male; 41.1% female). Genotypes 1a and 1b accounted for 75.7% of cases and the prevalent therapeutic regimen was sofosbuvir/simeprevir. Sustained viral response accounted for 98.9% and the METAVIR score F3/F4 for 50.8%. Increased alanine transferase was significantly correlated with an increase in α-fetoproteins (p = 0.01), and severe necro-inflammatory activity (p = 0.001). Associated comorbidities were found in 71.6%, mainly coronary artery and gastrointestinal disorders. The cumulative incidence in the region was 2.6 per 10,000 inhabitants. Our data highlight the role of reference hospitals in Brazil’s public health system in the treatment of HCV. Low incidence rates demonstrated the fragility of municipalities in the active search for patients.
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Amougou-Atsama M, Jean Adrien Atangana P, Noah Noah D, Fewou Moundipa P, Pineau P, Njouom R. The role of hepatitis C virus genotypes and core mutations in hepatocellular carcinoma in Cameroon. J Viral Hepat 2020; 27:880-885. [PMID: 32301239 DOI: 10.1111/jvh.13303] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 03/18/2020] [Accepted: 03/23/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is known to be an important risk factor for hepatocellular carcinoma (HCC) in Cameroon. However, the effect of HCV-related factors on HCC development still remains unknown in the Central Africa. In this study, we investigated the role of HCV genotypes and core mutations in HCC development in Cameroonian patients. METHODS A case-control study was conducted using patients with HCV-related HCC and matched controls individuals with chronic HCV infection but without HCC. HCV genotypes and mutations were determined using a hemi-nested amplification and sequencing analysis focus on the core and NS5B HCV regions. RESULTS We identify HCV genotype 1, 2 and 4 in both groups. Interestingly, genotype 4 was significantly more prevalent in HCC patients (53.3%). Overall, distribution of genotypes was very different between cases and controls (P = 4.2 E-7). The risk factors analysis showed that infection with HCV-4 is strongly associated with HCC development with odd ratio, 95% confidence interval and p-values of 7.4 (95% CI: 2.08-26.6; P = .001). Furthermore, the risk of developing HCC increased even more significantly in case of infection with HCV subtype 4f with the odd ratio of 20.8 (95% CI, 4.1-66.8; P < .001). Mutations K10R, T72E, K74R and G77A were significantly more frequent in patients with HCC. Remarkably, HCV-4f isolates from HCC patients carried significantly more mutations when compared to controls with HCV-4f or others genotypes (P = .0001). CONCLUSIONS Our results indicate that patients infected with HCV-4f or with selected variants affecting HCV core gene are at increased risk to develop HCC.
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Affiliation(s)
| | | | | | - Paul Fewou Moundipa
- Laboratory of Pharmacology and Toxicology of University of Yaoundé I, Yaoundé, Yaoundé, Cameroon
| | - Pascal Pineau
- Unité « Organisation nucléaire et Oncogenèse », INSERM U993, Institut Pasteur, Paris, France
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Fu N, Du H, Li D, Lu Y, Li W, Wang Y, Kong L, Du J, Zhao S, Ren W, Han F, Wang R, Zhang Y, Nan Y. Clusterin contributes to hepatitis C virus-related hepatocellular carcinoma by regulating autophagy. Life Sci 2020; 256:117911. [DOI: 10.1016/j.lfs.2020.117911] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 05/24/2020] [Accepted: 06/02/2020] [Indexed: 02/07/2023]
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Palayew A, Stumo SR, Cooke GS, Hutchinson SJ, Jauffret-Roustide M, Maticic M, Harris M, Metwally AM, Razavi H, Lazarus JV, on behalf of the Hep-CORE Study Group. The Hep-CORE policy score: A European hepatitis C national policy implementation ranking based on patient organization data. PLoS One 2020; 15:e0235715. [DOI: https:/doi.org/10.1371/journal.pone.0235715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2023] Open
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Palayew A, Stumo SR, Cooke GS, Hutchinson SJ, Jauffret-Roustide M, Maticic M, Harris M, Metwally AM, Razavi H, Lazarus JV, on behalf of the Hep-CORE Study Group. The Hep-CORE policy score: A European hepatitis C national policy implementation ranking based on patient organization data. PLoS One 2020; 15:e0235715. [PMID: 32722701 PMCID: PMC7386634 DOI: 10.1371/journal.pone.0235715] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 06/20/2020] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND New hepatitis C virus (HCV) treatments spurred the World Health Organization (WHO) in 2016 to adopt a strategy to eliminate HCV as a public health threat by 2030. To achieve this, key policies must be implemented. In the absence of monitoring mechanisms, this study aims to assess the extent of policy implementation from the perspective of liver patient groups. METHODS Thirty liver patient organisations, each representing a country, were surveyed in October 2018 to assess implementation of HCV policies in practice. Respondents received two sets of questions based on: 1) WHO recommendations; and 2) validated data sources verifying an existing policy in their country. Academic experts selected key variables from each set for inclusion into policy scores. The similarity scores were calculated for each set with a multiple joint correspondence analysis. Proxy reference countries were included as the baseline to contextualize results. We extracted scores for each country and standardized them from 0 to 10 (best). RESULTS Twenty-five countries responded. For the score based on WHO recommendations, Bulgaria had the lowest score whereas five countries (Cyprus, Netherlands, Portugal, Slovenia, and Sweden) had the highest scores. For the verified policy score, a two-dimensional solution was identified; first dimension scores pertained to whether verified policies were in place and second dimension scores pertained to the proportion of verified policies in-place that were implemented. Spain, UK, and Sweden had high scores for both dimensions. CONCLUSIONS Patient groups reported that the European region is not on track to meet WHO 2030 HCV goals. More action should be taken to implement and monitor HCV policies.
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Affiliation(s)
- Adam Palayew
- McGill University Department of Epidemiology, Biostatistics, and Occupational Health, Montreal, Quebec, Canada
| | - Samya R. Stumo
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Graham S. Cooke
- Division of Infectious Diseases, Imperial College, London, United Kingdom
| | - Sharon J. Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom
| | - Marie Jauffret-Roustide
- Cermes3 (Inserm U988/CNRS UMR 8211/Ecole des Hautes Etudes en Sciences Sociales/Paris Descartes University), Paris, France
| | - Mojca Maticic
- Clinic for Infectious Diseases and Febrile Illnesses, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Magdalena Harris
- Department of Public Health, Environments and Society, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Ammal M. Metwally
- Community Medicine Research Department, Medicine Research Division, National Research Centre, Giza, Egypt
- Association of Liver Patient Care, Dakhlyia, Egypt
| | - Homie Razavi
- Center for Disease Analysis Foundation, Lafayette, CO, United States of America
| | - Jeffrey V. Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain
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Distribution of Human T-Lymphotropic Virus (HTLV) and Hepatitis C Co-infection in Bahia, Brazil. PLoS One 2020; 15:e0223087. [PMID: 32692782 PMCID: PMC7373273 DOI: 10.1371/journal.pone.0223087] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Accepted: 06/29/2020] [Indexed: 02/07/2023] Open
Abstract
Both Human T-lymphotropic virus type 1 (HTLV-1) and hepatitis C virus (HCV) are endemic in Brazil. In Salvador, the capital of the state of Bahia, 2% and 1.5% of the general population is infected with HTLV-1 or HCV. This study aimed to estimate the prevalence and the distribution of HTLV/HCV coinfection in Bahia. This cross-sectional study was conducted at the Central Laboratory of Public Health for the state of Bahia (LACEN-BA). All samples in the LACEN database submitted to serological testing for anti-HCV (chemiluminescence) and anti-HTLV-1/2 (chemiluminescence/ELISA and Western blot) from 2004 to 2013 were included. Infection rate was expressed as the number of infected individuals per 100,000 inhabitants in a given municipality; municipalities were grouped by microregion for further analysis. A total of 120,192 samples originating from 358 of the 417 municipalities in Bahia (85.8%) were evaluated. The overall HCV coinfection rate in HTLV-positive was 14.31% [2.8 (ranging from 0.4 to 8.0) per 100,000 inhabitants.] Twenty-one (5%) of the municipalities reported at least one case of HTLV/HCV coinfection. Most cases (87%) were concentrated in three microregions (Salvador: 79%, Ilhéus/Itabuna: 5%, Porto Seguro: 3%). Coinfection occurred more frequently in males (51%) with a mean age of 59 [(IQR): 46–59] years. HTLV/HCV coinfection in the state of Bahia was more frequently found among males living in the microregions of Salvador, Ilhéus/Itabuna and Porto Seguro, all of which are known to be endemic for HTLV infection.
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Association of the Sialylation of Antibodies Specific to the HCV E2 Envelope Glycoprotein with Hepatic Fibrosis Progression and Antiviral Therapy Efficacy. DISEASE MARKERS 2020; 2020:8881279. [PMID: 32685058 PMCID: PMC7333057 DOI: 10.1155/2020/8881279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 05/27/2020] [Accepted: 06/05/2020] [Indexed: 12/30/2022]
Abstract
The E2 envelope glycoprotein of the hepatitis C virus (HCV) is a major target of broadly neutralizing antibodies that are closely related to a spontaneous cure of HCV infection. There is still no data about the diversity of E2-specific antibodies (Abs) glycosylation. The aim of this study was to analyze the level and sialylation of E2 IgG Abs, the relation of the respective changes to hepatic fibrosis (F) progression and their possible association with the efficacy of interferon-α-2a plus ribavirin (IFN-RBV) antiviral therapy. One hundred three HCV infected treatment-naive patients were examined using ELISA with E2 recombinant protein as antigen and sialic acid-specific Sambucus nigra agglutinin. The efficacy of the IFN-RBV treatment of patients with HCV dominant 1b and 3a genotypes (GT) was evaluated. A significant decrease of E2 Abs sialylation in the late stages of fibrosis was found irrespective of HCV genotype. On this basis, the F4 stage of fibrosis can be discriminated from its F0 or F1-3 stage by an about 75-79% accuracy. HCV infection of 1b genotype is associated with the production of lower sialylated E2 Abs, a higher frequency of F4 stage fibrosis, and a worse response to antiviral therapy. The increased SNA reactivity of E2 Abs was observed in patients with a sustained virological response (SVR). The proportion of SVR responders was significantly higher among patients with 3a genotype. However, for both dominant HCV genotypes (3a and 1b), an increased sialylation of E2 IgG was associated with a higher rate of patients with sustained virological response to antiviral therapy. Thus, the association of alterations of anti-E2 IgG Abs sialylation with hepatic fibrosis stage, HCV genotype, and the efficacy of antiviral therapy enables using these changes as novel noninvasive predictive biomarkers. The clinical potential of these findings is discussed.
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International Liver Transplantation Society Asian Consensus on the Management of Hepatitis C Virus Infection in Resource Limited Setting-From Noncirrhotic to Decompensated Disease and After Liver Transplantation. Transplantation 2019; 103:733-746. [PMID: 30335692 DOI: 10.1097/tp.0000000000002453] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The population of Asia exceeds 4.4 billion people. Chronic hepatitis C virus (HCV) infection in Asia is characterized by specific distribution of genotypes, lack of access to specific therapeutic agents, relatively high cost of treatment, and lack of experienced healthcare providers. Clear consensus on the diagnosis, management, and monitoring of HCV infection specific to the Asian region is a major unmet need. The consensus guidelines documents that have been published to date by major medical societies presume access to an array of direct acting antiviral agents and diagnostic tests that are not broadly applicable to resource limited settings, including Asia. METHODS To address the lack of an Asia-specific set of HCV treatment guidelines, we assembled a panel of 15 HCV experts in the field of hepatology from India, Indonesia, Myanmar, Vietnam, Pakistan, Philippines, and Mongolia convened in April 2017 to review the updated literature and provide recommendations on the diagnosis and management of chronic HCV infection that reflects local conditions. RESULTS An evidence-based comprehensive compilation of the literature supported by the graded recommendations from the expert panel for the optimization of the diagnosis, pretreatment, on treatment, and posttreatment assessments, and management of chronic HCV infection has been presented in this article. CONCLUSIONS With the evolving treatment landscape and addition of several new direct-acting antiviral agents and combination regimens into the therapeutic armamentarium, the current article may serve as a guide to the clinicians in optimizing the diagnosis and treatment selection for the management of chronic HCV infection in resource-limited settings.
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Brady Z, Stoykova Z. Hepatitis C virus genotype analysis in patients with chronic hepatitis in North Eastern Bulgaria. J Drug Assess 2019; 8:146-149. [PMID: 31552145 PMCID: PMC6746290 DOI: 10.1080/21556660.2019.1654484] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Accepted: 08/07/2019] [Indexed: 01/12/2023] Open
Abstract
Background: The main objective of this study was to analyse the spread of hepatitis C virus (HCV) genotype in patients with chronic liver disease; commenting on the molecular characterization of HCV and gender and age in Varna, Bulgaria. Across Europe and the world, HCV is a significant economic concern and public health crisis. Defined by genotype variations, HCV is the leading cause of chronic liver disease, liver related morbidity, and mortality worldwide. Active examination for asymptomatic patients is essential, initiating early treatment aimed at the specific HCV genotype, effective outcomes, and reducing transmission and mortality in Bulgaria. Methods and materials: Nucleic acid extraction and amplification were performed with commercially available test kits on 115 patients blood samples collected from March 2018 to October 2018. Male (n = 58) (50.43%, 95% CI = 41.29%-59.57%) and female (n = 57) (49.57%, 95% CI = 41.29%-59.57%) samples were equally distributed (mean age = 51.4 years; SD = ±16.5 years; range = 17-87 years old). Results: Genotype 1b predominated (73%, 95% CI = 64.89%-81.11%), followed by high prevalence of 1a (13.9%, 95% CI = 7.58%-20.22%) and 3 genotypes (11.3%, 95% CI = 5.51%-17.09%). Genotypes 2 and 4 were equally the least prevalent (0.9%, 95% CI = -0.83%-2.63%). In genotype 1b, 60.7% were women and 39.3% were men; in genotype 1a, 25% were women and 75% were men; and in genotype 3, only 7.7% were women and 92.3% were men. Males were most prevalent in genotypes 1a (75%) and 3 (92.3%), while women were most prevalent in genotype 1b (60.7%). Conclusions: HCV genotype lb is the predominant variant within the epidemiological pattern of HCV genotypes in patients with chronic liver diseases in North Eastern Bulgaria.
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Affiliation(s)
| | - Zhivka Stoykova
- Department of Microbiology and Virology, Medical Faculty, Medical University of Varna, Varna, Bulgaria
- Laboratory of Clinical Virology, University Hospital “St. Marina”, Varna, Bulgaria
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Petruzziello A, Loquercio G, Sabatino R, Balaban DV, Ullah Khan N, Piccirillo M, Rodrigo L, di Capua L, Guzzo A, Labonia F, Botti G. Prevalence of Hepatitis C virus genotypes in nine selected European countries: A systematic review. J Clin Lab Anal 2019; 33:e22876. [PMID: 30843304 PMCID: PMC6595292 DOI: 10.1002/jcla.22876,] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a global health problem especially for its increasing level of mortality. Detailed knowledge of HCV genotypes prevalence has clinical relevance since the efficacy of therapies is impacted by genotypes and subtypes distribution. Moreover, HCV exhibits a great genetic variability regionally. To date, there are no published studies assessing HCV genotypes distribution in specific countries of the Mediterranean basin. The aim of this study was to review data published from 2000 to 2017 with the purpose to estimate genotypes distribution of HCV infection in nine European countries all located in the Mediterranean basin. METHODS A systematic research of peer-reviewed journals indexed in PubMed, Scopus, and EMBASE databases selected if containing data regarding distribution of HCV genotypes in nine selected European countries (Albania, Bosnia, Croatia, France, Greece, Italy, Montenegro, Slovenia, and Spain) was performed. RESULTS Genotype 1 is the most common (61.0%), ranging from 80.0% in Croatia to 46.0% in Greece, followed by genotype 3 (20.0%), varying from 38.0% in Slovenia to 7.0% and 8.0%, respectively, in Italy and in Albania and by genotype 4 (10.0%) that shows an increase of 1.1% with respect to data obtained till 2014 probably due to the increasing migrants arrivals to Southern Europe. G2, the fourth most frequent genotype (8.5%), particularly common in Italy (27.0%) and Albania (18.0%) might be probably introduced in Southern Italy as a result of Albanian campaign during Second World War and more and more increased by the migration flows from Albania to Italy in the 90s. CONCLUSION Epidemiology of HCV infection shows a high variability across the European countries that border the Mediterranean Sea. HCV genotyping is a relevant tool to monitor the dynamic process influenced by both evolving transmission trends and new migration flows on HCV scenario.
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Affiliation(s)
| | - Giovanna Loquercio
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Rocco Sabatino
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Daniel Vasile Balaban
- Carol Davila" University of Medicine and Pharmacy, "Dr. Carol Davila" Central Military Emergency University HospitalBucharestRomania
| | - Najeeb Ullah Khan
- Institute of Biotechnology and Genetic Engineering (Health Davison)The University of AgriculturePeshawarPakistan
| | - Mauro Piccirillo
- Hepatobiliar and Pancreatic Unit, Department of Surgical OncologyIstituto Nazionale Tumori–Fondazione “G. Pascale”IRCCS ItaliaNaplesItaly
| | - Luis Rodrigo
- Gastroenterology ServiceHospital Universitario Central de Asturias, University of OviedoOviedoSpain
| | - Lucia di Capua
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Annunziata Guzzo
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Francesco Labonia
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Gerardo Botti
- Scientific DirectorIRCCS Fondazione PascaleNaplesItaly
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Petruzziello A, Loquercio G, Sabatino R, Balaban DV, Ullah Khan N, Piccirillo M, Rodrigo L, di Capua L, Guzzo A, Labonia F, Botti G. Prevalence of Hepatitis C virus genotypes in nine selected European countries: A systematic review. J Clin Lab Anal 2019; 33:e22876. [PMID: 30843304 PMCID: PMC6595292 DOI: 10.1002/jcla.22876] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Revised: 02/08/2019] [Accepted: 02/11/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a global health problem especially for its increasing level of mortality. Detailed knowledge of HCV genotypes prevalence has clinical relevance since the efficacy of therapies is impacted by genotypes and subtypes distribution. Moreover, HCV exhibits a great genetic variability regionally. To date, there are no published studies assessing HCV genotypes distribution in specific countries of the Mediterranean basin. The aim of this study was to review data published from 2000 to 2017 with the purpose to estimate genotypes distribution of HCV infection in nine European countries all located in the Mediterranean basin. METHODS A systematic research of peer-reviewed journals indexed in PubMed, Scopus, and EMBASE databases selected if containing data regarding distribution of HCV genotypes in nine selected European countries (Albania, Bosnia, Croatia, France, Greece, Italy, Montenegro, Slovenia, and Spain) was performed. RESULTS Genotype 1 is the most common (61.0%), ranging from 80.0% in Croatia to 46.0% in Greece, followed by genotype 3 (20.0%), varying from 38.0% in Slovenia to 7.0% and 8.0%, respectively, in Italy and in Albania and by genotype 4 (10.0%) that shows an increase of 1.1% with respect to data obtained till 2014 probably due to the increasing migrants arrivals to Southern Europe. G2, the fourth most frequent genotype (8.5%), particularly common in Italy (27.0%) and Albania (18.0%) might be probably introduced in Southern Italy as a result of Albanian campaign during Second World War and more and more increased by the migration flows from Albania to Italy in the 90s. CONCLUSION Epidemiology of HCV infection shows a high variability across the European countries that border the Mediterranean Sea. HCV genotyping is a relevant tool to monitor the dynamic process influenced by both evolving transmission trends and new migration flows on HCV scenario.
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Affiliation(s)
| | - Giovanna Loquercio
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Rocco Sabatino
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Daniel Vasile Balaban
- Carol Davila" University of Medicine and Pharmacy, "Dr. Carol Davila" Central Military Emergency University HospitalBucharestRomania
| | - Najeeb Ullah Khan
- Institute of Biotechnology and Genetic Engineering (Health Davison)The University of AgriculturePeshawarPakistan
| | - Mauro Piccirillo
- Hepatobiliar and Pancreatic Unit, Department of Surgical OncologyIstituto Nazionale Tumori–Fondazione “G. Pascale”IRCCS ItaliaNaplesItaly
| | - Luis Rodrigo
- Gastroenterology ServiceHospital Universitario Central de Asturias, University of OviedoOviedoSpain
| | - Lucia di Capua
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Annunziata Guzzo
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Francesco Labonia
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Gerardo Botti
- Scientific DirectorIRCCS Fondazione PascaleNaplesItaly
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Chikovani I, Ompad DC, Uchaneishvili M, Sulaberidze L, Sikharulidze K, Hagan H, Van Devanter NL. On the way to Hepatitis C elimination in the Republic of Georgia-Barriers and facilitators for people who inject drugs for engaging in the treatment program: A formative qualitative study. PLoS One 2019; 14:e0216123. [PMID: 31034530 PMCID: PMC6488087 DOI: 10.1371/journal.pone.0216123] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Accepted: 04/15/2019] [Indexed: 01/16/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a significant public health concern worldwide. Georgia is among the countries with a high burden of HCV infection. People who inject drugs (PWID) have the highest burden of infection in Georgia. In 2015, the Government of Georgia, with partners' support, initiated one of the world's first Hepatitis C Elimination Programs. Despite notable progress, challenges to achieving targets persist. This qualitative study is aimed to better understand some of the barriers and facilitators to HCV testing and treatment services for PWID to inform HCV treatment policies and practices. The study instrument examined social, structural, and individual factors influencing HCV testing and treatment practices. We started with key informant interviews to guide the study instrument development and compare the study findings against health care planners' and health care providers' views. Forty PWID with various HCV testing and treatment experiences were recruited through the snowball method. The study found that along with structural factors such as political commitment, co-financing of diagnostic and monitoring tests, and friendly clinic environments, knowledge about HCV infection and elimination program benefits, and support from family and peers also play facilitating roles in accessing testing and treatment services. On the other hand, inability to co-pay for diagnostic tests, fear of side effects associated with treatment, poor knowledge about HCV infection, and lack of social support hampered testing and treatment practices among PWID. Findings from this study are important for increasing the effectiveness of this unique program that targets a population at high risk of HCV infection.
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Affiliation(s)
| | - Danielle C. Ompad
- College of Global Public Health, New York University, New York, NY, United States of America
- Center for Drug Use and HIV Research, New York University, New York, NY, United States of America
| | | | | | | | - Holly Hagan
- College of Global Public Health, New York University, New York, NY, United States of America
- Center for Drug Use and HIV Research, New York University, New York, NY, United States of America
| | - Nancy L. Van Devanter
- College of Global Public Health, New York University, New York, NY, United States of America
- Rory Meyers College of Nursing, New York University, New York, NY, United States of America
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Wahid B, Naeem N, Altaf S, Ilyas N. Increasing Prevalence of Untypable and Mixed Genotypes of Hepatitis C Virus in Pakistan: Latest Trends in 2018. Viral Immunol 2019; 32:192-194. [PMID: 30939104 DOI: 10.1089/vim.2018.0152] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Hepatitis C virus (HCV) genotyping is a critical parameter that acts as predictor of treatment response. According to previously reported findings, about 11 million population of Pakistan are HCV infected. Accumulating data suggest that genotype is the most prevalent genotype and mixed and untypable genotypes are the least prevalent genotypes of HCV. We observed that overall prevalence of mixed genotype (5.03%) and untypable genotype (3.3%) of HCV is on constant rise. This study highlights that the emergence of novel quasispecies could be reason of treatment failure in patients receiving direct-acting antiviral drugs.
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Affiliation(s)
- Braira Wahid
- Department of Life Sciences, School of Science, University of Management and Technology, Lahore, Pakistan
| | - Nabiha Naeem
- Department of Life Sciences, School of Science, University of Management and Technology, Lahore, Pakistan
| | - Saba Altaf
- Department of Life Sciences, School of Science, University of Management and Technology, Lahore, Pakistan
| | - Nimra Ilyas
- Department of Life Sciences, School of Science, University of Management and Technology, Lahore, Pakistan
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Petruzziello A, Sabatino R, Loquercio G, Guzzo A, Di Capua L, Labonia F, Cozzolino A, Azzaro R, Botti G. Nine-year distribution pattern of hepatitis C virus (HCV) genotypes in Southern Italy. PLoS One 2019; 14:e0212033. [PMID: 30785909 PMCID: PMC6382136 DOI: 10.1371/journal.pone.0212033] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Accepted: 01/26/2019] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION It has been greatly described that different hepatitis C virus (HCV) genotypes are strictly correlated to various evolution, prognosis and response to therapy during the chronic liver disease. Aim of this study was to outline the changes in the epidemiology of Hepatitis C genotypes in Southern Italy regions from 2006 to 2014. MATERIAL/METHODS Prevalence of HCV genotypes was analyzed in 535 HCV-RNA positive patients with chronic Hepatitis C infection, selected during the period 2012-2014, and compared with our previous data, referred to periods 2006-2008 and 2009-2011. RESULTS In all the three periods analyzed, genotype 1b is predominant (51.8% in 2006-08, 48.3% in 2009-11 and 54.4% in 2012-14) while genotype 2 showed an increase in prevalence (27.9% in 2006-08, 31.7% in 2009-11 and 35.2% in 2012-14) and genotypes 3a and 1a a decrease during the same period (6.8% in 2006-08, 4.7% in 2009-11 and 3.2% in 2012-14 and 7.9% in 2006-08, 4.7% in 2009-11 and 2.6% in 2012-14, respectively). Subtype 1b seems to be equally distributed between males and females (52.7% vs 56.6%) and the prevalence in the age range 31-40 years is significantly higher in the 2012-14 period than in both previous periods (53.8% vs. 16.6% in 2009-11, p< 0.001 and 13.4% in 2006-08, p < 0.001). CONCLUSIONS Genotype 1b is still the most prevalent, even if shows a significantly increase in the under 40 years old population. Instead, genotype 3a seems to have a moderate increase among young people. Overall, the alarming finding is the "returning" role of the iatrogenic transmission as risk factor for the diffusion of Hepatitis C infection.
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Affiliation(s)
- Arnolfo Petruzziello
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Rocco Sabatino
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Giovanna Loquercio
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Annunziata Guzzo
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Lucia Di Capua
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Francesco Labonia
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Anna Cozzolino
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Rosa Azzaro
- Transfusion Service, Department of Hemathology, Istituto Nazionale Tumori—Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Gerardo Botti
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
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Bellin A, Franchin G, Bolcato J, Bettiol A, Pirolo R, Schiavon A, Giusti P, Tessarin M, Chinellato A. Twenty Years of Hepatitis C in the Treviso District (Local Health Unit 2): Treatments, Clinical Management and Cost Analysis. GLOBAL & REGIONAL HEALTH TECHNOLOGY ASSESSMENT 2019. [DOI: 10.1177/2284240319835865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- Annachiara Bellin
- Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Padova, Italy
| | - Giulia Franchin
- U.O.C. Politiche del Farmaco e Governo della Spesa Farmaceutica, Azienda ULSS2, Distretto di Treviso, Treviso, Italy
| | - Jenny Bolcato
- U.O.C. Politiche del Farmaco e Governo della Spesa Farmaceutica, Azienda ULSS2, Distretto di Treviso, Treviso, Italy
| | - Alessandra Bettiol
- Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Padova, Italy
| | - Roberta Pirolo
- U.O.C. Politiche del Farmaco e Governo della Spesa Farmaceutica, Azienda ULSS2, Distretto di Treviso, Treviso, Italy
| | - Alberto Schiavon
- Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Padova, Italy
| | - Pietro Giusti
- Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Padova, Italy
| | - Michele Tessarin
- U.O.C Direzione Sanitaria, Azienda ULSS2, Distretto di Treviso, Treviso, Italy
| | - Alessandro Chinellato
- U.O.C. Politiche del Farmaco e Governo della Spesa Farmaceutica, Azienda ULSS2, Distretto di Treviso, Treviso, Italy
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Karabulut N, Alacam S, Yolcu A, Onel M, Agacfidan A. Distribution of hepatitis C virus genotypes in Istanbul, Turkey. Indian J Med Microbiol 2018; 36:192-196. [PMID: 30084409 DOI: 10.4103/ijmm.ijmm_17_381] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Purpose The hepatitis C virus (HCV) has seven main genotypes and multiple subtypes. The distribution of HCV genotypes varies across geographical regions worldwide. Updated estimates of HCV genotype distributions have a critical importance for developing strategies to manage or eliminate HCV infection. The aim of this study was to determine the distribution of HCV genotypes in patients with HCV admitted to a university hospital in Istanbul, Turkey. Materials and Methods A total of 412 HCV RNA positive patients with 46.6% of males and 53.4% of females between January 2013 and September 2016 were included in the study. Genotyping of HCV of the study population was performed by a commercial reverse hybridisation line probe-based assay. Results Genotype 1 (82.5%) was dominant genotype, followed by genotype 3 (10.7%), genotype 2 (4.6%) and genotype 4 (2.2%). Among patients with genotype 1, subtype 1a, 1b and undetermined subtype were 6.3%, 38.8% and 37.4%, respectively. It was observed that genotype proportion was dependent on gender and age of the patients. Genotype 1 and genotype 2 were more prevalent in females, whereas genotypes 3 and 4 were more prevalent in males. Genotype 1 in the older patients and genotype 3 in the younger patients were more prevalent. Conclusion The majority of patients with HCV infection had genotype 1 (82.5%), followed by genotype 3, 2 and 4. Monitoring the change in HCV genotype distribution is critical for the development of effective strategies for HCV elimination.
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Affiliation(s)
- Nuran Karabulut
- Department of Medical Microbiology, Division of Virology and Fundamental Immunology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Sema Alacam
- Department of Medical Microbiology, Division of Virology and Fundamental Immunology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ayfer Yolcu
- Department of Medical Microbiology, Division of Virology and Fundamental Immunology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mustafa Onel
- Department of Medical Microbiology, Division of Virology and Fundamental Immunology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ali Agacfidan
- Department of Medical Microbiology, Division of Virology and Fundamental Immunology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Ruggeri M, Rolli FR, Kondili LA, Drago C, De Solda F, Nappi C, Cicchetti A. Cost-effectiveness analysis of Daclatasvir/Sofosbuvir for the treatment of the HCV patients failed after the first line with second generation of DAAs in Italy. Expert Rev Pharmacoecon Outcomes Res 2018; 19:363-374. [PMID: 30351994 DOI: 10.1080/14737167.2019.1537784] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Daclatasvir (DCV) combinated with Sofosbuvir (SOF) has shown good efficacy and safety profile for HCV patients. The aim was to evaluate the cost-effectiveness of DCV/SOF regimen versus HCV alternative treatments for patients who failed to achieve the SVR12 after a first DAA treatment from Italian perspective (PITER cohort). METHODS A Markov model of HCV chronically infected patients was used to develop two scenarios: 1) DCV+ SOF versus Ledipasvir (LDV)+ SOF in Genotype (Gt)1 and Gt4; 2) DCV+ SOF versus no retreatment option in Gt1, Gt3, and Gt4. The percentage of patients who failed the first line with SOF/Simeprevir/Ribavirin (RBV) or SOF/RBV and were retreated or not according to evidences from PITER cohort, were used to populate the model. HCV resources consumption and SVR rates were quantified using PITER data. Transition probabilities and utility rates were derived from the literature. The outcomes were expressed in terms of Quality adjusted life years (QALYs). Probabilistic sensitivity analysis (PSA) was performed considering a cost-effectiveness threshold of € 30,000/QALY. RESULTS In the base-case analysis, DCV+ SOF represents a cost-effectiveness therapy with ICERs lower than the threshold. The PSA showed robust results, ICERs remain below the threshold in 94% and 99% simulations in Scenario 1 and 2, respectively.
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Affiliation(s)
- M Ruggeri
- a Institute of Economic Policy and School of Health Economics and Management , Università Cattolica del Sacro Cuore , Rome , Italy
| | - F R Rolli
- b School of Health Economics and Management , Università Cattolica del Sacro Cuore , Rome , Italy
| | - L A Kondili
- c Center for Global Health , Istituto Superiore di Sanità , Rome , Italy
| | - C Drago
- d Università Niccolò Cusano , Rome , Italy
| | - F De Solda
- e Center for Global Health , Bristol-Myers Squibb , Rome , Italy
| | - C Nappi
- e Center for Global Health , Bristol-Myers Squibb , Rome , Italy
| | - A Cicchetti
- b School of Health Economics and Management , Università Cattolica del Sacro Cuore , Rome , Italy
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Are direct-acting antivirals safe and effective in hepatitis C virus-cryoglobulinemia? virological, immunological, and clinical data from a real-life experience. Eur J Gastroenterol Hepatol 2018; 30:1208-1215. [PMID: 30138160 DOI: 10.1097/meg.0000000000001239] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Hepatitis C virus (HCV) is the major cause of cryoglobulinemia. Direct-acting antivirals (DAAs) have markedly changed the therapeutic outcomes in the treatment of patients with HCV. We evaluate the efficacy, safety, immunological, and clinical response of different DAA regimens in HCV-cryoglobulinemia. PATIENTS AND METHODS Ninety-three cryoglobulinemic patients, divided into symptomatic [symptomatic cryoglobulinemic patients (SCP; n=35)] and asymptomatic [nonsymptomatic cryoglobulinemic patients (NSCP; n=60)], underwent DAAs. Eighty-nine comparable noncryoglobulinemic patients were selected as a control group. We evaluated the sustained virological response (SVR), the adverse effects, and the immune and symptomatic response. RESULTS Percentages of patients who achieved SVR and experienced adverse effects were not statistically different between the three groups (100, 95, 93.3% and 57.1, 53.3, 48.3%). In 68.5% of SCP and in 76.7% of NSCP, cryoglobulins disappeared at SVR. No risk factor was associated with the persistence of cryoglobulins. An increase was observed both in C4 (P=0.002; P=0.018) and in C3 (P=0.0037; P=0.031) in SCP and NSCP. About 70% of symptomatic patients showed a complete or partial symptomatic remission: persistence of symptoms is correlated to the type of clinical picture. CONCLUSION DAA regimens are safe and effective in patients with HCV-cryoglobulinemia. The achievement of SVR is necessary, but not sufficient, to achieve a complete immunological and clinical response.
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Kracht PAM, Arends JE, van Erpecum KJ, Urbanus A, Willemse JA, Hoepelman AIM, Croes EA. Strategies for achieving viral hepatitis C micro-elimination in the Netherlands. HEPATOLOGY, MEDICINE AND POLICY 2018; 3:12. [PMID: 30288334 PMCID: PMC6162944 DOI: 10.1186/s41124-018-0040-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 09/20/2018] [Indexed: 12/12/2022]
Abstract
The Netherlands is striving to achieve national elimination of the hepatitis C virus (HCV) as one of the first countries worldwide. The favorable HCV epidemiology with both low prevalence and incidence, together with access to care and treatment, present excellent conditions to further build on towards this objective. The Dutch national plan on viral hepatitis, introduced in 2016, defines targets in the HCV healthcare cascade and provides a structural framework for the development of elimination activities. Since many different stakeholders are involved in HCV care in the Netherlands, focus has been placed on micro-elimination initiatives as a pragmatic and efficient approach. These numerous micro-eliminations projects have brought the Netherlands closer to HCV elimination. In the near future, efforts specifically have to be made in order to optimize case-finding strategies and to successfully accomplish the nationwide implementation of the registration and monitoring system of viral hepatitis mono-infections, before this final goal can be reached. The upcoming years will then elucidate if the Dutch' hands on approach has resulted in sufficient progress against HCV and if the Netherlands will lead the way towards nationwide HCV elimination.
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Affiliation(s)
- P. A. M. Kracht
- Department of Internal medicine and Infectious disease, Utrecht University, University Medical Center Utrecht, Utrecht, the Netherlands
| | - J. E. Arends
- Department of Internal medicine and Infectious disease, Utrecht University, University Medical Center Utrecht, Utrecht, the Netherlands
| | - K. J. van Erpecum
- Department of Gastroenterology and Hepatology, Utrecht University, University Medical Center Utrecht, Utrecht, the Netherlands
| | - A. Urbanus
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - J. A. Willemse
- Dutch Liver Patient Association (NLV), Hoogland, the Netherlands
| | - A. I. M. Hoepelman
- Department of Internal medicine and Infectious disease, Utrecht University, University Medical Center Utrecht, Utrecht, the Netherlands
| | - E. A. Croes
- Netherlands Institute of Mental Health and Addiction (Trimbos Institute), Utrecht, the Netherlands
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Xiang Y, Lai XF, Chen P, Yang Y. The correlation of HCV RNA and HCV core antigen in different genotypes of HCV. J Clin Lab Anal 2018; 33:e22632. [PMID: 30069909 PMCID: PMC6430366 DOI: 10.1002/jcla.22632] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 06/29/2018] [Accepted: 07/05/2018] [Indexed: 12/23/2022] Open
Abstract
Background To analyze the correlation of HCV RNA and HCV core antigen (HCV cAg) in different genotypes of HCV. Methods One hundred and six patients who were diagnosed with HCV infection by HCV RNA test were included in the study. HCV genotypes were detected by PCR fluorescent probe. Detected HCV cAg's expression in serum quantitatively and qualitatively with chemiluminescent micro‐particle immuno assay (CMIA) and enzyme‐linked immunosorbent assay (ELISA), respectively, and compared positive rates. Analyzed the correlation of HCV RNA and HCV cAg in different genotypes. Results Distribution of HCV genotypes in 106 HCV infected patients were as follows: 1b genotype 46 (43.4%); 2a genotype 7 (6.6%); 3a genotype 18 (17.0%); 3b genotype 3 (2.8%); 6a genotype 9 (8.5%); 1b/3b mixed type 13 (12.3%); and unidentified type 10 (9.4%). Positive rates of HCV cAg detected by CMIA and ELISA were 100% and 56%, respectively, with statistical significance (χ2 = 60.38, P = 0.000). HCV cAg in 1b genotype group was higher than that in 3b and 1b/3b genotype groups, with statistical significance (U = 3.0, P = 0.006, U = 165, P = 0.014). HCV RNA and HCV cAg in genotype 1b demonstrated a positive correlation (r = 0.894, P = 0.04). Conclusion Major genetic subtype of HCV genotype was 1b. Compared with ELISA, detection of HCV cAg by CMIA increased the positive rate and facilitated early diagnosis and treatment of HCV‐infected patients. With the increase in HCV RNA load and the expression of HCV cAg, HCV cAg could be an early indicator for the diagnosis of HCV infection in 1b genotype.
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Affiliation(s)
- Yu Xiang
- Department of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiao-Fei Lai
- Department of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Pu Chen
- Department of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yang Yang
- Department of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Chang SW, Cheng ML, Shiao MS, Yeh CT, Wang CH, Fan CM, Chiu CT, Chang ML. Recovery of lipid metabolic alterations in hepatitis C patients after viral clearance: Incomplete restoration with accelerated ω-oxidation. J Clin Lipidol 2018; 12:756-766. [PMID: 29574072 DOI: 10.1016/j.jacl.2018.02.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Revised: 01/31/2018] [Accepted: 02/20/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND How hepatitis C virus (HCV)-associated lipid metabolic alterations recover after sustained virological response (SVR) remains elusive. OBJECTIVE The aforementioned recovery pattern was investigated. METHODS In a prospective cohort study of 438 chronic hepatitis C (CHC) patients with SVR after anti-HCV therapy, 164 sex- and age-matched genotype I (G1) and G2 patients underwent paired-serum liquid chromatography-tandem mass spectrometry analyses before and 24 weeks after therapy. Subjects without CHC served as controls (n = 100). RESULTS CHC patients had lower baseline lipid levels than controls. Among CHC patients, pre-therapy total cholesterol levels were positively associated with HCV RNA levels; G1 patients had higher pre-therapy HCV RNA levels than G2 patients. Repeated measures analysis of variance of CHC patients showed that lathosterol, lanosterol, total hydroxysphingomyelin, and total phosphatidylcholines levels, and total dicarboxyacylcarnitine/total acylcarnitine (indicators of ω-oxidation) and pre-β-lipoprotein ratios elevated 24 weeks after therapy compared with the levels before therapy. Levels of total lysophosphatidylcholines and α- and β-lipoprotein ratios decreased. Subgroup analyses showed elevated 7-dehydrocholesterol and lanosterol levels, particularly in G2 and male patients, who had broader spectra of altered phosphatidylcholines and acylcarnitines than G1 and female patients, respectively. Compared with controls, CHC patients had higher post-therapy levels of total lysophosphatidylcholines and hydroxysphingomyelins and ratios of total dicarboxyacylcarnitines/total acylcarnitines but lower cholesterol levels. CONCLUSIONS At 24 weeks after therapy, accelerated cholesterol biosynthesis, hepatic lipid export, ω-oxidation, and decreased systemic inflammation were noted in CHC patients with SVR, with greater efficiency in G2 and male patients. Regardless, HCV-associated lipid metabolic alterations required >24 weeks for restoration or were incompletely reversible after SVR.
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Affiliation(s)
- Su-Wei Chang
- Liver Research Centre, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Division of Allergy, Asthma, and Rheumatology, Department of Paediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Clinical Informatics and Medical Statistics Research Centre, Chang Gung University, Taoyuan, Taiwan
| | - Mei-Ling Cheng
- Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan; Metabolomics Core Laboratory, Healthy Aging Research Centre, Chang Gung University, Taoyuan, Taiwan; Clinical Phenome Centre, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Ming-Shi Shiao
- Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan
| | - Chau-Ting Yeh
- Liver Research Centre, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chao-Hung Wang
- Department of Internal Medicine, Division of Cardiology, Heart Failure Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chun-Ming Fan
- Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Tang Chiu
- Liver Research Centre, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ming-Ling Chang
- Liver Research Centre, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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Petruzziello A. Epidemiology of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Related Hepatocellular Carcinoma. Open Virol J 2018. [PMID: 29541276 PMCID: PMC5842386 DOI: 10.2174/1874357901812010026] [Citation(s) in RCA: 152] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Introduction Hepatocellular carcinoma (HCC) is one of the most prevalent primary malignant tumors and accounts for about 90% of all primary liver cancers. Its distribution varies greatly according to geographic location and it is more common in middle and low- income countries than in developed ones especially in Eastern Asia and Sub Saharan Africa (70% of all new HCCs worldwide), with incidence rates of over 20 per 100,000 individuals. Explanation The most important risk factors for HCC are Hepatitis B Virus (HBV) infection, Hepatitis C Virus (HCV) infection, excessive consumption of alcohol and exposition to aflatoxin B1. Its geographic variability and heterogeneity have been widely associated with the different distribution of HBV and HCV infections worldwide.Chronic HBV infection is one of the leading risk factors for HCC globally accounting for at least 50% cases of primary liver tumors worldwide. Generally, while HBV is the main causative agent in the high incidence HCC areas, HCV is the major etiological factor in low incidence HCC areas, like Western Europe and North America. Conclusion HBV-induced HCC is a complex, stepwise process that includes integration of HBV DNA into host DNA at multiple or single sites. On the contrary, the cancerogenesis mechanism of HCV is not completely known and it still remains controversial as to whether HCV itself plays a direct role in the development of tumorigenic progression.
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Affiliation(s)
- Arnolfo Petruzziello
- Department of Pathology, Virology and Molecular Biology Unit, Istituto Nazionale Tumori- IRCCS Fondazione G. Pascale, Naples, Italy
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Steinebrunner N, Stein K, Sandig C, Bruckner T, Stremmel W, Pathil A. Predictors of functional benefit of hepatitis C therapy in a ‘real-life’ cohort. World J Gastroenterol 2018; 24:852-861. [PMID: 29467555 PMCID: PMC5807943 DOI: 10.3748/wjg.v24.i7.852] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2017] [Revised: 12/31/2017] [Accepted: 01/15/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To define predictors of functional benefit of direct-acting antivirals (DAAs) in patients with chronic hepatitis C virus (HCV) infection and liver cirrhosis.
METHODS We analysed a cohort of 199 patients with chronic HCV genotype 1, 2, 3 and 4 infection involving previously treated and untreated patients with compensated (76%) and decompensated (24%) liver cirrhosis at two tertiary centres in Germany. Patients were included with treatment initiation between February 2014 and August 2016. All patients received a combination regimen of one or more DAAs for either 12 or 24 wk. Predictors of functional benefit were assessed in a univariable as well as multivariable model by binary logistic regression analysis.
RESULTS Viral clearance was achieved in 88% (175/199) of patients. Sustained virological response (SVR) 12 rates were as follows: among 156 patients with genotype 1 infection the SVR 12 rate was 90% (n = 141); among 7 patients with genotype 2 infection the SVR 12 rate was 57% (n = 4); among 30 patients with genotype 3 infection the SVR 12 rate was 87% (n = 26); and among 6 patients with genotype 4 infection the SVR 12 rate was 67% (n = 4). Follow-up MELD scores were available for 179 patients. A MELD score improvement was observed in 37% (65/179) of patients, no change of MELD score in 41% (74/179) of patients, and an aggravation was observed in 22% (40/179) of patients. We analysed predictors of functional benefit from antiviral therapy in our patients beyond viral eradication. We identified the Child-Pugh score, the MELD score, the number of platelets and the levels of albumin and bilirubin as significant factors for functional benefit.
CONCLUSION Our data may contribute to the discussion of potential risks and benefits of antiviral therapy with individual patients infected with HCV and with advanced liver disease.
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Affiliation(s)
- Niels Steinebrunner
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg 69120, Germany
| | - Kerstin Stein
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital of Magdeburg, Magdeburg 39120, Germany
| | - Catharina Sandig
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg 69120, Germany
| | - Thomas Bruckner
- Department of Medical Biometry, Institute of Medical Biometry and Informatics (IMBI), Heidelberg 69120, Germany
| | - Wolfgang Stremmel
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg 69120, Germany
| | - Anita Pathil
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg 69120, Germany
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Taherkhani R, Farshadpour F. Global elimination of hepatitis C virus infection: Progresses and the remaining challenges. World J Hepatol 2017; 9:1239-1252. [PMID: 29312527 PMCID: PMC5745585 DOI: 10.4254/wjh.v9.i33.1239] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2017] [Revised: 09/01/2017] [Accepted: 09/16/2017] [Indexed: 02/06/2023] Open
Abstract
Today, with the introduction of interferon-free direct-acting antivirals and outstanding progresses in the prevention, diagnosis and treatment of hepatitis C virus (HCV) infection, the elimination of HCV infection seems more achievable. A further challenge is continued transmission of HCV infection in high-risk population specially injecting drug users (IDUs) as the major reservoir of HCV infection. Considering the fact that most of these infections remain undiagnosed, unidentified HCV-infected IDUs are potential sources for the rapid spread of HCV in the community. The continuous increase in the number of IDUs along with the rising prevalence of HCV infection among young IDUs is harbinger of a forthcoming public health dilemma, presenting a serious challenge to control transmission of HCV infection. Even the changes in HCV genotype distribution attributed to injecting drug use confirm this issue. These circumstances create a strong demand for timely diagnosis and proper treatment of HCV-infected patients through risk-based screening to mitigate the risk of HCV transmission in the IDUs community and, consequently, in the society. Meanwhile, raising general awareness of HCV infection, diagnosis and treatment through public education should be the core activity of any harm reduction intervention, as the root cause of failure in control of HCV infection has been lack of awareness among young drug takers. In addition, effective prevention, comprehensive screening programs with a specific focus on high-risk population, accessibility to the new anti-HCV treatment regimens and public education should be considered as the top priorities of any health policy decision to eliminate HCV infection.
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Affiliation(s)
- Reza Taherkhani
- the Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr 7514633341, Iran
| | - Fatemeh Farshadpour
- the Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr 7514633341, Iran.
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Role of circulatory microRNAs in the pathogenesis of hepatitis C virus. Virusdisease 2017; 28:360-367. [PMID: 29291226 DOI: 10.1007/s13337-017-0407-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Accepted: 11/03/2017] [Indexed: 12/17/2022] Open
Abstract
Hepatitis C virus (HCV) is associated with one of the major health problem in world that ultimate results in the liver cirrhosis and leads to carcinoma of hepatocellular components round the world. More than 185 million people were found to be infected with HCV. MicroRNAs are small oligonucleotide RNA having 18-22 nucleotides. Circulating mi-RNAs regulate the replication of HCV and HCV-induced liver fibrosis and HCC. By comparing the expression profiles of mi-RNAs of normal individuals with HCV infected patients, aberrant changes in expression of different mi-RNAs have been observed so it can be predicted that these mi-RNAs are associated with and play a central role in the hepatitis C infection and diseases associated with it. This review demonstrates the major role of circulatory microRNAs in the HCV and HCV associated ailments.
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Genotype and genetic variation of HCV infections with low-risk factors in Putian coastal regions, China. Epidemiol Infect 2017; 145:3385-3397. [PMID: 29081304 DOI: 10.1017/s0950268817002357] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Hepatitis C virus (HCV) infection is one of the leading causes of death and morbidity associated with liver disease. Risk factors identified for the transmission of HCV include contaminated blood products, intravenous drug use, body piercing, an infected mother at birth, sexual activity, and dental therapy, among others. However, the exact diversity of the HCV genotype and genetic variation among patients with low-risk factors is still unknown. In this study, we briefly described and analysed the genotype distribution and genetic variation of HCV infections with low-risk factors using molecular biology techniques. The results suggested that genotype 1b was predominant, followed by genotypes 2a and 1a. Genetic variations in the 5' UTR sequences of HCV were identified, including point mutations, deletions, and insertions. The frequency of genetic variations in 1b was higher than in 2a. This study provides considerable value for the prevention and treatment of liver disease caused by HCV among patients with low-risk factors and for the development of HCV diagnostic reagents and vaccines.
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50
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Ali M, Khan T, Fatima K, Ali QUA, Ovais M, Khalil AT, Ullah I, Raza A, Shinwari ZK, Idrees M. Selected hepatoprotective herbal medicines: Evidence from ethnomedicinal applications, animal models, and possible mechanism of actions. Phytother Res 2017; 32:199-215. [PMID: 29047177 PMCID: PMC7167792 DOI: 10.1002/ptr.5957] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Revised: 08/30/2017] [Accepted: 09/26/2017] [Indexed: 02/06/2023]
Abstract
Insight into the hepatoprotective effects of medicinally important plants is important, both for physicians and researchers. Main reasons for the use of herbal medicine include their lesser cost compared with conventional drugs, lesser undesirable drug reactions and thus high safety, and reduced side effects. The present review focuses on the composition, pharmacology, and results of experimental trials of selected medicinal plants: Silybum marianum (L.) Gaertn., Glycyrrhiza glabra, Phyllanthus amarus Schumach. & Thonn., Salvia miltiorrhiza Bunge., Astragalus membranaceus (Fisch.) Bunge, Capparis spinosa (L.), Cichorium intybus (L.), Solanum nigrum (L.), Sapindus mukorossi Gaertn., Ginkgo biloba (L.), Woodfordia fruticosa (L.) Kurz, Vitex trifolia (L.), Schisandra chinensis (Turcz.) Baill., Cuscuta chinensis (Lam.), Lycium barbarum, Angelica sinensis (Oliv.) Diels, and Litsea coreana (H. Lev.). The probable modes of action of these plants include immunomodulation, stimulation of hepatic DNA synthesis, simulation of superoxide dismutase and glutathione reductase to inhibit oxidation in hepatocytes, reduction of intracellular reactive oxygen species by enhancing levels of antioxidants, suppression of ethanol-induced lipid accumulation, inhibition of nucleic acid polymerases to downregulate viral mRNA transcription and translation, free radical scavenging and reduction of hepatic fibrosis by decreasing the levels of transforming growth factor beta-1, and collagen synthesis in hepatic cells. However, further research is needed to identify, characterize, and standardize the active ingredients, useful compounds, and their preparations for the treatment of liver diseases.
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Affiliation(s)
- Muhammad Ali
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Tariq Khan
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan.,Department of Biotechnology, University of Malakand Chakdara Dir (L)-18000, Khyber Pakhtunkhwa, Pakistan
| | - Kaneez Fatima
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Qurat Ul Ain Ali
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Muhammad Ovais
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Ali Talha Khalil
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Ikram Ullah
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Abida Raza
- National Institute of Laser and Optronics, Nilore, 45650, Pakistan
| | - Zabta Khan Shinwari
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Muhammad Idrees
- Hazara University Mansehra, Khyber Pakhtunkhwa, 21120, Pakistan.,Center for Applied Molecular Biology (CAMB), University of the Punjab, Lahore, 53700, Pakistan
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