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Association of HLA Class II Alleles with Outcome of Hepatitis C Virus Infection: A Systematic Review and Meta-analysis. HEPATITIS MONTHLY 2021. [DOI: 10.5812/hepatmon.109493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Context: Hepatitis C Virus (HCV) infection is a major cause of chronic cirrhosis and hepatocellular carcinoma. Approximately 30% of infected persons with HCV spontaneously clear the viral infection; but, some of the remaining patients develop chronic HCV. Studies show that HLA molecules play an important role in the outcome of HCV infection by influencing the efficiency of the antiviral immune response to HCV infection. It is now known that polymorphisms in HLA loci are associated with HCV susceptibility or clearance. The purpose of the present study was to systematically review the studies that reported the association of HLA class II alleles (HLA-DQ and HLA-DR) with the outcome of HCV infection. Evidence Acquisition: Studies were identified by searching electronic databases, including PubMed and Scopus. A total of 12,265 relevant studies were identified by the electronic search, of which a total of 19 eligible papers were identified that were meta-analyzed for the association between HLA class II alleles and the outcome of HCV infection. Results: Subjects carrying HLA-DQB1*0301, HLA-DQB1*0501, HLA-DRB1*1303, HLA-DRB1*1201, HLA-DRB1*0401, HLA-DRB1*0101, and HLA-DRB1*1101 alleles were significantly associated with higher spontaneous clearance of HCV infection. Conclusions: The data from the current study confirm that several polymorphisms in HLA-DQ and HLA-DR loci are correlated with the clearance of HCV infection. Identifying these polymorphisms may contribute to a better understanding of immune mechanisms of HCV clearance or persistence.
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Yengo CK, Torimiro J, Kowo M, Lebon PA, Tiedeu BA, Luma H, Njoya O, Rowland-Jones S, Yindom LM. Variation of HLA class I (-A and -C) genes in individuals infected with hepatitis B or hepatitis C virus in Cameroon. Heliyon 2020; 6:e05232. [PMID: 33102855 PMCID: PMC7569220 DOI: 10.1016/j.heliyon.2020.e05232] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 09/10/2020] [Accepted: 10/08/2020] [Indexed: 12/22/2022] Open
Abstract
The Human Leucocyte Antigens (HLA) work in concert with other immune factors to modulate immunity to viral infections. Extensive variation has been reported in the genetic sequences and functions of classical HLA class I genes in many (mostly Western) populations, and several HLA associations with infectious disease outcomes have been reported. Little is known about their role in the susceptibility or resistance to hepatitis viruses in Central African populations. The aim of this study was to determine variants of two HLA class I genes (HLA-A and -C) in adults infected with hepatitis B (HBV)- or -C (HCV) virus in Cameroon. In this case-control study, a total of 169 unrelated adults comprising 68 HCV-infected, 38 HBV-infected and 63 uninfected (controls) individuals participated. Each consented participant was screened for HBV, HCV, and HIV infections and willingly donated a single blood sample for genomic DNA isolation and some clinical laboratory tests. HLA-A and HLA-C were genotyped using previously described sequence-based techniques (SBT). A total of 54 HLA alleles were identified in the study population (27 HLA-A and 27 HLA-C). HLA-A∗23:01 and HLA-C∗07:01 were the most common alleles with genotype frequencies of 31.4% and 29.3%, respectively. Hepatitis individuals were six times more likely to be HLA-A∗30:01 carriers than uninfected controls (OR = 6.30, p = 0.020 (HBV); OR = 6.21, p = 0.010 (HCV), respectively). Similarly, carriers of HLA-C∗17:01 were over-represented in the HBV-infected compared to the uninfected control group (21.9% vs. 6.4%, respectively) suggesting that this allele could play a role in the susceptibility to HBV infection. These findings demonstrate that carriers of HLA-A∗30:01 were over-represented in the hepatitis group compared to uninfected controls while HLA-C∗17:01 was completely absent in the HCV + group.
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Affiliation(s)
- Clauvis Kunkeng Yengo
- Department of Biochemistry, Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Judith Torimiro
- Molecular Biology Laboratory, Chantal Biya International Reference Centre for Research on Prevention and Management of HIV/AIDS (CIRCB), Yaoundé, Cameroon
- Department of Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Mathurin Kowo
- Department of Internal Medicine, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Patrick Awoumou Lebon
- Department of Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Barbara Atogho Tiedeu
- Department of Biochemistry, Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Henry Luma
- Department of Internal Medicine, Douala General Hospital, Douala, Cameroon
| | - Oudou Njoya
- Department of Internal Medicine, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Sarah Rowland-Jones
- Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Louis-Marie Yindom
- Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
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Provazzi PJS, Rossi LMG, Carneiro BM, Miura VC, Rosa PCR, de Carvalho LR, de Andrade STQ, Fachini RM, Grotto RMT, Silva GF, Valêncio CR, Neto PS, Cordeiro JA, Nogueira ML, Rahal P. Hierarchical assessment of host factors influencing the spontaneous resolution of hepatitis C infection. Braz J Microbiol 2018; 50:147-155. [PMID: 30637644 DOI: 10.1007/s42770-018-0008-3] [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: 08/25/2017] [Accepted: 04/06/2018] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is associated with chronic liver disease, resulting in cirrhosis and hepatocellular carcinoma. Approximately 20% of HCV infections are spontaneously resolved. Here, we assessed the hierarchical relevance of host factors contributing to viral clearance. METHODS DNA samples from 40 resolved infections and 40 chronic HCV patients paired by age were analyzed. Bivariate analysis was performed to rank the importance of each contributing factor in spontaneous HCV clearance. RESULTS Interestingly, 63.6% of patients with resolved infections exhibited the protective genotype CC for SNP rs12979860. Additionally, 59.3% of patients with resolved infections displayed the protective genotype TT/TT for SNP ss469415590. Moreover, a ranking of clearance factors was estimated. In order of importance, the IL28B CC genotype (OR 0.197, 95% CI 0.072-0.541) followed by the INFL4 TT/TT genotype (OR 0.237, 95% CI 0.083-0.679), and female gender (OR 0.394, 95% CI 0.159-0.977) were the main predictors for clearance of HCV infection. CONCLUSIONS HCV clearance is multifactorial and the contributing factors display a hierarchical order. Identifying all elements playing role in HCV clearance is of the most importance for HCV-related disease management. Dissecting the relevance of each contributing factor will certainly improve our understanding of the pathogenesis of HCV infection.
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Affiliation(s)
| | | | - Bruno Moreira Carneiro
- Department of Biology, São Paulo State University - UNESP, São José do Rio Preto, SP, 15054-000, Brazil
| | - Valeria Chamas Miura
- Department of Biology, São Paulo State University - UNESP, São José do Rio Preto, SP, 15054-000, Brazil
| | | | | | | | - Roberta Maria Fachini
- Department of Hepatology, São José do Rio Preto Medical School, São José do Rio Preto, SP, 15090-000, Brazil
| | | | - Giovanni Faria Silva
- Department of Internal Medicine, São Paulo State University - UNESP, Botucatu, SP, 18618-970, Brazil
| | - Carlos Roberto Valêncio
- Department of Computer Science and Statistics, São Paulo State University - UNESP, São José do Rio Preto, SP, 15054-000, Brazil
| | - Paulo Scarpelini Neto
- Department of Computer Science and Statistics, São Paulo State University - UNESP, São José do Rio Preto, SP, 15054-000, Brazil
| | - José Antonio Cordeiro
- Department of Computer Science and Statistics, São Paulo State University - UNESP, São José do Rio Preto, SP, 15054-000, Brazil
| | - Mauricio Lacerda Nogueira
- Laboratory of Virology, São José do Rio Preto Medical School, São José do Rio Preto, SP, 15090-000, Brazil
| | - Paula Rahal
- Department of Biology, São Paulo State University - UNESP, São José do Rio Preto, SP, 15054-000, Brazil.
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4
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Aisyah DN, Shallcross L, Hully AJ, O'Brien A, Hayward A. Assessing hepatitis C spontaneous clearance and understanding associated factors-A systematic review and meta-analysis. J Viral Hepat 2018; 25:680-698. [PMID: 29345844 DOI: 10.1111/jvh.12866] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Accepted: 12/14/2017] [Indexed: 12/11/2022]
Abstract
New advances in the treatment of hepatitis C provide high levels of sustained viral response but their expense limits availability in publicly funded health systems. The aim of this review was to estimate the proportion of patients who will spontaneously clear HCV, to identify factors that are associated with clearance and to support better targeting of directly acting antivirals. We searched Ovid EMBASE, Ovid MEDLINE and PubMed from 1 January 1994 to 30 June 2015 for studies reporting hepatitis C spontaneous clearance and/or demographic, clinical and behavioural factors associated with clearance. We undertook meta-analyses to estimate the odds of clearance for each predictor. Forty-three studies met the inclusion criteria, representing 20 110 individuals, and 6 of these studies included sufficient data to estimate spontaneous clearance. The proportion achieving clearance within 3, 6, 12 and 24 months following infection were, respectively, 19.8% (95% CI: 2.6%-47.5%), 27.9% (95% CI: 17.2%-41.8%), 36.1% (95% CI: 23.5%-50.9%) and 37.1% (95% CI: 23.7%-52.8%). Individuals who had not spontaneously cleared by 12 months were unlikely to do so. The likelihood of spontaneous clearance was lower in males and individuals with HIV co-infection, the absence of HBV co-infection, asymptomatic infection, black or nonindigenous race, nongenotype 1 infection, older age and alcohol or drug problems. This study suggests that patients continue to spontaneously clear HCV for at least 12 months following initial infection. However, injecting drug users are comparatively less likely to achieve clearance; thus, they should be considered a priority for early treatment given the continuing risks that these individuals pose for onwards transmission.
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Affiliation(s)
- D N Aisyah
- UCL Infectious Disease Informatics, Farr Institute of Health Informatics, London, UK.,Faculty of Public Health, Universitas Indonesia, Depok, Indonesia
| | - L Shallcross
- UCL Infectious Disease Informatics, Farr Institute of Health Informatics, London, UK
| | - A J Hully
- Kings College London School of Medicine, London, UK
| | - A O'Brien
- UCL Division of Medicine, London, UK
| | - A Hayward
- UCL Infectious Disease Informatics, Farr Institute of Health Informatics, London, UK.,Institute of Epidemiology and Health Care, University College London, London, UK
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5
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A Biomolecular Network Driven Proteinic Interaction in HCV Clearance. Cell Biochem Biophys 2018; 76:161-172. [PMID: 29313175 DOI: 10.1007/s12013-017-0837-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Accepted: 12/26/2017] [Indexed: 12/20/2022]
Abstract
Hepatitis C virus infection causes chronic liver disease that leads to cancer-related mortality. Presently around 30% of the HCV (infected) affected population get rid of the infection through spontaneous disease clearance. This phenomenon is conducted by a set of reported immune candidate genes. Hence, this study focuses only on these immune-response related genes with aid of network approach, where the idea is to disseminate the network for better understanding of key functional genes and their transcription control activity. Based on the network analysis the IFNG, TNF, IFNB1, STAT1, NFKB1, STAT3, SOCS1, and MYD88 genes are prioritized as hub genes along with their common transcription factors (TFs), IRF9, NFKB1, and STAT1. The dinucleotide frequency of TF binding elements indicated GG-rich motifs in these regulatory elements. On the other hand, gene enrichment report suggests the regulation of response to interferon gamma signaling pathway, which plays central role in the spontaneous HCV clearance. Therefore, our study tends to prioritize the genes, TFs, and their regulatory pathway towards HCV clearance. Even so, the resultant hub genes and their TFs and TF binding elements could be crucial in underscoring the clearance activity in specific populations.
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6
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Yan Z, Wang Y. Viral and host factors associated with outcomes of hepatitis C virus infection (Review). Mol Med Rep 2017; 15:2909-2924. [PMID: 28339063 DOI: 10.3892/mmr.2017.6351] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Accepted: 02/13/2017] [Indexed: 11/05/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a major health issue globally. Owing to the progress made in host genetics and HCV molecular virology, emerging data have suggested that the natural course and treatment response in patients with HCV infection are largely determined by complex host‑viral interactions. HCV genotype is the most important viral factor predicting the response to pegylated interferon‑α plus ribavirin therapy. The subtype of HCV genotype 1 is the key viral factor that predicts the efficacy of direct‑acting antiviral therapy. HCV genome heterogeneity and baseline viral load are additionally associated with the treatment response. Multiple host genetic variants localized in genes associated with the immune response have been identified as predictors of spontaneous disease course and therapy outcome in chronic HCV. However, most findings from candidate gene association studies have not been proven universal for all investigated populations and independent studies. Previous findings in independent large genome wide association studies confirmed that interferon‑λ3 gene polymorphisms are associated with spontaneous clearance and treatment responsiveness. A polymorphism of the inosine triphosphatase gene has been identified as a protective factor against ribavirin‑induced anemia and dose reductions. Another genetic variant in the patatin‑like phospholipase domain containing 3 genes is associated with hepatic steatosis and fibrosis in patients with HCV. The present review focused on the identified viral and host factors associated with outcomes of patients with HCV, and assessed the involvement of viral and host genetics in the natural history and treatment outcomes of HCV infection. This will provide novel ideas concerning personalized prevention and individualized clinical management.
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Affiliation(s)
- Zehui Yan
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Shapingba, Chongqing 400038, P.R. China
| | - Yuming Wang
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Shapingba, Chongqing 400038, P.R. China
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7
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Magri A, Barbaglia MN, Foglia CZ, Boccato E, Burlone ME, Cole S, Giarda P, Grossini E, Patel AH, Minisini R, Pirisi M. 17,β-estradiol inhibits hepatitis C virus mainly by interference with the release phase of its life cycle. Liver Int 2017; 37:669-677. [PMID: 27885811 PMCID: PMC5448036 DOI: 10.1111/liv.13303] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 10/31/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Oestrogen and oestrogen-mediated signalling protect from hepatitis C virus through incompletely understood mechanisms. We aimed to ascertain which phase(s) of hepatitis C virus life cycle is/are affected by oestrogens. METHODS Huh7 cells infected with the JFH1 virus (genotype 2a) were exposed to dehydroepiandrosterone, testosterone, progesterone and 17β-estradiol (tested with/without its receptor antagonist fulvestrant). Dose-response curves were established to calculate half maximal inhibitory concentration values. To dissect how 17β-estradiol interferes with phases of hepatitis C virus life cycle, its effects were measured on the hepatitis C virus pseudo-particle system (viral entry), the subgenomic replicon N17/JFH1 and the replicon cell line Huh7-J17 (viral replication). Finally, in a dual-step infection model, infectious supernatants, collected from infected cells exposed to hormones, were used to infect naïve cells. RESULTS Progesterone and testosterone showed no inhibitory effect on hepatitis C virus; dehydroepiandrosterone was only mildly inhibitory. In contrast, 17β-estradiol inhibited infection by 64%-67% (IC50 values 140-160 nmol/L). Fulvestrant reverted the inhibition by 17β-estradiol in a dose-dependent manner. 17β-estradiol exerted only a slight inhibition (<20%) on hepatitis C virus pseudo-particles, and had no effect on cells either transiently or stably (Huh7-J17 cells) expressing the N17/JFH1 replicon. In the dual-step infection model, a significant half maximal inhibitory concentration decline occurred between primary (134 nmol/L) and secondary (100 nmol/L) infections (P=.02), with extracellular hepatitis C virus RNA and infectivity being reduced to a higher degree in comparison to its intracellular counterpart. CONCLUSIONS 17β-estradiol inhibits hepatitis C virus acting through its intracellular receptors, mainly interfering with late phases (assembly/release) of the hepatitis C virus life cycle.
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Affiliation(s)
- Andrea Magri
- Department of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly,MRC‐University of Glasgow Centre for Virus ResearchGlasgowUK
| | - Matteo N. Barbaglia
- Department of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
| | - Chiara Z. Foglia
- Department of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
| | - Elisa Boccato
- Department of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
| | - Michela E. Burlone
- Department of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly,CRRF Mons. Luigi NovareseMoncrivelloVercelliItaly
| | - Sarah Cole
- MRC‐University of Glasgow Centre for Virus ResearchGlasgowUK
| | - Paola Giarda
- Department of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
| | - Elena Grossini
- Department of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
| | - Arvind H. Patel
- MRC‐University of Glasgow Centre for Virus ResearchGlasgowUK
| | - Rosalba Minisini
- Department of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
| | - Mario Pirisi
- Department of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
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8
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Xiong H, Rong X, Wang M, Xu R, Huang K, Liao Q, Huang J, Chen J, Li C, Tang X, Shan Z, Zhang M, Nelson K, Fu Y. HBV/HCV co-infection is associated with a high level of HCV spontaneous clearance among drug users and blood donors in China. J Viral Hepat 2017; 24:312-319. [PMID: 27943542 DOI: 10.1111/jvh.12644] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Accepted: 09/20/2016] [Indexed: 12/11/2022]
Abstract
Understanding the biology of spontaneous clearance of hepatitis C virus (HCV) infection could lead to improved strategies to prevent the sequelae associated with chronic HCV infection. Chronic infections with hepatitis virus are very common in China, but the factors associated with spontaneous clearance of HCV have not been adequately studied. We evaluated the spontaneous clearance of HCV among 1918 drug users and 1526 HCV-seropositive blood donors in Guangzhou, China. Among participants who were co-infected with hepatitis B virus (HBV), 41.38% of drug users and 39.47% of blood donors had cleared their HCV infection without antiviral therapy compared to 9.41% of drug users and 16.73% of blood donors who were mono-infected with a single virus (P<.01). The proportion of subjects who had cleared their HCV infection was significantly greater in the co-infected subjects whose serum HBV DNA was greater than 2000IU/mL than those with lower levels. A multiple logistic regression analysis found female gender, IL28B rs8099917 TT genotype, HBV co-infection and blood donors (vs drug users) associated with increased spontaneous clearance of HCV infection. Although acute HCV infections are common in China, the incidence of chronic HCV may be reduced among the high prevalence of chronic HBV and IL28B genotypes associated with spontaneous clearance of HCV in Chinese populations.
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Affiliation(s)
- H Xiong
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - X Rong
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - M Wang
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - R Xu
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - K Huang
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - Q Liao
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - J Huang
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - J Chen
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - C Li
- Department of Transfusion Medicine, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
| | - X Tang
- Department of Transfusion Medicine, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
| | - Z Shan
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - M Zhang
- Faculty of Infectious Diseases, Department of Epidemiology and Biostatistics, University of Georgia, Athens, GA, USA
| | - K Nelson
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
| | - Y Fu
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
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9
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Yang R, Yang X, Xiu B, Rao H, Fei R, Guan W, Liu Y, Wang Q, Feng X, Zhang H, Wei L. Hepatitis C Virus Genotype Analyses in Chronic Hepatitis C Patients and Individuals With Spontaneous Virus Clearance Using a Newly Developed Serotyping Assay. J Clin Lab Anal 2017; 31:e22014. [PMID: 27292225 PMCID: PMC6817036 DOI: 10.1002/jcla.22014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Accepted: 05/18/2016] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND We developed a novel HCV serotyping assay and detected the genotypes in chronic hepatitis C (CHC) patients and individuals with spontaneous viral clearance (SVC). METHODS Nine hundred and ninety-seven patients were enrolled in a previous study; their samples were genotyped originally using the molecular assays. Among them, 190 patients achieved sustained virological response; the post-treatment samples were also serotyped. Moreover, 326 samples from follow-up cohorts were serotyped, among whom 66 were from SVC individuals, and 260 from CHC patients. RESULTS Nine hundred and fifty-eight out of 997 samples were available for serotyping, among which 29 samples generated indeterminate serotyping results. The consistency between the genotyping and serotyping assays was 91.50% (850/929). The specificity and sensitivity were 98.45% and 88.77% for genotype 1, 96.42% and 93.97% for genotype 2, and 94.15% and 80.52% for non-genotype 1 or 2. However, only 41 of 60 genotype-6 samples were correctly serotyped. Little difference was found in the 190 paired serotyping results. No difference existed in the genotype distribution between the SVC and CHC groups (P = 0.08). CONCLUSIONS The assay provides an accurate alternative for determining HCV genotypes, whereas it is not recommended for detecting genotype 6. Furthermore, it facilitates identifying the genotypes in SVC individuals. HCV genotype has little impact on SVC.
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Affiliation(s)
- Ruifeng Yang
- Peking University People's HospitalPeking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijingChina
| | - Xiqin Yang
- Institute of Basic Medicine ScienceAcademy of Military Medical SciencesBeijingChina
| | - Bingshui Xiu
- Institute of Basic Medicine ScienceAcademy of Military Medical SciencesBeijingChina
| | - Huiying Rao
- Peking University People's HospitalPeking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijingChina
| | - Ran Fei
- Peking University People's HospitalPeking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijingChina
| | - Wenli Guan
- Peking University People's HospitalPeking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijingChina
| | - Yan Liu
- Peking University People's HospitalPeking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijingChina
| | - Qian Wang
- Peking University People's HospitalPeking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijingChina
| | - Xiaoyan Feng
- Institute of Basic Medicine ScienceAcademy of Military Medical SciencesBeijingChina
| | - Heqiu Zhang
- Institute of Basic Medicine ScienceAcademy of Military Medical SciencesBeijingChina
| | - Lai Wei
- Peking University People's HospitalPeking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijingChina
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10
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Chen Y, Shen C, Guha D, Ding M, Kulich S, Ashimkhanova A, Rinaldo C, Seaberg E, Margolick JB, Stosor V, Martínez-Maza O, Gupta P. Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV. BMC Infect Dis 2016; 16:693. [PMID: 27875997 PMCID: PMC5120459 DOI: 10.1186/s12879-016-2044-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Accepted: 11/16/2016] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Infection with human immunodeficiency virus (HIV) influences the outcome and natural disease progression of hepatitis C virus (HCV) infection. While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop chronic HCV infection, 20-46% of mono- and co-infected subjects spontaneously clear HCV infection. The mechanism underlying viral clearance is not clearly understood. Analysis of differential cellular gene expression (mRNA) between HIV-infected patients with persistent HCV infection or spontaneous clearance could provide a unique opportunity to decipher the mechanism of HCV clearance. METHODS Plasma RNA from HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV was sequenced using Ion Torrent technology. The sequencing results were analyzed to identify transcripts that are associated with HCV clearance by measuring differential gene expression in HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV. RESULTS We have identified plasma mRNA, the levels of which are significantly elevated (at least 5 fold, False Discovery Rate (FDR) <0.05) before HCV infection in subjects who cleared HCV compared to those who remained chronically infected. Upon further analysis of these differentially expressed genes, before and after HCV infection, we found that before HCV infection 12 genes were uniquely upregulated in the clearance group compared to the chronically infected group. Importantly, a number of these 12 genes and their upstream regulators (such as CCL3, IL17D, LBP, SOCS3, NFKBIL1, IRF) are associated with innate immune response functions. CONCLUSIONS These results suggest that subjects who spontaneously clear HCV may express these unique genes associated with innate immune functions.
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Affiliation(s)
- Yue Chen
- Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA.
| | - Chengli Shen
- Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA
| | - Debjani Guha
- Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA
| | - Ming Ding
- Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA
| | - Scott Kulich
- Department of Pathology, VA Hospital, Pittsburgh, Pa, USA
| | - Aiymkul Ashimkhanova
- Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA
| | - Charles Rinaldo
- Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA
| | - Eric Seaberg
- Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
| | - Joseph B Margolick
- Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
| | - Valentina Stosor
- Division of Infectious Diseases, School of Medicine, Northwestern University, Chicago, IL, USA
| | - Otoniel Martínez-Maza
- Department of Epidemiology, UCLA Fielding School of Public Health, and Departments of Obstetrics & Gynecology and Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Phalguni Gupta
- Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA
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Heim MH, Bochud PY, George J. Host - hepatitis C viral interactions: The role of genetics. J Hepatol 2016; 65:S22-S32. [PMID: 27641986 DOI: 10.1016/j.jhep.2016.07.037] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 07/29/2016] [Accepted: 07/29/2016] [Indexed: 12/15/2022]
Abstract
Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN)-induced genes, and a delayed induction of adaptive immune responses. There is a strong association between genetic variants in the IFNλ (IL28B) locus with the rate of spontaneous clearance. Individuals with the ancestral IFNλ4 allele capable of producing a fully active IFNλ4 are paradoxically not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability. In the chronic phase of HCV infection, the wild-type IFNλ4 genotype is strongly associated with an induction of hundreds of classical type I/type III IFN stimulated genes in hepatocytes. However, the activation of the endogenous IFN system in the liver is ineffective in clearing HCV, and is even associated with impaired therapeutic responses to pegylated (Peg)IFNα containing treatments. While the role of genetic variation in the IFNλ locus to the outcome of CHC treatment has declined, it is clear that variation not only at this locus, but also at other loci, modulate clinically important liver phenotypes, including inflammation, fibrosis progression and the development of hepatocellular cancer. In this review, we summarize current knowledge about the role of genetics in the host response to viral hepatitis and the potential future evolution of knowledge in understanding host-viral interactions.
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Affiliation(s)
- Markus H Heim
- Division of Gastroenterology and Hepatology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
| | - Pierre-Yves Bochud
- Infectious Diseases Service, University Hospital and University of Lausanne, Rue du Bugnon 46, 1011 Lausanne-CHUV, Switzerland.
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia.
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12
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Huang J, Huang K, Xu R, Wang M, Liao Q, Xiong H, Li C, Tang X, Shan Z, Zhang M, Rong X, Nelson K, Fu Y. The Associations of HLA-A*02:01 and DRB1*11:01 with Hepatitis C Virus Spontaneous Clearance Are Independent of IL28B in the Chinese Population. Sci Rep 2016; 6:31485. [PMID: 27511600 PMCID: PMC4980596 DOI: 10.1038/srep31485] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2016] [Accepted: 07/20/2016] [Indexed: 12/26/2022] Open
Abstract
Spontaneous clearance of hepatitis C virus (HCV) occurs in 10-40% of the infections. Specific human leukocyte antigen (HLA) alleles have been identified in associating with HCV clearance. However, data on the association of HLA with the spontaneous clearance of HCV are scarce in the Chinese population. In the current study we studied the HLA class I and class II genes in 231 Chinese voluntary blood donors who had cleared HCV infection spontaneously compared to 429 subjects with chronic HCV infections. We also studied their IL28B SNP (rs8099917) genotype, since a number of investigators have found a strong association of IL28B with spontaneous or treatment induced HCV clearance. We found that HLA-A*02:01 and DQB1*05:02 distributed differently between the two groups after Bonferroni correction (odds ratio [OR] = 1.839, Pc = 0.024 and OR = 0.547, Pc = 0.016, respectively). Multivariate logistic regression analysis suggested that A*02:01 and DRB1*11:01 (OR = 1.798, P = 0.008 and OR = 1.921, P = 0.005, respectively) were associated with HCV spontaneous clearance, independent of age, gender and IL28B polymorphism. We concluded that in the Chinese population, HLA-A*02:01 and DRB1*11:01 might be associated with the host capacity to clear HCV independent of IL28B, which suggesting that the innate and adaptive immune responses both play an important role in the control of HCV.
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Affiliation(s)
- Jieting Huang
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - Ke Huang
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - Ru Xu
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - Min Wang
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - Qiao Liao
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - Huaping Xiong
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - Chengyao Li
- Department of Transfusion Medicine, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
| | - Xi Tang
- Department of Transfusion Medicine, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhengang Shan
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - Ming Zhang
- Department of Epidemiology and Biostatistics, Faculty of Infectious Diseases, University of Georgia, Athens, GA, USA
| | - Xia Rong
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
| | - Kenrad Nelson
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Yongshui Fu
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- The Key Medical Disciplines and Specialties Program of Guangzhou, Guangdong, China
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13
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Prevalence of hepatitis C virus in an elderly population in rural areas of Sharkia governorate, Egypt. EGYPTIAN LIVER JOURNAL 2015. [DOI: 10.1097/01.elx.0000463678.53334.c7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Cho YK, Kim YN, Song BC. Predictors of spontaneous viral clearance and outcomes of acute hepatitis C infection. Clin Mol Hepatol 2014; 20:368-75. [PMID: 25548743 PMCID: PMC4278068 DOI: 10.3350/cmh.2014.20.4.368] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2014] [Revised: 11/26/2014] [Accepted: 12/01/2014] [Indexed: 12/18/2022] Open
Abstract
Background/Aims This study evaluated the predictors of spontaneous viral clearance (SVC), as defined by two consecutive undetectable hepatitis C virus (HCV) RNA tests performed ≥12 weeks apart, and the outcomes of acute hepatitis C (AHC) demonstrating SVC or treatment-induced viral clearance. Methods Thirty-two patients with AHC were followed for 12-16 weeks without administering antiviral therapy. Results HCV RNA was undetectable at least once in 14 of the 32 patients. SVC occurred in 12 patients (37.5%), among whom relapse occurred in 4. SVC was exhibited in 8 of the 11 patients exhibiting undetectable HCV RNA within 12 weeks. HCV RNA reappeared in three patients (including two patients with SVC) exhibiting undetectable HCV RNA after 12 weeks. SVC was more frequent in patients with low viremia than in those with high viremia (55.6% vs. 14.3%; P=0.02), and in patients with HCV genotype non-1b than in those with HCV genotype 1b (57.1% vs. 22.2%; P=0.04). SVC was more common in patients with a ≥2 log reduction of HCV RNA at 4 weeks than in those with a smaller reduction (90% vs. 9.1%, P<0.001). A sustained viral response was achieved in all patients (n=18) receiving antiviral therapy. Conclusions Baseline levels of HCV RNA and genotype non-1b were independent predictors for SVC. A ≥2 log reduction of HCV RNA at 4 weeks was a follow-up predictor for SVC. Undetectable HCV RNA occurring after 12 weeks was not sustained. All patients receiving antiviral therapy achieved a sustained viral response. Antiviral therapy should be initiated in patients with detectable HCV RNA at 12 weeks after the diagnosis.
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Affiliation(s)
- Yoo-Kyung Cho
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Young Nam Kim
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Byung-Cheol Song
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
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15
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Alric L, Bonnet D, Fort M. Association between female sex, IL28B genotype, but also DQB1*0301 allele and the outcome of acute hepatitis C virus infection. Hepatology 2014; 60:2127. [PMID: 24715649 DOI: 10.1002/hep.27164] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Accepted: 01/27/2014] [Indexed: 01/29/2023]
Affiliation(s)
- Laurent Alric
- Internal Medicine Digestive Department Purpan Hospital, UMR152, IRD Toulouse III University, Toulouse, France
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Vila Brunilda H, Lila S, Erjona A, Silva B, Tefta R. Prevalence of Hepatitis C Virus in the Population of Albania for the Period 2007-2010. Open Access Maced J Med Sci 2014. [DOI: 10.3889/oamjms.2014.094] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: Hepatitis C is a blood-borne, infectious, viral disease that is caused by a hepatotropic virus called Hepatitis C virus (HCV).AIM: The aim of this study is to determine the prevalence of active HCV infection (HCV–RNA) in the cases that were anti-HCV positive.MATERIAL AND METHODS: Plasma of 301 high-risk for HCV infection consecutive from University Hospital Centre “Mother Theresa†Tirana-Albania, during January 2007 to December 2010 was included in this study. To identify the presence of HCV RNA, the samples were examined by Cobas Amplicor HCV test (qualitative method).RESULTS: From 301 samples analyzed in total, 214 of them resulted positive for the presence of HCV-RNA's, corresponding to a prevalence of 71.1%, with 95% CI interval [65.8 - 75.9] for value of χ2 = 52.7 p value <0.0001. Divide by the sex 56% were males and 44% females, with statistically significant difference between them for value χ2 =4306 p value=0.0380. Among the age groups the highest prevalence was observed in the age groups > 25 years with a significant difference with other age groups for p value <0.001.CONCLUSION: Among tested samples, 71.1 % were confirmed to be positive for HCV –RNA infections. The prevalence of male was highest compared to female. For males and females infected the prevalence was highest in the age group of > 25 years.
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Clausen LN, Lundbo LF, Benfield T. Hepatitis C virus infection in the human immunodeficiency virus infected patient. World J Gastroenterol 2014; 20:12132-12143. [PMID: 25232248 PMCID: PMC4161799 DOI: 10.3748/wjg.v20.i34.12132] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Revised: 04/02/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same transmission routes; therefore, coinfection is frequent. An estimated 5-10 million individuals alone in the western world are infected with both viruses. The majority of people acquire HCV by injection drug use and, to a lesser extent, through blood transfusion and blood products. Recently, there has been an increase in HCV infections among men who have sex with men. In the context of effective antiretroviral treatment, liver-related deaths are now more common than Acquired Immune Deficiency Syndrome-related deaths among HIV-HCV coinfected individuals. Morbidity and mortality rates from chronic HCV infection will increase because the infection incidence peaked in the mid-1980s and because liver disease progresses slowly and is clinically silent to cirrhosis and end-stage-liver disease over a 15-20 year time period for 15%-20% of chronically infected individuals. HCV treatment has rapidly changed with the development of new direct-acting antiviral agents; therefore, cure rates have greatly improved because the new treatment regimens target different parts of the HCV life cycle. In this review, we focus on the epidemiology, diagnosis and the natural course of HCV as well as current and future strategies for HCV therapy in the context of HIV-HCV coinfection in the western world.
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18
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Wiessing L, Ferri M, Grady B, Kantzanou M, Sperle I, Cullen KJ, EMCDDA DRID group, Hatzakis A, Prins M, Vickerman P, Lazarus JV, Hope VD, Matheï C. Hepatitis C virus infection epidemiology among people who inject drugs in Europe: a systematic review of data for scaling up treatment and prevention. PLoS One 2014; 9:e103345. [PMID: 25068274 PMCID: PMC4113410 DOI: 10.1371/journal.pone.0103345] [Citation(s) in RCA: 191] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2014] [Accepted: 06/29/2014] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND People who inject drugs (PWID) are a key population affected by hepatitis C virus (HCV). Treatment options are improving and may enhance prevention; however access for PWID may be poor. The availability in the literature of information on seven main topic areas (incidence, chronicity, genotypes, HIV co-infection, diagnosis and treatment uptake, and burden of disease) to guide HCV treatment and prevention scale-up for PWID in the 27 countries of the European Union is systematically reviewed. METHODS AND FINDINGS We searched MEDLINE, EMBASE and Cochrane Library for publications between 1 January 2000 and 31 December 2012, with a search strategy of general keywords regarding viral hepatitis, substance abuse and geographic scope, as well as topic-specific keywords. Additional articles were found through structured email consultations with a large European expert network. Data availability was highly variable and important limitations existed in comparability and representativeness. Nine of 27 countries had data on HCV incidence among PWID, which was often high (2.7-66/100 person-years, median 13, Interquartile range (IQR) 8.7-28). Most common HCV genotypes were G1 and G3; however, G4 may be increasing, while the proportion of traditionally 'difficult to treat' genotypes (G1+G4) showed large variation (median 53, IQR 43-62). Twelve countries reported on HCV chronicity (median 72, IQR 64-81) and 22 on HIV prevalence in HCV-infected PWID (median 3.9%, IQR 0.2-28). Undiagnosed infection, assessed in five countries, was high (median 49%, IQR 38-64), while of those diagnosed, the proportion entering treatment was low (median 9.5%, IQR 3.5-15). Burden of disease, where assessed, was high and will rise in the next decade. CONCLUSION Key data on HCV epidemiology, care and disease burden among PWID in Europe are sparse but suggest many undiagnosed infections and poor treatment uptake. Stronger efforts are needed to improve data availability to guide an increase in HCV treatment among PWID.
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Affiliation(s)
- Lucas Wiessing
- European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Lisbon, Portugal
| | - Marica Ferri
- European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Lisbon, Portugal
| | - Bart Grady
- Cluster Infectious Diseases, Department of Research, Public Health Service, Amsterdam, The Netherlands
- Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, The Netherlands
| | - Maria Kantzanou
- National Reference Centre for Retroviruses, Laboratory of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece
| | - Ida Sperle
- Copenhagen HIV Programme (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Katelyn J. Cullen
- HIV & STI Department, Centre for Infectious Disease Surveillance and Control, Public Health England, London, United Kingdom
| | | | - Angelos Hatzakis
- National Reference Centre for Retroviruses, Laboratory of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece
| | - Maria Prins
- Cluster Infectious Diseases, Department of Research, Public Health Service, Amsterdam, The Netherlands
- Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, The Netherlands
| | - Peter Vickerman
- London School of Hygiene and Tropical Medicine (LSHTM), London, United Kingdom
- School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
| | - Jeffrey V. Lazarus
- Copenhagen HIV Programme (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Vivian D. Hope
- HIV & STI Department, Centre for Infectious Disease Surveillance and Control, Public Health England, London, United Kingdom
- London School of Hygiene and Tropical Medicine (LSHTM), London, United Kingdom
| | - Catharina Matheï
- Department of Public Health and Primary Care, KULeuven, Leuven, Belgium
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Sehgal M, Khan ZK, Talal AH, Jain P. Dendritic Cells in HIV-1 and HCV Infection: Can They Help Win the Battle? Virology (Auckl) 2013; 4:1-25. [PMID: 25512691 PMCID: PMC4222345 DOI: 10.4137/vrt.s11046] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Persistent infections with human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) are a major cause of morbidity and mortality worldwide. As sentinels of our immune system, dendritic cells (DCs) play a central role in initiating and regulating a potent antiviral immune response. Recent advances in our understanding of the role of DCs during HIV-1 and HCV infection have provided crucial insights into the mechanisms employed by these viruses to impair DC functions in order to evade an effective immune response against them. Modulation of the immunological synapse between DC and T-cell, as well as dysregulation of the crosstalk between DCs and natural killer (NK) cells, are emerging as two crucial mechanisms. This review focuses on understanding the interaction of HIV-1 and HCV with DCs not only to understand the immunopathogenesis of chronic HIV-1 and HCV infection, but also to explore the possibilities of DC-based immunotherapeutic approaches against them. Host genetic makeup is known to play major roles in infection outcome and rate of disease progression, as well as response to anti-viral therapy in both HIV-1 and HCV-infected individuals. Therefore, we highlight the genetic variations that can potentially affect DC functions, especially in the setting of chronic viral infection. Altogether, we address if DCs’ potential as critical effectors of antiviral immune response could indeed be utilized to combat chronic infection with HIV-1 and HCV.
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Affiliation(s)
- Mohit Sehgal
- Department of Microbiology and Immunology, and the Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
| | - Zafar K Khan
- Department of Microbiology and Immunology, and the Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
| | - Andrew H Talal
- Center for the Study of Hepatitis C, Weill Cornell Medical College, New York, NY
| | - Pooja Jain
- Department of Microbiology and Immunology, and the Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
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20
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Marangon AV, Silva GF, de Moraes CFV, Grotto RMT, Pardini MIMC, de Pauli DS, Visentainer JEL, Sell AM, Moliterno RA. Protective effect of HLA-DRB1 11 and predisposition of HLA-C 04 in the development of severe liver damage in Brazilian patients with chronic hepatitis C virus infection. Scand J Immunol 2012; 76:440-7. [PMID: 22803655 DOI: 10.1111/j.1365-3083.2012.02755.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The objective of this study was to investigate human leucocyte antigen (HLA) genes in patients chronically infected with hepatitis C virus (HCV) and to analyse the possible role of these genes in the progression of chronic hepatitis C. One hundred and forty-five (145) Brazilian patients infected only with HCV genotype 1 were evaluated. HLA class I (A, B, C) and class II (DRB1, DQA1, DQB1) typing were carried out by PCR-SSO, through Luminex technology. Associations were found with protection against development of liver damage by both DRB1 11 (5.0% versus 18.2%, P=0.0016, OR=0.23, CI 95% = 0.09-0.58; Pc=0.0208) and DRB1 11-DQA1 05-DQB1 03 haplotype (4.2% versus 15.3%, P=0.0032; OR = 0.24, CI 95% = 0.08-0.64). Liver damage was associated with HLA-C 04 in patients with <20 years of infection (38.4% versus 9.1%, P = 0.002, OR = 6.25, CI 95%=1.97-19.7; Pc=0.0238). It is concluded that HLA alleles can influence the development of liver damage in HCV type-1 chronically infected Brazilian patients.
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Affiliation(s)
- A V Marangon
- Immunogenetics Laboratory, Maringá State University, UEM, Maringá, PR, Brazil.
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21
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Grimes CZ, Hwang LY, Wei P, Shah DP, Volcik KA, Brown EL. Differentially regulated gene expression associated with hepatitis C virus clearance. J Gen Virol 2012; 94:534-542. [PMID: 23152368 DOI: 10.1099/vir.0.047738-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Human chronic hepatitis C virus (HCV) infections pose a significant public health threat, necessitating the development of novel treatments and vaccines. HCV infections range from spontaneous resolution to end-stage liver disease. Approximately 10-30% of HCV infections undergo spontaneous resolution independent of treatment by yet-to-be-defined mechanisms. These individuals test positive for anti-HCV antibodies in the absence of detectable viral serum RNA. To identify genes associated with HCV clearance, this study compared gene expression profiles between current drug users chronically infected with HCV and drug users who cleared their HCV infection. This analysis identified 91 differentially regulated (up- or downregulated by twofold or more) genes potentially associated with HCV clearance. The majority of genes identified were associated with immune function, with the remaining genes categorized either as cancer related or 'other'. Identification of factors and pathways that may influence virus clearance will be essential to the development of novel treatment strategies.
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Affiliation(s)
- Carolyn Z Grimes
- Division of Epidemiology, Human Genetics And Environmental Sciences, The University of Texas School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Lu-Yu Hwang
- Division of Epidemiology, Human Genetics And Environmental Sciences, The University of Texas School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Peng Wei
- Division of Biostatistics, The University of Texas School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Dimpy P Shah
- Division of Epidemiology, Human Genetics And Environmental Sciences, The University of Texas School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Kelly A Volcik
- Division of Epidemiology, Human Genetics And Environmental Sciences, The University of Texas School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Eric L Brown
- Division of Epidemiology, Human Genetics And Environmental Sciences, The University of Texas School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
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22
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Amini M, Poustchi H. Hepatitis C virus spontaneous clearance: immunology and genetic variance. Viral Immunol 2012; 25:241-8. [PMID: 22823386 DOI: 10.1089/vim.2011.0052] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Hepatitis C virus (HCV) infection is one of the most common chronic viral infections in the world. Approximately 80-90% of acutely infected individuals develop persistent infection, which is a major risk for liver cirrhosis and liver cancer. However, a small portion of patients (10-20%) clear the virus. Clinical outcomes of HCV infection are determined by the interplay between the host immune response, and viral and environmental factors. In regulating immune responses, cytokines play an indispensable role that controls the underlying pathogenesis and the resulting outcome of HCV infection. Cytokines themselves are manipulated by polymorphisms in their genes. In fact, the majority of genetic variants that apparently confer a significant risk for chronic HCV infection have been localized in genes involved in cytokine synthesis and the ultimate immune response. So far, treatment strategies for HCV infection have remained controversial. Genotyping of different polymorphisms will aid clinical decision making for both current standard and personalized care. Genotyping can potentially be useful for future integration of other agents, which provides an opportunity for clinicians to personalize treatment regimens for HCV patients. This review summarizes findings of different studies on host immune responses after HCV infection and the association between cytokine gene polymorphisms and the likelihood of HCV clearance.
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Affiliation(s)
- Marzyeh Amini
- Digestive Disease Research Centre, Shariati Hospital, Tehran University of Medical science, Tehran, Iran
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23
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Poustchi H, Esmaili S, Mohamadkhani A, Nikmahzar A, Pourshams A, Sepanlou SG, Merat S, Malekzadeh R. The impact of illicit drug use on spontaneous hepatitis C clearance: experience from a large cohort population study. PLoS One 2011; 6:e23830. [PMID: 21887326 PMCID: PMC3161071 DOI: 10.1371/journal.pone.0023830] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2011] [Accepted: 07/26/2011] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND AIMS Acute hepatitis C infection usually ends in chronic infection, while in a minority of patients it is spontaneously cleared. The current population-based study is performed on a large cohort in Golestan province of Iran to examine the demographic correlates of Spontaneous Hepatitis C Clearance. METHODS Serum samples used in this study had been stored in biorepository of Golestan Cohort Study. These samples were evaluated for anti hepatitis C Virus by third generation Enzyme-linked immunosorbent assay (ELISA). Subjects who tested positive were then invited and tested by Recombinant Immunoblot Assay (RIBA) and Ribonucleic Acid Polymerase Chain Reaction test (PCR). If tested positive for RIBA, subjects were recalled and the two tests were re-done after 6 months. Those subjects who again tested positive for RIBA but negative for PCR were marked as cases of spontaneous clearance. RESULTS 49,338 serum samples were evaluated. The prevalence of Chronic Hepatitis C Virus (CHCV) infection based on PCR results was 0.31%. Among those who had acquired hepatitis C, the rate of SC was 38%. In multivariate analysis, illicit drug use both Injecting Use (OR = 3.271, 95% CI: 1.784-6.000, p-value<0.001) and Non-Injecting Use (OR = 1.901, 95% CI: 1.068-3.386, p-value = 0.029) were significant correlates of CHCV infection versus SC. CONCLUSIONS Illicit drug use whether intravenous or non-intravenous is the only significant correlate of CHCV, for which several underlying mechanisms can be postulated including repeated contacts with hepatitis C antigen.
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Affiliation(s)
- Hossein Poustchi
- Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Tehran, Iran
| | - Saeed Esmaili
- Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Tehran, Iran
| | - Ashraf Mohamadkhani
- Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Tehran, Iran
| | - Aghbibi Nikmahzar
- Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Tehran, Iran
| | - Akram Pourshams
- Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Tehran, Iran
| | - Sadaf G. Sepanlou
- Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Tehran, Iran
| | - Shahin Merat
- Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Tehran, Iran
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Rolfe KJ, Curran MD, Alexander GJM, Woodall T, Andrews N, Harris HE. Spontaneous loss of hepatitis C virus RNA from serum is associated with genotype 1 and younger age at exposure. J Med Virol 2011; 83:1338-44. [PMID: 21618556 DOI: 10.1002/jmv.22115] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/16/2011] [Indexed: 01/27/2023]
Abstract
A variety of factors have been associated with spontaneous loss of hepatitis C virus (HCV)-RNA from serum, including infecting HCV type, although results are conflicting. This study aimed to investigate further whether infecting HCV type was linked to spontaneous loss of HCV-RNA. Serum samples from 321 untreated HCV antibody positive patients presenting at the Hepatology clinic at Addenbrooke's Hospital, Cambridge between 2004 and 2007 were tested. These individuals were classified either as HCV antibody and HCV-RNA positive (viremic, n = 219) or HCV antibody positive and repeatedly HCV-RNA negative (non-viremic, n = 102). Infecting HCV type was identified by genotyping (viremic) or serotyping (non-viremic). Binomial regression analysis investigated the independent effect of HCV type on spontaneous loss of HCV-RNA from serum by comparing the two groups. Ninety-one percent of patients were found to be either genotype 1 or genotype 3. The prevalence of type 1 infection was greater among non-viremic (64.5%) than viremic individuals (45%). After controlling for the effects of potential confounding factors, multivariable analyses showed that individuals with type 1 infections were more likely to be non-viremic than genotype 3 infections (RR = 2.07; 95% CI: 1.25, 3.43; P = 0.005). Individuals infected at an older age were also less likely to become HCV-RNA negative spontaneously (RR = 0.42 comparing those infected at ≥20 years of age against those infected at <20 years of age, 95% CI: 0.25, 0.72; P = 0.002). In conclusion, the results suggest that HCV genotype 1 infections are more likely than genotype 3 infections to become spontaneously non-viremic, as are infections acquired at younger age.
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Affiliation(s)
- K J Rolfe
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
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Ali A, Ahmad H, Ali I, Khan S, Zaidi G, Idrees M. Prevalence of active hepatitis c virus infection in district Mansehra Pakistan. Virol J 2010; 7:334. [PMID: 21092143 PMCID: PMC2996369 DOI: 10.1186/1743-422x-7-334] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2010] [Accepted: 11/22/2010] [Indexed: 12/17/2022] Open
Abstract
Prevalence of active hepatitis C virus (HCV) infection in apparently healthy inhabitants of District Mansehra, Pakistan was surveyed during September, 2009 to May, 2010. Subjects of different age and gender groups were analyzed through random blood sampling from people of three areas viz; Tehsil Mansehra, Tehsil Balakot and Tehsil Oghi. Sum of 400 individuals, 300 male and 100 females with age groups from 10 years to 50 and above were included in the study. All the individuals were screened for antibodies against HCV. The positive samples thus screened, were subjected to polymerase chain reaction (PCR) analysis for detection of HCV-RNA. The results showed that 3.5% of the people of District Mansehra are actively infected with HCV whereas 7% of the population in general, has the presence of antibodies against HCV in their blood. It was also concluded that the prevalence of active HCV infection was high 4% in males as compared to females (2%). The prevalence of HCV proportionality increases with the increase in age of the people. Its incidence was highest (7.69%) in the people of the age group of 51 years and above, whereas no sign of infection was recorded for the age group of 10-20 years.
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Affiliation(s)
- Amjad Ali
- Department of Genetics, Hazara University Mansehra, Pakistan
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Grünhage F, Nattermann J. Viral hepatitis: human genes that limit infection. Best Pract Res Clin Gastroenterol 2010; 24:709-23. [PMID: 20955972 DOI: 10.1016/j.bpg.2010.07.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2010] [Revised: 07/20/2010] [Accepted: 07/22/2010] [Indexed: 01/31/2023]
Abstract
Treatment response and susceptibility to chronic viral hepatitis C and B may be modified by host genetic factors. The majority of genetic variants that confer a significant risk have been localized in genes involved in immune response. However, many findings could not be replicated and almost none of the identified risk factors had a noticeable impact on clinical decisions. In contrast, recent findings in independent large genome wide association studies confirmed genetic variants in the interferon gamma gene locus as strong predictors of outcome with outstanding clinical relevance. This review gives an overview on significant genetic susceptibility factors for susceptibility and treatment outcome in chronic viral hepatitis C and B that have been identified by the classical candidate gene approach and genome wide studies and also highlights some recent findings on genetic factors for common adverse drug reactions.
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Affiliation(s)
- Frank Grünhage
- Medical Department II, Saarland University Hospital, Kirrbergerstr. 1, 66421 Homburg, Germany.
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27
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Tobler LH, Bahrami SH, Kaidarova Z, Pitina L, Winkelman VK, Vanderpool SK, Guiltinan AM, Cooper S, Busch MP, Murphy EL. A case-control study of factors associated with resolution of hepatitis C viremia in former blood donors (CME). Transfusion 2010; 50:1513-23. [PMID: 20345567 PMCID: PMC3660404 DOI: 10.1111/j.1537-2995.2010.02634.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Nucleic acid testing (NAT) is performed on blood collected in the United States allowing for the classification of hepatitis C virus (HCV) antibody-positive donors into resolved and chronic hepatitis C infections. We report a case-control study of factors associated with HCV resolution. STUDY DESIGN AND METHODS Blood donors with resolved (HCV antibody positive, RNA negative defined as "cases") or chronic (HCV antibody positive, RNA positive defined as "controls") based on their index donation HCV test results were enrolled. Participants completed a risk factor, symptoms, and treatment questionnaire followed by HCV antibody, HCV RNA, and liver biochemical testing. RESULTS We enrolled 100 cases and 202 controls. In a multivariate logistic regression model, significant independent effects for spontaneous viral clearance were observed for African American (inverse; odds ratio [OR], 0.11; 95% confidence interval [CI], 0.01-0.87), autologous blood donation (OR, 4.70; 95% CI, 2.02-10.94), alcohol intake (OR, 2.39; 95% CI, 1.13-5.03), and transfusion before May 1990 (inverse; OR, 0.36; 95% CI, 0.14-0.91). Cases admitting injection drug use had shorter time since first injection than did controls. Forty-nine index RNA positive controls received antiviral therapy and 25 (51%) were RNA negative at enrollment; surprisingly several RNA-negative cases received liver biopsies and/or antiviral treatment. CONCLUSIONS We document the role donor screening plays in the identification, subsequent medical evaluation, and treatment among individuals who presumably did not know that they were at risk for HCV infection. Additionally, we confirmed race/ethnicity as a determinant of clearance and suggest infectious dose and route of infection may play a role in clearance.
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Affiliation(s)
- Leslie H Tobler
- Blood Systems Research Institute, San Francisco, California, USA.
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Fazili J, Mallonee S, Tierney WM, Bader TF, Sachdev AK, Bird PC, Schmidt RD, Mesiya SA, Lackey CL. Outcome of a hepatitis C outbreak among patients in a pain management clinic. Dig Dis Sci 2010; 55:1738-43. [PMID: 20411419 DOI: 10.1007/s10620-010-1228-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2009] [Accepted: 03/25/2010] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIMS The aims of this study are to evaluate the natural history and response to therapy of patients following a hepatitis C outbreak in a pain management clinic. METHODS A retrospective cohort study was conducted on patients who acquired hepatitis C virus (HCV) at a pain management clinic. Medical records were retrospectively reviewed for 77% of patients with hepatitis C included in the outbreak to obtain data regarding laboratory results, treatment, and outcomes. Chi-square, Fisher's exact, and Student's t-test were used to determine variables that were significantly associated with spontaneous clearance or sustained virologic response to therapy. RESULTS Fifty Caucasian patients (31 women, 19 men; mean age 52 years) were included. Eleven of 50 (22%) patients cleared HCV spontaneously (clearers). The mean age of clearers was 47 years as compared with 57 years for nonclearers (P = 0.04). Liver biopsies were obtained by treating gastroenterologists in 31 patients with mean grade and stage of 2.1 and 1.7, respectively. Gastroenterologists treated 31 of 39 patients with pegylated interferon and ribavirin after a median of 354 (range 140-1,099) days post exposure. Sustained viral response (SVR) was observed in 65% (20/31) on an intention-to-treat basis. In patients who completed therapy, 91% (20/22) achieved SVR. Age, sex, weight, pretreatment alanine aminotransferase (ALT), and histologic parameters were not associated with SVR. CONCLUSIONS In this large cohort of US immunocompetent patients with recent HCV infection, 22% resolved spontaneously. Younger age was the only predictor of spontaneous clearance. In patients with early chronic HCV, 65% achieved SVR.
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Affiliation(s)
- Javid Fazili
- Digestive Diseases, Internal Medicine, University of Oklahoma Health Sciences Center, Williams Pavilion 1360, Oklahoma City, OK 73104, USA.
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Kuniholm MH, Kovacs A, Gao X, Xue X, Marti D, Thio CL, Peters MG, Terrault NA, Greenblatt RM, Goedert JJ, Cohen MH, Minkoff H, Gange SJ, Anastos K, Fazzari M, Harris TG, Young MA, Strickler HD, Carrington M. Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia. Hepatology 2010; 51:1514-22. [PMID: 20169624 PMCID: PMC2946382 DOI: 10.1002/hep.23515] [Citation(s) in RCA: 87] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
UNLABELLED Studies of human leukocyte antigen (HLA) alleles and their relation with hepatitis C virus (HCV) viremia have had conflicting results. However, these studies have varied in size and methods, and few large studies assessed HLA class I alleles. Only one study conducted high-resolution class I genotyping. The current investigation therefore involved high-resolution HLA class I and II genotyping of a large multiracial cohort of U.S. women with a high prevalence of HCV and HIV. Our primary analyses evaluated associations between 12 HLA alleles identified through a critical review of the literature and HCV viremia in 758 HCV-seropositive women. Other alleles with >5% prevalence were also assessed; previously unreported associations were corrected for multiple comparisons. DRB1*0101 (prevalence ratio [PR] = 1.7; 95% confidence interval [CI] = 1.1-2.6), B*5701 (PR=2.0; 95% CI = 1.0-3.1), B*5703 (PR = 1.7; 95% CI = 1.0-2.5), and Cw*0102 (PR = 1.9; 95% CI = 1.0-3.0) were associated with the absence of HCV RNA (i.e., HCV clearance), whereas DRB1*0301 (PR = 0.4; 95% CI = 0.2-0.7) was associated with HCV RNA positivity. DQB1*0301 was also associated with the absence of HCV RNA but only among HIV-seronegative women (PR = 3.4; 95% CI = 1.2-11.8). Each of these associations was among those predicted. We additionally studied the relation of HLA alleles with HCV infection (serostatus) in women at high risk of HCV from injection drug use (N = 838), but no significant relationships were observed. CONCLUSION HLA genotype influences the host capacity to clear HCV viremia. The specific HLA associations observed in the current study are unlikely to be due to chance because they were a priori hypothesized.
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Affiliation(s)
- Mark H Kuniholm
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
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De Re V, Caggiari L, Monti G, Libra M, Spina M, Dolcetti R, De Zorzi M, Racanelli V, Crovatto M, Toffoli G. HLA DR-DQ combination associated with the increased risk of developing human HCV positive non-Hodgkin's lymphoma is related to the type II mixed cryoglobulinemia. ACTA ACUST UNITED AC 2009; 75:127-35. [PMID: 20002609 DOI: 10.1111/j.1399-0039.2009.01414.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
This investigation was focused on the contribution of individual human leukocyte antigen (HLA)-DR and -DQ alleles to the human hepatitis C virus (HCV)(+) non-Hodgkin's lymphoma (NHL), with and without mixed cryoglobulinemia (MC), to study whether individual HLA class II alleles are expressed preferentially or equally in human HCV-specific NHL. For this purpose, peripheral blood mononuclear cells were obtained from two groups of patients with HCV(+) NHL and with or without MC (70 and 71 cases, respectively), and from 4575 blood donors. Eighty-three subjects with HCV infection only, and 118 patients with MC, only without lymphoma, were added as additional control groups. Individual HLA-DR and -DQ alleles were determined using high-resolution sequence-based typing and then data were collected by considering the HLA-DRB1 and DQB1 supertypes on the basis of common structural and functional features, proposed by in silico Bioinformatic studies. From the data, it is evidenced that the DR5-DQ3 HLA combination was strongly associated with the HCV (+) MC (+) NHL group of patients compared with bone marrow donor population (P<or= 0.001, RR = 2.498), while the contribution of DR1-DQ1 was higher in HCV (+) NHL without MC (P<or= 0.001, RR = 2.519). Thus, cryoglobulinemia clinical manifestation was found to be correlated with the preferential use of HLA DR-DQ combination in HCV-associated NHL. These data provide new insight into HCV-associated lymphoproliferative pathogenesis.
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Affiliation(s)
- V De Re
- Centro di Riferimento Oncologico, IRCCS, National Cancer Institute, Aviano, Italy.
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Rauch A, Gaudieri S, Thio C, Bochud PY. Host genetic determinants of spontaneous hepatitis C clearance. Pharmacogenomics 2009; 10:1819-37. [DOI: 10.2217/pgs.09.121] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
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Page K, Hahn JA, Evans J, Shiboski S, Lum P, Delwart E, Tobler L, Andrews W, Avanesyan L, Cooper S, Busch MP. Acute hepatitis C virus infection in young adult injection drug users: a prospective study of incident infection, resolution, and reinfection. J Infect Dis 2009; 200:1216-26. [PMID: 19764883 DOI: 10.1086/605947] [Citation(s) in RCA: 242] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection, clearance, and reinfection are best studied in injection drug users (IDUs), who have the highest incidence of HCV and are likely to represent most infections. METHODS A prospective cohort of HCV-negative young IDUs was followed up from January 2000 to September 2007, to identify acute and incident HCV and prospectively study infection outcomes. RESULTS Among 1,191 young IDUs screened, 731 (61.4%) were HCV negative, and 520 (71.1%) of the 731 were enrolled into follow-up. Cumulative HCV incidence was 26.7/100 person-years of observation (95% confidence interval [CI], 21.5-31.6). Of 135 acute/incident HCV infections, 95 (70.4%) were followed; 20 (21.1%) of the 95 infections cleared. Women had a significantly higher incidence of viral clearance than did men (age-adjusted hazard ratio, 2.91 [95% CI, 1.68-5.03]) and also showed a faster rate of early HCV viremia decline (P < .01). The estimated reinfection rate was 24.6/100 person-years of observation (95% CI, 11.7-51.6). Among 7 individuals, multiple episodes of HCV reinfection and reclearance were observed. CONCLUSIONS In this large sample of young IDUs, females show demonstrative differences in their rates of viral clearance and kinetics of early viral decline. Recurring reinfection and reclearance suggest possible protection against persistent infection. These results should inform HCV clinical care and vaccine development.
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Affiliation(s)
- Kimberly Page
- Department of Epidemiology and Biostatistics, University of California, San Francisco, 50 Beale St, Ste 1200, San Francisco, CA 94105, USA.
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Bengsch B, Thimme R, Blum HE. Role of host genetic factors in the outcome of hepatitis C virus infection. Viruses 2009; 1:104-125. [PMID: 21994541 PMCID: PMC3185494 DOI: 10.3390/v1020104] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2009] [Revised: 07/23/2009] [Accepted: 07/28/2009] [Indexed: 12/15/2022] Open
Abstract
The natural history of hepatitis C virus (HCV) infection is determined by a complex interplay between host genetic, immunological and viral factors. This review highlights genes involved in innate and adaptive immune responses associated with different outcomes of HCV infection. For example, an association of HCV clearance with certain HLA alleles has been demonstrated. The mechanisms responsible for these associations have been linked to specific T cell responses for some particular alleles (e.g., HLA-B27). Genetic associations involved in T cell regulation and function further underline the role of the adaptive immune response in the natural history of HCV infection. In addition, some genes involved in innate NK cell responses demonstrate the complex interplay between components of the immune system necessary for a successful host response to HCV infection.
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Affiliation(s)
| | - Robert Thimme
- Author to whom correspondence should be addressed; ; Tel.: +49-761-270-3280; Fax: +49-761-270-3725
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Martin-Blondel G, Gales A, Bernad J, Cuzin L, Delobel P, Barange K, Izopet J, Pipy B, Alric L. Low interleukin-10 production by monocytes of patients with a self-limiting hepatitis C virus infection. J Viral Hepat 2009; 16:485-91. [PMID: 19302337 DOI: 10.1111/j.1365-2893.2009.01094.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Host factors seem to be crucial for the spontaneous clearance of hepatitis C virus (HCV). Monocytes play a pivotal role in innate immunity and help regulate adaptive responses. This study assesses the characteristics of monocytes from patients with self-limiting HCV infections. We studied 35 consecutive patients [11 with a self-limiting HCV infection, 16 chronically infected with HCV and sustained virological responders (SVR) following antiviral therapy, and eight chronically infected HCV but untreated] and eight healthy donors (HD). The production of interleukin (IL)-10, tumour necrosis factor-alpha (TNF-alpha) and IL-12p40 by monocytes stimulated with lipopolysaccharides(LPS) or HCV Core protein was measured by enzyme-linked immunoassay. Monocyte surface markers were analysed by flow cytometry. LPS and Core protein triggered IL-10 and TNF-alpha production, but monocytes from self-limiting infection patients produced significantly less IL-10 and TNF-alpha than those of SVR, chronically infected or HD (P < 0.05), while IL-12p40 production was unchanged. This cytokine production profile did not appear to be due to expansion of the CD14(+) CD16(+) monocyte subset or to a classical or alternative activation monocyte profile. Monocytes from self-limiting infection patients had more CCR7 than those from SVR or chronically infected patients (P < 0.05). Monocytes of self-limiting infection patients appear to produce little IL-10 and TNF-alpha in response to viral or unspecific stimulation and to have a higher CCR7 expression. This profile seems to be independent to a particular monocyte subset or activation state. Low IL-10 production may help establish an effective immune response and spontaneous HCV clearance.
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Affiliation(s)
- G Martin-Blondel
- EA2405 UMR3 MD-UM-UPS, Université Paul Sabatier Toulouse III, France
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de Arias AE, Haworth SE, Belli LS, Burra P, Pinzello G, Vangeli M, Minola E, Guido M, Boccagni P, De Feo TM, Torelli R, Cardillo M, Scalamogna M, Poli F. Killer cell immunoglobulin-like receptor genotype and killer cell immunoglobulin-like receptor-human leukocyte antigen C ligand compatibility affect the severity of hepatitis C virus recurrence after liver transplantation. Liver Transpl 2009; 15:390-9. [PMID: 19326408 DOI: 10.1002/lt.21673] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
In 20% to 30% of infected individuals, hepatitis C virus (HCV) can cause cirrhosis and hepatocellular carcinoma, for which liver transplantation is the best treatment available. HCV re-infection is universal, and hepatitis disease recurrence occurs in most cases with a 30% probability of progression to graft cirrhosis at 5 years post-transplant. The immunological response to HCV involves natural killer (NK) cells and killer cell immunoglobulin-like receptors (KIRs), which specifically recognize human leukocyte antigen (HLA) class I antigens present on target cells. The effector functions of NK cells are influenced by inhibitory KIR interaction with self-HLA class I ligands, with HLA-C being the most predominant. This study examines the roles of KIR genotypes and their HLA ligands in both HCV disease recurrence and its progression. A total of 151 patients were included in the cohort, and their clinical details were recorded. Liver biopsies were used to define the absence/presence of recurrent hepatitis, the degree of fibrosis, and the progression to cirrhosis over a 10-year period. Mismatching of KIR-HLA-C ligands between donor-recipient pairs was associated with the recurrence of hepatitis (P = 0.008). The presence of KIR2DL3 in the recipient correlated with progression to liver fibrosis (P = 0.04). The mismatching of HLA-KIR ligands favored the progression of the recurrent hepatitis to fibrosis only in the presence of KIR2DL3 (P = 0.04). These preliminary results indicate that the KIR genotype and KIR-HLA-C ligand compatibility play roles in the recurrence and progression of hepatitis C disease in liver transplant recipients.
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Affiliation(s)
- Alejandro Espadas de Arias
- Department of Regenerative Medicine, Organ and Tissue Transplantation Immunology, Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy
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Takahama Y, Uto H, Kanmura S, Oketani M, Ido A, Kusumoto K, Hasuike S, Nagata K, Hayashi K, Stuver S, Okayama A, Tsubouchi H. Association of a genetic polymorphism in ectonucleotide pyrophosphatase/phosphodiesterase 1 with hepatitis C virus infection and hepatitis C virus core antigen levels in subjects in a hyperendemic area of Japan. J Gastroenterol 2008; 43:942-50. [PMID: 19107338 DOI: 10.1007/s00535-008-2256-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2008] [Accepted: 07/03/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND The clinical course of chronic hepatitis C virus (HCV) infection is strongly associated with insulin resistance and obesity. The K121Q polymorphism in the ectonucleotide pyrophosphatase/phosphodiesterase (ENPP)-1 gene and the rs7566605 genotype located near insulin-induced gene 2 have been shown to be associated with insulin resistance and obesity. This study examined whether the K121Q polymorphism in ENPP1 or the rs7566605 genotype is associated with the clinical course of HCV infection. METHODS The relationships between the clinical characteristics of 469 anti-HCV antibody-seropositive subjects (353 were positive for HCV core antigen or RNA, whereas 116 were negative for HCV RNA) and the polymorphisms were analyzed. RESULTS No significant differences in body mass index, plasma glucose level, serum insulin level, and other biochemical markers were observed between subgroups of subjects with different genotypes at the K121Q polymorphism or rs7566605. The frequency of the homozygous wild-type genotype at K121Q in HCV carriers, however, was significantly higher than that in subjects who were negative for HCV RNA (84.5% vs. 75.9%; P < 0.05). Moreover, in HCV carriers, HCV core antigen levels in subjects homozygous for the wild-type genotype at K121Q were significantly higher than in heterozygous carriers of K121Q (5358 fmol/l vs. 4002 fmol/l; P = 0.04). In contrast, the rs7566605 genotype was not associated with hepatitis C viremia or with the HCV core antigen level. CONCLUSIONS The K121Q variant of ENPP1 may be associated with hepatitis C viremia and core antigen levels in HCV carriers.
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Affiliation(s)
- Yuka Takahama
- Miyazaki Prefectural Industrial Support Foundation, Miyazaki, Japan
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El-Chennawi FA, Auf FA, Metwally SS, Mosaad YM, El-Wahab MA, Tawhid ZE. HLA-class II alleles in Egyptian patients with hepatocellular carcinoma. Immunol Invest 2008; 37:661-74. [PMID: 18821214 DOI: 10.1080/08820130802111605] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
UNLABELLED Hepatocellular carcinoma (HCC) is linked to environmental, dietary, and life style factors. Its incidence and distribution vary widely among ethnic groups, sex, and geographic regions. HBV and HCV Infection, liver cirrhosis, male gender, and old age are important risk factors of HCC. Variability in outcome following exposure, and the clustering of HCC within families raise the possibility that genetic factors are also involved in susceptibility to HCC. The Major Histocompatibility Complex (MHC) plays a key role in anti-virus and tumor defense. HLA polymorphism is implicated in conferring genetic susceptibility to a large number of immune-mediated diseases, including some cancers. The association between HLA class II antigen and HCC in different ethnic populations that has been reported is controversial. Therefore, the aim of this work was to study the association between HLA class II-DRB1 and DQB1 polymorphism and HCC in Egyptian patients and to investigate their role as risk factors for the development of HCC. METHODS HLA-class II (DRB1 and DQB1) typing was done by SSP for 100 subjects; 50 patients suffering from HCC (45 males and 5 females) with age range 40-64 years (51.16 years (y) +/- 6.16); and 50 normal healthy control subjects. RESULTS 1. A significantly increased frequency of DRB1*04, and DQB1 *02 in HCC patients versus control group (p = 0.016, and 0.032, respectively) was found; 2. A significantly decreased frequency of DQB1*06 (p = 0.032) was found; 3. A significantly increased frequency of DRB1*07 (odds ratio (OR) = 4.929) was found; and 4. A significantly decreased frequency of DRB1*15 (OR = 0.316) was seen. In conclusion, while some alleles are significantly associated with HCC (DRB1*04, DQB1*02) and others are not associated (DQB1*06); therefore, it can be concluded that the DRB1*04 and DQB1*02 alleles might be risk factors for the occurrence of HCC (OR = 4.373 and 3.807, respectively), and DQB1*06 may be a protective allele (OR = 0.259).
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Affiliation(s)
- Farha A El-Chennawi
- Clinical Immunology Unit, Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura, Egypt.
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Bruno R, Sacchi P. Spontaneous Hepatitis C Virus Clearance in HIV‐Infected Patients: New Insights for Improving Management. J Infect Dis 2008; 198:1262-4. [DOI: 10.1086/592173] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
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Yu RB, Hong X, Ding WL, Tan YF, Zhang YX, Sun NX, Wu GL, Zhan SW, Ge DF. The association between the genetic polymorphism of HLA-DQA1, DQB1, and DRB1 and serum alanine aminotransferase levels in chronic hepatitis C in the Chinese population. J Gastroenterol Hepatol 2008; 23:1394-402. [PMID: 18028350 DOI: 10.1111/j.1440-1746.2007.05215.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND AND AIM To investigate a possible association between HLA genes with serum alanine aminotransferase (ALT) levels and evaluate whether the HLA-DQA1, DQB1, and DRB1 genes could influence the development of liver damage in chronic hepatitis C. METHODS A total of 145 patients with chronic hepatitis C virus (HCV) infection (36 patients with persistently normal ALT values; 109 patients with elevated ALT levels) and 160 uninfected healthy controls were examined for HLA-DQA1, DQB1, and DRB1 molecules by using polymerase chain reaction-sequencing based typing (PCR-SBT). RESULTS Among the patients chronically infected with HCV, the frequencies of DQA1*0501, DQB1*0301, and DRB1*0401 alleles were significantly increased in the normal ALT group compared with those with abnormal ALT levels, whereas that of DQB1*0201 was significantly lower. As compared to uninfected healthy controls, DQA1*0501, DQB1*0301, and DRB1*0401 allele frequencies were also statistically higher in the normal ALT group, whereas that of DQB1*0201 was the inverse. The haplotype frequencies of DQA1*0301-DQB1*0301, DQA1*0501-DQB1*0301, and DRB1*1101-DQB1*0301 were found to be significantly higher in the normal ALT group. Multivariate logistic regression indicated that female sex, and the DQB1*0301 allele and DRB1*0401 allele were independently associated with normal ALT values, whereas DQB1*0201 allele was the inverse. CONCLUSIONS These results suggest that particular HLA alleles may have an influence on the serum ALT level of chronic HCV infection as a host genetic factor in the Chinese population. The DQA1*0501, DQB1*0301, and DRB1*0401 alleles, and the DQA1*0301-DQB1*0301, DQA1*0501-DQB1*0301, and DRB1*1101-DQB1*0301 haplotypes seem to be associated with low hepatitis activity; whereas DQB1*0201 allele is closely correlated with the progression of liver injury in chronic HCV infection.
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Affiliation(s)
- Rong-Bin Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Jiangsu Province Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, China
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40
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Seal KH, Monto A, Dove L, Shen H, Vittinghoff E, Tracy D, Miller E, Lau E, Wright TL. The association of human immunodeficiency virus infection with spontaneously resolved hepatitis C virus infection and level of viremia among injection drug users. Dig Dis Sci 2007; 52:3423-30. [PMID: 17443407 DOI: 10.1007/s10620-006-9277-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2005] [Accepted: 03/01/2006] [Indexed: 12/09/2022]
Abstract
This study aimed to investigate whether HIV and HIV-related factors are associated with spontaneously resolved hepatitis C virus (HCV) infection and levels of hepatitis C viremia. Among 351 anti-HCV(+) injection drug users, with and without HIV infection, multivariate methods were used to evaluate whether HIV status and HIV viral load, CD4 T-cell count, and concurrent HIV antiretroviral therapy were associated with (1) spontaneously resolved HCV infection and (2) HCV RNA levels. In 186 HIV patients, decreased HCV resolution was independently associated with Black race and modestly associated with CD4 T-cell count <200 cells/ml. Among 310 patients with persistent HCV infection, higher HCV RNA levels were independently associated with HIV status but not with other HIV-related factors. HIV may be associated with persistent HCV infection in patients with low CD4 T-cell counts. Moreover, HIV is associated with increased HCV viral load, which may attenuate response to HCV antiviral treatment in coinfected patients.
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Affiliation(s)
- Karen H Seal
- San Francisco Veteran's Administration Medical Center, San Francisco, California 94121, USA.
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41
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Cursino-Santos JR, Donadi EA, Martinelli ALC, Louzada-Junior P, Martinez-Rossi NM. Evolution of hepatitis C virus infection under host factor influence in an ethnically complex population. Liver Int 2007; 27:1371-8. [PMID: 18036100 DOI: 10.1111/j.1478-3231.2007.01600.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND The ethnic influence makes it difficult to reach a consensual definition of host-dependent genetic factors controlling the hepatitis C virus (HCV) disease course. AIMS To investigate, in an ethnically complex Brazilian population, whether human leucocyte antigen (HLA) molecules are associated with susceptibility to HCV infection, self-limiting viral clearance and predisposition to chronic disease. METHODS One hundred and four HCV-antibody-positive patients (stratified into groups with spontaneous viral clearance and chronic HCV infection) and 166 healthy controls were submitted to HLA genotyping. RESULTS Two strong associations were observed between the susceptibility to HCV infection and DRB3 [odds ratio (OR), 4.03; 95% confidence interval (CI), 2.40-6.77; P(c)=0.0000041] and DQB1*02 (OR, 1.72; 95% CI, 1.05-2.84; P=0.041), and between the spontaneous viral clearance and DRB1*01 (OR, 4.59; 95% CI, 1.70-12.41; P=0.003) and DQB1*03 (OR, 2.83; 95% CI, 1.14-7.02; P=0.029). No evidence was observed regarding the epidemiology or viral genotype influence on the disease course. CONCLUSION We could confirm with a highly admixed population the association of viral clearance with two allele groups (DRB1*01 and DQB1*03) previously reported in homogeneous populations. The identification of DRB1*01 and DQB1*03 involved with self-limiting hepatitis in different ethnic groups is a very important finding that will contribute to the current knowledge about HCV-host interaction and the development of therapeutic vaccines.
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Affiliation(s)
- Jeny R Cursino-Santos
- Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
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42
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Grebely J, Raffa JD, Lai C, Krajden M, Conway B, Tyndall MW. Factors associated with spontaneous clearance of hepatitis C virus among illicit drug users. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2007; 21:447-51. [PMID: 17637948 PMCID: PMC2657966 DOI: 10.1155/2007/796325] [Citation(s) in RCA: 89] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Spontaneous clearance of hepatitis C virus (HCV) occurs in approximately 25% of individuals. METHODS To better understand the characteristics associated with clearance, the present study evaluated HCV clearance in a community-based cohort study. The Community Health and Safety Evaluation project recruited 3553 individuals via community organizations and door-to-door canvassing of a random sample of single occupancy hotels in the community to monitor uptake of health services and to estimate the incidence of communicable infections. Cohort data were linked with longitudinal laboratory databases, including HCV antibody and polymerase chain reaction assay results. RESULTS Overall, 762 individuals had HCV antibody and RNA testing performed between 1999 and 2005. Spontaneous HCV clearance was observed in 179 individuals (23.5%), while HCV persistence was observed in 583 individuals (76.5%). The ability to develop protective immunity against HCV, as demonstrated by viral clearance, occurred more often in individuals of Aboriginal ethnicity (adjusted OR [AOR] 2.9, 95% CI 2.0 to 4.3; P<0.001) and female individuals (AOR 1.6, 95% CI 1.1 to 2.4; P=0.01). The rate of spontaneous HCV clearance was reduced in individuals using any type of illicit drugs (AOR 0.54, 95% CI 0.29 to 1.00; P=0.05) and those with HIV coinfection (AOR 0.58, 95% CI 0.38 to 0.88; P=0.01). Of 218 HIV-infected subjects, 48 of 51 (94%) in whom the order of HCV and HIV infection was established were infected with HCV a median of 2.4 years (range 0.2 to 10 years) before becoming infected with HIV. CONCLUSIONS Aboriginal ethnicity and female sex were associated with increased rates of HCV clearance, while HIV coinfection and illicit drug use were associated with increased HCV persistence.
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Affiliation(s)
- Jason Grebely
- Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
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Alric L, Thebault S, Selves J, Peron JM, Mejdoubi S, Fortenfant F, Vinel JP. Characterization of overlap syndrome between primary biliary cirrhosis and autoimmune hepatitis according to antimitochondrial antibodies status. ACTA ACUST UNITED AC 2007; 31:11-6. [PMID: 17273127 DOI: 10.1016/s0399-8320(07)89322-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
AIMS Codification of variant forms between Primary Biliary Cirrhosis (PBC) and Autoimmune Hepatitis (AIH) has not been definitively standardized. The aim of this study was to compare among 102 consecutive patients, 2 subsets of overlap syndrome (OS, N=21) with and without antimitochondrial antibody (AMA) to two groups of patients with typical PBC (N=43) or AIH (N=38). METHODS OS was defined by the presence in the same patient of at least 2 of 3 accepted criteria of PBC and AIH. Twelve patients with OS were AMA negative and 9 were AMA positive. RESULTS A lower level of alanine transaminase (139+/-48 vs 269+/-154 IU/L, P<0.05) and a trend towards a higher level of alkaline phosphatase or gamma-glutamyl transpeptidase was observed in OS without AMA than in OS with AMA (693+/-200 vs 544+/-124 IU/L; 370+/-66 vs 241+/-77 IU/L, respectively). All AMA-negative patients with OS had antinuclear and/or anti-smooth muscle antibodies. OS without AMA differed from those with AMA in that they had more severe bile duct damage including destructive cholangitis (P<0.05), ductopenia (P<0.05), ductular hyperplasia (P<0.05) and a higher METAVIR fibrosis score (2.5+/-0.3 vs 1.3+/-0.3, P<0.05). The response to therapy was not different between PBC, AIH and OS. CONCLUSIONS According to the presence of AMA, 2 homogeneous subgroups of patients with overlap syndrome between PBC and AIH may be identified. AMA status affects clinical presentation and liver disease severity of OS.
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MESH Headings
- Adult
- Alanine Transaminase/blood
- Alkaline Phosphatase/blood
- Antibodies, Antinuclear/blood
- Autoantibodies/blood
- Cohort Studies
- Female
- Follow-Up Studies
- Hepatitis, Autoimmune/diagnosis
- Hepatitis, Autoimmune/drug therapy
- Hepatitis, Autoimmune/enzymology
- Hepatitis, Autoimmune/immunology
- Humans
- Liver/immunology
- Liver Cirrhosis, Biliary/diagnosis
- Liver Cirrhosis, Biliary/drug therapy
- Liver Cirrhosis, Biliary/enzymology
- Liver Cirrhosis, Biliary/immunology
- Liver Function Tests
- Male
- Middle Aged
- Mitochondria, Liver/immunology
- Syndrome
- Treatment Outcome
- gamma-Glutamyltransferase/blood
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Affiliation(s)
- Laurent Alric
- Service de Médecine Interne, Fédération Digestive, Pavillon Dieulafoy, CHU Purpan, Toulouse.
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Singh R, Kaul R, Kaul A, Khan K. A comparative review of HLA associations with hepatitis B and C viral infections across global populations. World J Gastroenterol 2007; 13:1770-1787. [PMID: 17465466 PMCID: PMC4149952 DOI: 10.3748/wjg.v13.i12.1770] [Citation(s) in RCA: 179] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2006] [Revised: 01/26/2006] [Accepted: 03/07/2007] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B (HBV) and hepatitis C (HCV) viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma (HCC). Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen (HLA) associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1*11/*12 alleles and DQB1*0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1*03 and *07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors (KIR) of natural killer (NK) cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance of chronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific therapeutic strategies for clearance of HBV and HCV infections or co-infections across global populations and aid in identification of HBV-HCV combined vaccine. HLA associations of chronic HBV or HCV development with confounding host factors including alcohol, drug abuse, insulin resistance, age and gender are lacking and warrant detailed investigation across global populations.
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Affiliation(s)
- Rashmi Singh
- Department of Biochemistry and Microbiology, Oklahoma States University-Center of Health sciences, 1111 W. 17th St. Tulsa, OK 74107, United States.
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Harris HE, Eldridge KP, Harbour S, Alexander G, Teo CG, Ramsay ME. Does the clinical outcome of hepatitis C infection vary with the infecting hepatitis C virus type? J Viral Hepat 2007; 14:213-20. [PMID: 17305887 DOI: 10.1111/j.1365-2893.2006.00795.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Whether differences in the natural history of hepatitis C virus (HCV) can be explained by differences in the infecting HCV type is unknown. The aim of this study was to investigate whether the HCV type might influence the clinical outcome of infection. Study serum samples were assembled from 749 individuals enrolled into the UK HCV National Register from which data on clinical outcomes were extracted. HCV-RNA-positive specimens were genotyped and HCV-RNA-negative specimens serotyped. Logistic regression analysis was used to investigate the independent effect of HCV type on viral clearance by comparing patients who were HCV RNA negative (n = 86) with those who were HCV RNA positive (n = 508). The same method was used to investigate whether HCV type was associated with histological stage of liver disease. The prevalence of HCV type 1 among those who cleared infection was 69% and among those who remained HCV RNA positive was 51%: Type 1 infections were more likely to be HCV RNA negative than non-1 types (OR 0.47, 95% CI 0.29-0.78, P = 0.003). Type 1 infections were also more likely to be associated with histological stage scores above the median when compared with non-1 types (OR 2.03, 95% CI 1.07-3.83, P = 0.03). In conclusion, HCV type 1 infection was more often HCV RNA negative, suggesting that spontaneous clearance may occur more commonly with this type. Among the RNA-positive infections, type 1 infection may be more aggressive than types 2/3.
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Affiliation(s)
- H E Harris
- Immunisation Department, Centre for Infections, Health Protection Agency, London, UK.
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46
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Lloyd AR, Jagger E, Post JJ, Crooks LA, Rawlinson WD, Hahn YS, Ffrench RA. Host and viral factors in the immunopathogenesis of primary hepatitis C virus infection. Immunol Cell Biol 2006; 85:24-32. [PMID: 17130897 DOI: 10.1038/sj.icb.7100010] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Individuals infected with hepatitis C virus (HCV) have two possible outcomes of infection, clearance or persistent infection. The focus of this review is the host mechanisms that facilitate clearance. The interaction between HCV viral components and the immune system ultimately determines the balance between the virus and host. Strong evidence points to the aspects of cellular immune response as the key determinants of outcome. The recent discovery of viral evasion strategies targeting innate immunity suggests that the interferon-alpha/beta induction pathways are also critical. A growing body of evidence has implicated polymorphisms in both innate and adaptive immune response genes as determinants of viral clearance in individuals infected with HCV.
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Affiliation(s)
- Andrew R Lloyd
- Centre for Infection and Inflammation Research, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
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Hong X, Yu RB, Sun NX, Wang B, Xu YC, Wu GL. Human leukocyte antigen class II DQB1*0301, DRB1*1101 alleles and spontaneous clearance of hepatitis C virus infection: a meta-analysis. World J Gastroenterol 2006; 11:7302-7. [PMID: 16437632 PMCID: PMC4725151 DOI: 10.3748/wjg.v11.i46.7302] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the associations of human leukocyte antigen (HLA) class II DQB1*0301 and/or DRB1*1101 allele with spontaneous hepatitis C virus (HCV) clearance by meta-analysis of individual dataset from all studies published till date. METHODS To clarify the impact of HLA class II polymorphisms on viral clearance, we performed a meta-analysis of the published data from 11 studies comparing the frequencies of DQB1*0301 and DRB1*1101 alleles in individuals with spontaneous resolution to those with persistent infection. As we identified the heterogeneity between studies, summary statistical data were calculated based on a random-effect model. RESULTS Meta-analyses yielded summary estimates-odds ratio (OR) of 2.36 [95%CI (1.62, 3.43), P<0.00001] and 2.02 [95%CI (1.56, 2.62), P<0.00001] for the effects of DQB1*0301 and DRB1*1101 alleles on spontaneous clearance of HCV, respectively. CONCLUSION These results support the hypothesis that specific HLA class II alleles might influence the susceptibility or resistance to persistent HCV infection. Both DQB1*0301 and DRB1*1101 are protective alleles and present HCV epitopes more effectively to CD4(+)T lymphocytes than others, and subjects with these two alleles are at a lower risk of developing chronic HCV infection. Large, multi-ethnic confirmatory and well-designed studies are needed to determine the host genetic determinants of HCV infection.
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Affiliation(s)
- Xin Hong
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
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48
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Patel K, Norris S, Lebeck L, Feng A, Clare M, Pianko S, Portmann B, Blatt LM, Koziol J, Conrad A, McHutchison JG. HLA class I allelic diversity and progression of fibrosis in patients with chronic hepatitis C. Hepatology 2006; 43:241-9. [PMID: 16440356 DOI: 10.1002/hep.21040] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Patients infected with HIV-1 who are heterozygous at HLA class I loci present greater variety of antigenic peptides to CD8+ cytotoxic T lymphocytes, slowing progression to AIDS. A similar broad immune response in chronic hepatitis C (CHC) infection could result in greater hepatic injury. Although specific HLA class II alleles may influence outcome in CHC patients, the role of HLA class I heterogeneity is generally less clearly defined. Our aims were to determine whether HLA class I allelic diversity is associated with disease severity and progression of fibrosis in CHC. The study population consisted of 670 adults with CHC, including 155 with advanced cirrhosis, and 237 non-HCV-infected controls. Serological testing for HLA class I antigens was performed via microlymphocytotoxicity assay. Peptide expression was defined as heterozygous (i.e., a different allele at each locus) or homozygous. Fibrosis staging was determined using METAVIR classification. Heterozygosity at the B locus (fibrosis progression rate [FPR] 0.08 vs. 0.06 units/yr; P = .04) and homozygosity at the A locus (FPR 0.10 vs. 0.08 units/yr; P = .04) predicted a higher median FPR. Age at infection, genotype, and duration of infection were also predictors of FPR. A higher proportion of patients with stage F2-F4 expressed HLA-B18 compared with controls (OR 2.2, 95% CI 1.17-4.23; P = .02). These differences were not observed in patients with advanced cirrhosis. HLA zygosity at 1, 2, or 3 alleles was not associated with fibrosis stage, liver inflammation, or treatment outcome. In conclusion, HLA class I allelic diversity has a minor influence on FPRs and disease severity in CHC.
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Affiliation(s)
- Keyur Patel
- Division of Gastroenterology, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27715, USA
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Silva LK, Silva MBSD, Lopes GB, Rodart IF, Costa FQ, Santana NP, Paraná R, Santana A, Reis MGD. Prevalence of hepatitis C virus infection and HCV genotypes among hemophiliacs in the State of Bahia, Northeastern Brazil: analysis of serological and virological parameters. Rev Soc Bras Med Trop 2006; 38:496-502. [PMID: 16410926 DOI: 10.1590/s0037-86822005000600010] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
The objective of the present study was to analyze HCV serological and virological parameters from hemophiliacs in the State of Bahia. Anti-HCV was investigated by ELISA in a cohort of 268 hemophiliacs A/B who were followed-up in a reference unit for hemotherapy in the State of Bahia. HCV viremia and genotypes were also determined from a subset of 66 anti-HCV seropositive hemophiliacs. Seroprevalence among hemophiliacs was 42.2% (95% CI 36.5-48.1) and was significantly higher (p<0.05) according to age > or =10 years, presence of factor VIII/IX inhibitory antibodies and other infection markers. None of the hemophiliacs less than 5 years of age were anti-HCV seropositive. Viremia was detectable in 77.3% (51/66). HCV genotype 1 (74%) was the most prevalent followed by genotype 3 (22%) and genotype 2 (4%). Our results indicate that HCV prevalence is still high among hemophiliacs, although HCV transmission was not observed in young hemophiliacs.
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Affiliation(s)
- Luciano Kalabric Silva
- Laboratory of Pathology and Molecular Biology, Gonçalo Moniz Research Center, Fundação Oswaldo Cruz, Salvador, BA, Brazil
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Micallef JM, Kaldor JM, Dore GJ. Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies. J Viral Hepat 2006; 13:34-41. [PMID: 16364080 DOI: 10.1111/j.1365-2893.2005.00651.x] [Citation(s) in RCA: 634] [Impact Index Per Article: 33.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
A large number of studies have reported on spontaneous viral clearance rates in acute hepatitis C infection, however most have been small, and reported rates have varied quite widely. To improve the precision of the estimated rate of spontaneous viral clearance, a systematic review was conducted of longitudinal studies. Factors associated with viral clearance were also examined. Inclusion criteria for studies were: longitudinal assessment from time of acute hepatitis C; hepatitis C virus RNA analysis as determinant of viral clearance; untreated for acute hepatitis C. Information on study population, and factors that may influence viral clearance were extracted from each study. Viral clearance was defined among individuals with at least 6 months follow-up following acute hepatitis C. The number of subjects with viral clearance was expressed as a proportion for each study and a weighted mean for proportion was calculated. A total of 31 studies were examined. Study populations included nine studies of post-transfusion hepatitis, 19 of acute clinical hepatitis, and three of sero-incident cases. In total, data was available for 675 subjects and the mean study population was 22 (range 4-67). The proportion with viral clearance ranged from 0.0 to 0.8, with a weighted mean of 0.26 (95% CI 0.22-0.29). Factors associated with viral clearance were female gender and acute clinical hepatitis C study population. Further studies are required to more clearly define predictors of clearance and guide therapeutic intervention strategies.
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Affiliation(s)
- J M Micallef
- National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Darlinghurst, Sydney, NSW, Australia
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