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Uribe-Noguez LA, Prieto-Torres ME, Uribe-Noguez LO, Mata-Marín JA, Arroyo-Anduiza CI, Paquentín-Jimenez R, Chaparro-Sanchez A, Vazquez-Gonzalez WG, Santos Coy-Arechavaleta A, Pompa-Mera EN, Gaytán-Martínez J, Alvarado-Yaah JE, Santacruz-Tinoco CE, Ocaña-Mondragón A. Prevalence and Risk Factors of Occult HCV Infection in the Adult Population of Mexico City. Viruses 2025; 17:236. [PMID: 40006991 PMCID: PMC11860181 DOI: 10.3390/v17020236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 01/31/2025] [Accepted: 02/03/2025] [Indexed: 02/27/2025] Open
Abstract
Occult HCV infection (OCI) is defined by the presence of HCV RNA in hepatocytes and/or peripheral blood mononuclear cells (PBMCs) without detectable HCV RNA or anti-HCV antibodies in plasma. OCI is underrecognized and may contribute to HCV transmission. This study estimated OCI prevalence and associated risk factors in adults from Mexico City. Methods: A retrospective cross-sectional study was conducted, analyzing 507 general population volunteers. Demographic data and potential risk factors were collected via questionnaire. Anti-HCV detection was performed using two techniques: immunochromatographic rapid test and chemiluminescent microparticle immunoassay (CMIA). Nested PCR was employed to detect HCV RNA in plasma and PBMCs. Positive samples were genotyped through sequencing and phylogenetic analysis of the Core/E1 region. Results: Of 507 participants, four were anti-HCV positive. HCV RNA was found in PBMCs of 27 individuals, while plasma samples tested negative, indicating a 5.3% OCI prevalence. OCI was significantly associated with blood donation (p = 0.015), drug use (p = 0.019), particularly cocaine (p = 0.001), and endoscopy (p = 0.043). Genotypes 1b, 1a, 2b, 3a, and 2j were detected in OCI cases. Conclusions: OCI prevalence in Mexico City's general population is notable, with significant links to blood donation, cocaine use, and endoscopy. Enhanced diagnostic strategies are crucial to detect OCI and mitigate HCV transmission.
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Affiliation(s)
- Luis Antonio Uribe-Noguez
- Laboratorio Central de Epidemiología, División de Laboratorios Especializados, Centro Médico Nacional (CMN) “La Raza”, IMSS, México City 02990, Mexico; (W.G.V.-G.); (A.S.C.-A.); (J.E.A.-Y.); (A.O.-M.)
| | - María Erandhi Prieto-Torres
- Coordinación de Información y Análisis Estratégico, Instituto Mexicano del Seguro Social (IMSS), Mexico City 77503, Mexico;
| | | | - José Antonio Mata-Marín
- Departamento de Enfermedades Infecciosas, Hospital de Infectología, CMN “La Raza”, IMSS, Mexico City 02990, Mexico; (J.A.M.-M.); (A.C.-S.); (J.G.-M.)
| | | | - Rebeca Paquentín-Jimenez
- Inflammatory Eye Disease Clinic, Asociación Para Evitar la Ceguera en México, Hospital “Dr. Luis Sánchez Bulnes”, México City 04030, Mexico;
| | - Alberto Chaparro-Sanchez
- Departamento de Enfermedades Infecciosas, Hospital de Infectología, CMN “La Raza”, IMSS, Mexico City 02990, Mexico; (J.A.M.-M.); (A.C.-S.); (J.G.-M.)
| | - Wendy Guadalupe Vazquez-Gonzalez
- Laboratorio Central de Epidemiología, División de Laboratorios Especializados, Centro Médico Nacional (CMN) “La Raza”, IMSS, México City 02990, Mexico; (W.G.V.-G.); (A.S.C.-A.); (J.E.A.-Y.); (A.O.-M.)
| | - Andrea Santos Coy-Arechavaleta
- Laboratorio Central de Epidemiología, División de Laboratorios Especializados, Centro Médico Nacional (CMN) “La Raza”, IMSS, México City 02990, Mexico; (W.G.V.-G.); (A.S.C.-A.); (J.E.A.-Y.); (A.O.-M.)
| | - Ericka Nelly Pompa-Mera
- Unidad de Investigación en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, CMN “Siglo XXI”, IMSS, Mexico City 06720, Mexico;
| | - Jesus Gaytán-Martínez
- Departamento de Enfermedades Infecciosas, Hospital de Infectología, CMN “La Raza”, IMSS, Mexico City 02990, Mexico; (J.A.M.-M.); (A.C.-S.); (J.G.-M.)
| | - Julio Elias Alvarado-Yaah
- Laboratorio Central de Epidemiología, División de Laboratorios Especializados, Centro Médico Nacional (CMN) “La Raza”, IMSS, México City 02990, Mexico; (W.G.V.-G.); (A.S.C.-A.); (J.E.A.-Y.); (A.O.-M.)
| | | | - Alicia Ocaña-Mondragón
- Laboratorio Central de Epidemiología, División de Laboratorios Especializados, Centro Médico Nacional (CMN) “La Raza”, IMSS, México City 02990, Mexico; (W.G.V.-G.); (A.S.C.-A.); (J.E.A.-Y.); (A.O.-M.)
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Occult Infection with Hepatitis C Virus: Looking for Clear-Cut Boundaries and Methodological Consensus. J Clin Med 2021; 10:jcm10245874. [PMID: 34945170 PMCID: PMC8707082 DOI: 10.3390/jcm10245874] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 12/11/2021] [Accepted: 12/13/2021] [Indexed: 02/07/2023] Open
Abstract
The sustained virologic response and elimination of HCV is widely viewed as a true cure of chronic hepatitis C as it associates with amelioration of histological liver damage and improved clinical outcomes. Therefore, the existence and clinical burden of occult HCV infection (OCI) has been a controversial issue for many years. In this review, we summarize recently published data that adds new information on the molecular and clinical background of OCI and its epidemiological significance. We also identify and discuss the most important methodological pitfalls, which can be a source of inconsistency between studies. Data that have accumulated so far, strongly support the existence of extrahepatic HCV replication in individuals negative for serum HCV-RNA by conventional clinical tests. OCI emerges as a condition where the immune system is unable to fully resolve infection but it is continuously stimulated by low levels of HCV antigens, leading to progression of liver pathology and extrahepatic HCV-related complications. Moreover, the development of monitoring strategies or management guidelines for OCI is still hampered by the lack of clear definition and the confusion regarding its clinical significance. Careful study design and the introduction of uniform protocols for the detection of low-level HCV-RNA are crucial for obtaining reliable data on OCI.
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Hedayati-Moghaddam MR, Soltanian H, Ahmadi-Ghezeldasht S. Occult hepatitis C virus infection in the Middle East and Eastern Mediterranean countries: A systematic review and meta-analysis. World J Hepatol 2021; 13:242-260. [PMID: 33708353 PMCID: PMC7934012 DOI: 10.4254/wjh.v13.i2.242] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 11/25/2020] [Accepted: 12/08/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The presence of hepatitis C virus (HCV) RNA in liver tissue or peripheral blood mononuclear cells with no identified virus genome in the serum has been reported worldwide among patients with either normal or elevated serum liver enzymes. The characterization of occult HCV infection (OCI) epidemiology in the Middle East and Eastern Mediterranean (M and E) countries, a region with the highest incidence and prevalence rates of HCV infection in the world, would be effective for more appropriate control of the infection. AIM To estimate the pooled prevalence of OCI in M and E countries using a systematic review and meta-analysis. METHODS A systematic literature search was performed using international, regional and local electronic databases. Some conference proceedings and references from bibliographies were also reviewed manually. The search was carried out during May and June 2020. Original observational surveys were considered if they assessed the prevalence of OCI among the population of M and E countries by examination of HCV nucleic acid in peripheral blood mononuclear cells in at least 30 cases selected by random or non-random sampling methods. The meta-analysis was performed using Comprehensive Meta-analysis software based on heterogeneity assessed by Cochran's Q test and I-square statistics. Data were considered statistically significant at a P value < 0.05. RESULTS A total of 116 non-duplicated citations were found in electronic sources and grey literature. A total of 51 non-overlapping original surveys were appraised, of which 37 met the inclusion criteria and were included in the analysis. Data were available from 5 of 26 countries including Egypt, Iran, Pakistan, Saudi Arabia, and Turkey. The overall prevalence rate of OCI was estimated at 10.04% (95%CI: 7.66%-13.05%). The lowest OCI rate was observed among healthy subjects (4.79%, 95%CI: 2.86%-7.93%). The higher rates were estimated for patients suffering from chronic liver diseases (12.04%, 95%CI: 5.87%-23.10%), and multi-transfused patients (8.71%, 95%CI: 6.05%-12.39%). Subgroup analysis indicated that the OCI rates were probably not associated with the studied subpopulations, country, year of study, the detection method of HCV RNA, sample size, patients' HCV serostatus, and sex (all P > 0.05). Meta-regression analyses showed no significant time trends in OCI rates among different groups. CONCLUSION This review estimated high rates of OCI prevalence in M and E countries, especially among multi-transfused patients as well as patients with chronic liver diseases.
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Affiliation(s)
- Mohammad Reza Hedayati-Moghaddam
- Blood Borne Infections Research Center, Academic Center for Education, Culture and Research (ACECR), Razavi Khorasan Branch, Mashhad 91779-49367, Iran.
| | - Hossein Soltanian
- Blood Borne Infections Research Center, Academic Center for Education, Culture and Research (ACECR), Razavi Khorasan Branch, Mashhad 91779-49367, Iran
| | - Sanaz Ahmadi-Ghezeldasht
- Blood Borne Infections Research Center, Academic Center for Education, Culture and Research (ACECR), Razavi Khorasan Branch, Mashhad 91779-49367, Iran
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Armandi A, Caviglia GP, Saracco GM, DE MARCO L, FAGOONEE S, PELLICANO R. Seronegative occult hepatitis C virus infection: what is its clinical relevance? MINERVA BIOTECNOL 2021; 32. [DOI: 10.23736/s1120-4826.20.02637-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
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An T, Dean M, Flower R, Tatzenko T, Chan HT, Kiely P, Faddy HM. Understanding occult hepatitis C infection. Transfusion 2020; 60:2144-2152. [PMID: 33460181 DOI: 10.1111/trf.16006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 06/16/2020] [Accepted: 06/18/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Occult hepatitis C infection (OCI) is a type of hepatitis C virus (HCV) infection, defined as the presence of HCV RNA in hepatocytes or peripheral blood mononuclear cells (PBMCs) and the absence of HCV RNA in serum. STUDY DESIGN AND METHODS A literature review was conducted to identify articles that characterized OCI as a disease, including its epidemiology, mode of transmission, pattern of infection, progression, and treatment. RESULTS OCI patients experience a milder degree of inflammatory and cirrhotic changes than patients with chronic hepatitis C. OCI is transmissible parenterally both in vivo and in vitro, however the duration and outcome of OCI remains unclear. OCI is most consistently found in patients with previous hepatitis C disease and hemodialysis patients. Beyond the at-risk populations, OCI has also been demonstrated among healthy individuals and blood donors. CONCLUSIONS This review summarises our current understanding of OCI and suggests areas for further research to improve our understanding of this phenomenon, including a better understanding of its epidemiology and full clinical course. The current understanding of OCI and its clinical implications remain limited. Further standardized detection methods, ongoing surveillance, and investigation of its potential transmissions are required.
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Affiliation(s)
- Timothy An
- Research and Development, Australia Red Cross Lifeblood, Kelvin Grove, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Melinda Dean
- Research and Development, Australia Red Cross Lifeblood, Kelvin Grove, Queensland, Australia.,School of Health and Sports Science, University of the Sunshine Coast, Brisbane, Queensland, Australia
| | - Robert Flower
- Research and Development, Australia Red Cross Lifeblood, Kelvin Grove, Queensland, Australia
| | - Tayla Tatzenko
- Research and Development, Australia Red Cross Lifeblood, Kelvin Grove, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Hiu Tat Chan
- Australia Red Cross Lifeblood, Melbourne, Victoria, Australia
| | - Philip Kiely
- Australia Red Cross Lifeblood, Melbourne, Victoria, Australia
| | - Helen M Faddy
- Research and Development, Australia Red Cross Lifeblood, Kelvin Grove, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,School of Health and Sports Science, University of the Sunshine Coast, Brisbane, Queensland, Australia
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Naveed M, Ali A, Sheikh N, Rafique S, Idrees M. Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs. APMIS 2020; 128:326-334. [PMID: 31863490 DOI: 10.1111/apm.13024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 12/17/2019] [Indexed: 12/20/2022]
Abstract
Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.
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Affiliation(s)
- Mariam Naveed
- Centre for Applied Molecular Biology (CAMB), University of the Punjab, Lahore, Pakistan
| | - Amjad Ali
- Department of Genetics, Hazara University, Mansehra, Pakistan
| | - Nadeem Sheikh
- Department of Zoology, University of the Punjab, Lahore, Pakistan
| | - Shazia Rafique
- Center of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
| | - Muhammad Idrees
- Center of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
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7
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Agi E, Asghari S, Namvar A, Khairkhah N, Naderi N, Anvar A, Azizi Saraji A, Bolhassani A. Molecular Study of Occult Hepatitis C Infection among Iranian Hemophilia Patients Treated with Direct-acting Antiviral Agents. JOURNAL OF MEDICAL MICROBIOLOGY AND INFECTIOUS DISEASES 2020. [DOI: 10.29252/jommid.8.1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
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Donyavi T, Bokharaei-Salim F, Khanaliha K, Sheikh M, Bastani MN, Moradi N, Babaei R, Habib Z, Fakhim A, Esghaei M. High prevalence of occult hepatitis C virus infection in injection drug users with HIV infection. Arch Virol 2019; 164:2493-2504. [PMID: 31346769 DOI: 10.1007/s00705-019-04353-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 06/25/2019] [Indexed: 12/12/2022]
Abstract
One of the pathological forms of chronic hepatitis C is occult HCV infection (OCI), in which there is no detectable HCV RNA in plasma specimens but HCV RNA is present in PBMCs and liver biopsy specimens. The aim of this study is to estimate the prevalence of OCI in HIV-positive people who are injection drug users (IDUs). From April 2015 to August 2018, 161 Iranian IDUs with HIV infection enrolled in the study. Viral RNA was extracted from plasma and PBMC samples of participants, and the presence of HCV RNA was examined using RT nested PCR with primers from two conserved regions (5´-UTR and NS5B). HCV genotyping was performed using RFLP and sequencing methods. Of the 161 patients, 134 (83.2%) were positive for anti-HCV antibodies. All 27 patients who were negative for anti-HCV were also negative for HCV RNA in plasma, but five of them (18.5%) were positive for HCV RNA in PBMCs. Importantly, 9 out of 50 patients (18.0%) who apparently had recovered from HCV infection (i.e., were anti-HCV positive and HCV RNA negative) were positive for HCV RNA in PBMCs. Overall, 18.1% of the patients who had no signs of previous HCV infection or had apparently recovered from the disease had OCI. The HCV genotypes of the cases with OCI were as follows: five patients (35.7%) were infected with subtype 1a, eight patients (57.1%) were infected with subtype 3a, and one patient (7.1%) was infected with genotype 4. Thus, it seems that the prevalence of OCI in HIV-positive IDUs is extremely significant in Iran and is likely to delay the global eradication of HCV infection until 2030.
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Affiliation(s)
| | - Farah Bokharaei-Salim
- Iran University of Medical Sciences, Tehran, Iran.
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Khadijeh Khanaliha
- Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Sheikh
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad-Navid Bastani
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | | | - Zahra Habib
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Atousa Fakhim
- Department of Architectural Engineering, Faculty of Engineering, Islamic Azad University, South Tehran Branch, Tehran, Iran
| | - Maryam Esghaei
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Hanafy AS, Seleem WM, Basha MAA, Marei AM. Residual hepatitis C virus in peripheral blood mononuclear cell as a risk factor for hepatocellular carcinoma after achieving a sustained virological response: a dogma or fiction. Eur J Gastroenterol Hepatol 2019; 31:1275-1282. [PMID: 31149912 DOI: 10.1097/meg.0000000000001459] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND Clinical worsening after achieving a sustained virological response (SVR) needs to be clarified and explained. Persistence of hepatitis C virus (HCV) core antigen interacts with the host proteins to interfere with signaling pathways and increases the susceptibility to hepatic carcinogenesis. OBJECTIVE This study aimed to investigate the risk factors that increase the progression of liver disease and hepatocellular carcinoma in a subgroup of HCV patients who achieved a SVR. PATIENTS AND METHODS Eighty-nine HCV patients with hepatic decompensation were selected 8.2 ± 1.8 months after achieving SVR24. HCV core antigen and HCV RNA were detected in peripheral blood mononuclear cells. Matched control (n = 100) and training (n = 200) groups were recruited. RESULTS Eighty-five patients showed a progression of Child-Turcotte-Pugh and model for end-stage liver disease scores, with positive RNA in peripheral blood mononuclear cell (357.4 ± 42.1 IU/million cell) and positive hepatitis C virus core antigen (n = 73); four patients were excluded. Susceptibility to decompensation and hepatocellular carcinoma after direct-acting antiviral drugs increased with age [odds ratio (OD) = 1.87], and was associated with male sex (OD = 1.65), diabetes (OD = 3.68), thrombocytopenia (OD = 2.44), pretreatment Alfa-fetoprotein (OD = 3.41), and occult HCV (OD = 4.1). CONCLUSION Clinical deterioration after SVR could be explained by occult HCV mainly in older male patients with diabetes and thrombocytopenia.
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Affiliation(s)
- Amr S Hanafy
- Internal Medicine Department, Hepatology Division
| | | | | | - Ayman M Marei
- Immunology Department, Faculty of Medicine, Zagazig University, Zagazig
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Nalbantoglu I, Jain D. Cryptogenic cirrhosis: Old and new perspectives in the era of molecular and genomic medicine. Semin Diagn Pathol 2019; 36:389-394. [PMID: 31395291 DOI: 10.1053/j.semdp.2019.07.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Cryptogenic cirrhosis (CC) is defined as cirrhosis of unknown etiology despite extensive clinical, laboratory and pathologic work-up, and constitutes approximately 5-10% of all cirrhosis cases. Histologic examination can provide important clues and help identify the potential etiology of CC. Most CC cases can still be classified into four histologic patterns: hepatitic, steatotic, biliary, and patternless (bland). The use of genetic testing has significantly improved diagnostic ability and treatment, especially in pediatric patients with acute and chronic liver diseases. More recently, whole exome sequencing has been used for identifying genetic alterations that lead to a diagnosis in adults with liver disease of unknown etiology. Recent advances in genomic analysis has allowed the unraveling of the underlying etiology in a subset of CC cases, and also helped identify new disorders. Providing a diagnosis for these patients has several important implications for treatment, possible genetic counseling, and transplant eligibility. However, detailed clinical and histologic characterization of the patients still remains an important part of the CC work-up, since clinicopathologic and genomic correlation is crucial in making a diagnosis, or in some cases, discovery of a new entity. This article summarizes the main histologic findings that can be observed in CC cases, potential causes of CC, and recent advances in the field.
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Affiliation(s)
- Ilke Nalbantoglu
- Yale School of Medicine, Department of Anatomic Pathology, 20 York Street EP2-608B, New Haven, CT, USA.
| | - Dhanpat Jain
- Yale School of Medicine, Department of Anatomic Pathology, 20 York Street EP2-608B, New Haven, CT, USA
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Wang Y, Rao H, Chi X, Li B, Liu H, Wu L, Zhang H, Liu S, Zhou G, Li N, Niu J, Wei L, Zhao J. Detection of residual HCV-RNA in patients who have achieved sustained virological response is associated with persistent histological abnormality. EBioMedicine 2019; 46:227-235. [PMID: 31345785 PMCID: PMC6711338 DOI: 10.1016/j.ebiom.2019.07.043] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 07/15/2019] [Accepted: 07/16/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Whether achieving sustained virological response (SVR) in patients with hepatitis C attains complete elimination of hepatitis C virus (HCV) is unknown, because occult HCV infection (OCI), defined as the detection of HCV-RNA in hepatocytes or peripheral blood mononuclear cells (PBMC) in absence of serum HCV-RNA, may occur. We thus investigated the prevalence and clinical relevance of OCI. METHODS Subjects from three hospitals who had achieved serum HCV clearance, including 60 of Direct-acting antiviral agents (DAAs) induced SVR, 50 of pegylated interferon plus ribavirin (PR) induced SVR, and 30 of spontaneous resolution, were subjected to detect HCV-RNA in liver by robust RNAscope assay and PBMC by qPCR. Paired liver biopsies at baseline and at SVR24 were analyzed. RESULTS OCI was detected in 16 of 140 subjects (11.4%), with 15.0% in DAA-based group, 10.0% in PR group and 6.7% in spontaneously resolved group. In DAA-based subgroups, the incidence of OCI was gradually increased in group of solely DAA(s) therapy, combining DAA and PR therapy and combining DAA and ribavirin therapy. OCI is more frequent in patients with genotype 3. No correlation between baseline viral load, interleukin-28B genotype, baseline transaminases, post-SVR transaminases and OCI were found. However, OCI was significantly linked with severity of fibrosis and active inflammation at post-SVR, even considering basal fibrosis status. In addition, both the magnitude and the frequency of fibrosis regression were lower in patients with OCI than in those without OCI. In the multivariate analysis, PR therapy was identified an independent negative prognostic factor for both hepatic inflammation (P = .022) and fibrosis regression (P = .015). Importantly, we found HCV relapse in one of the OCI patients at 48 weeks after the end of PR treatment. CONCLUSIONS HCV-RNA can persist in hepatocytes and/or PBMC in a certain of patients who achieved spontaneous or treatment-induced HCV RNA clearance from serum and associated with persistent histological abnormality. Our findings provide new insights into cure of HCV and could influence the following-up scenario after SVR.
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Affiliation(s)
- Yijin Wang
- Department of Pathology and Hepatology, the 5th Medical Center, Chinese PLA General Hospital, China
| | - Huiying Rao
- Peking University Hepatology Institute, Peking University People's Hospital, Peking University Health Science Center, Beijing, China
| | - Xiumei Chi
- Department of Hepatology, the First Hospital of Jilin University, Changchun, China
| | - Boan Li
- Center for Clinical Laboratory, the 5th Medical Center, Chinese PLA General Hospital, China
| | - Hongyang Liu
- Department of Pathology and Hepatology, the 5th Medical Center, Chinese PLA General Hospital, China
| | - Liyuan Wu
- Department of Pathology and Hepatology, the 5th Medical Center, Chinese PLA General Hospital, China
| | - Hao Zhang
- Center for Clinical Laboratory, the 5th Medical Center, Chinese PLA General Hospital, China
| | - Shuhong Liu
- Department of Pathology and Hepatology, the 5th Medical Center, Chinese PLA General Hospital, China
| | - Gaungde Zhou
- Department of Pathology and Hepatology, the 5th Medical Center, Chinese PLA General Hospital, China
| | - Na Li
- Advanced Cell Diagnostics, 3960 Point Eden Way, Hayward, CA 94545, USA
| | - Junqi Niu
- Department of Hepatology, the First Hospital of Jilin University, Changchun, China.
| | - Lai Wei
- Beijing Tsinghua Changgung Hospital, Tsinghua University, China.
| | - Jingmin Zhao
- Department of Pathology and Hepatology, the 5th Medical Center, Chinese PLA General Hospital, China.
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Ayadi A, Nafari AH, Irani S, Mohebbi E, Mohebbi F, Sakhaee F, Vaziri F, Siadat SD, Fateh A. Occult hepatitis C virus infection in patients with beta-thalassemia major: Is it a neglected and unexplained phenomenon? J Cell Biochem 2019; 120:11908-11914. [PMID: 30775813 DOI: 10.1002/jcb.28472] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 12/17/2018] [Indexed: 01/24/2023]
Abstract
Occult hepatitis C virus (HCV) infection (OCI) is described as the presence of viral genome in both hepatocytes and peripheral blood mononuclear cells (PBMCs) despite constant negative results on serum HCV RNA tests. Beta-thalassemia major (BTM) describes a group of inherited blood diseases. Patients with BTM require repeated blood transfusions, increasing the risk of exposure to infectious agents. We aimed to assess the prevalence of OCI in Iranian BTM patients and to identify the role of host factors in OCI positivity. A total of 181 BTM patients with HCV negative markers were selected. HCV RNA was tested in PBMCs using nested polymerase chain reaction assay. The positive samples were then genotyped via restriction fragment-length polymorphism (RFLP) and 5'-untranslated region sequencing. Six (3.3%) out of 181 BTM patients had viral HCV genomes in PBMC samples. Three (50.0%), two (33.3%), and one (16.7%) out of these six patients were infected with HCV-1b, HCV-1a, and HCV-3a, respectively. OCI positivity was significantly associated with the serum level of uric acid (P = 0.045) and ABO blood group (P = 0.032). Also, OCI patients had unfavorable IFNL3 rs12979860 TT, IFNL3 rs8099917 GG, IFNL3 rs12980275 GG, and IFNL4 ss469415590 ∆G/∆G genotypes. In conclusion, we indicated the low frequency of OCI in BTM patients. Nevertheless, more attention is warranted considering the importance of this infection. Also, further studies are necessary to determine the actual prevalence of OCI among BTM patients in Iran.
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Affiliation(s)
- Ahmad Ayadi
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Amir Hossein Nafari
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Shiva Irani
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Elham Mohebbi
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Fahimeh Mohebbi
- Department of Network Science and Technology, University of Tehran, Tehran, Iran
| | - Fatemeh Sakhaee
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
| | - Farzam Vaziri
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Seyed Davar Siadat
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Abolfazl Fateh
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
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13
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Moayedi J, Moini M, Geramizadeh B, Malekhosseini SA, Yaghobi R. Seropositive Form of Occult Hepatitis B Virus Infection in Iranian Patients with Cryptogenic Liver Cirrhosis. HEPATITIS MONTHLY 2019; In Press. [DOI: 10.5812/hepatmon.84806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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14
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The frequency of varicella-zoster virus infection in patients with multiple sclerosis receiving fingolimod. J Neuroimmunol 2019; 328:94-97. [DOI: 10.1016/j.jneuroim.2018.12.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2018] [Revised: 12/08/2018] [Accepted: 12/25/2018] [Indexed: 12/20/2022]
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15
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Mekky MA, Sayed HI, Abdelmalek MO, Saleh MA, Osman OA, Osman HA, Morsy KH, Hetta HF. Prevalence and predictors of occult hepatitis C virus infection among Egyptian patients who achieved sustained virologic response to sofosbuvir/daclatasvir therapy: a multi-center study. Infect Drug Resist 2019; 12:273-279. [PMID: 30774394 PMCID: PMC6348965 DOI: 10.2147/idr.s181638] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background Occult hepatitis C virus (HCV) infection (OCI) is characterized by the detection of HCV-RNA in non-serum reservoirs, such as peripheral blood mononuclear cells (PBMCs) and/or hepatocytes with undetectable HCV-RNA or antibodies in the serum. In this study, we tried to evaluate the prevalence and possible predictors of OCI in patients who achieved sustained virologic response (SVR) post sofosbuvir/daclatasvir (SOF/DCV) therapy. Patients and methods A cross-sectional multicenter study was designed to enroll 1,280 HCV-infected patients who received SOF (400 mg) plus DCV (60 mg) once daily ± ribavirin regimen for 12 weeks and achieved SVR 12 weeks post treatment. They were randomly recruited from three dedicated Egyptian centers for management of HCV. Real-time PCR was performed to detect HCV-RNA in serum and PBMCs and to evaluate the different risk factors pertaining to the existence of OCI. Results HCV-RNA was detected in PBMCs of 50 (3.9%) of them. All OCI cases exhibited significant fibrosis score and raised pre-treatment alanine aminotransferase (ALT) levels. Logistic regression analysis comparing OCI with non-OCI revealed that high pre-treatment viral load, raised ALT, advanced fibrosis score, prolonged prothrombin time, low albumin, Child B score, antiviral experienced patients, and raised bilirubin are the most significant predictor for the possibility of OCI presence with Odds Ratio as 7.03, 5.13, 4.4, 2.68, 2.52, 1.9, 1.5, and 1.2, respectively. Conclusion In spite of its remote possibility, OCI post SOF/DCV therapy may be present in some cases, and this may entail a re-auditing for the definition of SVR by dual testing in both serum and PBMCs.
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Affiliation(s)
- Mohamed A Mekky
- Department of Tropical Medicine and Gastroenterology, Assiut University Hospital, Assiut, Egypt
| | - Hani I Sayed
- Center for Management of Viral Hepatitis, Ministry of Health, Assiut, Egypt
| | - Mohamed O Abdelmalek
- Department of Tropical Medicine and Gastroenterology, Assiut University Hospital, Assiut, Egypt
| | - Medhat A Saleh
- Department of Public Health and Community Medicine, Assiut University, Assiut, Egypt
| | - Osman A Osman
- Department of Tropical Medicine and Gastroenterology, Assiut University Hospital, Assiut, Egypt
| | - Heba A Osman
- Department of Tropical Medicine and Gastroenterology, South Valley University Hospital, Qena, Egypt
| | - Khairy H Morsy
- Department of Tropical Medicine and Gastroenterology, Sohag University Hospital, Sohag, Egypt
| | - Helal F Hetta
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt, .,Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA,
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16
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Molecular diagnosis of occult hepatitis C virus infection in Iranian injection drug users. Arch Virol 2018; 164:349-357. [PMID: 30390150 DOI: 10.1007/s00705-018-4066-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 09/20/2018] [Indexed: 12/12/2022]
Abstract
Occult HCV infection (OCI) has been described as the presence of hepatitis C virus (HCV) genomic RNA in hepatocytes and/or peripheral blood mononuclear cell (PBMC) specimens and the lack of HCV genomic RNA and anti-HCV antibodies (Abs) in plasma samples. Injection drug users (IDUs) are the most important high-risk group for infection with blood-borne viruses, particularly HCV. The purpose of this study was to determine the presence of OCI in IDUs. A prospective cross-sectional study of 126 consecutive Iranian IDUs was performed from March 2017 to January 2018. PBMCs were separated from blood samples from the participants, and after extraction of the viral RNA from the plasma and PBMC specimens, HCV RNA was detected in the samples using RT-nested PCR by amplification of the 5'-NTR of HCV. HCV genotyping was carried out using restriction a fragment length polymorphism (RFLP) assay. The viral RNA was amplified using RT-nested PCR with specific primers for the NS5B gene, and the PCR products were sequenced to confirm the results obtained by HCV RNA detection and HCV genotyping. Out of the 126 IDUs studied, 105 (83.3%) were negative for anti-HCV Abs and HCV RNA in plasma samples, whereas HCV RNA was detected in the PBMC samples of six (5.7%) participants, indicating that these individuals had OCI. Moreover, HCV genomic RNA was detected in PBMC samples from five (23.8%) of the 21 IDUs studied who were positive for anti-HCV Abs and negative for HCV genomic RNA in plasma specimens. These IDUs also had OCI. The HCV genotypes in the PBMC samples from the subjects with OCI were determined. Six (54.5%) subjects were infected with HCV subtype 3a, and five (45.5%) were infected with HCV subtype 1a. This study showed that 8.7% of the Iranian IDUs had OCI, and therefore, a study focusing on the diagnosis of OCI in these individuals can be valuable and informative.
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17
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Yaghobi R, Kazemi MJ, Geramizadeh B, Malek Hosseini SA, Moayedi J. Significance of Occult Hepatitis C Virus Infection in Liver Transplant Patients With Cryptogenic Cirrhosis. EXP CLIN TRANSPLANT 2018; 18:206-209. [PMID: 30346262 DOI: 10.6002/ect.2017.0332] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES Investigations into the viral causes of end-stage liver disease in liver transplant patients with cryptogenic underlying disease remain of interest. Hepatitis C virus infection, especially in its silent (occult) form, may play a key role in the introduction and development of cryptogenic cirrhosis. We aimed to determine the prevalence of occult hepatitis C virus infection in liver transplant recipients with cryptogenic cirrhosis. MATERIALS AND METHODS In this cross-sectional study, 127 liver transplant recipients confirmed to have cryptogenic cirrhosis were included. Plasma samples of the patients underwent evaluation for hepatitis C virus antibody using the enzyme-linked immunosorbent assay method. Plasma samples and paraffin-embedded liver tissue samples were tested for hepatitis C virus RNA using nested reverse transcriptase-polymerase chain reaction. RESULTS Hepatitis C virus RNA was detected in liver tissue sections of 10 patients (7.9%). However, none of the cryptogenic patients had hepatitis C virus RNA or antibody in their plasma samples. None of the patients had hepatitis C or G virus coinfection, but simultaneous detection of hepatitis B and hepatitis C virus was diagnosed in 4 liver tissue samples. CONCLUSIONS A finding of hepatitis C virus RNA in liver tissue samples of transplant recipients presents the historical possibility of occult hepatitis C virus infection as underlying disease in our patients with cryptogenic cirrhosis. Results present an important and determinative role of occult hepatitis C virus infection in the pathogenesis of cryptogenic cirrhosis, which needs further confirmation in additional studies.
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Affiliation(s)
- Ramin Yaghobi
- >From the Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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18
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Kahyesh-Esfandiary R, Sadigh ZA, Esghaei M, Bastani MN, Donyavi T, Najafi A, Fakhim A, Bokharaei-Salim F. Detection of HCV genome in peripheral blood mononuclear cells of Iranian seropositive and HCV RNA negative in plasma of patients with beta-thalassemia major: Occult HCV infection. J Med Virol 2018; 91:107-114. [PMID: 30091793 DOI: 10.1002/jmv.25279] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 07/14/2018] [Indexed: 12/24/2022]
Abstract
Beta (β) thalassemia major is a genetic blood disorder with a deficiency in the hemoglobin beta chain, requiring blood transfusion therapy. Multiple blood transfusions increase the risk of transmitting blood-borne infections. The aim of this study is to determine the frequency of hepatitis C virus (HCV) infection in Iranian individuals with β-thalassemia major. A total of 164 patients with β-thalassemia major were recruited for this study. HCV RNA testing was done on plasma and peripheral blood mononuclear cells (PBMCs) from the HCV seropositive samples (with reverse transcriptase-nested polymerase chain reaction [PCR] method using primers from the 5'-untranslated region [UTR]), and all HCV RNA positive samples were genotyped by the restriction fragment length polymorphism assay. For confirmation of the HCV genotyping in PBMCs of occult HCV infection [OCI]-positive patients, the PCR products of two different regions of HCV (5'-UTR and nonstructural protein 5B [NS5B]) were sequenced. Of 164 patients, 29.3% were positive for anti-HCV antibodies, and HCV RNA was detected in the plasma specimens of 13.4% patients and in the PBMC samples of 15.2% participants. The genomic HCV-RNA was detected in PBMC samples in 3 (6.3%) of the total 48 individuals who were HCV seropositive, and plasma HCV-RNA negative (occult HCV infection). The subtypes of HCV in the plasma and PBMC samples of three participants were not identical. This study shows that among this group of Iranian patients with β-thalassemia major, 13.4% had active HCV infection and 6.3% had occult HCV infection as evidenced by HCV RNA detected in PBMC specimens. Therefore, the design of a prospective study that focuses on the diagnosis of OCI can be very valuable and provide more information.
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Affiliation(s)
| | - Zohreh-Azita Sadigh
- Human Viral Vaccine Department, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
| | - Maryam Esghaei
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad-Navid Bastani
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Tahereh Donyavi
- HIV Laboratory of National Center, Iran University of Medical Sciences, Tehran, Iran
| | - Alireza Najafi
- HIV Laboratory of National Center, Iran University of Medical Sciences, Tehran, Iran
| | - Atousa Fakhim
- Faculty of Engineering, Islamic Azad University, South Tehran Branch, Tehran, Iran
| | - Farah Bokharaei-Salim
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,HIV Laboratory of National Center, Iran University of Medical Sciences, Tehran, Iran
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19
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Austria A, Wu GY. Occult Hepatitis C Virus Infection: A Review. J Clin Transl Hepatol 2018; 6:155-160. [PMID: 29951360 PMCID: PMC6018308 DOI: 10.14218/jcth.2017.00053] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Revised: 12/26/2017] [Accepted: 01/09/2018] [Indexed: 12/12/2022] Open
Abstract
Occult hepatitis C virus (HCV) infection (OCI), first described in 2004, is defined as the presence of HCV RNA in hepatocytes or peripheral blood mononuclear cells without detectable HCV RNA in the serum. Here, we aimed to review the epidemiology, diagnostic methods, clinical implications and potential management recommendations currently described in the literature, as well as the future directions for investigation of this entity. PubMed and Cochrane databases were searched with combination of the following keywords: "occult", "hepatitis C virus", and "occult HCV infection". There are data to support OCI as a potential culprit in cryptogenic liver disease. There are also consistent data demonstrating the existence of OCI in specific populations, such as dialysis, human immunodeficiency virus-infected and hepatitis B virus-infected patients, and also in the general population. While the gold standard for diagnosis is liver biopsy, examination of peripheral blood mononuclear cells may be a reliable, safer alternative method of diagnosis. Occult HCV infection is likely associated with liver fibrosis and progression of liver disease. Additional studies are required to determine the infectivity of OCI patients, as well as clarify the natural course and specific clinical implications of OCI. Lastly, studies are needed to determine whether treatment of OCI leads to decreased morbidity and/or mortality.
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Affiliation(s)
- Alyssa Austria
- Division of Gastroenterology-Hepatology, Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
- *Correspondence to: Alyssa Austria, Department of Medicine, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030, USA. Tel: +1-860-679-4477, Fax: +1-860-679-1025, E-mail:
| | - George Y. Wu
- Division of Gastroenterology-Hepatology, Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
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20
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Dehghani-Dehej F, Sarvari J, Esghaei M, Hosseini SY, Garshasbi S, Kalantari S, Monavari SH, Fakhim A, Keyvani H, Bokharaei-Salim F. Presence of different hepatitis C virus genotypes in plasma and peripheral blood mononuclear cell samples of Iranian patients with HIV infection. J Med Virol 2018; 90:1343-1351. [DOI: 10.1002/jmv.24925] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 07/31/2017] [Indexed: 01/05/2023]
Affiliation(s)
- Farzaneh Dehghani-Dehej
- Department of Bacteriology and Virology; School of Medicine; Shiraz University of Medical Sciences; Shiraz Iran
| | - Jamal Sarvari
- Department of Bacteriology and Virology; School of Medicine; Shiraz University of Medical Sciences; Shiraz Iran
- Gastroenterohepatology Research Center; Shiraz University of Medical Sciences; Shiraz Iran
| | - Maryam Esghaei
- Department of Virology; School of Medicine; Iran University of Medical Sciences; Tehran Iran
| | - Seyed Y. Hosseini
- Department of Bacteriology and Virology; School of Medicine; Shiraz University of Medical Sciences; Shiraz Iran
| | - Saba Garshasbi
- HIV Laboratory of National Center; Deputy of Health; Iran University of Medical Sciences; Tehran Iran
| | - Saeed Kalantari
- Departments of Infectious Diseases and Tropical Medicine; Iran University of Medical Sciences; Tehran Iran
| | - Seyed H. Monavari
- Department of Virology; School of Medicine; Iran University of Medical Sciences; Tehran Iran
| | - Atousa Fakhim
- Department of Architectural Engineering; Faculty of Engineering; Islamic Azad University; South Tehran Branch; Tehran Iran
| | - Hossein Keyvani
- Department of Virology; School of Medicine; Iran University of Medical Sciences; Tehran Iran
| | - Farah Bokharaei-Salim
- Department of Virology; School of Medicine; Iran University of Medical Sciences; Tehran Iran
- HIV Laboratory of National Center; Deputy of Health; Iran University of Medical Sciences; Tehran Iran
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21
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Abd Alla MDA, Elibiary SA, Wu GY, El-Awady MK. Occult HCV Infection (OCI) Diagnosis in Cirrhotic and Non-cirrhotic Naïve Patients by Intra-PBMC Nested Viral RNA PCR. J Clin Transl Hepatol 2017; 5:319-326. [PMID: 29226098 PMCID: PMC5719189 DOI: 10.14218/jcth.2017.00034] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Revised: 07/25/2017] [Accepted: 08/11/2017] [Indexed: 12/11/2022] Open
Abstract
Background and Aims: Occult HCV infections (OCIs) include IgG antibody seronegative cryptogenic (COCIs), as well as seropositive secondary naïve (SNOCIs) and experienced (SEOCIs) cases. We used peripheral-blood-mononuclear-cell (PBMC)-PCR to evaluate COCIs and SNOCIs prevalence, serum HCV spontaneous disappearance (SCSD) in naïve cirrhotics and non-cirrhotics, intra-PBMC HCV-RNA strands in relation to cirrhosis density in naïve non-viremia cases, and HCV-RNA seroconversion after 1 year of solitary naïve intra-PBMC infection. Methods: The anti-HCV IgG antibody-positive naïve-patients (n = 785) were classified into viremic (n = 673) and non-viremic [n = 112, including non-cirrhotics (n = 55) and cirrhotics (n = 57)], and 62 controls without evidence of HCV-infection. Controls and post-HCV non-viremia cases (n = 62+112 = 174) were submitted to hepatic Fibroscan-Elastography evaluation. All subjects (n = 847) were screened for intra-PBMC HCV-RNA sense and antisense strands by nested-PCR. Results: Naïve-OCI cases (4.84%) that were diagnosed by PBMC-PCR significantly raised the total numbers of HCV-infection to 714 (p = 0.01). The percent positivity of SNOCIs (34.82%) was significantly higher than for asymptomatic-COCIs (3.125%, p = 0.0001). Comparing PBMC-PCR with single-step-reverse-transcription (SRT)-PCR for identification of SCSD in naïve IgG antibody-positive non-viremia patients (n = 112) revealed a decline in SCSD prevalence by PBMC-PCR (from 14.27% to 9.3%), regardless of presence of hepatic cirrhosis (p = 0.03). SCSD was found to be higher by PBMC-PCR in non-cirrhotics compared to cirrhotics (p = 0.0001), with an insignificant difference when using SRT-PCR (p = 0.45). Intra-PBMC HCV-RNA infection was significantly more frequent in cirrhotics compared to both non-cirrhotics and controls (p < 0.0005). An increased hepatic fibrosis density was recognized in intra-PBMC HCV-RNA infection with sense (p = 0.0001) or antisense strand (p = 0.003). HCV-RNA seroconversion was associated with intra-PBMC infection when both sense and antisense strands were detected (p = 0.047). Conclusions: Intracellular HCV-RNA evaluation is crucial for diagnosing OCIs and addressing relapse probability.
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Affiliation(s)
- Mohamed Darwish Ahmed Abd Alla
- Tropical Medicine Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
- *Correspondence to: Mohamed Darwish Ahmed Abd Alla, El-Hussein University Hospital, Al-Azhar University, Gouhar Al-Kaed Street, Al-Darasah, Cairo 11675, Egypt. Tel: +20-109-417-5209, Fax: +20-25123091, E-mail:
| | - Saleh Ahmed Elibiary
- Tropical Medicine Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - George Y. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
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22
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Dolatimehr F, Khosravi MH, Rezaee-Zavareh MS, Alavian SM. Prevalence of Occult HCV Infection in Hemodialysis and Kidney-Transplanted Patients: A Systematic Review. Future Virol 2017; 12:315-322. [DOI: 10.2217/fvl-2016-0138] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2016] [Accepted: 02/13/2017] [Indexed: 12/11/2022]
Affiliation(s)
- Fardin Dolatimehr
- Student Research Committee Baqiyatallah University of Medical Sciences
Tehran
Iran
- Baqiyatallah Research Center for Gastroenterology & Liver Diseases (BRCGL) Baqiyatallah University of Medical Sciences
Tehran
Iran
- Middle East Liver Diseases (MELD) Center
Tehran
Iran
| | - Mohammad Hossein Khosravi
- Student Research Committee Baqiyatallah University of Medical Sciences
Tehran
Iran
- Baqiyatallah Research Center for Gastroenterology & Liver Diseases (BRCGL) Baqiyatallah University of Medical Sciences
Tehran
Iran
- Middle East Liver Diseases (MELD) Center
Tehran
Iran
| | - Mohammad Saeid Rezaee-Zavareh
- Student Research Committee Baqiyatallah University of Medical Sciences
Tehran
Iran
- Baqiyatallah Research Center for Gastroenterology & Liver Diseases (BRCGL) Baqiyatallah University of Medical Sciences
Tehran
Iran
- Middle East Liver Diseases (MELD) Center
Tehran
Iran
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology & Liver Diseases (BRCGL) Baqiyatallah University of Medical Sciences
Tehran
Iran
- Middle East Liver Diseases (MELD) Center
Tehran
Iran
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Suzuki S, Mori KI, Higashino A, Iwasaki Y, Yasutomi Y, Maki N, Akari H. Persistent replication of a hepatitis C virus genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B in a New World monkey. Microbiol Immunol 2016; 60:26-34. [PMID: 26634303 DOI: 10.1111/1348-0421.12349] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Revised: 11/26/2015] [Accepted: 11/30/2015] [Indexed: 12/22/2022]
Abstract
The development of effective hepatitis C virus (HCV) vaccines is essential for the prevention of further HCV dissemination, especially in developing countries. Therefore the aim of this study is to establish a feasible and immunocompetent surrogate animal model of HCV infection that will help in evaluation of the protective efficacy of newly developing HCV vaccine candidates. To circumvent the narrow host range of HCV, an HCV genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B (GBV-B), which is closely related to HCV, was generated. The chimera between HCV and GBV-B, named HCV/G, replicated more efficiently as compared with the HCV clone in primary marmoset hepatocytes. Furthermore, it was found that the chimera persistently replicated in a tamarin for more than 2 years after intrahepatic inoculation of the chimeric RNA. Although relatively low (<200 copies/mL), the viral RNA loads in plasma were detectable intermittently during the observation period. Of note, the chimeric RNA was found in the pellet fraction obtained by ultracentrifugation of the plasma at 73 weeks, indicating production of the chimeric virus. Our results will help establish a novel non-human primate model for HCV infection on the basis of the HCV/G chimera in the major framework of the HCV genome.
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Affiliation(s)
- Saori Suzuki
- Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506
| | - Ken-Ichi Mori
- Advanced Life Science Institute, 2-10-23 Maruyamadai, Wako, Saitama 351-0112
| | - Atsunori Higashino
- Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506
| | - Yuki Iwasaki
- Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506
| | - Yasuhiro Yasutomi
- Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843
| | - Noboru Maki
- Advanced Life Science Institute, 2-10-23 Maruyamadai, Wako, Saitama 351-0112
| | - Hirofumi Akari
- Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506.,Laboratory of Evolutional Virology, Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
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24
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Bokharaei-Salim F, Keyvani H, Esghaei M, Zare-Karizi S, Dermenaki-Farahani SS, Hesami-Zadeh K, Fakhim S. Prevalence of occult hepatitis C virus infection in the Iranian patients with human immunodeficiency virus infection. J Med Virol 2016; 88:1960-6. [PMID: 27463051 DOI: 10.1002/jmv.24474] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/05/2016] [Indexed: 12/23/2022]
Abstract
Occult hepatitis C virus (HCV) infection is a new form of chronic HCV infection described by the presence of the genomic HCV-RNA in liver biopsy and/or peripheral blood mononuclear cell (PBMC) samples, and undetectable levels or absence of HCV-RNA and in the absence or presence of anti HCV antibodies in the plasma specimens. The aim of the present study was to evaluate the occurrence of occult HCV infection (OCI) among Iranian subjects infected with human immunodeficiency virus (HIV) using RT-nested PCR. From March 2014 until April 2015, 109 Iranian patients with established HIV infection were enrolled in this cross-sectional study. After extraction of viral RNA from the plasma and PBMC samples, HCV-RNA status was examined by RT-nested PCR using primers from the 5'-NTR. HCV genotyping was conducted using RFLP analysis. For the confirmation of HCV genotyping by RFLP method, the PCR products were sequenced. Of the 109 patients, 50 were positive for antibodies against HCV. The HCV-RNA was detected in PBMC specimens in 6 (10.2%) out of the total 59 patients negative for anti-HCV Abs and undetectable plasma HCV-RNA and also from 4 (8.0%) out of the total 50 patients positive for anti-HCV Abs and undetectable plasma HCV-RNA. HCV genotyping analysis showed that 6 (60.0%) patients were infected with HCV subtype 3a, 3 (30.0%) were infected with HCV subtype 1a and 1 (10.0%) patient was infected with HCV subtype 1b. This study revealed the incidence of OCI (9.2%) in HIV-infected Iranian patients. Hence, designing prospective studies focusing on the detection of OCI in these patients would provide more information. J. Med. Virol. 88:1960-1966, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Farah Bokharaei-Salim
- Department of Virology, Iran University of Medical Sciences, Tehran, Iran.,HIV Laboratory of National Center, Deputy of Health, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Keyvani
- Department of Virology, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Esghaei
- Department of Virology, Iran University of Medical Sciences, Tehran, Iran
| | - Shohreh Zare-Karizi
- Department of Genetic, Islamic Azad University, Varamin Pishva Branch, Tehran, Iran
| | | | | | - Shahin Fakhim
- Faculty of Engineering, Department of Civil Engineering, Payame Noor University, Karaj, Iran
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Bastani MN, Bokharaei-Salim F, Keyvani H, Esghaei M, Monavari SH, Ebrahimi M, Garshasebi S, Fakhim S. Prevalence of occult hepatitis C virus infection in Iranian patients with beta thalassemia major. Arch Virol 2016; 161:1899-1906. [PMID: 27132015 DOI: 10.1007/s00705-016-2862-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Accepted: 04/06/2016] [Indexed: 12/15/2022]
Abstract
Occult hepatitis C virus infection (OCI) is a new pathological form of chronic hepatitis virus (HCV) infection characterized by the presence of HCV RNA in liver biopsy and/or peripheral blood mononuclear cell (PBMC) specimens and the absence of HCV RNA and anti-HCV antibodies (Abs) in plasma samples. β-thalassemia major is a hereditary recessive blood disease with deficiency in the hemoglobin beta chain. Thalassemic patients need blood transfusion therapy; repeated blood transfusion increases the risk of viral blood-borne infection. The aim of this study was to determine the prevalence of OCI in Iranian patients with β-thalassemia major. From February 2015 to November 2015, a total of 147 Iranian patients with β-thalassemia major were enrolled in this cross-sectional study. After extraction of viral RNA from the plasma and PBMC samples, HCV genomic RNA in the specimens was amplified by RT-nested PCR using primers from the 5'-UTR. The HCV genotypes of the positive specimens were tested using the RFLP assay. To confirm the HCV genotypes, the 5'-UTR fragment was amplified and cloned into the pJET1.2/blunt cloning vector and then sequenced. Out of 147 patients, 106 (72.1 %) were negative for anti-HCV Abs and HCV RNA. HCV RNA was found in PBMC specimens of six (5.7 %) patients, from a total of 106 patients with undetectable plasma HCV RNA and anti-HCV Abs. Therefore, six out of 106 patients had OCI. HCV genotyping revealed that three patients were infected with HCV subtype 1b, two patients were infected with HCV subtype 3a, and one patient was infected with HCV subtype 1a. These results revealed that Iranian patients with beta-thalassemia major might have OCI. Therefore, it seems that the design of a study to identify this infection in patients with β-thalassemia major would provide valuable information.
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Affiliation(s)
- Mohammad-Navid Bastani
- Department of Virology, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran
| | - Farah Bokharaei-Salim
- Department of Virology, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran.
- HIV Laboratory of National Center, Deputy of Health, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran.
| | - Hossein Keyvani
- Department of Virology, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran
| | - Maryam Esghaei
- Department of Virology, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran
| | | | - Mojtaba Ebrahimi
- Iranian Blood Transfusion Organization (IBTO), Thalassemia Center, Tehran, Islamic Republic of Iran
| | - Saba Garshasebi
- HIV Laboratory of National Center, Deputy of Health, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran
| | - Shahin Fakhim
- Department of Civil Engineering, Faculty of Engineering, Payame Noor University, Karaj, Islamic Republic of Iran
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Hesamizadeh K, Keyvani H, Bokharaei-Salim F, Monavari SH, Esghaei M, Jahanbakhsh Sefidi F. Molecular Epidemiology of Kaposi's Sarcoma-Associated Herpes Virus, and Risk Factors in HIV-infected Patients in Tehran, 2014. IRANIAN RED CRESCENT MEDICAL JOURNAL 2016; 18:e32603. [PMID: 28191343 PMCID: PMC5292624 DOI: 10.5812/ircmj.32603] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/23/2015] [Revised: 10/26/2015] [Accepted: 11/24/2015] [Indexed: 12/15/2022]
Abstract
Background Kaposi’s sarcoma (KS) remains the most common malignancy among HIV-infected patients. Human herpesvirus type-8 (HHV-8) is regarded as the infectious etiological agent of Kaposi’s sarcoma (KSHV). Diagnostic procedures associated with KSHV are not routinely performed in HIV-infected subjects. Objectives The main objective of this study is to obtain information on KSHV epidemiology in Iranian HIV-infected individuals. Patients and Methods In the present cross-sectional study, 109 patients with established HIV infection, who visited a governmental and referral center for HIV screening in Tehran (Tehran west health center (TWHC)) between May 2014 and July 2015 were enrolled according to the convenience sample strategy. After peripheral blood collection, isolation of plasma and peripheral blood mononuclear cell (PBMC) compartments, DNA extraction was performed. KSHV DNA was analyzed by nested polymerase chain reaction (nested PCR) using primers from ORF-26 (virus minor capsid). Results Among all 109 HIV-infected patients, 67 (61.5%) were male, with an age range of 2 - 64 years (mean ± standard deviation 35.8 ± 13.3). KSHV DNA was found in PBMC and plasma samples of six (5.5%) and four (3.6%) patients, respectively. Conclusions This study revealed a considerable prevalence of KSHV DNA, during latent and lytic phases, among HIV-infected patients. Risk factors for KSHV infection acquisition and concurrent. 0+infection with HIV were also evaluated. Diagnosis of KSHV in the group could be helpful for prognosis of Kaposi’s sarcoma and clinical management.
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Affiliation(s)
- Khashayar Hesamizadeh
- Department of Virology, Iran University of Medical Sciences, Tehran, IR Iran
- Middle East Liver Diseases (MELD) Center, Tehran, IR Iran
| | - Hossein Keyvani
- Department of Virology, Iran University of Medical Sciences, Tehran, IR Iran
| | - Farah Bokharaei-Salim
- Department of Virology, Iran University of Medical Sciences, Tehran, IR Iran
- HIV Laboratory of National Center, Deputy of Health, Iran University of Medical Sciences, Tehran, IR Iran
| | | | - Maryam Esghaei
- Department of Virology, Iran University of Medical Sciences, Tehran, IR Iran
- Corresponding Author: Maryam Esghaei, Department of Virology, Iran University of Medical Sciences, Tehran, IR Iran. Tel: +98-2186703014, E-mail:
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Rezaee-Zavareh MS, Hadi R, Karimi-Sari H, Hossein Khosravi M, Ajudani R, Dolatimehr F, Ramezani-Binabaj M, Miri SM, Alavian SM. Occult HCV Infection: The Current State of Knowledge. IRANIAN RED CRESCENT MEDICAL JOURNAL 2015; 17:e34181. [PMID: 26734487 PMCID: PMC4698335 DOI: 10.5812/ircmj.34181] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Accepted: 11/02/2015] [Indexed: 12/12/2022]
Abstract
CONTEXT Occult HCV infection (OCI) is defined as the presence of HCV-RNA in hepatocytes and the absence of HCV in the serum according to usual tests. We aimed to define OCI and provide information about the currently available diagnostic methods. Then we focus on specific groups that are at high risk of OCI and finally investigate immune responses to OCI and the available treatment approaches. EVIDENCE ACQUISITION PubMed, Scopus and Google Scholar were comprehensively searched with combination of following keywords: "occult", "hepatitis C virus" and "occult HCV infection". The definition of OCI, diagnostic methods, specific groups that are at high risk and available treatment approaches were extract from literature. An analysis of available articles on OCI also was done based on Scopus search results. RESULTS OCI has been reported in several high-risk groups, especially in hemodialysis patients and subjects with cryptogenic liver disease. Furthermore, some studies have proposed a specific immune response for OCI in comparison with chronic hepatitis C (CHC). CONCLUSIONS With a clinical history of approximately 11 years, occult HCV infection can be considered an occult type of CHC. Evidences suggest that considering OCI in these high-risk groups seems to be necessary. We suggest that alternative diagnostic tests should be applied and that there is a need for the participation of all countries to determine the epidemiology of this type of HCV infection. Additionally, evaluating OCI in blood transfusion centers and in patients who receive large amounts of blood and clotting factors, such as patients with hemophilia, should be performed in future projects.
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Affiliation(s)
- Mohammad Saeid Rezaee-Zavareh
- Students’ Research Committee, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
- Middle East Liver Diseases Center (MELD), Tehran, IR Iran
| | - Reza Hadi
- Middle East Liver Diseases Center (MELD), Tehran, IR Iran
| | - Hamidreza Karimi-Sari
- Students’ Research Committee, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | | | - Reza Ajudani
- Students’ Research Committee, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Fardin Dolatimehr
- Students’ Research Committee, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Mahdi Ramezani-Binabaj
- Students’ Research Committee, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Seyyed Mohammad Miri
- Middle East Liver Diseases Center (MELD), Tehran, IR Iran
- Kowsar Medical Institute, Heerlen, The Netherlands
| | - Seyed Moayed Alavian
- Middle East Liver Diseases Center (MELD), Tehran, IR Iran
- Baqiyatallah Research Center for Gasteroenterology and Liver Disease (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, IR Iran
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Taherkhani R, Farshadpour F. Epidemiology of hepatitis C virus in Iran. World J Gastroenterol 2015; 21:10790-10810. [PMID: 26478671 PMCID: PMC4600581 DOI: 10.3748/wjg.v21.i38.10790] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Revised: 05/20/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
In Iran, the prevalence of hepatitis C virus (HCV) infection is relatively low according to the population-based epidemiological studies. However, the epidemiology of HCV is changing and the rate of HCV infection is increasing due to the growth in the number of injecting drug users in the society. In addition, a shift has occurred in the distribution pattern of HCV genotypes among HCV-infected patients in Iran. Genotype 1a is the most prevalent genotype in Iran, but in recent years, an increase in the frequency of 3a and a decrease in 1a and 1b have been reported. These variations in the epidemiology of HCV reflect differences in the routes of transmission, status of public health, lifestyles, and risk factors in different groups and geographic regions of Iran. Health policy makers should consider these differences to establish better strategies for control and prevention of HCV infection. Therefore, this review was conducted to present a clear view regarding the current epidemiology of HCV infection in Iran.
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Eslamifar A, Ramezani A, Ehteram H, Razeghi E, Ahmadi F, Amini M, Banifazl M, Etemadi G, Keyvani H, Bavand A, Aghakhani A. Occult hepatitis C virus infection in Iranian hemodialysis patients. J Nephropathol 2015; 4:116-20. [PMID: 26457258 PMCID: PMC4596295 DOI: 10.12860/jnp.2015.22] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Accepted: 06/13/2015] [Indexed: 12/18/2022] Open
Abstract
Background: Occult hepatitis C virus (HCV) infection is defined as the presence of HCV-RNA in liver or peripheral blood mononuclear cells (PBMCs) in the absence of detectable hepatitis C antibody (anti-HCV) or HCV-RNA in the serum. Low concentrations of HCV-RNA may be detected in PBMCs of hemodialysis (HD) patients and this could have a great impact on the management of HD patients.
Objectives: The aim of this study was to detect the occult HCV infection in Iranian HD patients.
Patients and Methods: A total of 70 anti-HCV negative HD patients from three dialysis units in Tehran, Iran were included in this study. In these cases, presence of HCV-RNA in plasma samples was tested by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR). In cases with negative anti-HCV and plasma HCV-RNA, genomic HCV-RNA was checked in PBMC specimens by RT-nested PCR.
Results: Seventy anti-HCV negative HD patients were enrolled in the study. 32.85% and 1.43% of cases had elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) respectively. 7.14% of patients had elevated levels of both ALT and AST. HCV-RNA was negative in plasma samples of all anti-HCV negative HD subjects. The genomic HCV-RNA was not detected in any PBMC samples of HD cases with negative anti-HCV and plasma HCV-RNA.
Conclusions: Occult HCV infection was not detected in our HD patients despite of elevated levels of liver enzymes in some participants. Further studies involving larger number of HD patients are required to elucidate the rate of occult HCV infection in HD cases.
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Affiliation(s)
- Ali Eslamifar
- Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran
| | - Amitis Ramezani
- Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran
| | - Hassan Ehteram
- Department of Pathology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Effat Razeghi
- Nephrology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Farrokhlagha Ahmadi
- Nephrology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Manouchehr Amini
- Nephrology Department, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Banifazl
- Iranian Society for Support of Patients with Infectious Diseases, Tehran, Iran
| | | | - Hossein Keyvani
- Department of Virology, Iran University of Medical Sciences, Tehran, Iran
| | - Anahita Bavand
- Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran
| | - Arezoo Aghakhani
- Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran
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Rezaee-Zavareh MS, Ramezani-Binabaj M, Moayed Alavian S. Screening for occult hepatitis C virus infection: Does it need special attention? Hepatology 2015; 62:321-322. [PMID: 25476196 DOI: 10.1002/hep.27626] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Mohammad Saeid Rezaee-Zavareh
- Students' Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran
- Middle East Liver Diseases Center, Tehran, Iran
| | - Mahdi Ramezani-Binabaj
- Students' Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran
- Middle East Liver Diseases Center, Tehran, Iran
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Attar BM, Van Thiel D. A New Twist to a Chronic HCV Infection: Occult Hepatitis C. Gastroenterol Res Pract 2015; 2015:579147. [PMID: 26221136 PMCID: PMC4495183 DOI: 10.1155/2015/579147] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2014] [Revised: 04/15/2015] [Accepted: 05/24/2015] [Indexed: 02/07/2023] Open
Abstract
Background. The prevalence of occult hepatitis C infection (OCI) in the population of HCV-RNA negative but anti-HCV positive individuals is presently unknown. OCI may be responsible for clinically overt recurrent disease following an apparent sustained viral response (SVR) weeks to years later. Purpose. To review the available current literature regarding OCI, prevalence, pathogenic mechanisms, clinical characteristics, and future directions. Data Sources. Searching MEDLINE, article references, and national and international meeting abstracts for the diagnosis of OCI (1990-2014). Data Synthesis. The long-term followup of individuals with an OCI suggests that the infection can be transient with the loss of detectable HCV-RNA in PPBMCs after 12-18 months or alternatively exist intermittently and potentially long term. The ultimate outcome of HCV infection is decided by interplay between host immune responses, antiviral therapies, and the various well-identified viral evasion mechanisms as well as the presence of HCV infection within extrahepatic tissues. Conclusion. The currently widely held assumption of a HCV-cure in individuals having had "SVR" after 8-12 weeks of a course of DAA therapy as recently defined may not be entirely valid. Careful longitudinal followup utilizing highly sensitive assays and unique approaches to viral isolation are needed.
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Affiliation(s)
- Bashar M. Attar
- Division of Gastroenterology and Hepatology, Cook County Health and Hospitals System, 1901 West Harrison Street, Chicago, IL 60612, USA
- Rush University Medical Center, Chicago, IL 60612, USA
| | - David Van Thiel
- Advanced Liver and Gastrointestinal Disease Center, Berwyn, IL 60402, USA
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Abstract
A large spectrum of renal pathology is associated with hepatitis C virus (HCV). According to novel evidence, occult HCV infection (HCV-RNA in peripheral blood mononuclear cells or in serum after ultracentrifugation) could be involved in the pathogenesis of glomerular nephropathy among patients negative for conventional markers of HCV. Additional studies with appropriate size and technology are in progress to confirm the relationship between occult HCV and glomerular disease, which has multiple implications from the clinical standpoint.
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Imani F, Motavaf M, Safari S, Alavian SM. The therapeutic use of analgesics in patients with liver cirrhosis: a literature review and evidence-based recommendations. HEPATITIS MONTHLY 2014; 14:e23539. [PMID: 25477978 PMCID: PMC4250965 DOI: 10.5812/hepatmon.23539] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Revised: 09/30/2014] [Accepted: 10/04/2014] [Indexed: 12/11/2022]
Abstract
CONTEXT Pain management in cirrhotic patients is a major clinical challenge for medical professionals. Unfortunately there are no concrete guidelines available regarding the administration of analgesics in patients with liver cirrhosis. In this review we aimed to summarize the available literature and suggest appropriate evidence-based recommendations regarding to administration of these drugs. EVIDENCE ACQUISITION An indexed MEDLINE search was conducted in July 2014, using keywords "analgesics", "hepatic impairment", "cirrhosis", "acetaminophen or paracetamol", "NSAIDs or nonsteroidal anti-inflammatory drugs", "opioid" for the period of 2004 to 2014. All randomized clinical trials, case series, case report and meta-analysis studies with the above mentioned contents were included in review process. In addition, unpublished information from the Food and Drug Administration are included as well. RESULTS Paracetamol is safe in patients with chronic liver disease but a reduced dose of 2-3 g/d is recommended for long-term use. Non-steroidal anti-inflammatory drugs (NSAIDs) are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Most opioids can have deleterious effects in patients with cirrhosis. They have an increased risk of toxicity and hepatic encephalopathy. They should be administrated with lower and less frequent dosing in these patients and be avoided in patients with a history of encephalopathy or addiction to any substance. CONCLUSIONS No evidence-based guidelines exist on the use of analgesics in patients with liver disease and cirrhosis. As a result pain management in these patients generates considerable misconception among health care professionals, leading under-treatment of pain in this population. Providing concrete guidelines toward the administration of these agents will lead to more efficient and safer pain management in this setting.
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Affiliation(s)
- Farnad Imani
- Department of Anesthesiology and Pain Medicine, Iran University of Medical Sciences, Tehran, IR Iran
| | - Mahsa Motavaf
- Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IR Iran
- Department of Molecular Hepatology, Middle East Liver Disease Center, Tehran, IR Iran
| | - Saeid Safari
- Department of Anesthesiology and Pain Medicine, Iran University of Medical Sciences, Tehran, IR Iran
| | - Seyed Moayed Alavian
- Department of Molecular Hepatology, Middle East Liver Disease Center, Tehran, IR Iran
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
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Seronegative occult hepatitis C virus infection: clinical implications. J Clin Virol 2014; 61:315-20. [PMID: 25304062 DOI: 10.1016/j.jcv.2014.09.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Revised: 08/29/2014] [Accepted: 09/20/2014] [Indexed: 02/06/2023]
Abstract
Occult hepatitis C virus infection (OCI) was first described in anti-HCV and serum HCV-RNA negative patients with abnormal values of liver enzymes but who presented HCV-RNA in liver and in peripheral blood mononuclear cells. Up to now, two types of OCI are recognized: seronegative OCI (anti-HCV and serum HCV-RNA negative) and seropositive OCI (anti-HCV positive and serum HCV-RNA negative). The concept of OCI is still a matter of debate, probably because both types of OCI are not considered as different entities. This review focuses on seronegative OCI. The existence of seronegative OCI has been documented all around the world with the implication of different HCV genotypes (1-4). Seronegative OCI is associated with cryptogenic chronic hepatitis and liver cirrhosis and it may be involved in the appearance of hepatocellular carcinoma. Also seronegative OCI may increase the histological liver damage in chronic hepatitis B and in HIV-infected patients. It may have a negative influence in the natural history of hemodialysis patients and in immune-mediated glomerulonephritis. Seronegative OCI has been detected also in patients with haematological diseases, among healthy subjects and in drug users. Other publications indicate the potential infectivity of seronegative OCI in the setting of family members, sexual partners and liver transplantation. In summary, seronegative OCI may play a role in liver diseases and other human pathologies and may be present in healthy people but larger studies are needed to confirm these findings.
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35
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Mutations in the NS5A gene of hepatitis C virus subtype 1b and response to peg-IFNα-2a/RBV combination therapy in Azerbaijani patients. Arch Virol 2014; 159:2893-9. [DOI: 10.1007/s00705-014-2133-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2014] [Accepted: 05/26/2014] [Indexed: 11/30/2022]
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Yu YC, Wang Y, He CL, Wang MR, Wang YM. Management of hepatitis C virus infection in hemodialysis patients. World J Hepatol 2014; 6:419-425. [PMID: 25018852 PMCID: PMC4081616 DOI: 10.4254/wjh.v6.i6.419] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
The prevalence of hepatitis C virus (HCV) infection in patients on maintenance hemodialysis (MHD) is relatively higher than those without MHD. Chronic HCV infection detrimentally affects the life quality and expectancy, leads to renal transplant rejection, and increases the mortality of MHD patients. With the application of erythropoietin to improve uremic anemia and avoid blood transfusion, the new HCV infections during MHD in recent years are mainly caused by the lack of stringent universal precautions. Strict implementation of universal precautions for HCV transmission has led to markedly decreased HCV infections in many hemodialysis units, but physicians still should be alert for the anti-HCV negative HCV infection and occult HCV infection in MHD patients. Standard interferon alpha and pegylated interferon alpha monotherapies at a reduced dose are currently the main treatment strategies for MHD patients with active HCV replication, but how to increase the sustained virological response and decrease the side effects is the key problem. IFNα-free treatments with two or three direct-acting antivirals without ribavirin in MHD patients are waiting for future investigations.
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Vidimliski PD, Nikolov I, Geshkovska NM, Dimovski A, Rostaing L, Sikole A. Review: Occult hepatitis C virus infection: still remains a controversy. J Med Virol 2014; 86:1491-8. [PMID: 24895180 DOI: 10.1002/jmv.23979] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/29/2014] [Indexed: 02/06/2023]
Abstract
Occult hepatitis C virus (HCV) infection is characterized by the presence of HCV RNA in the liver cells or peripheral blood mononuclear cells of the patients whose serum samples test negative for HCV RNA, with or without presence of HCV antibodies. The present study reviews the existing literature on the persistence of occult hepatitis C virus infection, with description of the clinical characteristics and methods for identification of occult hepatitis C. Occult hepatitis C virus infection was detected in patients with abnormal results of liver function tests of unknown origin, with HCV antibodies and HCV RNA negativity in serum, and also in patients with spontaneous or treatment-induced recovery from hepatitis C. The viral replication in the liver cells and/or peripheral blood mononuclear cells was present in all clinical presentations of occult hepatitis C. The peripheral blood mononuclear cells represent an extra-hepatic site of HCV replication. The reason why HCV RNA was not detectable in the serum of patients with occult hepatitis C, could be the low number of circulating viral particles not detectable by the diagnostic tests with low sensitivity. It is uncertain whether occult hepatitis C is a different clinical entity or just a form of chronic hepatitis C virus infection. Data accumulated over the last decade demonstrated that an effective approach to the diagnosis of HCV infection would be the implementation of more sensitive HCV RNA diagnostic assays, and also, examination of the presence of viral particles in the cells of the immune system.
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Sadeghi F, Bokharaei-Salim F, Salehi-Vaziri M, Monavari SH, Alavian SM, Salimi S, Vahabpour R, Keyvani H. Associations between human TRIM22 gene expression and the response to combination therapy with Peg-IFNα-2a and ribavirin in Iranian patients with chronic hepatitis C. J Med Virol 2014; 86:1499-506. [PMID: 24889558 DOI: 10.1002/jmv.23985] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/06/2014] [Indexed: 12/12/2022]
Abstract
Interferons are able to exert an antiviral effect against hepatitis C virus (HCV) infection via induction of interferon-stimulated genes (ISGs). This study tested whether differential expression of an important ISG with antiviral properties, tripartite motif 22 (TRIM22), correlates with a response to Peg-IFNα-2a/RBV combination therapy in treatment-naive patients with chronic hepatitis C. A total of 32 patients with chronic hepatitis C were enrolled in this study and received standard Peg-IFNα-2a/RBV combination therapy. HCV viral load was measured during treatment, at the end of treatment, and 6 months later to determine the treatment outcome. Quantitative real-time PCR was used to assess the expression levels of TRIM22 in peripheral blood mononuclear cells (PBMCs) of the patients before antiviral therapy. Of the 32 patients, 26 (81.3%) were males. In this study, there were 16 (50%) individuals with a sustained virologic response (SVR), and a virologic relapse was observed in the remaining half of the subjects. Testing for the presence of genomic HCV RNA in blood during therapy revealed a rapid virologic response (RVR) in 10 (31.2%) and a partial and complete early virologic response (EVR) in 8 (25%) and 24 (75%) of the cases, respectively. TRIM22 mRNA levels were significantly higher in patients with a sustained virologic response than in relapsers (P = 0.002) and in patients with a rapid virologic response than in the others (P = 0.040). No statistically significant difference was seen in the expression of TRIM22 between patients with a partial early virologic response and a complete early virologic response. This study showed that pretreatment upregulation of TRIM22 may be associated with responsiveness to Peg-IFNα-2a/RBV combination therapy.
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Affiliation(s)
- Farzin Sadeghi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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Ashrafi Hafez A, Baharlou R, Mousavi Nasab SD, Ahmadi Vasmehjani A, Shayestehpour M, Joharinia N, Ahmadi NA. Molecular epidemiology of different hepatitis C genotypes in serum and peripheral blood mononuclear cells in jahrom city of iran. HEPATITIS MONTHLY 2014; 14:e16391. [PMID: 24976833 PMCID: PMC4071316 DOI: 10.5812/hepatmon.16391] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/25/2013] [Revised: 12/23/2013] [Accepted: 04/13/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND The Hepatitis C Virus (HCV) is considered essentially hepatotropic, yet the virus compartments have also been found in important extra hepatic sites. Detection of HCV RNA in extra hepatic reservoirs such as peripheral blood mononuclear cells (PBMCs) is important for determining disease progression and treatment effectiveness. OBJECTIVES The present study aimed to determine different HCV genotypes in patients' plasma and PBMC specimens, in Jahrom city of Iran. PATIENTS AND METHODS Blood samples of 137 patients with established HCV were collected at the Honari clinic. These patients were anti-HCV and plasma HCV RNA positive. After plasma RNA extraction and obtaining a pellet of approximately 3-5 × 10(6) PBMCs, Real-time PCR was performed, using specific-genotype primers. Finally, data analysis was done by the Statistical Package for Social Sciences (SPSS) software. RESULTS Subtype 3 was the most common genotype in plasma (57.7%) and PBMCs (51.1%). Subtype 1a was detected in 36.5% and 30.7% of plasma samples and PBMCs, respectively whereas subtype 4 was not detected in any of the cases. There was a genotype difference between plasma and PBMCs of 12.4% of patients. In four patients no genotype was detected in their plasma but genotype 3 was detected in the PBMCs. CONCLUSIONS It is suggested that determination of the target genotype by plasma subtyping for choosing the proper antiviral therapy is essential but may result in therapy failure. HCV genotyping in PBMC samples, along with plasma specimens, might be more beneficial. Therefore determining the HCV genotype in PBMCs, before beginning the therapy is useful due to the possibility of occult infection detection.
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Affiliation(s)
- Asghar Ashrafi Hafez
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Rasoul Baharlou
- Department of Microbiology, Jahrom University of Medical Sciences, Jahrom, IR Iran
| | | | - Abbas Ahmadi Vasmehjani
- Department of Microbiology, Jahrom University of Medical Sciences, Jahrom, IR Iran
- Corresponding Author: Abbas Ahmadi Vasmehjani, Department of Microbiology, Jahrom University of Medical Sciences, Jahrom, IR Iran. Tel: +98-7913336086, Fax: +98-791341509, E-mail:
| | | | - Negar Joharinia
- Department of Microbiology, Jahrom University of Medical Sciences, Jahrom, IR Iran
| | - Nayeb Ali Ahmadi
- Department of Medical Lab Technology and Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
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Castillo I, Martinez-Ara J, Olea T, Bartolomé J, Madero R, Hernández E, Bernis C, Aguilar A, Quiroga JA, Carreño V, Selgas R. High prevalence of occult hepatitis C virus infection in patients with primary and secondary glomerular nephropathies. Kidney Int 2014; 86:619-24. [PMID: 24646855 DOI: 10.1038/ki.2014.68] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2013] [Revised: 01/17/2014] [Accepted: 01/23/2014] [Indexed: 12/16/2022]
Abstract
The association of hepatitis C virus (HCV) infection and glomerulonephritis is well known. However, the relationship between immune-mediated glomerulonephritis and occult HCV, characterized by the presence of HCV-RNA in liver or in peripheral blood mononuclear cells in the absence of serological markers, is unknown. We tested this in 113 anti-HCV-negative patients; 87 with immune-mediated glomerulonephritis and 26 controls with hereditary glomerular nephropathies. All patients were serum HCV-RNA negative by conventional real-time PCR. Significantly, occult HCV-RNA (detectable viral RNA in peripheral blood mononuclear cells or in serum after ultracentrifugation) was found in 34 of 87 patients with immune-mediated glomerulonephritis versus 1 of 26 control patients. The serum creatinine levels were significantly higher in patients with immune-mediated glomerulonephritis with than in those without occult HCV (1.5 versus 1.1 mg/dl, respectively). A multivariate analysis adjusted for gender showed a significantly increased risk of occult HCV in patients with immune-mediated glomerulonephritis versus the controls (odds ratio of 13.29). Progression to end-stage renal disease tended to be faster in patients with immune-mediated glomerulonephritis and occult HCV than in the negative cases. Thus, occult HCV is strongly associated with immune-mediated glomerulonephritis and may have a role in the progression of the disease.
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Affiliation(s)
| | - Jorge Martinez-Ara
- Department of Nephrology, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain
| | - Teresa Olea
- Department of Nephrology, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain
| | - Javier Bartolomé
- Fundación para el Estudio de las Hepatitis Virales, Madrid, Spain
| | - Rosario Madero
- Department of Biostatistics, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain
| | - Eduardo Hernández
- 1] Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain [2] REDinREN, Madrid, Spain
| | - Carmen Bernis
- Department of Nephrology, Hospital Universitario La Princesa, Madrid, Spain
| | - Ana Aguilar
- Department of Nephrology, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain
| | - Juan A Quiroga
- Fundación para el Estudio de las Hepatitis Virales, Madrid, Spain
| | - Vicente Carreño
- Fundación para el Estudio de las Hepatitis Virales, Madrid, Spain
| | - Rafael Selgas
- 1] Department of Nephrology, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain [2] REDinREN, Madrid, Spain
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