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1
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Jadoul M, Awan A, Berenguer M, Bruchfeld A, Fabrizi F, Goldberg D, Jia J, Kamar N, Mohamed R, Pessôa M, Pol S, Sise M, Martin P. KDIGO 2022 Clinical Practice Guideline FOR the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int 2022; 102:S129-S205. [PMID: 36410841 DOI: 10.1016/j.kint.2022.07.013] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 07/27/2022] [Indexed: 11/19/2022]
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2
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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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3
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Sikorska-Wiśniewska M, Sikorska K, Wróblewska A, Liberek T, Perkowska-Ptasińska A, Dębska-Ślizień A. Recurrence of Cryoglobulinemia Secondary to Hepatitis C in a Patient with HCV RNA (-) Negative in the Serum. Case Rep Nephrol Dial 2021; 11:110-115. [PMID: 34250027 PMCID: PMC8255656 DOI: 10.1159/000515587] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 02/28/2021] [Indexed: 12/14/2022] Open
Abstract
Hepatitis C virus infection is associated with many extrahepatic manifestations such as mixed cryoglobulinemia (MC). Renal manifestation of HCV infection might present as cryo-positive membranoproliferative glomerulonephritis (MPGN). First-line therapy includes antiviral treatment as the underlying infection leads to formation of immune complexes. After introducing direct-acting antiviral agents (DAAs) cure rates of HCV infection increased. Sustained virologic response (SVR) is defined as the absence of HCV RNA in serum by a sensitive test performed 12 or 24 weeks after the end of antiviral treatment. Although HCV RNA is undetectable in the serum, it may be present in hepatocytes and peripheral blood mononuclear cells (occult HCV infection). However, the impact of DAA treatment on occult HCV infection is not clear. We report a case of recurrence of MC with MPGN and development of lymphoproliferative disorder 2 years after achieving SVR.
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Affiliation(s)
| | - Katarzyna Sikorska
- Department of Tropical Medicine and Epidemiology, Medical University of Gdansk, Gdansk, Poland
| | - Anna Wróblewska
- Department of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk, Gdansk, Poland
| | - Tomasz Liberek
- Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland
| | - Agnieszka Perkowska-Ptasińska
- Department of Transplantation Medicine and Nephrology, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland
| | - Alicja Dębska-Ślizień
- Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland
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4
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Maslennikov R, Ivashkin V, Efremova I, Shirokova E. Immune disorders and rheumatologic manifestations of viral hepatitis. World J Gastroenterol 2021; 27:2073-2089. [PMID: 34025065 PMCID: PMC8117740 DOI: 10.3748/wjg.v27.i18.2073] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 02/28/2021] [Accepted: 04/22/2021] [Indexed: 02/06/2023] Open
Abstract
Infection with hepatotropic viruses is not limited to the liver and can lead to the development of various immunological disorders (the formation of cryoglobulins, rheumatoid factor, antinuclear antibodies, autoantibodies specific for autoimmune hepatitis and primary biliary cholangitis, and others), which can manifest as glomerulonephritis, arthritis, uveitis, vasculitis (cryoglobulinemic vasculitis, polyarteritis nodosa, Henoch-Schonlein purpura, isolated cutaneous necrotizing vasculitis), and other rheumatologic disorders, and be a trigger for the subsequent development of autoimmune hepatitis and primary biliary cholangitis. A further study of the association between autoimmune liver diseases and hepatotropic virus infection would be useful to assess the results of treatment of these associated diseases with antiviral drugs. The relationship of these immune disorders and their manifestations with hepatotropic viruses is best studied for chronic hepatitis B and C. Only isolated cases of these associations are described for hepatitis A. These links are least studied, and are often controversial for hepatitis E, possibly due to their relatively rare diagnoses. Patients with uveitis, glomerulonephritis, arthritis, vasculitis, autoimmune liver diseases should be tested for biomarkers of viral hepatitis, and if present, these patients should be treated with antiviral drugs.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow 119435, Russia
- Department of Internal Medicine 1, Сonsultative and Diagnostic Center 2 of the Moscow City Health Department, Moscow 107564, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Shirokova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
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5
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Scurt FG, Bose K, Canbay A, Mertens PR, Chatzikyrkou C. [Chronic kidney injury in patients with liver diseases - Reappraising pathophysiology and treatment options]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:560-579. [PMID: 33728618 DOI: 10.1055/a-1402-1502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Acute and chronic kidney disease concurs commonly with liver disease and is associated with a wide array of complications including dialysis dependency and increased mortality. Patients with liver disease or liver cirrhosis show a higher prevalence of chronic kidney disease. This is attributed to concomitant comorbidities, such as metabolic syndrome, chronic inflammation, hypercoagulability, hyperfibrinolysis, diabetes mellitus and dyslipidaemias. But chronic progressive kidney disease is not always due to hepatorenal syndrome. Beyond that, other diseases or disease entities should be considered. Among them are diabetic nephropathy, secondary IgA nephropathy, hepatitis C -associated membranoproliferative Glomerulonephritis (MPGN) and hepatitis B-associated membranous nephropathy.Coexisting diseases, similar underlying pathophysiologic mechanisms, or simultaneously concurring pathophysiological processes and overlapping clinical manifestations, impede the etiologic diagnosis and corresponding treatment of chronic kidney disease in the setting of chronic liver disease. In this review, we focus on common and rare pathologies, which can lead to chronic kidney disease in this particular patient group and try to summarize the most recent therapeutic modalities.
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Affiliation(s)
- Florian Gunnar Scurt
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany
| | - Katrin Bose
- Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany.,Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland
| | - Ali Canbay
- Ruhr-Universität Bochum, Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Deutschland
| | - Peter R Mertens
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany
| | - Christos Chatzikyrkou
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany
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6
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Abdelhamid WAR, Shendi A, Zahran M, Elbary EA, Fadda S. Hepatitis C-related membranoproliferative glomerulonephritis in the era of direct antiviral agents. ACTA ACUST UNITED AC 2021; 44:291-295. [PMID: 33605311 PMCID: PMC9269171 DOI: 10.1590/2175-8239-jbn-2020-0148] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 09/18/2020] [Indexed: 12/11/2022]
Abstract
Membranoproliferative glomerulonephritis (MPGN) is the most typical Hepatitis C virus (HCV)-associated glomerulopathy, and the available data about the utilization of direct-acting antivirals (DAA) in HCV-associated glomerulonephritis is inadequate. We evaluated the renal and viral response in two cases of HCV-related MPGN; the first caused by cryoglobulinemia while the second was cryoglobulin-negative. Both patients received immunosuppression besides DAA in different regimens. They achieved partial remission but remained immunosuppression-dependent for more than 6 months after DAA despite sustained virological response, which enabled safer but incomplete immunosuppression withdrawal. Both patients were tested for occult HCV in peripheral blood mononuclear cells and found to be negative. Hence, the treatment of HCV-related MPGN ought to be according to the clinical condition and the effects of drug therapy. It is important to consider that renal response can lag behind the virological response.
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Affiliation(s)
| | - Ali Shendi
- Zagazig University, Faculty of Medicine, Internal Medicine Department, Zagazig, Egypt
| | - Mahmoud Zahran
- Zagazig University, Faculty of Medicine, Internal Medicine Department, Zagazig, Egypt
| | - Eman Abd Elbary
- Zagazig University, Faculty of Medicine, Pathology Department, Zagazig, Egypt
| | - Sawsan Fadda
- Cairo University, Faculty of Medicine, Pathology Department, Cairo, Egypt
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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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8
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Jamshidi S, Bokharaei-Salim F, Esghaei M, Bastani MN, Garshasbi S, Chavoshpour S, Dehghani-Dehej F, Fakhim S, Khanaliha K. Occult HCV and occult HBV coinfection in Iranian human immunodeficiency virus-infected individuals. J Med Virol 2020; 92:3354-3364. [PMID: 32232978 DOI: 10.1002/jmv.25808] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 03/01/2020] [Accepted: 03/17/2020] [Indexed: 12/12/2022]
Abstract
The presence of hepatitis C virus (HCV) genome in liver biopsy or peripheral blood mononuclear cell (PBMC) specimens in the absence of detectable HCV-RNA in plasma of the people with or without anti-HCV antibodies has defined as occult HCV infection (OCI), whereas occult hepatitis B virus infection (OBI) is detection of hepatitis B virus (HBV) genome in the absence of traceable hepatitis B surface antigen in the plasma samples of patients. The purpose of this study is to determine the presence of OBI and OCI in human immunodeficiency virus (HIV)-infected individuals. In this cross-sectional research, 190 Iranian HIV-infected individuals were enrolled from September 2015 to February 2019. All participants were tested regarding various serological markers for HCV and HBV infections. Viral RNA and DNA were extracted from plasma and PBMC specimens, and the presence of HCV-RNA in plasma and PBMC samples was tested using reverse transcriptase-nested polymerase chain reaction (PCR), HBV viral load was determined in plasma samples using COBAS TaqMan 48 Kit, and also the presence of the HBV-DNA in PBMC samples was tested by real-time PCR. In this study, the prevalence of OBI and OCI in HIV-infected individuals was 3.1% and 11.4%, respectively. The genotypes of HCV in the patients with OCI were as follows: 57.1% were infected with subtype 3a, 35.7% were infected with subtype 1a, and 7.1% was infected with subtype 1b. It is noteworthy that in this study, two patients (1.1%) had OCI/OBI coinfections. The present study revealed that 1.1% of Iranian HIV-infected individuals had OBI and OCI at the same time. Therefore, it seems that designing prospective surveys to determine the presence of this coinfection in HIV-infected individuals is informative.
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Affiliation(s)
- Sogol Jamshidi
- 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
| | - 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
| | - Saba Garshasbi
- Vice Chancellor for Health, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Sara Chavoshpour
- Department of Virology, School of Public Health, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | | | - Shahin Fakhim
- Department of Civil Engineering, Faculty of Engineering, Payame Noor University, Karaj, Iran
| | - Khadijeh Khanaliha
- Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
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9
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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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10
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Abstract
Renal dysfunction in cirrhosis is common and is associated with increased mortality. Identifying and treating reversible causes of renal disease can significantly improve outcomes. The etiology, approach, and evaluation of renal disease in this group of patients is similar to the noncirrhosis patient, with a few specific caveats. Renal disease may be unrelated to the cause of cirrhosis (eg, prerenal acute kidney injury, acute tubular necrosis), occur as a manifestation of the same systemic disease responsible for the liver disease (eg, chronic viral hepatitis B and C infection) or as a consequence of cirrhosis (hepatorenal syndrome). Kidney impairment may be underrecognized in patients with cirrhosis due to over-reliance on creatinine-based glomerular filtration rate equations used in clinical practice. The first steps of evaluation for the renal disease include a thorough medical history to identify the underlying cause of cirrhosis and any potential trigger for renal dysfunction, physical examination, and review of prior laboratory records for baseline renal function. Renal imaging and urinalysis should be performed on all cirrhotic patients with renal dysfunction to establish the presence of urinary obstruction, chronicity and intrinsic renal disease.
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11
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Nada A, Abbasy M, Sabry A, Abdu Allah AM, Shehab-Eldeen S, Elnaidany N, Elimam H, Mohamed Ibraheem KI, Essa A. Serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) in HCV-Positive Egyptian Patients Treated with Sofosbuvir. Can J Gastroenterol Hepatol 2020; 2020:1632959. [PMID: 32083035 PMCID: PMC7007947 DOI: 10.1155/2020/1632959] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 12/23/2019] [Indexed: 02/06/2023] Open
Abstract
Background Direct-acting antivirals (DAAs) made a drastic change in the management of HCV infection. Sofosbuvir is one of the highly potent DAAs, eliminated mainly through the kidney. But concerns about renal safety during treatment may limit its use. Neutrophil gelatinase-associated lipocalin (NGAL) has been proven as a predictor of renal tubular injury. Hence, the aim of this work was to assess serum neutrophil gelatinase-associated lipocalin (NGAL) in HCV-positive patients before and after treatment with the sofosbuvir-based antiviral regimen. Methods This prospective study included 87 Egyptian patients with chronic HCV infection treated with sofosbuvir plus daclatasvir with or without ribavirin for 12 weeks. Serum NGAL was measured before and at the end of treatment (EOT). Analysis of NGAL and estimated glomerular filtration rate (eGFR) evolution was done. Results Our results showed a statistically significant decrease in serum NGAL (P=0.02) with a nonsignificant reduction in eGFR (P=0.02) with a nonsignificant reduction in eGFR (P=0.02) with a nonsignificant reduction in eGFR (P=0.02) with a nonsignificant reduction in eGFR (P=0.02) with a nonsignificant reduction in eGFR (. Conclusions Sofosbuvir appears to have no nephrotoxic effects and is safe to treat patients with chronic HCV infection.
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Affiliation(s)
- Ali Nada
- Hepatology Department, National Liver Institute, Menoufia University, Shebin-Elkom, Egypt
| | - Mohamed Abbasy
- Hepatology Department, National Liver Institute, Menoufia University, Shebin-Elkom, Egypt
| | - Aliaa Sabry
- Hepatology Department, National Liver Institute, Menoufia University, Shebin-Elkom, Egypt
| | - Azza Mohamed Abdu Allah
- Biochemistry and Molecular Biology Department, Faculty of Medicine, Menoufia University, Shebin-Elkom, Egypt
| | - Somaia Shehab-Eldeen
- Tropical Medicine Department, Faculty of Medicine, Menoufia University, Shebin-Elkom, Egypt
| | - Nada Elnaidany
- Faculty of Pharmacy, MSA University, 6th of October City, Egypt
| | - Hanan Elimam
- Biochemistry Department, Faculty of Pharmacy, University of Sadat City, Sadat City, Egypt
| | | | - Abdallah Essa
- Tropical Medicine Department, Faculty of Medicine, Menoufia University, Shebin-Elkom, Egypt
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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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13
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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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14
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Sette LHBC, Lopes EPDA, Guedes dos Anjos NC, Valente LM, Vieira de Oliveira SA, Lucena-Silva N. High prevalence of occult hepatitis C infection in predialysis patients. World J Hepatol 2019; 11:109-118. [PMID: 30705723 PMCID: PMC6354127 DOI: 10.4254/wjh.v11.i1.109] [Citation(s) in RCA: 5] [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: 10/28/2018] [Revised: 12/20/2018] [Accepted: 01/04/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Occult hepatitis C virus (HCV) infection (OCI) may be associated with extrahepatic diseases and it is known that the patients with chronic kidney disease (CKD) who are on hemodialysis (HD) present a higher prevalence of this type of infection than the general population, with a worse clinical outcome. However, there are no data in the literature to assess the presence of OCI in patients prior to the initiation of renal replacement therapy (RRT). Therefore, this study aimed to evaluate the occurrence and epidemiological aspects of OCI in patients with Predialysis CKD. We hypothesize that this infection could occur before RRT initiation.
AIM To research the status in predialysis patients when HD patients have high prevalence of OCI.
METHODS A cross-sectional study was conducted between 2015 and 2017. Adults with creatinine clearance < 60 mL/min·1.73 m2 (predialysis patients) were recruited to the study. Pregnant and postpartum women, patients with glomerulopathies, and patients showing positivity for serological markers of hepatitis B virus (HBV), HCV or human immunodeficiency virus infection were excluded. Patients were diagnosed with OCI according to test results of anti-HCV antibody negativity and HCV RNA positivity in either ultracentrifuged serum or, if serum-negative, in peripheral blood mononuclear cells.
RESULTS Among the 91 total patients included in the study, the prevalence of OCI was 16.5%. Among these 15 total OCI patients, 1 was diagnosed by 14 ultracentrifuged serum results and 14 were diagnosed by peripheral blood mononuclear cell results. Compared to the non-OCI group, the OCI patients presented higher frequency of older age (P = 0.002), patients with CKD of mixed etiology (P = 0.019), and patients with markers of previous HBV infection (i.e., combined positivity for anti-hepatitis B core protein antibody and anti-hepatitis B surface protein antibody) (P = 0.001).
CONCLUSION Among predialysis patients, OCI involved the elderly, patients with CKD of mixed etiology, and patients with previous HBV infection.
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Affiliation(s)
| | | | | | - Lucila Maria Valente
- Nephrology-Department of Clinical Medicine, Federal University of Pernambuco, Pernambuco 50670-901, Brazil
| | | | - Norma Lucena-Silva
- Laboratory of Immunogenetics of the Aggeu Magalhães Institute - Fiocruz Pernambuco, Pernambuco 50670-420, Brazil
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Soliman AR, Ahmed RM, Soliman M, Abdallah A, Zayed B. The effect of co-infection with hepatitis B and hepatitis C viruses on the prevalence of proteinuria and loss of renal function: a single-center experience. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2018. [DOI: 10.4103/ejim.ejim_51_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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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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KDIGO 2018 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int Suppl (2011) 2018; 8:91-165. [PMID: 30675443 PMCID: PMC6336217 DOI: 10.1016/j.kisu.2018.06.001] [Citation(s) in RCA: 116] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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18
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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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19
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Fabrizi F, Aghemo A, Lampertico P, Fraquelli M, Cresseri D, Moroni G, Passerini P, Donato FM, Messa P. Immunosuppressive and antiviral treatment of hepatitis C virus-associated glomerular disease: A long-term follow-up. Int J Artif Organs 2018; 41:306-318. [PMID: 29595085 DOI: 10.1177/0391398818762358] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The evidence in the medical literature on the treatment of hepatitis C virus-associated glomerular disease is extremely limited. The advent of nonconventional immunosuppressive agents and direct-acting antivirals promises high efficacy and safety. AIMS We conducted an open-label, single-arm clinical study to examine the efficacy and safety of a combined approach for hepatitis C virus-associated glomerular disease. METHODS In the first phase of the study, patients with hepatitis C virus-associated glomerular disease received interferon-based antiviral therapy and immunosuppressive agents; since 2013, interferon-free antiviral therapy was adopted and novel immunosuppressants (including B-cell depleting agents and mycophenolate mofetil) or immunomodulators (ribavirin) were choiced. Virological and clinical responses were evaluated over a long observation period (median follow-up of 60 weeks and 46.5 months after the end of treatment with interferon and direct-acting antiviral agents, respectively). RESULTS We enrolled 25 consecutive patients with hepatitis C virus-associated glomerular disease, 8 being liver transplant recipients for hepatitis C. A total of 13 patients received therapy with direct-acting antivirals and experienced sustained viral response (serum hepatitis C virus RNA <12 IU/mL, 12 weeks after treatment ended, sustained viral response12). The mean (±standard deviation) proteinuria decreased from 2.61 ± 1.01 at baseline to 1.71 ± 1.43 (g/day) at sustained viral response 48, p = 0.031; microscopic hematuria and serum cryoglobulins disappeared in six (50%) and seven (64%) patients, respectively, after sustained viral response by direct-acting antivirals. Adverse events occurred in 69% (9/13) of patients and were mild, with four cases of ribavirin-related anemia requiring blood transfusions (no drop-outs). After sustained viral response by direct-acting antivirals, immunosuppressive and immunomodulatory agents were initiated in clinical relapsers ( n = 2) and nonresponders ( n = 3) with some benefit. Among patients on interferon-based regimens ( n = 12), viral response (sustained viral response 24) and dropout rates were 58% (7/12) and 33% (4/12), respectively. After sustained viral response by interferon-based therapy, clinical relapsers ( n = 3) were successfully managed with immunosuppressive agents in two patients. CONCLUSION Treatment with direct-acting antivirals provides excellent rates of viral response and safety in patients with hepatitis C virus-related glomerular disease; viral response was frequently accompanied by clinical improvement. The absence of hepatitis C virus RNA from serum allowed immunosuppressive and immunomodulatory therapies with benefits for glomerular abnormalities and no concern on hepatitis C virus replication.
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Affiliation(s)
- Fabrizio Fabrizi
- 1 Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milano, Italy
| | - Alessio Aghemo
- 2 Division of Gastroenterology and Hepatology, Maggiore Hospital and IRCCS Foundation, Milano, Italy
| | - Pietro Lampertico
- 2 Division of Gastroenterology and Hepatology, Maggiore Hospital and IRCCS Foundation, Milano, Italy
- 3 School of Medicine, University of Milan, Italy
| | - Mirella Fraquelli
- 2 Division of Gastroenterology and Hepatology, Maggiore Hospital and IRCCS Foundation, Milano, Italy
| | - Donata Cresseri
- 1 Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milano, Italy
| | - Gabriella Moroni
- 1 Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milano, Italy
| | - Patrizia Passerini
- 1 Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milano, Italy
| | - Francesca M Donato
- 2 Division of Gastroenterology and Hepatology, Maggiore Hospital and IRCCS Foundation, Milano, Italy
| | - Piergiorgio Messa
- 1 Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milano, Italy
- 3 School of Medicine, University of Milan, Italy
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20
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Lin MS, Chen TH, Lin WY, Liu CH, Hsieh YY, Chiu WN, Chang CH, Chen MY, Chung CM, Lin YS. Add-on neurological benefits of antiviral therapy in HCV patients with chronic kidney disease - a nationwide cohort study. BMC Gastroenterol 2017; 17:99. [PMID: 28814273 PMCID: PMC5559858 DOI: 10.1186/s12876-017-0653-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2017] [Accepted: 07/31/2017] [Indexed: 12/18/2022] Open
Abstract
Background Hepatitis C virus (HCV)-infected patients with chronic kidney disease (CKD) have rarely been studied because they rarely accept interferon-based therapy (IBT) and have been difficult to follow up. We investigated long-term outcomes of IBT on the population. Methods This population-based cohort study used the Taiwan National Health Insurance Research Database as its data source. HCV patients diagnosed with CKD between Jan. 1, 2003, and Dec. 31, 2013, were selected. They were then divided into two groups based on whether they had undergone IBT. All-cause mortality, acute myocardial infarction (AMI), ischemic stroke (IS), hemorrhagic stroke, and new-onset dialysis were evaluated using a Cox proportional hazard regression analysis after propensity score matching. Results We enrolled 9872 HCV patients with CKD: 1684 patients in the treated cohort and 8188 patients in the untreated cohort. The annual incidence of all-cause mortality (19.00 vs. 42.89 events per 1000 person-years; p < 0.001) and the incidences of hemorrhagic stroke (1.21 vs. 4.19 events per 1000 person-years; p = 0.006) were lower in the treated cohort. New-onset dialysis was also lower in the treated cohort (aHR: 0.31; 95% CI: 0.20–0.48; p < 0.001). Conclusion Antiviral therapy might provide protective benefits on all-cause mortality, hemorrhagic stroke, and new-onset dialysis in HCV-infected patients with CKD. Electronic supplementary material The online version of this article (doi:10.1186/s12876-017-0653-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Ming-Shyan Lin
- Department of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan
| | - Tien-Hsing Chen
- Department of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan
| | - Wey-Yil Lin
- Stroke Center and Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chi-Hung Liu
- Stroke Center and Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Yung-Yu Hsieh
- Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Wen-Nan Chiu
- Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Yunlin, Taiwan
| | - Chih-Hsiang Chang
- Department of Nephrology, Kidney research center, Chang Gung Memorial Hospital, Chang Gung University, College of medicine, Taoyuan, Taiwan
| | - Mei-Yen Chen
- College of Nursing, Chang Gung University of Science and Technology (CGUST), Taoyuan, Taiwan.,Department of Nursing, Chang Gung University, Taoyuan, Taiwan
| | - Chang-Min Chung
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan County, Taiwan. .,Department of Cardiology, Chiayi Chang Gung Memorial Hospital, 6, Sec. West Chai-Pu Road, Pu-TZ City, Chai Yi Hsien, 61363, Taiwan.
| | - Yu-Sheng Lin
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan County, Taiwan. .,Department of Cardiology, Chiayi Chang Gung Memorial Hospital, 6, Sec. West Chai-Pu Road, Pu-TZ City, Chai Yi Hsien, 61363, Taiwan.
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21
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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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22
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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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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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24
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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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25
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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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Azmi AN, Tan SS, Mohamed R. Hepatitis C and kidney disease: An overview and approach to management. World J Hepatol 2015; 7:78-92. [PMID: 25624999 PMCID: PMC4295197 DOI: 10.4254/wjh.v7.i1.78] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Revised: 10/13/2014] [Accepted: 11/10/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C infection and chronic kidney disease are major health burden worldwide. Hepatitis C infection is associated with a wide range of extra-hepatic manifestations in various organs including the kidneys. A strong association between hepatitis C and chronic kidney disease has come to light. Hemodialysis in supporting the end stage renal disease patients unfortunately carries a risk for hepatitis C infection. Despite much improvement in the care of this group of patients, the prevalence of hepatitis C infection in hemodialysis patients is still higher than the general population. Hepatitis C infection has a negative effect on the survival of hemodialysis and renal transplant patients. Treatment of hepatitis C in end stage renal disease patients using conventional or pegylated interferon with or without ribavirin remains a clinical challenge with low response rate, high dropout rate due to poor tolerability and many unmet needs. The approval of new direct acting antiviral agents for hepatitis C may dramatically change the treatment approach in hepatitis C infected patients with mild to moderate renal impairment. However it remains to be confirmed if the newer Hepatitis C therapies are safe in individuals with severe renal impairment. This review article discusses the relationship between hepatitis C and chronic kidney disease, describe the various types of renal diseases associated with hepatitis C and the newer as well as the existing treatments for hepatitis C in the context of this subpopulation of hepatitis C patients.
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28
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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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