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1
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Kandathil AJ, Balagopal A. Human Hepegivirus-1: Innocent Traveler, Helpful Symbiote, or Insidious Pathogen? Clin Infect Dis 2021; 71:1229-1231. [PMID: 31671171 DOI: 10.1093/cid/ciz947] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 10/08/2019] [Indexed: 12/28/2022] Open
Affiliation(s)
- Abraham J Kandathil
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ashwin Balagopal
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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2
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Pozzato G, Mazzaro C, Gattei V. Hepatitis C virus-associated non-Hodgkin lymphomas: the endless history. Minerva Med 2020; 112:215-227. [PMID: 33263375 DOI: 10.23736/s0026-4806.20.07184-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Hepatitis C virus (HCV) is a global population problem due to its high prevalence worldwide. In the prognosis of patients with HCV not only hepatic but increasingly frequent of extrahepatic HCV manifestations, such as mixed cryoglobulinemia (MC) and non-Hodgkin's lymphoma (NHL), are important. The role of the HCV virus in the pathogenesis of lymphoproliferative diseases is confirmed by a large number of epidemiological studies, as well as by the effectiveness of antiviral therapy in patients with non-Hodgkin's lymphoma (NHL). The purpose of the review was to provide an overview of epidemiological and biological data explaining the role of HCV in the development of NHL. The review also discusses HCV-associated NHL treatment by the traditional antiviral therapy (interferon and ribavirin) and by the new direct antiviral agents.
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Affiliation(s)
- Gabriele Pozzato
- Department of Clinical and Surgical Sciences, Maggiore Hospital, University of Trieste, Trieste, Italy -
| | - Cesare Mazzaro
- Unit of Clinical and Experimental Onco-Hematology, CRO Aviano National Cancer Institute IRCCS, Aviano, Pordenone, Italy
| | - Valter Gattei
- Unit of Clinical and Experimental Onco-Hematology, CRO Aviano National Cancer Institute IRCCS, Aviano, Pordenone, Italy
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3
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Heffron AS, Lauck M, Somsen ED, Townsend EC, Bailey AL, Sosa M, Eickhoff J, Capuano III S, Newman CM, Kuhn JH, Mejia A, Simmons HA, O’Connor DH. Discovery of a Novel Simian Pegivirus in Common Marmosets ( Callithrix jacchus) with Lymphocytic Enterocolitis. Microorganisms 2020; 8:microorganisms8101509. [PMID: 33007921 PMCID: PMC7599636 DOI: 10.3390/microorganisms8101509] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 09/26/2020] [Accepted: 09/28/2020] [Indexed: 11/30/2022] Open
Abstract
From 2010 to 2015, 73 common marmosets (Callithrix jacchus) housed at the Wisconsin National Primate Research Center (WNPRC) were diagnosed postmortem with lymphocytic enterocolitis. We used unbiased deep-sequencing to screen the blood of deceased enterocolitis-positive marmosets for viruses. In five out of eight common marmosets with lymphocytic enterocolitis, we discovered a novel pegivirus not present in ten matched, clinically normal controls. The novel virus, which we named Southwest bike trail virus (SOBV), is most closely related (68% nucleotide identity) to a strain of simian pegivirus A isolated from a three-striped night monkey (Aotus trivirgatus). We screened 146 living WNPRC common marmosets for SOBV, finding an overall prevalence of 34% (50/146). Over four years, 85 of these 146 animals died or were euthanized. Histological examination revealed 27 SOBV-positive marmosets from this cohort had lymphocytic enterocolitis, compared to 42 SOBV-negative marmosets, indicating no association between SOBV and disease in this cohort (p = 0.0798). We also detected SOBV in two of 33 (6%) clinically normal marmosets screened during transfer from the New England Primate Research Center, suggesting SOBV could be exerting confounding influences on comparisons of common marmoset studies from multiple colonies.
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Affiliation(s)
- Anna S. Heffron
- Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53711, USA; (A.S.H.); (M.L.); (E.D.S.); (E.C.T.); (C.M.N.)
| | - Michael Lauck
- Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53711, USA; (A.S.H.); (M.L.); (E.D.S.); (E.C.T.); (C.M.N.)
| | - Elizabeth D. Somsen
- Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53711, USA; (A.S.H.); (M.L.); (E.D.S.); (E.C.T.); (C.M.N.)
| | - Elizabeth C. Townsend
- Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53711, USA; (A.S.H.); (M.L.); (E.D.S.); (E.C.T.); (C.M.N.)
| | - Adam L. Bailey
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA;
| | - Megan Sosa
- Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; (M.S.); (S.C.III); (A.M.); (H.A.S.)
| | - Jens Eickhoff
- Department of Biostatistics & Medical Informatics, University of Wisconsin-Madison, Madison, WI 53705, USA;
| | - Saverio Capuano III
- Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; (M.S.); (S.C.III); (A.M.); (H.A.S.)
| | - Christina M. Newman
- Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53711, USA; (A.S.H.); (M.L.); (E.D.S.); (E.C.T.); (C.M.N.)
| | - Jens H. Kuhn
- Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA;
| | - Andres Mejia
- Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; (M.S.); (S.C.III); (A.M.); (H.A.S.)
| | - Heather A. Simmons
- Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; (M.S.); (S.C.III); (A.M.); (H.A.S.)
| | - David H. O’Connor
- Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53711, USA; (A.S.H.); (M.L.); (E.D.S.); (E.C.T.); (C.M.N.)
- Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; (M.S.); (S.C.III); (A.M.); (H.A.S.)
- Correspondence: ; Tel.: +1-608-890-0845
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Beyond Cytomegalovirus and Epstein-Barr Virus: a Review of Viruses Composing the Blood Virome of Solid Organ Transplant and Hematopoietic Stem Cell Transplant Recipients. Clin Microbiol Rev 2020; 33:33/4/e00027-20. [PMID: 32847820 DOI: 10.1128/cmr.00027-20] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Viral primary infections and reactivations are common complications in patients after solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) and are associated with high morbidity and mortality. Among these patients, viral infections are frequently associated with viremia. Beyond the usual well-known viruses that are part of the routine clinical management of transplant recipients, numerous other viral signatures or genomes can be identified in the blood of these patients. The identification of novel viral species and variants by metagenomic next-generation sequencing has opened up a new field of investigation and new paradigms. Thus, there is a need to thoroughly describe the state of knowledge in this field with a review of all viral infections that should be scrutinized in high-risk populations. Here, we review the eukaryotic DNA and RNA viruses identified in blood, plasma, or serum samples of pediatric and adult SOT/HSCT recipients and the prevalence of their detection, with a particular focus on recently identified viruses and those for which their potential association with disease remains to be investigated, such as members of the Polyomaviridae, Anelloviridae, Flaviviridae, and Astroviridae families. Current knowledge of the clinical significance of these viral infections with associated viremia among transplant recipients is also discussed. To ensure a comprehensive description in these two populations, individuals described as healthy (mostly blood donors) are considered for comparative purposes. The list of viruses that should be on the clinicians' radar is certainly incomplete and will expand, but the challenge is to identify those of possible clinical significance.
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5
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Pozzato G, Mazzaro C, Gattei V. Hepatitis C Virus-Associated Non-Hodgkin Lymphomas: Biology, Epidemiology, and Treatment. Clin Liver Dis 2017; 21:499-515. [PMID: 28689589 DOI: 10.1016/j.cld.2017.03.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Eradication of hepatitis C virus (HCV) in indolent non-Hodgkin lymphomas (NHLs), especially in marginal zone lymphomas, determines the regression of the hematologic disorder in a significant fraction of cases. Because direct antiviral agents show an excellent profile in terms of efficacy, safety, and rapid onset of action, these drugs can be used in any clinical situation and in the presence of any comorbidities. To avoid the progression of the NHL, despite HCV eradication, antiviral therapy should be provided as soon as the viral infection is discovered; before that, the chronic antigenic stimulation determines the irreversible proliferation of neoplastic B cells.
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Affiliation(s)
- Gabriele Pozzato
- Department of Clinical and Surgical Sciences, University of Trieste, Ematologia Clinica, Ospedale Maggiore, Piazza Ospedale 1, Trieste 34121, Italy.
| | - Cesare Mazzaro
- Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano 33081, Italy
| | - Valter Gattei
- Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano 33081, Italy
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6
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Vannata B, Arcaini L, Zucca E. Hepatitis C virus-associated B-cell non-Hodgkin's lymphomas: what do we know? Ther Adv Hematol 2015; 7:94-107. [PMID: 27054025 DOI: 10.1177/2040620715623924] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Epidemiological studies have shown an increased risk of developing B-cell lymphomas in patients with chronic hepatitis C virus (HCV) infection. There is, however, a great geographic variability and it remains unclear whether additional environmental and genetic factors are involved or whether the international discrepancies represent simply a consequence of the variable prevalence of HCV infection in different countries. Other confounding factors may affect the comparability of the different studies, including the method of HCV assessment, the selection of normal controls, the lymphoma classification used and the year of publication. The most convincing evidence for a causal relationship comes from the observation, mainly limited to some indolent subtypes, of B-cell lymphoma regressions after successful HCV eradication with antiviral treatment. Yet, the molecular mechanism of HCV-induced lymphomagenesis are mainly hypothetical. According to most plausible models, lymphoma growth is a consequence of continuous antigenic stimulation induced by the chronic viral infection. This review will summarize the current knowledge on HCV-associated lymphomas and their management.
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Affiliation(s)
- Barbara Vannata
- Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
| | - Luca Arcaini
- Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo and Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Emanuele Zucca
- Lymphoma Unit, Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona 6500, Switzerland
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7
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Fiorino S, Bacchi-Reggiani L, de Biase D, Fornelli A, Masetti M, Tura A, Grizzi F, Zanello M, Mastrangelo L, Lombardi R, Acquaviva G, di Tommaso L, Bondi A, Visani M, Sabbatani S, Pontoriero L, Fabbri C, Cuppini A, Pession A, Jovine E. Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma: A systematic review. World J Gastroenterol 2015; 21:12896-12953. [PMID: 26668515 PMCID: PMC4671046 DOI: 10.3748/wjg.v21.i45.12896] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2015] [Revised: 08/05/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To summarize the current knowledge about the potential relationship between hepatitis C virus (HCV) infection and the risk of several extra-liver cancers. METHODS We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews: (1) HCV and haematopoietic malignancies; (2) HCV and cholangiocarcinoma; (3) HCV and pancreatic cancer; (4) HCV and breast cancer; (5) HCV and kidney cancer; (6) HCV and skin or oral cancer; and (7) HCV and thyroid cancer. RESULTS According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with: (1) a higher incidence of some B-cell Non-Hodgkin-Lymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%; (2) an increased risk of intra-hepatic cholangiocarcinoma; and (3) a correlation between HCV prevalence and pancreatic cancer (PAC) incidence. CONCLUSION To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are required to confirm or deny this association.
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8
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Visco C, Finotto S. Hepatitis C virus and diffuse large B-cell lymphoma: Pathogenesis, behavior and treatment. World J Gastroenterol 2014; 20:11054-11061. [PMID: 25170194 PMCID: PMC4145748 DOI: 10.3748/wjg.v20.i32.11054] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2013] [Revised: 02/25/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
A significant association between hepatitis C virus (HCV) infection and B-cell lymphoma has been reported by epidemiological studies, most of them describing a strong relationship between indolent lymphomas and HCV. Furthermore, the curative potential of antiviral therapy on HCV related indolent lymphomas supports a specific role for the virus in lymphomagenesis. These observations are reinforced by numerous laboratory experiments that led to several hypothetical models of B-cell transformation by HCV. Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype in the western countries, has been associated to HCV infection despite its aggressive nature. This association seems particularly prominent in some geographical areas. Clinical presentation of HCV-associated DLBCL has consistently been reported to differ from the HCV-negative counterpart. Nevertheless, histopathology, tolerance to standard-of-care chemo-immunotherapy (R-CHOP or CHOP-like regimens) and final outcome of HCV-positive DLBCL patients is still matter of debate. Addition of rituximab has been described to enhance viral replication but the probability of severe hepatic complications remains low, with some exceptions (i.e., hepatitis B virus or immune immunodeficiency virus co-infected patients, presence of grade > 2 transaminases elevation, cirrhosis or hepatocarcinoma). HCV viral load in this setting is not necessarily directly associated with liver damage. Overall, treatment of HCV associated DLBCL should be performed in an interdisciplinary approach with hepatologists and hematologists with close monitoring of liver function. Available reports reveal that the final outcome of HCV-positive DLBCL that receive standard immunochemotherapy is not inferior to their HCV-negative counterpart. This review summarizes data on epidemiology, pathogenesis and therapeutic approach on HCV-associated DLBCL. Several issues that are matter of debate like clinical management of patients with transaminase elevation, criteria for discontinuing or starting immuno-chemotherapy, as well as the exact role of monoclonal antibodies will be analyzed.
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MESH Headings
- Animals
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Antiviral Agents/therapeutic use
- Cell Transformation, Viral
- Drug Resistance, Neoplasm
- Hepacivirus/drug effects
- Hepacivirus/pathogenicity
- Hepatitis C/diagnosis
- Hepatitis C/drug therapy
- Hepatitis C/epidemiology
- Hepatitis C/virology
- Humans
- Lymphoma, Large B-Cell, Diffuse/diagnosis
- Lymphoma, Large B-Cell, Diffuse/drug therapy
- Lymphoma, Large B-Cell, Diffuse/epidemiology
- Lymphoma, Large B-Cell, Diffuse/virology
- Treatment Outcome
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9
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Waldenström macroglobulinemia in hepatitis C: case report and review of the current literature. Case Rep Oncol Med 2014; 2014:165670. [PMID: 25247100 PMCID: PMC4163423 DOI: 10.1155/2014/165670] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2014] [Accepted: 08/12/2014] [Indexed: 12/16/2022] Open
Abstract
Background. Recent literature has associated hepatitis C virus with the development of non-Hodgkin lymphoma. Hepatitis C virus infection appears to promote lymphoproliferation, providing a plausible mechanism for a causative association; however, despite prior reports of patients with comorbid hepatitis C infection and Waldenström macroglobulinemia, the literature is in disagreement regarding whether there exists an association between these two conditions. Case Presentation. This case report describes a 57-year-old African-American male with chronic hepatitis C infection and cryoglobulinemia who presented with several episodes of transient confusion and paralysis and was found to have symptomatic hyperviscosity. The recognition of his condition was facilitated by characteristic findings on ophthalmologic examination. He was subsequently diagnosed with Waldenström macroglobulinemia on bone marrow biopsy. Conclusions. An up to date, comprehensive review of the literature suggests an association between hepatitis C and Waldenström macroglobulinemia. Data on optimal treatment of patients with comorbid hepatitis C infection and Waldenström macroglobulinemia is limited. We have provided a comprehensive review of previously explored treatment options to guide management of other similar patients. Our patient has since been treated with repeated plasmapheresis with a plan to pursue antiviral therapy.
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10
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Human pegivirus (GB virus C) NS3 protease activity inhibits induction of the type I interferon response and is not inhibited by HCV NS3 protease inhibitors. Virology 2014; 456-457:300-9. [PMID: 24889249 DOI: 10.1016/j.virol.2014.03.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Revised: 03/08/2014] [Accepted: 03/17/2014] [Indexed: 11/20/2022]
Abstract
We previously found that human pegivirus (HPgV; formerly GBV-C) NS3 protease activity inhibits Human Immunodeficiency Virus (HIV) replication in a CD4+ T cell line. Given the protease׳s similarity to the Hepatitis C virus (HCV) NS3 protease, we characterized HPgV protease activity and asked whether it affects the type I interferon response or is inhibited by HCV protease antagonists. We characterized the activity of proteases with mutations in the catalytic triad and demonstrated that the HCV protease inhibitors Telaprevir, Boceprevir, and Danoprevir do not affect HPgV protease activity. HPgV NS3 protease cleaved MAVS but not TRIF, and it inhibited interferon responses sufficiently to enhance growth of an interferon-sensitive virus. Therefore, HPgV׳s inhibition of the interferon response could help promote HPgV persistence, which is associated with clinical benefits in HIV-infected patients. Our results also imply that HCV protease inhibitors should not interfere with the beneficial effects of HPgV in HPgV/HCV/HIV infected patients.
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11
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Anggorowati N, Yano Y, Subronto YW, Utsumi T, Heriyanto DS, Mulya DP, Rinonce HT, Widasari DI, Lusida MI, Soetjipto, Hayashi Y. GB virus C infection in Indonesian HIV-positive patients. Microbiol Immunol 2013; 57:298-308. [PMID: 23590588 DOI: 10.1111/1348-0421.12033] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2012] [Revised: 01/10/2013] [Accepted: 01/20/2013] [Indexed: 11/27/2022]
Abstract
GB virus C (GBV-C), a human virus of the Flaviviridae family that is structurally and epidemiologically closest to hepatitis C virus (HCV), has been reported to confer beneficial outcomes in HIV-positive patients. However, the prevalence of GBV-C in HIV-positive individuals in Indonesia is unknown. Since GBV-C is more prevalent in anti-HCV positive patients than in anti-HCV negative subjects, transmission of GBV-C and HCV could be by the same method. This study examined the prevalence and molecular characteristics of GBV-C infection in HIV patients in Yogyakarta, Indonesia. The prevalence of GBV-C among HIV patients (n = 125, median age 31 years) based on the 5'UTR region was 111/125 (88.8%), including 39/48 (81.3%) and 72/77 (93.5%) HIV-infected patients with and without HCV infection, respectively. GBV-C isolates were of genotype 2a, 3 and 6 in 58.3%, 12.6% and 28.4% of patients, respectively. Patients with genotype 3 were significantly younger than those with genotypes 2a or 6 (P = 0.001 and P = 0.012, respectively). Genotypes 3 and 6 were significantly associated with injection drug use (P = 0.004 and P = 0.002, respectively) and HCV co-infection (P < 0.001 for both genotypes), indicating a shared transmission route with HCV. In conclusion, the prevalence of GBV-C among HIV-positive patients in Indonesia is high, and three genotypes were detected, namely genotype 2a, 3 and 6.
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Affiliation(s)
- Nungki Anggorowati
- Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan
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12
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Ernst D, Greer M, Akmatova R, Pischke S, Wedemeyer H, Heiken H, Tillmann HL, Schmidt RE, Stoll M. Impact of GB virus C viraemia on clinical outcome in HIV-1-infected patients: a 20-year follow-up study. HIV Med 2013; 15:245-50. [DOI: 10.1111/hiv.12094] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/26/2013] [Indexed: 11/27/2022]
Affiliation(s)
- D Ernst
- Department of Immunology and Rheumatology; Hannover Medical School; Hannover Germany
| | - M Greer
- Department of Pulmonology; Hannover Medical School; Hannover Germany
| | - R Akmatova
- Republican ‘AIDS’ Center of Health Ministry of Kyrgyz Republic; Bishkek Kyrgyzstan
| | - S Pischke
- Department of Gastroenterology, Hepatology and Endocrinology; Hannover Medical School; Hannover Germany
| | - H Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology; Hannover Medical School; Hannover Germany
| | - H Heiken
- Department of Immunology and Rheumatology; Hannover Medical School; Hannover Germany
| | - HL Tillmann
- Clinical Research Institute; Duke University; Durham NC USA
| | - RE Schmidt
- Department of Immunology and Rheumatology; Hannover Medical School; Hannover Germany
| | - M Stoll
- Department of Immunology and Rheumatology; Hannover Medical School; Hannover Germany
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13
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Högfeldt T, Bahnassy AA, Kwiecinska A, Osterborg A, Tamm KP, Porwit A, Zekri ARN, Lundahl J, Khaled HM, Mellstedt H, Moshfegh A. Patients with activated B-cell like diffuse large B-cell lymphoma in high and low infectious disease areas have different inflammatory gene signatures. Leuk Lymphoma 2012; 54:996-1003. [PMID: 23046110 DOI: 10.3109/10428194.2012.738365] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with an association with inflammation and viral infections. We hypothesize that environmental factors may be involved in the pathogenesis of DLBCL. In this study, we compared gene expression profiles of lymph node tissues from patients with DLBCL from two different geographical areas with diverse environmental exposures. Specimens from Egyptian and Swedish patients with DLBCL as well as controls were studied. Gene expression analysis using microarray and quantitative polymerase chain reaction demonstrated significantly higher expression of signal transducer and activator of transcription 3 (STAT3) in Swedish as compared to Egyptian patients and control materials from both countries. This was confirmed at protein level using confocal microscopy. The receptor tyrosine kinase ROR1, a "survival factor" for malignant cells, was overexpressed and significantly related to the STAT3 expression pattern. The difference in the expression of genes involved in inflammatory responses and in the tumorigenic process of DLBCL might relate to infectious agents and/or other environmental exposures.
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Affiliation(s)
- Therese Högfeldt
- Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
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