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Boyle J, Ward MH, Cerhan JR, Rothman N, Wheeler DC. Assessing and attenuating the impact of selection bias on spatial cluster detection studies. Spat Spatiotemporal Epidemiol 2024; 49:100659. [PMID: 38876558 PMCID: PMC11180222 DOI: 10.1016/j.sste.2024.100659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 05/09/2024] [Accepted: 05/10/2024] [Indexed: 06/16/2024]
Abstract
Spatial cluster analyses are commonly used in epidemiologic studies of case-control data to detect whether certain areas in a study region have an excess of disease risk. Case-control studies are susceptible to potential biases including selection bias, which can result from non-participation of eligible subjects in the study. However, there has been no systematic evaluation of the effects of non-participation on the findings of spatial cluster analyses. In this paper, we perform a simulation study assessing the effect of non-participation on spatial cluster analysis using the local spatial scan statistic under a variety of scenarios that vary the location and rates of study non-participation and the presence and intensity of a zone of elevated risk for disease for simulated case-control studies. We find that geographic areas of lower participation among controls than cases can greatly inflate false-positive rates for identification of artificial spatial clusters. Additionally, we find that even modest non-participation outside of a true zone of elevated risk can decrease spatial power to identify the true zone. We propose a spatial algorithm to correct for potentially spatially structured non-participation that compares the spatial distributions of the observed sample and underlying population. We demonstrate its ability to markedly decrease false positive rates in the absence of elevated risk and resist decreasing spatial sensitivity to detect true zones of elevated risk. We apply our method to a case-control study of non-Hodgkin lymphoma. Our findings suggest that greater attention should be paid to the potential effects of non-participation in spatial cluster studies.
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Affiliation(s)
- Joseph Boyle
- Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, USA.
| | - Mary H Ward
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - James R Cerhan
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Nathaniel Rothman
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - David C Wheeler
- Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, USA
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2
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Zhang Y, Guo W, Zhan Z, Bai O. Carcinogenic mechanisms of virus-associated lymphoma. Front Immunol 2024; 15:1361009. [PMID: 38482011 PMCID: PMC10932979 DOI: 10.3389/fimmu.2024.1361009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Accepted: 02/12/2024] [Indexed: 04/17/2024] Open
Abstract
The development of lymphoma is a complex multistep process that integrates numerous experimental findings and clinical data that have not yet yielded a definitive explanation. Studies of oncogenic viruses can help to deepen insight into the pathogenesis of lymphoma, and identifying associations between lymphoma and viruses that are established and unidentified should lead to cellular and pharmacologically targeted antiviral strategies for treating malignant lymphoma. This review focuses on the pathogenesis of lymphomas associated with hepatitis B and C, Epstein-Barr, and human immunodeficiency viruses as well as Kaposi sarcoma-associated herpesvirus to clarify the current status of basic information and recent advances in the development of virus-associated lymphomas.
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Affiliation(s)
| | | | | | - Ou Bai
- Department of Hematology, The First Hospital of Jilin University, Changchun, Jilin, China
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3
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Levin LI, Ramirez CM, Liao EL, Guo H, Kim BK, Marrogi AJ, Magpantay LI, Breen EC, Martínez-Maza O. Longitudinal Changes in Immune Activation Serum Biomarkers Prior to Diagnosis and Risk of B-cell NHL Subtypes. Cancer Epidemiol Biomarkers Prev 2023; 32:233-241. [PMID: 36409490 PMCID: PMC9905313 DOI: 10.1158/1055-9965.epi-22-0247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 07/14/2022] [Accepted: 11/14/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND To examine the contribution of B-cell activation molecules to B-cell follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), a prospective study was conducted using pre-diagnosis serial serum samples from the US Department of Defense Serum Repository. METHODS Each case (n = 142 FL, n = 211 DLBCL) was matched to two controls on age, gender, race, military branch, and blood collection dates. Immune activation molecules (IL1β, IL2, IL4, IL5, IL6, IL10, IL12, CXCL13, IL8, TNFα, IFNγ, GM-CSF, VEGF, sCD30, IgE) were quantified using ELISA or multiplex immunometric (Luminex) assay. Longitudinal data were analyzed using linear mixed modeling. As serial specimens were collected over several years before diagnosis, we evaluated the temporal dynamics of these markers. RESULTS Increased serum levels of sCD30, CXCL13, and to a lesser extent IL10, were associated with both FL and DLBCL in cases compared with controls, with a median follow-up of 5.5 years from the earliest specimen collection to diagnosis date. Significant increasing sCD30 and CXCL13 trajectories for FL and DLBCL subtypes were noted starting at the earliest time points and with IL10 levels increasing significantly at time points closer to diagnosis. CONCLUSIONS These results suggest that sCD30, CXCL13, and IL10 may contribute to the etiology of FL and DLBCL and are potential biomarkers for these non-Hodgkin lymphoma subtypes. IMPACT The increasing trajectories of the B-cell activation molecules, sCD30, CXCL13, and to a lesser extent IL10, may indicate early disease-induced effects or reflect the chronic stimulation of B-cells that promotes the development of FL and DLBCL subtypes.
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Affiliation(s)
- Lynn I Levin
- Statistics and Epidemiology Branch, Walter Reed Army Institute of Research, Silver Spring, MD
| | - Christina M Ramirez
- Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, CA
| | - Eileen L Liao
- Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, CA
| | - Hongyu Guo
- Statistics and Epidemiology Branch, Walter Reed Army Institute of Research, Silver Spring, MD
| | - Bong K Kim
- Armed Forces Institute of Pathology, Washington DC
| | - Aizen J Marrogi
- Experimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD
| | - Larry I Magpantay
- Department of Obstetrics & Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Elizabeth C Breen
- Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Otoniel Martínez-Maza
- Department of Obstetrics & Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA.,Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA.,Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA.,UCLA AIDS Institute, Los Angeles, CA.,Jonsson Comprehensive Cancer Center, Los Angeles, CA
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4
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Willis SJ, Kim HN, Achenbach CJ, Cachay ER, Christopoulos KA, Crane HM, Franco RA, Hurt CB, Kitahata MM, Moore RD, Silverberg MJ, Tien PC, Westreich D, Marcus JL. Hepatitis C coinfection and extrahepatic cancer incidence among people living with HIV. HIV Med 2022; 23:620-628. [PMID: 34951105 PMCID: PMC9177743 DOI: 10.1111/hiv.13218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/10/2021] [Accepted: 12/03/2021] [Indexed: 12/09/2022]
Abstract
OBJECTIVES We assessed the incidence of extrahepatic cancer among people with HIV/HCV coinfection and the potential impact of direct-acting antivirals (DAAs) on extrahepatic cancer risk among people with HIV/HCV coinfection. DESIGN Our study cohort included adults who initiated HIV care at a CNICS site in the US during 1995-2017, excluding those with previous cancer and without HCV testing. METHODS We used Cox regression to estimate hazard ratios for extrahepatic cancer incidence among patients with HIV/HCV coinfection compared with those with HIV monoinfection. Standardized morbidity ratio (SMR) weights were used to create a 'pseudopopulation' in which all patients were treated with antiretroviral therapy (ART), and to compare extrahepatic cancer incidence among patients with untreated HIV/HCV coinfection with the incidence that would have been observed if they had been successfully treated for HCV. RESULTS Of 18 422 adults, 1775 (10%) had HCV RNA and 10 899 (59%) were on ART at baseline. Incidence rates of any extrahepatic cancer among patients with HIV/HCV coinfection and HIV monoinfection were 1027 and 771 per 100 000 person-years, respectively. In SMR-weighted analyses, the risk of any extrahepatic cancer among patients with untreated HCV coinfection at baseline was similar to the risk if they had been successfully treated for HCV. Patients with untreated HCV coinfection at baseline had higher incidence of kidney, lung and inflammation-related cancers than if their HCV had been successfully treated, but these associations were not statistically significant. CONCLUSIONS We did not find evidence that treating HCV coinfection with DAAs would reduce the incidence of extrahepatic cancers among people with HIV receiving ART.
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Affiliation(s)
| | - H Nina Kim
- University of Washington, Seattle, Washington, USA
| | | | - Edward R Cachay
- University of California San Diego, San Diego, California, USA
| | | | | | | | - Christopher B Hurt
- Institute for Global Health & Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | | | - Richard D Moore
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | | | - Phyllis C Tien
- University of California San Francisco, San Francisco, California, USA
- Veterans Affairs Medical Center, San Francisco, California, USA
| | - Daniel Westreich
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Torre P, Aglitti A, Masarone M, Persico M. Viral hepatitis: Milestones, unresolved issues, and future goals. World J Gastroenterol 2021; 27:4603-4638. [PMID: 34366625 PMCID: PMC8326259 DOI: 10.3748/wjg.v27.i28.4603] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/11/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
In this review the current overall knowledge on hepatitis A, B, C, D, and E will be discussed. These diseases are all characterized by liver inflammation but have significant differences in distribution, transmission routes, and outcomes. Hepatitis B virus and hepatitis C virus are transmitted by exposure to infected blood, and in addition to acute infection, they can cause chronic hepatitis, which in turn can evolve into cirrhosis. It is estimated that more than 300 million people suffer from chronic hepatitis B or C worldwide. Hepatitis D virus, which is also transmitted by blood, only affects hepatitis B virus infected people, and this dual infection results in worse liver-related outcomes. Hepatitis A and E spread via the fecal-oral route, which corresponds mainly to the ingestion of food or water contaminated with infected stools. However, in developed countries hepatitis E is predominantly a zoonosis. Although hepatitis A virus and hepatitis E virus are usually responsible for a self-limiting hepatitis, a serious, rarely fatal illness is also possible, and in immunosuppressed patients, such as organ transplant recipients, hepatitis E virus infection can become chronic. The description of goals achieved, unresolved issues, and the latest research on this topic may make it possible to speculate on future scenarios in the world of viral hepatitis.
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Affiliation(s)
- Pietro Torre
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Andrea Aglitti
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Mario Masarone
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Marcello Persico
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
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Alkrekshi A, Kassem A, Park C, Tse W. Risk of Non-Hodgkin's Lymphoma in HCV Patients in the United States Between 2013 and 2020: A Population-Based Study. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2021; 21:e832-e838. [PMID: 34330674 DOI: 10.1016/j.clml.2021.06.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 06/09/2021] [Accepted: 06/19/2021] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus (HCV) is a significant healthcare problem affecting ~1% of the United States population. Meta-analyses of epidemiological studies reported a strong association between non-Hodgkin's lymphoma (NHL) and HCV. Direct oncogenic properties of HCV proteins and chronic antigenic stimulation are possible etiologies. We explored if NHL's prevalence has changed since older HCV therapy based on interferon that shared antiviral and anti-lymphoma properties was replaced with interferon-free direct-acting antivirals (DAA). We reviewed data from a nationwide database (Explorys, IBM) that aggregates records from 26 health-care-systems. We identified patients with chronic hepatitis C infection between June 2013 and June 2020. The control group was gender, race, and age-matched HCV-negative population. Statistical analysis used the odds ratio (OR) with P value <.001 for significance. There were 940 cases of NHL of 129,970 patients in the HCV group versus 107,480 cases of NHL of 37,961,970 in the control cohort [OR 2.6, 95% confidence interval (CI) 2.4-2.7]. A positive association was present for chronic lymphocytic leukemia, follicular lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma, diffuse large B-cell lymphoma, Burkitt's lymphoma, non-Hodgkin T-cell lymphoma, and primary cutaneous T-cell lymphoma. There were no differences in Mantle cell lymphoma. The increased risk of HCV-associated lymphoma was persistent across genders, Caucasians and African-Americans, and age groups. While the risk of NHL in the HCV-negative population was higher in Caucasians than African-Americans (OR 1.8, 95% CI 1.7-1.8), the risk of HCV-associated NHL was not different. Further prospective studies examining the risk of HCV-associated lymphoma following DAA are warranted.
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Affiliation(s)
- Akram Alkrekshi
- Department of Hematology and Oncology, The MetroHealth System campus of Case Western Reserve University, Cleveland, OH.
| | - Ahmad Kassem
- Department of Hematology and Oncology, The MetroHealth System campus of Case Western Reserve University, Cleveland, OH
| | - Changsu Park
- Department of Hematology and Oncology, The MetroHealth System campus of Case Western Reserve University, Cleveland, OH
| | - William Tse
- Department of Hematology and Oncology, The MetroHealth System campus of Case Western Reserve University, Cleveland, OH
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Fama A, Larson MC, Link BK, Habermann TM, Feldman AL, Call TG, Ansell SM, Liebow M, Xiang J, Maurer MJ, Slager SL, Nowakowski GS, Stapleton JT, Cerhan JR. Human Pegivirus Infection and Lymphoma Risk: A Systematic Review and Meta-analysis. Clin Infect Dis 2020; 71:1221-1228. [PMID: 31671178 PMCID: PMC7442854 DOI: 10.1093/cid/ciz940] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 09/20/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Human pegivirus (HPgV) is a single-strand RNA virus belonging to the Flaviviridae. Although no definitive association between HPgV infection and disease has been identified, previous studies have suggested an association of HPgV viremia with risk of lymphomas. METHODS We conducted a systematic review and meta-analysis, including 1 cohort study and 14 case-control studies, assessing the association of HPgV viremia with adult lymphomas. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model, overall and by geographic region and lymphoma subtype. RESULTS The overall OR for lymphoma was 2.85 (95% CI, 1.98-4.11), with statistically significantly elevated ORs observed in 8 of 15 studies. There was a small amount of heterogeneity among studies (I2 = 28.9%; Q = 18.27, P = .16), and the funnel plot provided no evidence for publication bias. The strongest association with lymphoma risk was observed for studies from Southern Europe (OR, 5.68 [95% CI, 1.98-16.3]), whereas weaker ORs (with 95% CIs) were observed for studies from North America (2.24 [1.76-2.85]), Northern Europe (2.90 [.45-18.7), and the Middle East (2.51 [.87-7.27]), but all of similar magnitude. Participants with HPgV viremia had statistically significantly increased risks (OR [95% CI]) for developing diffuse large B-cell (3.29 [1.63-6.62]), follicular (3.01 [1.95-4.63]), marginal zone (1.90 [1.13-3.18]), and T-cell (2.11 [1.17-3.89]) lymphomas, while the risk for Hodgkin lymphoma (3.53 [.48-25.9]) and chronic lymphocytic leukemia (1.45 [.45-4.66]) were increased but did not achieve statistical significance. CONCLUSIONS This meta-analysis supports a positive association of HPgV viremia with lymphoma risk, overall and for the major lymphoma subtypes.
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Affiliation(s)
- Angelo Fama
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Ematologia, Azienda Unità Sanitaria Locale, Istituto di Ricovero e Cura a Carattere Scientificodi Reggio Emilia, Reggio Emilia, Italy
| | - Melissa C Larson
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Brian K Link
- Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
| | - Thomas M Habermann
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Andrew L Feldman
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Timothy G Call
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Stephen M Ansell
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Mark Liebow
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Jinhua Xiang
- Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
- Iowa City Veterans Affairs Medical Center, Iowa City, Iowa, USA
| | - Matthew J Maurer
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Susan L Slager
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Grzegorz S Nowakowski
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Jack T Stapleton
- Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
- Iowa City Veterans Affairs Medical Center, Iowa City, Iowa, USA
| | - James R Cerhan
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
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Wan Z, Liu J, Hu F, Shui J, Li L, Wang H, Tang X, Hu C, Liang Y, Zhou Y, Cai W, Tang S. Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication. Emerg Microbes Infect 2020; 9:485-495. [PMID: 32100631 PMCID: PMC7054972 DOI: 10.1080/22221751.2020.1730247] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The second human pegivirus HPgV-2 is a novel blood-borne virus that is strongly associated with the hepatitis C virus (HCV) infection. However, the molecular evidence for their association as well as the natural history and tissue tropism of HPgV-2 remain to be elucidated. In this longitudinal study, a total of 753 patients including 512 HIV-1 and HCV co-infected patients were enrolled to characterize the natural history of HPgV-2 infection. Peripheral blood mononuclear cells (PBMCs) and liver biopsies were collected to determine the tissue tropism of HPgV-2 using immunohistochemical staining of the HPgV-2 antigen and in situ hybridization of HPgV-2 RNA. We documented both persistent HPgV-2 infection with the presence of HPgV-2 viral RNA and antibodies up to 4.6 years and resolved HPgV-2 infection, accompanied by a simultaneous decline of anti-HPgV-2 antibodies and clearance of HPgV-2 viremia. Furthermore, we observed the clearance of HCV, but not HPgV-2, by treatment with direct-acting antivirals (DAAs). Biochemical tests and pathological analyses did not reveal any indication of hepatic impairment caused by HPgV-2. HPgV-2 RNA and nonstructural antigen were detected in the lymphocytes, but not in the hepatocytes present in the liver biopsy samples. In addition, both positive- and negative-strand HPgV-2 RNAs were detected in PBMCs, especially in B cells. The present study is the first to provide evidence that HPgV-2 is a lymphotropic, but not a hepatotropic virus and that HPgV-2 replication is independent of HCV viremia. These new findings let us gain insights into the evolution and persistent infection of RNA viruses in humans.
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Affiliation(s)
- Zhengwei Wan
- Department of Epidemiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, People's Republic of China
| | - Junwei Liu
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Fengyu Hu
- Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Jingwei Shui
- Department of Epidemiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, People's Republic of China
| | - Linghua Li
- Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Haiying Wang
- Department of Epidemiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, People's Republic of China
| | - Xiaoping Tang
- Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Chengguang Hu
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Yuanhao Liang
- Department of Epidemiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, People's Republic of China
| | - Yuanping Zhou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Weiping Cai
- Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Shixing Tang
- Department of Epidemiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, People's Republic of China.,Dermatology Hospital, Southern Medical University, Guangzhou, People's Republic of China
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Epeldegui M, Hussain SK. The Role of Microbial Translocation and Immune Activation in AIDS-Associated Non-Hodgkin Lymphoma Pathogenesis: What Have We Learned? Crit Rev Immunol 2020; 40:41-51. [PMID: 32421978 PMCID: PMC7241309 DOI: 10.1615/critrevimmunol.2020033319] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Human immunodeficiency virus (HIV) infection is associated with greatly increased risk for development of non-Hodgkin lymphoma (NHL). Nearly all acquired immunodeficiency syndrome (AIDS)-associated NHL (AIDS-NHL) is of B-cell origin. Two major mechanisms are believed to contribute to the genesis of AIDS-NHL: (1) loss of immunoregulation of Epstein-Barr virus (EBV)+ B cells, resulting from impaired T-cell function late in the course of HIV disease and (2) chronic B-cell activation, leading to DNA-modifying events that contribute to oncogene mutations/ translocations. HIV infection has long been known to be associated with chronic inflammation and polyclonal B-cell activation, and more recently, microbial translocation. Microbial translocation is bacterial product leakage from gut lumen into the peripheral circulation, resulting in high levels of lipopolysaccharide (LPS) in the peripheral circulation, leading to chronic immune activation and inflammation. We review recent literature linking microbial translocation to lymphom-agenesis. This includes epidemiological studies of biomarkers of microbial translocation with risk of AIDS-NHL and emerging data on the mechanisms by which microbial translocation may lead to AIDS-NHL development.
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Affiliation(s)
- Marta Epeldegui
- Department of Obstetrics and Gynecology, UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles
| | - Shehnaz K. Hussain
- Cedars-Sinai Cancer and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles
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10
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Lymphoma-Associated Monoclonal Cryoglobulinemic Glomerulonephritis and Relationship with Hepatitis C Virus Infection: A Case Report. Case Rep Nephrol 2019; 2019:7940291. [PMID: 31531252 PMCID: PMC6719345 DOI: 10.1155/2019/7940291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 07/17/2019] [Indexed: 12/04/2022] Open
Abstract
We report a case of type I cryoglobulinemic glomerulonephritis in a patient with chronic hepatitis C who presented with acute renal failure. The renal biopsy revealed membranoproliferative GN (MPGN) due to cryoglobulinemia with unexpected monoclonal Kappa restriction on immunofluorescence microscopy, suggesting an underlying hematopoietic malignancy. The bone marrow biopsy revealed presence of marginal zone lymphoma. Our case raises awareness regarding possibility of monoclonality in the renal biopsy of HCV-infected patients and exemplifies the crucial role the renal biopsy plays in detecting lymphoid malignancies where clinical features are ambiguous.
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11
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Masarone M, Persico M. Hepatitis C virus infection and non-hepatocellular malignancies in the DAA era: A systematic review and meta-analysis. Liver Int 2019; 39:1292-1306. [PMID: 30983083 DOI: 10.1111/liv.14119] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 03/12/2019] [Accepted: 04/05/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Direct antiviral agents have greatly improved therapeutic options for chronic hepatitis C. Indeed, former "difficult-to-treat" patients can now be treated and can achieve sustained response. Hepatitis C virus (HCV) is associated with hepatocellular carcinoma and with B-cell non-Hodgkin lymphoma (B-NHL). Other malignancies have been reported to be associated with HCV infection albeit with various grades of evidence. Antineoplastic treatment is often reduced or suspended in HCV-positive cancer patients to avoid "HCV reactivation." In this setting, antiviral therapy combined with antineoplastic protocols may improve the outcome. For this reason, we conducted a systematic review and a meta-analysis to update the association between HCV infection and non-hepatocellular malignancies, and to shed light on the effects exerted by antiviral treatment on the natural history of oncological diseases. METHODS Relevant studies were identified by searching PUBMED, EMBASE and MEDLINE up to 1 August 2018. Pooled risk estimates were calculated with random-effects models according to PRISMA guidelines. RESULTS A total of 58 studies were included in the analysis: 27 studies of the association between HCV and B-NHL(OR 3.36; 95% CI 2.40-4.72;P < 0.00001);13 studies of the association between sustained virological response and progression-free survival (PFS) in B-NHL patients(OR 9.34; 95% CI 4.90-17.79; P < 0.00001); 13 studies of the association between HCV and intrahepatic-cholangio-carcinoma (OR 3.95;95% CI 2.25-6.94; P < 0.00001); and 5 studies of the association between HCV infection and pancreatic adeno-carcinoma(OR 1.60; 95% CI:1.25-2.04; P = 0.0002). CONCLUSIONS This study updates the strong association between B-NHL and HCV infection, confirms the association between HCV and non-hepatocellular tumours, and demonstrates a very strong association between viral eradication and a better outcome of HCV-positive B-NHL.
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Affiliation(s)
- Mario Masarone
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| | - Marcello Persico
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
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12
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Fama A, Xiang J, Link BK, Allmer C, Klinzman D, Feldman AL, Nowakowski GS, Liebow M, Larson MC, Maurer MJ, Ansell SM, Novak AJ, Asmann YW, Slager SL, Call TG, Habermann TM, Cerhan JR, Stapleton JT. Human Pegivirus infection and lymphoma risk and prognosis: a North American study. Br J Haematol 2018; 182:644-653. [PMID: 29808922 DOI: 10.1111/bjh.15416] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 03/26/2018] [Indexed: 12/12/2022]
Abstract
We evaluated the association of Human Pegivirus (HPgV) viraemia with risk of developing lymphoma, overall and by major subtypes. Because this virus has also been associated with better prognosis in the setting of co-infection with human immunodeficiency virus, we further assessed the association of HPgV with prognosis. We used risk factor data and banked plasma samples from 2094 lymphoma cases newly diagnosed between 2002 and 2009 and 1572 frequency-matched controls. Plasma samples were tested for HPgV RNA by reverse transcription polymerase chain reaction (RT-PCR), and those with RNA concentrations <5000 genome equivalents/ml were confirmed using nested RT-PCR methods. To assess the role of HPgV in lymphoma prognosis, we used 2948 cases from a cohort study of newly diagnosed lymphoma patients (included all cases from the case-control study). There was a positive association of HPgV viraemia with risk of lymphoma overall (Odds ratio = 2·14; 95% confidence interval [CI] 1·63-2·80; P < 0·0001), and for all major subtypes except Hodgkin lymphoma and chronic lymphocytic leukaemia/small lymphocytic lymphoma, and this was not confounded by other lymphoma risk factors. In contrast, there was no association of HPgV viraemia with event-free survival (Hazard ratio [HR] = 1·00; 95% CI 0·85-1·18) or overall survival (HR = 0·97; 95% CI 0·79-1·20) for lymphoma overall, or any of the subtypes. These data support the hypothesis for a role of HPgV in the aetiology of multiple lymphoma subtypes.
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Affiliation(s)
- Angelo Fama
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.,Ematologia, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Jinhua Xiang
- Department of Internal Medicine, University of Iowa and Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA
| | - Brian K Link
- Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
| | - Cristine Allmer
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Donna Klinzman
- Department of Internal Medicine, University of Iowa and Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA
| | - Andrew L Feldman
- Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA
| | - Grzegorz S Nowakowski
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Mark Liebow
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Melissa C Larson
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Matthew J Maurer
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Stephen M Ansell
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Anne J Novak
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Yan W Asmann
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA
| | - Susan L Slager
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Timothy G Call
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Thomas M Habermann
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - James R Cerhan
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Jack T Stapleton
- Department of Internal Medicine, University of Iowa and Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA
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13
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Abstract
Infectious agents, such as HCV, account for ∼15% of human cancers. HCV infects not only hepatocytes but also extrahepatic cells. Chronic HCV infection can induce chronic inflammation with qualitative and quantitative alterations of the immune repertoire and tissue microenvironment, which could induce various neoplasias. Epidemiological studies and meta-analyses suggest an increased rate of extrahepatic cancers in patients with chronic HCV infection along with a higher risk of intrahepatic cholangiocarcinoma, pancreatic cancer and non-Hodgkin lymphoma (NHL), highlighting the need to screen for HCV infection in patients with these cancers. Development of B cell NHL has been associated with HCV infection, with a relative risk of ∼1.5. Direct transformation related to the presence of the virus and chronic antigenic stimulation are the two major non-exclusive mechanisms involved in HCV-related lymphomagenesis. HCV infection alters survival of patients with lymphoma, and sustained virologic response (SVR) substantially improves prognosis. Antiviral treatments might induce remission of indolent lymphoma when SVR is achieved even without chemotherapy, emphasizing the role of HCV in lymphomagenesis in this context. However, studies are needed to provide prospective evidence of a causal relationship between chronic HCV infection and other extrahepatic cancers and to determine whether the risk of extrahepatic cancers is reduced with SVR. In this Review, we report on recent studies analysing the risk of extrahepatic cancers associated with chronic HCV infection. Although there is no doubt regarding the direct and indirect causality between HCV and NHL, an increased risk of other cancers is less clear, with the exception of cholangiocarcinoma.
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14
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Sonmez M, Bektas O, Yilmaz M, Durmus A, Akdogan E, Topbas M, Erturk M, Ovali E, Omay SB. The Relation of Lymphomaand Hepatitis B Virus/Hepatitis C Virus Infections in the Region of East Black Sea, Turkey. TUMORI JOURNAL 2018; 93:536-9. [DOI: 10.1177/030089160709300603] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Aim and background Hepatitis B virus (HBV) and hepatitis C virus (HCV) are not only hepatotropic, but also lymphotropic viruses. Infections with these viruses induce chronic antigenicity and may stimulate clonal expansion of malignant B-cell neoplasms. Moreover, these viruses can proliferate in lymphatic structures and bone marrow. However, the relationship between lymphomas and HBV/HCV infections is not clear. In our region of the East Black Sea, Turkey (the city of Trabzon), we intended to demonstrate a relation of lymphoma and HBV/HCV infections with a case-controlled study. Methods A total of 109 patients diagnosed with lymphoma between 2002–2005 in the Black Sea Technical University Hospital was investigated. Seventy-one patients had a high-grade and 38 patients a low-grade lymphoma. Hepatitis B surface antigen (HBsAg) and anti-HCV antibodies (anti-HCV Ab) were screened. The control group consisted of patients (n = 551) from other departments with diagnoses other than lymphoma. Results HBsAg was 3.7% and anti-HCV Ab positivity was 2.8% in lymphoma patients, compared with control of 5.3%, 5.1%, respectively. There was no statistically significant difference between two groups ( P = 0.7, OR = 0.69, 95% CI, 0.20–2.10; P = 0.4, OR = 0.53, 95% CI, 0.13–1.86, respectively). Conclusion Our findings suggest that the incidence of HBV and HCV infections in lymphoma patients is no different than that of nonlymphoma patients. Therefore, no direct correlation can be deduced between lymphoma and HBV-HCV infections in our East Black Sea region of Turkey.
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Affiliation(s)
- Mehmet Sonmez
- Department of Haematology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Ozlen Bektas
- Deparment of Internal Medicine, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Mustafa Yilmaz
- Department of Haematology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Ahmet Durmus
- Department of Haematology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Elif Akdogan
- Department of Haematology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Murat Topbas
- Department of Public Health, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Murat Erturk
- Department of Microbiology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Ercument Ovali
- Department of Haematology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Serdar Bedii Omay
- Department of Haematology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
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15
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Kanakry JA, Ambinder RF. Virus-Associated Lymphoma. Hematology 2018. [DOI: 10.1016/b978-0-323-35762-3.00083-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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16
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Shimono J, Miyoshi H, Kato T, Sugio T, Miyawaki K, Kamimura T, Miyagishima T, Eto T, Imaizumi Y, Kato K, Nagafuji K, Akashi K, Seto M, Teshima T, Ohshima K. Hepatitis C virus infection is an independent prognostic factor in follicular lymphoma. Oncotarget 2017; 9:1717-1725. [PMID: 29416725 PMCID: PMC5788593 DOI: 10.18632/oncotarget.23138] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Accepted: 11/13/2017] [Indexed: 01/08/2023] Open
Abstract
Hepatitis C virus (HCV) is a single-stranded RNA virus that not only affects hepatocytes, by B cells as well. It is thought that HCV is involved in the onset of B-cell lymphoma. The clinicopathological characteristics of HCV-positive diffuse large B-cell lymphoma (DLBCL) and HCV-positive splenic marginal zone lymphoma (SMZL) are known, but there has been no report on HCV-positive follicular lymphoma (FL). In this study, the clinicopathological characteristics of HCV-positive FL were examined in 263 patients with FL who were classified into a HCV-positive group with HCV antibody and negative groups without one. The number of patients with HCV-positive FL and HCV-negative FL was 10 (3.8%) and 253 (96.2%), respectively. The patients with HCV-positive FL commonly had more than one region of lymphadenopathy, Ann Arbor stage III/IV, hemoglobin <120 g/l, elevated lactate dehydrogenase level, and high-risk categorization of Follicular Lymphoma International Prognostic Index (FLIPI) than in patients with HCV-negative FL. Overall survival and progression-free survival were poorer in patients with HCV-positive FL than in those with HCV-negative FL (p < 0.0001 and 0.006, respectively). Also, multivariate analysis revealed that positive HCV antibody was a poor prognostic factor of OS. In conclusion, HCV-positive FL has unique clinical features and may have a great impact on the overall survival of affected patients.
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Affiliation(s)
- Joji Shimono
- Department of Pathology, Kurume University, School of Medicine, Kurume, Japan.,Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Hiroaki Miyoshi
- Department of Pathology, Kurume University, School of Medicine, Kurume, Japan
| | - Takeharu Kato
- Department of Hematology, Sasebo City General Hospital, Sasebo, Japan.,Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan
| | - Takeshi Sugio
- Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan
| | - Kohta Miyawaki
- Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan
| | | | | | - Tetsuya Eto
- Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
| | - Yoshitaka Imaizumi
- Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan
| | - Koji Kato
- Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan
| | - Koji Nagafuji
- Department of Hematology, Kurume University, School of Medicine, Kurume, Japan
| | - Koichi Akashi
- Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan
| | - Masao Seto
- Department of Pathology, Kurume University, School of Medicine, Kurume, Japan
| | - Takanori Teshima
- Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Koichi Ohshima
- Department of Pathology, Kurume University, School of Medicine, Kurume, Japan
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17
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Dörr G, Del Bello A, Abravanel F, Marion O, Cointault O, Ribes D, Lavayssière L, Esposito L, Nogier MB, Hebral AL, Sauné K, Izopet J, Kamar N. Malignancies in hepatitis C virus-positive and -negative kidney transplant recipients: A case-controlled study. Transpl Infect Dis 2017; 19. [PMID: 28509330 DOI: 10.1111/tid.12725] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Revised: 02/16/2017] [Accepted: 02/22/2017] [Indexed: 01/15/2023]
Abstract
BACKGROUND Malignancies and lymphoma are common complications after kidney transplantation. However, no link has been made between the incidence of malignancies and hepatitis C virus (HCV) infection in this setting. This case-controlled study compared the incidence of malignancies, including lymphoma, between kidney transplant (KT) patients with or without HCV replication. PATIENTS AND METHODS A total of 99 HCV-positive RNA-positive KT patients were matched with 198 (1:2) anti-HCV-negative patients according to age, gender, and date of transplantation, and were followed for 145.8±78.4 months. RESULTS During the follow-up period, 28 HCV-positive (28%) cases developed at least one cancer, and 64 (32%) patients developed cancer in the HCV-negative group (P=not significant [ns]). Survival without a cancer was similar between both groups. Thirteen HCV-positive patients (13%) developed at least one solid cancer vs 29 (15%) HCV-negative patients (P=ns). Survival without a solid cancer was similar between both groups. Three patients from the HCV-positive and 4 from the HCV-negative group developed a lymphoma. Only 2 patients from the HCV group died from hepatocellular carcinoma. Survival without a skin cancer was similar between both groups. Patient and death-censored graft survival rates were significantly lower in the HCV group. CONCLUSION The incidences and types of malignancies were similar in the HCV-positive and HCV-negative KT patients.
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Affiliation(s)
- Gaëlle Dörr
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - Arnaud Del Bello
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - Florence Abravanel
- INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.,Université Paul Sabatier, Toulouse, France.,Laboratory of Virology, CHU Purpan, Toulouse, France
| | - Olivier Marion
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - Olivier Cointault
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - David Ribes
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - Laurence Lavayssière
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - Laure Esposito
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | | | - Anne Laure Hebral
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - Karine Sauné
- INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.,Université Paul Sabatier, Toulouse, France.,Laboratory of Virology, CHU Purpan, Toulouse, France
| | - Jacques Izopet
- INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.,Université Paul Sabatier, Toulouse, France.,Laboratory of Virology, CHU Purpan, Toulouse, France
| | - Nassim Kamar
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.,INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.,Université Paul Sabatier, Toulouse, France
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18
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Fetica B, Pop B, Blaga ML, Fulop A, Dima D, Zdrenghea MT, Vlad CI, Bojan AS, Achimas-Cadariu P, Lisencu CI, Irimie A, Weisenburger DD. High prevalence of viral hepatitis in a series of splenic marginal zone lymphomas from Romania. Blood Cancer J 2016; 6:e498. [PMID: 27834940 PMCID: PMC5148050 DOI: 10.1038/bcj.2016.102] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Affiliation(s)
- B Fetica
- Department of Pathology, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania
| | - B Pop
- Department of Pathology, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania.,Department of Pathology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - M L Blaga
- Department of Epidemiology and Biostatistics, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania
| | - A Fulop
- Department of Pathology, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania
| | - D Dima
- Department of Hematology, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania
| | - M T Zdrenghea
- Department of Hematology, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania.,Department of Hematology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - C I Vlad
- Department of Surgery, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania.,Department of Surgery and Gynecologic Oncology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - A S Bojan
- Department of Hematology, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania.,Department of Hematology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - P Achimas-Cadariu
- Department of Surgery, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania.,Department of Surgery and Gynecologic Oncology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - C I Lisencu
- Department of Surgery, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania.,Department of Surgery and Gynecologic Oncology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - A Irimie
- Department of Surgery, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania.,Department of Surgery and Gynecologic Oncology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - D D Weisenburger
- Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA
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19
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Abstract
Chronic hepatitis B infection (CHB) is a known risk factor for malignancy. Unlike hepatocellular carcinoma (HCC), less is known about the risk of non-HCC malignancy. However, epidemiology and pathologic evidence suggests a strong association between non-Hodgkin lymphoma and CHB. Data regarding the risk of other malignancies, such as pancreatic adenocarcinoma and intrahepatic cholangiocarcinoma, are mixed. Surveillance and appropriate treatment of infection and malignancy in these patients is essential. Further study of these associations is needed and may bring new insights in the pathogenesis and treatment of these diseases.
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Affiliation(s)
- Ryan M Kwok
- Gastroenterology Fellowship Program, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA.
| | - Tram T Tran
- Gastroenterology Fellowship Program, Cedars Sinai Medical Center, Geffen School of Medicine at University of California Los Angeles, 8900 Beverly Boulevard, Los Angeles, CA 90048, USA
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20
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Alric L, Besson C, Lapidus N, Jeannel J, Michot JM, Cacoub P, Canioni D, Pol S, Davi F, Rabiega P, Ysebaert L, Bonnet D, Hermine O. Antiviral Treatment of HCV-Infected Patients with B-Cell Non-Hodgkin Lymphoma: ANRS HC-13 Lympho-C Study. PLoS One 2016; 11:e0162965. [PMID: 27749916 PMCID: PMC5066969 DOI: 10.1371/journal.pone.0162965] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Accepted: 08/31/2016] [Indexed: 12/31/2022] Open
Abstract
Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted. METHODS First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL. In a second series, interferon-free regimens using a newly optimal combination therapy with direct-acting antiviral drugs (DAAs) were evaluated in 10 patients with HCV and B-NHL. RESULTS The main lymphoma type was diffuse large B-cell lymphoma (38%) followed by marginal zone lymphoma (31%). In the multivariate analysis, patients with B-NHL treated by Peg-IFN-based therapy exhibited a greater SVR rate compared with controls, 50.8% vs 30.8%, respectively, p<0.01, odds ratio (OR) = 11.2 [2.3, 52.8]. B-NHL response was better (p = 0.02) in patients with SVR (69%) than in patients without SVR (31%). Premature discontinuation of Peg-IFN-based therapy was significantly more frequent in the B-NHL group (19.6%) compared with the control group (6.3%), p<0.02. Overall, survival was significantly enhanced in the controls than in the B-NHL group (hazard ratio = 34.4 [3.9, 304.2], p< 0.01). Using DAAs, SVR was achieved in 9/10 patients (90%). DAAs were both well tolerated and markedly efficient. CONCLUSIONS The virologic response of HCV-associated B-NHL is high. Our study provides a comprehensive evaluation of different strategies for the antiviral treatment of B-NHL associated with HCV infection.
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Affiliation(s)
- Laurent Alric
- Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France
| | - Caroline Besson
- Université Paris sud Faculté de Médecine Kremlin Bicêtre, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, IMVA INSERM U1184, Paris, France
| | - Nathanael Lapidus
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136), Department of Public Health, Hôpital Saint-Antoine, AP-HP, Paris, France
| | - Juliette Jeannel
- Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France
| | - Jean-Marie Michot
- Université Paris sud Faculté de Médecine Kremlin Bicêtre, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, IMVA INSERM U1184, Paris, France
| | - Patrice Cacoub
- Paris 6 Pierre et Marie Curie University, UMR 7211, INSERM, UMR S 959, CNRS, UMR 7211, AP-HP, Department of Internal Medicine, Hôpital Pitié-Salpêtrière, Paris, France
| | - Danielle Canioni
- Paris 5 Descartes University, AP-HP, Department of Pathology, Hôpital Necker, Paris, France
| | - Stanislas Pol
- Université Descartes, Inserm U-318 Institut Pasteur, AP-HP, Department of hepatology, Hôpital Cochin, Paris, France
| | - Frédéric Davi
- Paris 6 Pierre et Marie Curie University, AP-HP, Department of Biological Hematology and Cytogenetic, Hôpital Pitié-Salpêtrière, Paris, France
| | - Pascaline Rabiega
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136), Department of Public Health, Hôpital Saint-Antoine, AP-HP, Paris, France
| | - Loic Ysebaert
- Department of Hematology IUCT oncopole, CHU, Toulouse, France
| | - Delphine Bonnet
- Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France
| | - Olivier Hermine
- Paris 5 Descartes University, AP-HP, INSERM U 1163, CNRS ERL 8254, Department of Adult Hematology and Imagine Institute, Hôpital Necker, Paris, France
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21
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Högfeldt T, Jaing C, Loughlin KM, Thissen J, Gardner S, Bahnassy AA, Gharizadeh B, Lundahl J, Österborg A, Porwit A, Zekri ARN, Khaled HM, Mellstedt H, Moshfegh A. Differential expression of viral agents in lymphoma tissues of patients with ABC diffuse large B-cell lymphoma from high and low endemic infectious disease regions. Oncol Lett 2016; 12:2782-2788. [PMID: 27698858 PMCID: PMC5038175 DOI: 10.3892/ol.2016.5012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Accepted: 05/23/2016] [Indexed: 12/11/2022] Open
Abstract
Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin's lymphoma (NHL) in adults, accounts for approximately 30-40% of newly diagnosed lymphomas worldwide. Environmental factors, such as viruses and bacteria, may contribute to cancer development through chronic inflammation and the integration of oncogenes, and have previously been indicated in cervical cancer, hepatocellular carcinoma, gastric cancer and lymphoproliferative disorders. In the present study, the presence of microbial agents was analyzed in the lymphoma tissue of patients with activated B-cell like (ABC) DLBCL. The present study compared two groups of patients from geographically varied regions that possess a difference in the prevalence of viral and other microbial agents. The patient populations were from Sweden (a low endemic infectious disease region) and Egypt (a high endemic infectious disease region). A differential expression of several viruses in lymphoma tissues was noted when comparing Swedish and Egyptian patients. JC polyomavirus (JCV) was detected in Swedish and Egyptian patients and, uniquely, the complete hepatitis B virus (HBV) genome was detected only in Egyptian lymphoma patients. None of these viruses were detected in control lymph tissues from Sweden or Egypt. In total, 38% of the Egyptian patients were found to have HBV surface antigens (HBsAgs) in their serum; however, HBsAgs were not found in any of the Swedish patients. The percentage of serum HBsAgs in Egyptian patients with ABC DLBCL was significantly increased compared with the general Egyptian population (P<0.05). The present study may support a notion that viral agents, including JCV and HBV, may be involved in the tumorigenesis of DLBCL in regions of high infectious disease.
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Affiliation(s)
- Therese Högfeldt
- Department of Oncology and Pathology, Karolinska Institute, 171 77 Stockholm, Sweden
| | - Crystal Jaing
- Chemistry, Materials, Earth and Life Sciences, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
| | - Kevin Mc Loughlin
- Computation, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
| | - James Thissen
- Chemistry, Materials, Earth and Life Sciences, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
| | - Shea Gardner
- Computation, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
| | - Abeer A. Bahnassy
- Department of Pathology, National Cancer Institute, Cairo University, Cairo 11796, Egypt
| | - Baback Gharizadeh
- Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304, USA
| | - Joachim Lundahl
- Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, 171 76 Stockholm, Sweden
| | - Anders Österborg
- Department of Oncology and Pathology, Karolinska Institute, 171 77 Stockholm, Sweden
| | - Anna Porwit
- Department of Oncology and Pathology, Karolinska Institute, 171 77 Stockholm, Sweden
| | - Abdel-Rahman N. Zekri
- Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11796, Egypt
| | - Hussein M. Khaled
- Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo 11796, Egypt
| | - Håkan Mellstedt
- Department of Oncology and Pathology, Karolinska Institute, 171 77 Stockholm, Sweden
| | - Ali Moshfegh
- Department of Oncology and Pathology, Karolinska Institute, 171 77 Stockholm, Sweden
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22
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Canioni D, Michot JM, Rabiega P, Molina TJ, Charlotte F, Lazure T, Davi F, Settegrana C, Berger F, Alric L, Cacoub P, Terrier B, Suarez F, Sibon D, Dupuis J, Feray C, Tilly H, Pol S, Deau Fischer B, Roulland S, Thieblemont C, Leblond V, Carrat F, Hermine O, Besson C, national ANRS HC13 LymphoC study. In Situ Hepatitis C NS3 Protein Detection Is Associated with High Grade Features in Hepatitis C-Associated B-Cell Non-Hodgkin Lymphomas. PLoS One 2016; 11:e0156384. [PMID: 27257992 PMCID: PMC4892517 DOI: 10.1371/journal.pone.0156384] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 05/15/2016] [Indexed: 12/15/2022] Open
Abstract
Hepatitis C Virus (HCV) infection is associated with the B-cell non-Hodgkin lymphomas (NHL), preferentially marginal zone lymphomas (MZL) and diffuse large B-cell lymphomas (DLBCL). While chronic antigenic stimulation is a main determinant of lymphomagenesis in marginal zone lymphomas (MZL), a putative role of HCV infection of B-cells is supported by in vitro studies. We performed a pathological study within the "ANRS HC-13 LymphoC" observational study focusing on in situ expression of the oncogenic HCV non structural 3 (NS3) protein. Lympho-C study enrolled 116 HCV-positive patients with B-NHL of which 86 histological samples were collected for centralized review. Main histological subtypes were DLBCL (36%) and MZL (34%). Almost half of DLBCL (12/26) were transformed from underlying small B-cell lymphomas. NS3 immunostaining was found positive in 17 of 37 tested samples (46%). There was a striking association between NS3 detection and presence of high grade lymphoma features: 12 out of 14 DLBCL were NS3+ compared to only 4 out of 14 MZL (p = 0.006). Moreover, 2 among the 4 NS3+ MZL were enriched in large cells. Remarkably, this study supports a new mechanism of transformation with a direct oncogenic role of HCV proteins in the occurrence of high-grade B lymphomas.
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Affiliation(s)
- Danielle Canioni
- Department of Pathology, Paris Descartes University, AP-HP, Sorbonne Paris Cité, Hôpital Necker, Paris, France
- * E-mail: (CB); (DC); (OH)
| | - Jean-Marie Michot
- Department of Hematology and Drug Development, Gustave Roussy Institute, Villejuif, F-94805, France
| | - Pascaline Rabiega
- Institut Pierre Louis d’Epidémiologie et de Santé Publique INSERM UMR S1136, Paris 6 Pierre et Marie Curie University, Paris, France
| | - Thierry J. Molina
- Department of Pathology, Paris Descartes University, AP-HP, Sorbonne Paris Cité, Hôpital Necker, Paris, France
| | - Frédéric Charlotte
- Department of Pathology, HôpitalPitié-Salpétrière, Paris 6 Pierre et Marie Curie University, Paris, France
| | - Thierry Lazure
- Department of Pathology, Paris 11 Sud University, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Frédéric Davi
- Department of Biological Hematology, Paris 6 Pierre et Marie Curie University, AP-HP, Hôpital Pitié-Salpétrière, Paris, France
| | - Catherine Settegrana
- Department of Biological Hematology, Paris 6 Pierre et Marie Curie University, AP-HP, Hôpital Pitié-Salpétrière, Paris, France
| | - Françoise Berger
- Department of Pathology, Hopital Lyon Sud, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Lyon, France
| | - Laurent Alric
- Department of Internal Medicine and Digestive Diseases, Toulouse 3 University, UMR 152 IRD, Hôpital Purpan, Toulouse, France
| | - Patrice Cacoub
- Department of Internal Medicine, APHP, Hôpital Pitié-Salpétrière, Paris 6 Pierre et Marie Curie University, UMR 7211, INSERM, UMR S 959, CNRS, Paris, France
| | - Benjamin Terrier
- Department of Internal Medicine, APHP, Hôpital Pitié-Salpétrière, Paris 6 Pierre et Marie Curie University, UMR 7211, INSERM, UMR S 959, CNRS, Paris, France
| | - Felipe Suarez
- Department of Adult Hematology, Paris 5 Descartes University, AP-HP, Hôpital Necker, Paris, France
- Imagine Institute, University Sorbonne Paris Cité, INSERM U 1163, CNRS ERL 8254, Paris, France
| | - David Sibon
- Department of Adult Hematology, Paris 5 Descartes University, AP-HP, Hôpital Necker, Paris, France
- Imagine Institute, University Sorbonne Paris Cité, INSERM U 1163, CNRS ERL 8254, Paris, France
| | - Jehan Dupuis
- Department of Lymphoid Malignancies and Clinical Hematology, Paris 12 Est Créteil University, AP-HP, Hôpital Henri-Mondor, Créteil, France
| | - Cyrille Feray
- Department of Hepatology, Nantes University, Hôpital de Nantes, Nantes, France
| | - Hervé Tilly
- Department of Hematology, Rouen University, Centre Henri Becquerel, Rouen, France
| | - Stanislas Pol
- Department of Hepatology, Paris 5 Descartes University, INSERM U-1016, AP-HP, Hôpital Cochin, Paris, France
| | - Bénédicte Deau Fischer
- Department of Hematology, Paris Descartes University, AP-HP, Hôpital Cochin, Paris, France
| | - Sandrine Roulland
- Centre d'Immunologie de Marseille Luminy, Aix-Marseille Université INSERM U1104 CNRS UMR7280, Marseille, France
| | - Catherine Thieblemont
- Department of Hemato-oncology, University Paris Sorbonne P7, INSERM U728, AP-HP, Hôpital Saint-Louis, Paris, France
| | - Véronique Leblond
- Department of Clinical Hematology, Paris 6 Pierre et Marie Curie, Paris, France
| | - Fabrice Carrat
- Institut Pierre Louis d’Epidémiologie et de Santé Publique INSERM UMR S1136, Paris 6 Pierre et Marie Curie University, Paris, France
| | - Olivier Hermine
- Department of Adult Hematology, Paris 5 Descartes University, AP-HP, Hôpital Necker, Paris, France
- Imagine Institute, University Sorbonne Paris Cité, INSERM U 1163, CNRS ERL 8254, Paris, France
- * E-mail: (CB); (DC); (OH)
| | - Caroline Besson
- Department of Internal Medicine & Clinical Immunology Biological Immunology and Hematology, Paris 11 Sud University, AP-HP, Hôpital Bicêtre, INSERM U 1184, Le Kremlin-Bicêtre, France
- * E-mail: (CB); (DC); (OH)
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23
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Foster LH, Portell CA. The role of infectious agents, antibiotics, and antiviral therapy in the treatment of extranodal marginal zone lymphoma and other low-grade lymphomas. Curr Treat Options Oncol 2016; 16:28. [PMID: 25975444 DOI: 10.1007/s11864-015-0344-6] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OPINION STATEMENT There is strong evidence to corroborate the association with Helicobacter pylori (Hp) to gastric extranodal marginal zone lymphoma (ENMZL) and hepatitis C virus (HCV) to splenic/nodal marginal zone lymphoma. Koch's postulates generally hold for these two associations and eradication of the infectious agent is well supported. Hp eradication (HPE) is recommended as front-line therapy for early stage gastric ENMZL regardless of Hp status. Complete response (CR) rate for Hp-negative patients is not as high as for Hp-positive patients; however, the benign nature of HPE and high rates of salvage allow this strategy to be safe while sparing some Hp-negative patients from systemic therapy or radiation. Similarly for HCV-seropositive patients, treatment with antivirals should be strongly considered as first-line for those who do not require immediate cytoreductive therapy or at some point even after completing chemoimmunotherapy. The controversy regarding the role for antibiotics is greatest for primary ocular adnexal lymphoma (POAL). Considering the low incidence of Chlamydia psittaci (Cp) infection with OAL and the challenges to reliably identifying Cp, we typically do not consider doxycycline in POAL treatment. Involved-field radiotherapy (IFRT) remains the treatment of choice for most with unilateral POAL. However, if reliable detection of Cp is available and Cp is identified, patients with unilateral low tumor stage POAL who do not require immediate radiotherapy could be considered for doxycycline as front-line treatment. Other infectious associations to indolent lymphomas have been made, including Borrelia borgdorferi (Bb) in cutaneous lymphoma and Campylobacter in immunoproliferative small intestinal disease (IPSID), but these associations are not as strong and primary treatment targeting the infectious agents is not recommended.
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Affiliation(s)
- Laahn H Foster
- Division of Hematology and Oncology, University of Virginia School of Medicine, PO Box 800716, Charlottesville, VA, 22908-0716, USA
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Infectious Aetiology of Marginal Zone Lymphoma and Role of Anti-Infective Therapy. Mediterr J Hematol Infect Dis 2016; 8:e2016006. [PMID: 26740867 PMCID: PMC4696464 DOI: 10.4084/mjhid.2016.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Accepted: 11/16/2015] [Indexed: 02/08/2023] Open
Abstract
Marginal zone lymphomas have been associated with several infectious agents covering both viral and bacterial pathogens and in some cases a clear aetiological role has been established. Pathogenetic mechanisms are currently not completely understood. However, the role of chronic stimulation of the host immune response with persistent lymphocyte activation represents the most convincing explanation for lymphoproliferation. Gastric MALT lymphoma is strictly associated with Helicobacter pylori infection and various eradicating protocols, developed due to increasing antibiotic resistance, represent the first line therapy for gastric MALT. The response rate to eradication is good with 80% of response at 1 year; this finding is also noteworthy because it recapitulates cancer cured only by the antibacterial approach and it satisfies the Koch postulates of causation, establishing a causative relationship between Hp and gastric MALT lymphoma. Patients with chronic HCV infection have 5 times higher risk to develop MZL, in particular, an association with splenic and nodal MZL has been shown in several studies. Moreover, there is evidence of lymphoma regression after antiviral therapy with interferon+ribavirin, thus raising hope that newly available drugs, extremely efficient against HCV replication, could improve outcome also in HCV-driven lymphomas. Another case-study are represented by those rare cases of MZL localized to orbital fat and eye conjunctivas that have been associated with Chlamydophila psittaci infection carried by birds. Efficacy of antibacterial therapy against C. psittaci are conflicting and generally poorer than gastric MALT. Finally, some case reports will cover the relationship between primary cutaneous B-cell Lymphomas and Borrelia Burgdorferi.
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25
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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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26
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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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27
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Ferri C, Sebastiani M, Giuggioli D, Colaci M, Fallahi P, Piluso A, Antonelli A, Zignego AL. Hepatitis C virus syndrome: A constellation of organ- and non-organ specific autoimmune disorders, B-cell non-Hodgkin's lymphoma, and cancer. World J Hepatol 2015; 7:327-43. [PMID: 25848462 PMCID: PMC4381161 DOI: 10.4254/wjh.v7.i3.327] [Citation(s) in RCA: 95] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Revised: 12/27/2014] [Accepted: 01/09/2015] [Indexed: 02/06/2023] Open
Abstract
The clinical course of chronic hepatitis C virus (HCV) infection is characterized by possible development of both liver and extrahepatic disorders. The tropism of HCV for the lymphoid tissue is responsible for several immune-mediated disorders; a poly-oligoclonal B-lymphocyte expansion, commonly observed in a high proportion of patients with HCV infection, are responsible for the production of different autoantibodies and immune-complexes, such as mixed cryoglobulins. These serological alterations may characterize a variety of autoimmune or neoplastic diseases. Cryoglobulinemic vasculitis due to small-vessel deposition of circulating mixed cryoglobulins is the prototype of HCV-driven immune-mediated and lymphoproliferative disorders; interestingly, in some cases the disease may evolve to frank malignant lymphoma. In addition, HCV shows an oncogenic potential as suggested by several clinico-epidemiological and laboratory studies; in addition to hepatocellular carcinoma that represents the most frequent HCV-related malignancy, a causative role of HCV has been largely demonstrated in a significant percentage of patients with isolated B-cells non-Hodgkin's lymphomas. The same virus may be also involved in the pathogenesis of papillary thyroid cancer, a rare neoplastic condition that may complicate HCV-related thyroid involvement. Patients with HCV infection are frequently asymptomatic or may develop only hepatic alteration, while a limited but clinically relevant number can develop one or more autoimmune and/or neoplastic disorders. Given the large variability of their prevalence among patients' populations from different countries, it is possible to hypothesize a potential role of other co-factors, i.e., genetic and/or environmental, in the pathogenesis of HCV-related extra-hepatic diseases.
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Affiliation(s)
- Clodoveo Ferri
- Clodoveo Ferri, Marco Sebastiani, Dilia Giuggioli, Michele Colaci, Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
| | - Marco Sebastiani
- Clodoveo Ferri, Marco Sebastiani, Dilia Giuggioli, Michele Colaci, Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
| | - Dilia Giuggioli
- Clodoveo Ferri, Marco Sebastiani, Dilia Giuggioli, Michele Colaci, Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
| | - Michele Colaci
- Clodoveo Ferri, Marco Sebastiani, Dilia Giuggioli, Michele Colaci, Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
| | - Poupak Fallahi
- Clodoveo Ferri, Marco Sebastiani, Dilia Giuggioli, Michele Colaci, Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
| | - Alessia Piluso
- Clodoveo Ferri, Marco Sebastiani, Dilia Giuggioli, Michele Colaci, Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
| | - Alessandro Antonelli
- Clodoveo Ferri, Marco Sebastiani, Dilia Giuggioli, Michele Colaci, Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
| | - Anna Linda Zignego
- Clodoveo Ferri, Marco Sebastiani, Dilia Giuggioli, Michele Colaci, Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
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28
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Abstract
Non-Hodgkin lymphoma (NHL) consists of many histologically and biologically distinct lymphoid malignancies with poorly understood, but possibly distinct, etiologies. The patterns of incidence and time trend vary not only by age, sex, and race/ethnicity in the USA, but also show significant geographic differences, suggesting the potential role of infectious agents, environmental factors, and lifestyle factors in addition to host genetic status in the development of NHL. Important pathogenetic mechanisms include immune modulation and chronic antigen stimulation. Epidemiologic studies in the past two decades have provided intriguing new insights on the possible causes of lymphoma and support the idea that there is some mechanistic commonality of lymphomagenesis, but significant etiologic heterogeneity clearly exists. This review presents a summary of the current understanding of the descriptive epidemiology and etiology of NHL and suggests areas of focus for future epidemiologic research.
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29
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Min C, Higuchi T, Koyamada R, Yamaguchi N, Okada S. Pulmonary Extranodal Marginal Zone Lymphoma with Macroglobulinemia and Mixed Cryoglobulinemia Developed in a Patient with Chronic Hepatitis C. Intern Med 2015; 54:2061-4. [PMID: 26278303 DOI: 10.2169/internalmedicine.54.3968] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
We report a 65-year-old woman with a chronic hepatitis C virus infection who developed pulmonary extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissues complicated with macroglobulinemia and mixed cryoglobulinemia. She was treated with immunochemotherapy which resulted in the reduction of both the tumors and the serum immunoglobulin (Ig) M level. This case exemplifies an extensive stimulation upon immune system with derangement in the production of immunoglobulines associated with EMZL, and suggests that it is necessary to consider the possibility of B-cell lymphoma when IgM paraprotein is detected.
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Affiliation(s)
- Chisun Min
- Internal Medicine, St. Luke's International Hospital, Japan
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30
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Vannata B, Zucca E. Hepatitis C virus-associated B-cell non-Hodgkin lymphomas. HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2014; 2014:590-598. [PMID: 25696916 DOI: 10.1182/asheducation-2014.1.590] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Epidemiological studies have demonstrated an increased risk of developing B-cell lymphomas in patients with chronic hepatitis C virus (HCV) infection. However, the strength of the association shows great geographic discrepancies, with higher relative risk in countries with high HCV prevalence. It remains unclear whether additional environmental and genetic factors are involved or if the international variability is simply a consequence of the variable infection prevalence. Therefore, a causal relationship remains controversial. 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 proof is the observation, mainly limited to some indolent subtypes, of B-cell lymphoma regressions after HCV eradication with IFN and ribavirin. However, the molecular mechanisms of the HCV-induced lymphomagenesis are mainly hypothetical. According to the model considered to be most plausible, lymphoma growth is a consequence of the continuous antigenic stimulation of the B-cell immunologic response induced by the chronic viral infection. This review summarizes the current epidemiological and biological evidence of a role of HCV in lymphomagenesis, describing the putative mechanisms for a causative relationship. The clinical characteristics and management difficulties of the HCV-associated lymphomas are also discussed. HCV treatment with IFN cannot be given safely in concomitance with cytotoxic lymphoma treatment because of hematological and liver toxicity. However, novel and better tolerated antiviral regimens are under development and will hopefully make the treatment of both lymphoma and hepatitis easier in the future.
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Affiliation(s)
- Barbara Vannata
- Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
| | - Emanuele Zucca
- Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
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31
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Hepatitis C virus and lymphoma. Crit Rev Oncol Hematol 2014; 93:246-56. [PMID: 25457774 DOI: 10.1016/j.critrevonc.2014.10.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 08/19/2014] [Accepted: 10/14/2014] [Indexed: 12/16/2022] Open
Abstract
Hepatitis C virus (HCV) is a hepatotrophic and lymphotrophic virus and is a global health problem. Cirrhosis and hepatocellular cancer are the most common complications of HCV. Association between HCV and B cell non-Hodgkin lymphomas (B-NHL) has been shown in epidemiological studies in the last 20 years. High prevalence of HCV infection among patients with NHL has been reported in the early 1990s by Ferri in Italy and this association has been confirmed in later studies. Geographically, HCV related NHL is highly variable and chronic rather than cleared HCV infection is required for lymphomagenesis. Although anti-HCV antibody test is the most commonly used technique in epidemiological studies, HCV-RNA is more useful test to detect the association between HCV and NHL. The optimal management of HCV related NHL is not clear. However, anti-viral treatment may be sufficient for cases with low grade and/or asymptomatic lymphomas, while immuno-chemotherapy is necessary, in spite of probable hepatic toxicity, in cases with high grade lymphomas.
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32
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Common infection-related conditions and risk of lymphoid malignancies in older individuals. Br J Cancer 2014; 110:2796-803. [PMID: 24691420 PMCID: PMC4037821 DOI: 10.1038/bjc.2014.173] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2013] [Revised: 03/06/2014] [Accepted: 03/08/2014] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Chronic antigenic stimulation may initiate non-Hodgkin (NHL) and Hodgkin lymphoma (HL) development. Antecedent, infection-related conditions have been associated, but evidence by lymphoproliferative subtype is limited. METHODS From the US SEER-Medicare database, 44,191 NHL, 1832 HL and 200,000 population-based controls, frequency-matched to all SEER cancer cases, were selected. Logistic regression models, adjusted for potential confounders, compared infection-related conditions in controls with HL and NHL patients and by the NHL subtypes diffuse large B-cell, T-cell, follicular and marginal zone lymphoma (MZL). Stratification by race was undertaken. RESULTS Respiratory tract infections were broadly associated with NHL, particularly MZL. Skin infections were associated with a 15-28% increased risk of NHL and with most NHL subtypes, particularly cellulitis with T-cell lymphoma (OR 1.36, 95%CI 1.24-1.49). Only herpes zoster remained associated with HL following Bonferroni correction (OR 1.55, 95% CI 1.28-1.87). Gastrointestinal and urinary tract infections were not strongly associated with NHL or HL. In stratified analyses by race, sinusitis, pharyngitis, bronchitis and cellulitis showed stronger associations with total NHL in blacks than whites (P<0.001). CONCLUSIONS Infections may contribute to the aetiologic pathway and/or be markers of underlying immune modulation. Precise elucidation of these mechanisms may provide important clues for understanding how immune disturbance contributes to lymphoma.
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33
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Fénéant L, Levy S, Cocquerel L. CD81 and hepatitis C virus (HCV) infection. Viruses 2014; 6:535-72. [PMID: 24509809 PMCID: PMC3939471 DOI: 10.3390/v6020535] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2013] [Revised: 01/29/2014] [Accepted: 02/02/2014] [Indexed: 12/16/2022] Open
Abstract
Hepatitis C Virus (HCV) infection is a global public health problem affecting over 160 million individuals worldwide. Its symptoms include chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV is an enveloped RNA virus mainly targeting liver cells and for which the initiation of infection occurs through a complex multistep process involving a series of specific cellular entry factors. This process is likely mediated through the formation of a tightly orchestrated complex of HCV entry factors at the plasma membrane. Among HCV entry factors, the tetraspanin CD81 is one of the best characterized and it is undoubtedly a key player in the HCV lifecycle. In this review, we detail the current knowledge on the involvement of CD81 in the HCV lifecycle, as well as in the immune response to HCV infection.
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Affiliation(s)
- Lucie Fénéant
- Center for Infection and Immunity of Lille, CNRS-UMR8204, Inserm-U1019, Institut Pasteur de Lille, Université Lille Nord de France, Institut de Biologie de Lille, 1 rue du Pr Calmette, CS50447, 59021 Lille Cedex, France.
| | - Shoshana Levy
- Department of Medicine, Division of Oncology, CCSR, Stanford University Medical Center, Stanford, CA 94305, USA.
| | - Laurence Cocquerel
- Center for Infection and Immunity of Lille, CNRS-UMR8204, Inserm-U1019, Institut Pasteur de Lille, Université Lille Nord de France, Institut de Biologie de Lille, 1 rue du Pr Calmette, CS50447, 59021 Lille Cedex, France.
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Edlefsen KL, Martínez-Maza O, Madeleine MM, Magpantay L, Mirick DK, Kopecky KJ, LaCroix AZ, De Roos AJ. Cytokines in serum in relation to future non-Hodgkin lymphoma risk: evidence for associations by histologic subtype. Int J Cancer 2014; 135:913-22. [PMID: 24488825 DOI: 10.1002/ijc.28724] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2013] [Accepted: 12/19/2013] [Indexed: 02/06/2023]
Abstract
Specific associations for lymphoma in the general population suggest that chronic immune dysfunction/dysregulation may be associated with the development of B-cell non-Hodgkin lymphoma (NHL). Furthermore, polymorphisms in several cytokine genes have been associated with increased lymphoma risk, most consistently with genes for TNF and IL10. To evaluate the hypothesis that prediagnostic circulating cytokine levels would be associated with increased B-cell lymphoma risk, we conducted a nested case-control study within the Women's Health Initiative Observational Study cohort involving 491 B-cell NHL cases and 491 controls. Levels of eleven cytokines, including IL1β, IL2, IL4, IL5, IL6, IL10, IL12, IL13, TNF, IFNγ and GM-CSF, were measured using a Luminex suspension bead-based multiplexed array in prediagnostic serum samples collected a median of 6 years prior to the lymphoma diagnosis. We observed a modestly increased risk of all B-cell NHL in women with increased levels of the cytokines TNF and IL10 (OR1.22, CI 1.07-1.38 and OR 1.09, CI 1.04-1.15, respectively, per doubling in the serum cytokine concentration) and this association showed some variation according to histologic subtype. The increased risk was strongest for those neoplasms diagnosed in close proximity to the blood draw for some histologic subtypes but not others, suggesting a component of reverse causation. Further study will be required to better understand how genetic polymorphisms in TNF and IL10 genes may interact with circulating cytokine levels and states of chronic immune dysfunction/stimulation to contribute to the risk of B-cell NHL.
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Affiliation(s)
- Kerstin L Edlefsen
- Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA
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Wang SS, Nieters A. Unraveling the interactions between environmental factors and genetic polymorphisms in non-Hodgkin lymphoma risk. Expert Rev Anticancer Ther 2014; 10:403-13. [DOI: 10.1586/era.09.194] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Tarella C, Gueli A, Ruella M, Cignetti A. Lymphocyte transformation and autoimmune disorders. Autoimmun Rev 2013; 12:802-13. [DOI: 10.1016/j.autrev.2012.11.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Yu SC, Lin CW. Early-stage splenic diffuse large B-cell lymphoma is highly associated with hepatitis C virus infection. Kaohsiung J Med Sci 2012; 29:150-6. [PMID: 23465418 DOI: 10.1016/j.kjms.2012.08.025] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2012] [Accepted: 05/07/2012] [Indexed: 02/07/2023] Open
Abstract
Splenic marginal zone lymphoma (SMZL) and splenic diffuse large B-cell lymphoma (DLBCL) are the most common types of lymphomas involving the spleen. Geographic variation in hepatitis C virus (HCV) seroprevalence is characteristic of splenic lymphomas. In Italy, HCV seroprevalence was higher in patients with SMZL and splenic DLBCL than in patients with all types of lymphoma. In Japan, HCV seroprevalence was higher in patients with splenic DLBCL than in patients with all types of lymphoma; however, HCV seroprevalence in patients with SMZL was similar to that in patients with all types of lymphoma. In this study, clinicopathological data of 74 splenic lymphoma cases between 1988 and 2011 collected from the Department of Pathology at National Taiwan University Hospital were analyzed. Serology for HCV infection was available for 41 cases. Splenic DLBCL and SMZL accounted for 36% (n = 27) and 42% (n = 31) of splenic lymphomas, respectively. Microscopically, most cases of DLBCL (26/27) presented with circumscribed tumor and most cases of SMZL (28/31) presented with white pulp expansion. HCV seroprevalence in patients with DLBCL and SMZL was 44% and 10%, respectively (7/16 vs. 2/20, p = 0.020). The pattern identified in this study is closer to that in Japan than in Italy. HCV seroprevalence in patients with early-stage (I/II) and late-stage (III/IV) DLBCL was 100% and 10%, respectively (6/6 vs. 1/10, p < 0.001). Early-stage DLBCL is clinically considered a form of primary splenic lymphoma rather than a systemic lymphoma with splenic involvement. High HCV seroprevalence in patients with early-stage DLBCL suggests a role of HCV in the pathogenesis of primary DLBCL.
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MESH Headings
- Female
- Hepatitis C/complications
- Hepatitis C/epidemiology
- Hepatitis C/pathology
- Humans
- Lymphoma, B-Cell, Marginal Zone/complications
- Lymphoma, B-Cell, Marginal Zone/epidemiology
- Lymphoma, B-Cell, Marginal Zone/pathology
- Lymphoma, Large B-Cell, Diffuse/complications
- Lymphoma, Large B-Cell, Diffuse/epidemiology
- Lymphoma, Large B-Cell, Diffuse/pathology
- Male
- Middle Aged
- Neoplasm Staging
- Seroepidemiologic Studies
- Spleen/pathology
- Splenic Neoplasms/complications
- Splenic Neoplasms/epidemiology
- Splenic Neoplasms/pathology
- Taiwan/epidemiology
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Affiliation(s)
- Shan-Chi Yu
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
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Zakerinia M, Namdari M, Amirghofran S. The Relationship between Exposure to Pesticides and the Occurrence of Lymphoid Neoplasm. IRANIAN RED CRESCENT MEDICAL JOURNAL 2012; 14:337-44. [PMID: 22924112 PMCID: PMC3420024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/10/2012] [Accepted: 03/25/2012] [Indexed: 11/24/2022]
Abstract
BACKGROUND The etiology of malignant lymphoma is still largely unknown. This study determines the relationship between exposure to pesticides and the occurrence of lymphoid neoplasms in Shiraz, Southern Iran. METHODS Between 2007 and 2008, in a case control study conducted in Nemazee Hospital in Shiraz, Southern Iran, 200 subjects diagnosed with lymphoma according to the World Health Organization (WHO) classification were enrolled. Controls (n=200) were frequency matched to the cases by sex, age, and center. Subjects who were a farmer were compared with all other occupations. RESULTS Out of the 200 cases that were diagnosed as lymphoid neoplasms, 100 were non-Hodgkin's lymphoma, 54 Hodgkin's lymphoma and 46 multiple myeloma. Seventy two percent of the NHL's were of the B-cell type, 15% of the T-cell type and the rest were not classified. Furthermore, subjects exposed to pesticides were at an increased risk of non-Hodgkin lymphoma and MM, but not Hodgkin lymphoma. CONCLUSION Risk of non-Hodgkin lymphoma and MM was highest for exposure to pesticides, among them, insecticide's risk was confirmed.
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Affiliation(s)
- M Zakerinia
- Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran,Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran,Correspondence: Maryam Zakerinina, MD, Associate Professor of Internal Medicine, The Director of Bone Marrow Transplant Unit, Department of Internal Medicine, Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Tel.: +98-711-6474301, Fax: +98-711-6474301, E-mail:
| | - M Namdari
- Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - S Amirghofran
- Kish International Branch, Shiraz University of Medical Sciences, Shiraz, Iran
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Chronic viral hepatitis and risk of lymphoid malignancies: a retrospective twelve-year population-based cohort study in Côte d'Or, France. Dig Liver Dis 2012; 44:160-5. [PMID: 21975433 DOI: 10.1016/j.dld.2011.08.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2011] [Revised: 08/23/2011] [Accepted: 08/28/2011] [Indexed: 02/06/2023]
Abstract
BACKGROUND The association between hepatitis C infection and lymphoid malignancies is still a matter of debate. The hypothesis of a relationship between hepatitis B and lymphoid neoplasms is more recent and has been far less thoroughly explored. AIM The aim of this study was to evaluate the association between hepatitis C and B infections and B cell non-Hodgkin and Hodgkin lymphomas. METHODS We took advantage of the co-existence in the French administrative area of Côte d'Or of two specialized registries - one for viral hepatitis and one for haematological diseases - to conduct a population-based, cohort study covering a 12-year period. The databases were anonymized and then linked using a probabilistic model. RESULTS There were 8234 person-years at risk in the hepatitis C cohort and 2784 in the hepatitis B cohort. We found 6 cases of non-Hodgkin lymphoma in the hepatitis C cohort, resulting in an overall adjusted standardized incidence ratio of 3.42 (CI: 1.25-7.45). Three of these 6 cases were diffuse-large-B-cell-lymphoma. Cirrhosis was associated with a higher risk of non-Hodgkin lymphoma in the hepatitis C cohort (relative risk=8.4, p<0.01, using a Poisson regression). We found one case of chronic lymphocytic leukaemia amongst the hepatitis B carriers. CONCLUSION Hepatitis C carriers are at a higher risk of developing non-Hodgkin lymphoma than the general population. The role of cirrhosis and the association between hepatitis B and lymphoid malignancies deserve to be further assessed.
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Nicolosi Guidicelli S, Lopez-Guillermo A, Falcone U, Conconi A, Christinat A, Rodriguez-Abreu D, Grisanti S, Lobetti-Bodoni C, Piffaretti JC, Johnson PW, Mombelli G, Cerny A, Montserrat E, Cavalli F, Zucca E. Hepatitis C virus and GBV-C virus prevalence among patients with B-cell lymphoma in different European regions: a case-control study of the International Extranodal Lymphoma Study Group. Hematol Oncol 2011; 30:137-42. [PMID: 22105737 DOI: 10.1002/hon.1015] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2011] [Revised: 08/18/2011] [Accepted: 08/21/2011] [Indexed: 12/24/2022]
Abstract
Hepatitis C virus (HCV) infection is associated with some B-cell non-Hodgkin lymphoma (B cell-NHLs). Patients with HCV infection frequently show co-infections with GB virus C (GBV-C, formerly known as hepatitis G virus), and some studies have suggested a higher incidence of GBV-C infection in patients with B cell-NHLs. The aim of this study was to prospectively evaluate the association between HCV and/or GBV-C infection and B cell-NHLs in different geographic areas. One hundred thirty-seven lymphoma cases and 125 non-lymphoma matched controls were enrolled in an international case-control study conducted in Switzerland (Bellinzona), Spain (Barcelona) and England (Southampton) on samples collected from 2001 to 2002. In Bellinzona (41 cases and 81 controls), the overall prevalence of HCV was 3.3% (4.9% in NHLs), and the overall prevalence of GBV-C was 24% (22% in NHLs). In Barcelona (46 cases and 44 controls), the prevalence of HCV was 10% (8.7% in NHLs) and the prevalence of GBV-C 20% (13% in NHLs). There was no statistically significant difference in the frequency of both infections between patients with NHL and controls. In Southampton, 50 NHL cases were analysed, none of them was found to be HCV-positive; therefore, no control group was analysed and GBV-C analysis was not performed, too. Both in Bellinzona and in Barcelona, the seropositivity rate was significantly lower for HCV than for GBV-C, suggesting that their transmission can be independent. The incidence of HCV was significantly higher in Barcelona than that in Bellinzona. This study confirmed the existence of marked geographic differences in the prevalence of HCV in NHL but cannot provide any significant evidence for an association between HCV and/or GBV-C and B-cell NHLs.
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41
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Varma S, Menon MC, Garg A, Malhotra P, Sharma A, Chawla YK, Dhiman RK. Hepatitis C virus infection among patients with non-Hodgkin's lymphoma in northern India. Hepatol Int 2011; 5:688-92. [PMID: 21484139 DOI: 10.1007/s12072-010-9244-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2010] [Accepted: 12/19/2010] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Hepatitis C virus (HCV) has been postulated to be an etiological agent for lymphoid malignancies. Whereas a high prevalence of HCV infection in non-Hodgkin's lymphoma (NHL) patients has been shown to exist in many geographical areas of high HCV prevalence, studies from other parts have not established any form of association. In India, there is a scarcity of data to show either a positive or a negative association between NHL and HCV infection. Therefore, we determined the prevalence of HCV infection in patients with NHL. METHODS A total of 228 subjects were included, out of which, the number of newly diagnosed consecutive patients with lymphoproliferative disorders (NHL and CLL) were 57 [mean age, 48.7 years (range: 18-80)] and the control group consisted of 171 subjects [mean age, 48.6 years (range: 18-80)]. We used third generation enzyme immunoassay to detect HCV antibodies. HCV RNA was detected by nested RT-PCR. RESULTS Among the 57 patients of NHL, 44 (77.2%) had high-grade disease (diffuse large B cell), 6 (10.5%) intermediate-grade (follicular lymphoma), and 7 (12.3%) low-grade (small lymphocytic); 26 patients had B symptoms at diagnosis. None of the patient tested positive for antibody to hepatitis C virus (anti-HCV) while 1 patient (1.75%) tested positive for HCV RNA. Among the age- and sex- matched controls, 2 (1.17%) subjects tested positive for anti-HCV; both were also positive for HCV RNA. CONCLUSIONS HCV infection is unlikely to be associated with lymphoproliferative disorders in northern India and does not play a major role in the pathogenesis of lymphoproliferative disorders.
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Affiliation(s)
- Subhash Varma
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
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42
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Gold LS, De Roos AJ, Brown EE, Lan Q, Milliken K, Davis S, Chanock SJ, Zhang Y, Severson R, Zahm SH, Zheng T, Rothman N, Baris D. Associations of common variants in genes involved in metabolism and response to exogenous chemicals with risk of multiple myeloma. Cancer Epidemiol 2009; 33:276-80. [PMID: 19736056 PMCID: PMC2808169 DOI: 10.1016/j.canep.2009.08.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2009] [Accepted: 08/14/2009] [Indexed: 11/20/2022]
Abstract
BACKGROUND We examined risk of multiple myeloma (MM) associated with variants in genes involved in metabolism and response to exogenous chemicals [cytochrome P450 enzymes (CYP1B1, CYP2C9), epoxide hydrolase (EPHX1), paraoxonase 1 (PON1), arylhydrocarbon hydroxylase receptor (AHR), and NAD(P)H:quinone oxidoreductase (NQO1)]. METHODS This study included 279 MM cases and 782 controls in a pooled analysis of two population-based case-control studies. One common variant from each candidate gene was genotyped using DNA from blood or buccal cells. We estimated risk of MM associated with each genotype, controlling for race, gender, study site, and age, using odds ratios (OR) and 95% confidence intervals (CI). RESULTS Evaluations of the CYP1B1 V432L variant (rs1056836) suggested increased risk of MM among persons with the CG and GG genotypes compared to the CC genotype [OR (95% CI)=1.4 (1.0-2.0)]. Similar results were seen in analyses stratified by race and gender. We did not find any associations between MM and the CYP2C9, EPHX1, NQO1, or PON1 genes. CONCLUSIONS CYP1B1 activates chemicals such as polycyclic aromatic hydrocarbons and dioxins to create oxidized, reactive intermediates, and higher gene activity has been shown for the G allele. We conducted the largest analysis to date on MM and these genetic variants and our results provide preliminary evidence that variation in CYP1B1 may influence susceptibility to MM.
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Affiliation(s)
- Laura S Gold
- Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
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Hepatitis C and lymphoproliferative disorders: from mixed cryoglobulinemia to non-Hodgkin's lymphoma. Clin Gastroenterol Hepatol 2009; 7:900-5. [PMID: 19362606 DOI: 10.1016/j.cgh.2009.03.035] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2008] [Revised: 03/02/2009] [Accepted: 03/28/2009] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Hepatitis C virus is associated with both mixed cryoglobulinemia and non-Hodgkin's lymphoma, particularly B-cell non-Hodgkin's Lymphoma. Although there are geographic discrepancies in the incidence and prevalence of hepatitis C virus-related lymphomas, large epidemiologic studies and meta-analyses confirm this relationship in both patients with and without mixed cryoglobulinemia. Other factors such as gene translocation, somatic hypermutation and direct infection may also play a role in the malignant transformation of B-cells. METHODS Recent advances in our understanding between the complex relationship between hepatitis C virus and its interactions with cell proteins on B-cell surface membranes has led to proposed mechanisms on how hepatitis C virus leads to chronic antigenic stimulation resulting in lymphoproliferation. RESULTS Hepatitis C virus is more weakly associated with T-cell lymphomas, Waldenstrom's macroglobulinemia and other monoclonal gammopathies. Remission of mixed cryoglobulinemia is strongly associated with reduction of hepatitis C virus viral load and recurrence of disease corresponds with viral relapse. Similarly, some studies have shown complete remissions of low grade lymphomas with sustained viral response after antiviral therapy for hepatitis C virus. CONCLUSIONS Further studies are needed to more clearly understand the pathogenesis and management of hepatitis C virus-related lymphoproliferative disorders.
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Purdue MP, Severson RK, Colt JS, Stewart P, De Roos AJ, Cerhan JR, Cozen W, Davis S, Hartge P, Schenk M, Blair A. Degreasing and risk of non-Hodgkin lymphoma. Occup Environ Med 2009; 66:557-60. [PMID: 19017696 PMCID: PMC2995288 DOI: 10.1136/oem.2008.040386] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
OBJECTIVE To investigate the relationship between selected solvent-related workplace tasks (degreasing, painting, gluing, stripping paint, staining) and risk of non-Hodgkin lymphoma (NHL). METHODS We analysed occupational data from a large population-based case-control study of NHL conducted in the USA. For participants reporting occupations with possible exposure to organic solvents, job-specific interview modules were administered to elicit in-depth information on solvent-related workplace tasks and other exposure-related factors (225 cases, 189 controls). Unconditional logistic regression models were fit to calculate odds ratios (ORs) and 95% CI for average frequency, maximal frequency and cumulative number of hours having performed each task. Individuals with jobs rated as unexposed to organic solvents in the workplace (180 cases, 213 controls) were used as a reference group. RESULTS We observed an increased risk of NHL among subjects in the highest category of maximal degreasing frequency (>520 h/year: OR 2.1, 95% CI 0.9 to 4.9, trend test p = 0.02). We found similar associations for the highest levels of average frequency and, among men, cumulative number of hours. Other solvent-related tasks were not associated with NHL. CONCLUSION Findings from this case-control analysis of solvent-related tasks suggest that frequent degreasing work may be associated with an elevated risk of NHL.
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Affiliation(s)
- M P Purdue
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, EPS 8114, 6120 Executive Blvd, Bethesda, MD 20892, USA.
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Kristinsson SY, Goldin LR, Björkholm M, Koshiol J, Turesson I, Landgren O. Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies. Haematologica 2009; 94:1581-9. [PMID: 19586941 DOI: 10.3324/haematol.2009.008979] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
There are data to support a role for genetic and immune-related factors in the pathogenesis of lymphomas and plasma cell diseases. In this paper, we review our published large population-based studies and other relevant studies in Hodgkin's and non-Hodgkin's lymphomas, multiple myeloma, and the precursor condition monoclonal gammopathy of undetermined significance. We discuss the overlap in risk factors between related malignancies and explore the underlying mechanisms. Based on these studies, we provide clinical implications and discuss the relevance of these data for patient counseling and clinical follow-up. Finally, we suggest future directions for new studies designed to increase our current knowledge and to define underlying biological mechanisms of our findings.
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Affiliation(s)
- Sigurdur Y Kristinsson
- Department of Medicine, Division of Hematology, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden
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46
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Coiffier B. Hepatitis B Virus Reactivation in Patients Receiving Chemotherapy for Cancer Treatment: Role of Lamivudine Prophylaxis. Cancer Invest 2009; 24:548-52. [PMID: 16939967 DOI: 10.1080/07357900600815232] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatitis B virus (HBV) reactivation is a frequent complication in inactive HBV carriers at time of chemotherapy or following this chemotherapy. This complication appeared during or after chemotherapy and was not increased by the use of rituximab alone or combined with chemotherapy. This is a severe complication most frequently seen in lymphoma patients. Lamivudine have efficacy to treat the patients once the clinical disease is present. However, lamivudine prophylaxis beginning before chemotherapy and until at least 6 months after the end of chemotherapy is recommended for all HBV carriers. Hepatitis C virus is usually not associated with reactivation and prophylaxis should not be used.
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Blinder V, Fisher SG. The Role of Environmental Factors in the Etiology of Lymphoma. Cancer Invest 2009; 26:306-16. [DOI: 10.1080/07357900701805686] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Abstract
For more than 50 years, links between autoimmunity and lymphomas have been described based on human and animal studies. Over the last 3 decades, many studies have addressed specific hypotheses about these associations using population level data. This has been accomplished by assessing previous autoimmune history in case-control studies of patients with lymphoma (mainly non-Hodgkin lymphoma) and myeloma, and by following cohorts of patients with various autoimmune diseases for subsequent development of lymphoma and multiple myeloma. In this article, we review our recently published series of association studies based on data from Scandinavia and from US Veterans and other relevant findings. We also discuss what these associations have revealed about the mechanisms and pathways underlying both autoimmunity and lymphoma. Finally, we discuss the future directions involving a combination of population and molecular studies that are needed to better define underlying biological mechanisms.
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Affiliation(s)
- Lynn R Goldin
- Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892-7236, USA.
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Cerhan JR, Engels EA, Cozen W, Davis S, Severson RK, Morton LM, Gridley G, Hartge P, Linet M. Blood transfusion, anesthesia, surgery and risk of non-Hodgkin lymphoma in a population-based case-control study. Int J Cancer 2008; 123:888-94. [PMID: 18506687 PMCID: PMC3913466 DOI: 10.1002/ijc.23561] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The incidence of NHL has increased dramatically since at least the 1950s, and during this timeframe there has been a major increase in the use of blood transfusions, invasive surgical procedures and anesthesia, all of which can impact immune function. We evaluated these factors with NHL risk in a population-based study of 759 cases and 589 frequency-matched controls. Risk factor data were collected during in-person interviews. Unconditional logistic regression was used to estimate ORs and 95% CIs, adjusted for the matching factors. History of transfusion was associated with a 26% higher risk of NHL (95% CI 0.91-1.73), and the elevated risk was specific to transfusions first given 5-29 years before the reference date (OR = 1.69; 95% CI 1.08-2.62) and transfusions given for a medical condition (OR = 2.09; 95% CI 1.03-4.26). The total number of surgeries and dental procedures (OR = 1.53 for 26+ surgeries compared to 0-6; 95% CI 1.02-2.29) and to a lesser extent the total number of exposures to general or local/regional anesthesia (OR = 1.35 for 24+ times compared to 0-6; 95% CI 0.91-2.02) were positively associated with risk of NHL. Inclusion of transfusion and surgery or transfusion and anesthesia in the same model did not attenuate these associations. All results were broadly consistent for both DLBCL and follicular subtypes. Blood transfusions were associated with NHL risk, but appear to be a marker for underlying medical conditions. Multiple surgical procedures and/or repeated administration of anesthesia have not been previously reported to be associated with risk of NHL and these exposures warrant further evaluation.
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Affiliation(s)
- James R Cerhan
- Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 5905, USA.
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50
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de Sanjose S, Benavente Y, Vajdic CM, Engels EA, Morton LM, Bracci PM, Spinelli JJ, Zheng T, Zhang Y, Franceschi S, Talamini R, Holly EA, Grulich AE, Cerhan JR, Hartge P, Cozen W, Boffetta P, Brennan P, Maynadié M, Cocco P, Bosch R, Foretova L, Staines A, Becker N, Nieters A. Hepatitis C and non-Hodgkin lymphoma among 4784 cases and 6269 controls from the International Lymphoma Epidemiology Consortium. Clin Gastroenterol Hepatol 2008; 6:451-8. [PMID: 18387498 PMCID: PMC3962672 DOI: 10.1016/j.cgh.2008.02.011] [Citation(s) in RCA: 257] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Increasing evidence points towards a role of hepatitis C virus (HCV) infection in causing malignant lymphomas. We pooled case-control study data to provide robust estimates of the risk of non-Hodgkin's lymphoma (NHL) subtypes after HCV infection. METHODS The analysis included 7 member studies from the International Lymphoma Epidemiology Consortium (InterLymph) based in Europe, North America, and Australia. Adult cases of NHL (n = 4784) were diagnosed between 1988 and 2004 and controls (n = 6269) were matched by age, sex, and study center. All studies used third-generation enzyme-linked immunosorbent assays to test for antibodies against HCV in serum samples. Participants who were human immunodeficiency virus positive or were organ-transplant recipients were excluded. RESULTS HCV infection was detected in 172 NHL cases (3.60%) and in 169 (2.70%) controls (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.40-2.25). In subtype-specific analyses, HCV prevalence was associated with marginal zone lymphoma (OR, 2.47; 95% CI, 1.44-4.23), diffuse large B-cell lymphoma (OR, 2.24; 95% CI, 1.68-2.99), and lymphoplasmacytic lymphoma (OR, 2.57; 95% CI, 1.14-5.79). Notably, risk estimates were not increased for follicular lymphoma (OR, 1.02; 95% CI, 0.65-1.60). CONCLUSIONS These results confirm the association between HCV infection and NHL and specific B-NHL subtypes (diffuse large B-cell lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma).
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Affiliation(s)
- Silvia de Sanjose
- Unit of Infections and Cancer, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge, Centro de Investigación Biomédica en Red Epidemiología y Salud Pública, Barcelona, Spain.
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