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Su Y, Mei L, Wu Y, Li C, Jiang T, Zhao Y, Feng X, Sun T, Li Y, Wang Z, Ji Y. Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of papillary thyroid carcinoma via the BRAF-ERK1/2-P53 signaling pathway. J Endocrinol Invest 2025; 48:633-652. [PMID: 39487939 DOI: 10.1007/s40618-024-02481-5] [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: 05/21/2024] [Accepted: 10/19/2024] [Indexed: 11/04/2024]
Abstract
BACKGROUND Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Xenotropic and polytropic retrovirus receptor 1 (XPR1), identified as a cellular receptor, plays roles in many pathophysiological processes. However, the underlying function and molecular mechanisms of XPR1 in PTC remain unclear. Therefore, this study aimed to elucidate the role of XPR1 in the process of PTC and the potential mechanisms. METHODS RNA-sequencing was performed for gene differential expression analysis in PTC patients' tissues. Immunohistochemical assay, real-time PCR, and western blotting assay were used to determine the expression of XPR1, BRAF, and P53 in PTC tissues. The function of XPR1 on the progression of PTC was explored using in vitro and in vivo experiments. The molecular mechanism of XPR1 was investigated using gene silencing, ELISA, immunofluorescence, western blotting, and real-time PCR assays. RESULTS We found that XPR1 was markedly upregulated in PTC tissues compared to adjacent noncancerous tissues, suggesting that high expression of XPR1 could be correlated with poor patient disease-free survival in PTC. In addition, the expression of BRAF and P53 in PTC tissues was substantially higher than in adjacent noncancerous tissues. Silencing of XPR1 reduced the proliferation, migration, and invasion capacities of TPC-1 cells in vitro and effectively inhibited the tumorigenecity of PTC in vivo. More importantly, silencing of XPR1 in TPC-1 cells significantly decreased the expression of XPR1, BRAF, and P53 both in vitro and in vivo. Interestingly, we demonstrated that XPR1 may positively activate the BRAF-ERK-P53 signaling pathway, further promoting PTC progression. CONCLUSION The findings reveal a crucial role of XPR1 in PTC progression and prognosis via the BRAF-ERK1/2-P53 signaling pathway, providing potential therapeutic targets for treating PTC.
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MESH Headings
- Humans
- Proto-Oncogene Proteins B-raf/genetics
- Proto-Oncogene Proteins B-raf/metabolism
- Thyroid Cancer, Papillary/metabolism
- Thyroid Cancer, Papillary/pathology
- Thyroid Cancer, Papillary/genetics
- Thyroid Neoplasms/metabolism
- Thyroid Neoplasms/pathology
- Thyroid Neoplasms/genetics
- Tumor Suppressor Protein p53/metabolism
- Mice
- Disease Progression
- Animals
- Xenotropic and Polytropic Retrovirus Receptor
- Cell Proliferation
- Receptors, G-Protein-Coupled/metabolism
- Receptors, G-Protein-Coupled/genetics
- Male
- Prognosis
- MAP Kinase Signaling System/physiology
- Female
- Gene Expression Regulation, Neoplastic
- Signal Transduction/physiology
- Cell Movement
- Middle Aged
- Mice, Nude
- Biomarkers, Tumor/metabolism
- Biomarkers, Tumor/genetics
- Apoptosis
- Cell Line, Tumor
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Affiliation(s)
- Yuanhao Su
- Department of Geriatric General Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Lin Mei
- Scientific Research Center and Precision Medical Institute, The Second Affiliated Hospital, Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, Shaanxi, China
| | - Yongke Wu
- Department of Geriatric General Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Cheng Li
- Department of Geriatric General Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Tiantian Jiang
- Department of Geriatric General Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Yiyuan Zhao
- Department of Geriatric General Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Xin Feng
- Department of Geriatric General Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Tingkai Sun
- Department of Geriatric General Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Yunhao Li
- Department of Geriatric General Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Zhidong Wang
- Department of Geriatric General Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China.
| | - Yuanyuan Ji
- Scientific Research Center and Precision Medical Institute, The Second Affiliated Hospital, Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, Shaanxi, China.
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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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Wang SS. Epidemiology and etiology of diffuse large B-cell lymphoma. Semin Hematol 2023; 60:255-266. [PMID: 38242772 PMCID: PMC10962251 DOI: 10.1053/j.seminhematol.2023.11.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 11/15/2023] [Accepted: 11/21/2023] [Indexed: 01/21/2024]
Abstract
As the most common non-Hodgkin lymphoma subtype, diffuse large B-cell lymphoma (DLBCL) incidence patterns generally parallel that for NHL overall. Globally, DLBCL accounts for a third of all NHLs, ranging between 20% and 50% by country. Based on United States (U.S.) cancer registry data, age-standardized incidence rate for DLBCL was 7.2 per 100,000. DLBCL incidence rises with age and is generally higher in males than females; in the U.S., incidence is highest among non-Hispanic whites (9.2/100,000). Like NHL incidence, DLBCL incidence rose in the first half of the 20th century but has largely plateaued. However, there is some evidence that incidence rates are rising in areas of historically low rates, such as Asia; there are also estimates for rising DLBCL incidence in the near future due to the changing demographics in developed countries whose aging population is growing. Established risk factors for DLBCL include those that result in severe immune deficiency such as HIV/AIDS, inherited immunodeficiency syndromes, and organ transplant recipients. Factors that lead to chronic immune dysregulations are also established risk factors, and include a number of autoimmune conditions (eg, Sjögren syndrome, systemic lupus erythematosus, rheumatoid arthritis), viral infections (eg, HIV, KSHV/HHV8, HCV, EBV), and obesity. Family history of NHL/DLBCL, personal history of cancer, and multiple genetic susceptibility loci are also well-established risk factors for DLBCL. There is strong evidence for multiple environmental exposures in DLBCL etiology, including exposure to trichloroethylene, benzene, and pesticides and herbicides, with recent associations noted with glyphosate. There is also strong evidence for associations with other viruses, such as HBV. Recent estimates suggest that obesity accounts for nearly a quarter of DLBCLs that develop, but despite recent gains in the understanding of DLBCL etiology, the majority of disease remain unexplained. An understanding of the host and environmental contributions to disease etiology, and concerted efforts to expand our understanding to multiple race/ethnic groups, will be essential for constructing clinically relevant risk prediction models and develop effective strategies for disease prevention.
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Affiliation(s)
- Sophia S Wang
- City of Hope Comprehensive Cancer Center, Duarte, CA.
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4
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Wu J, He D, Yu F, Huang Y, Bian M, Yu C, Liu J, Cai Z, Zhao Y. Mycoplasma infection mimicking a malignancy in a waldenstrom macroglobulinemia patient. BMC Infect Dis 2023; 23:219. [PMID: 37029352 PMCID: PMC10080790 DOI: 10.1186/s12879-023-08163-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Accepted: 03/15/2023] [Indexed: 04/09/2023] Open
Abstract
BACKGROUND Mycoplasma hominis infection is common in urinary tract. 18F-FDG-PET/CT is a valuable tool for tumor and infection diagnosis. Few studies have shown the 18F-FDG-PET/CT images after mycoplasma infection. CASE PRESENTATION Here we described a case of Waldenstrom macroglobulinemia with thickened bladder wall. The 18F-FDG-PET/CT showed the SUVmax up to 36.1 mimicking bladder cancer. The results of histopathological examination and metagenomic sequencing of the blood and urinary revealed the Mycoplasma hominis infection. CONCLUSION The full consideration should be given to the possibility of infection besides tumor in lesions with high SUV value in 18F-FDG-PET/CT, especially in immunodeficiency patients.
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Affiliation(s)
- Junqing Wu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 310000, China
| | - Donghua He
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 310000, China
| | - Fang Yu
- Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China
| | - Yue Huang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China
| | - Meiru Bian
- Department of Hematology, The Second People's Hospital of Huai'an, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huaian, 223001, China
| | - Chengxuan Yu
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Ministry of Education, Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China
| | - Jiao Liu
- Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, 310000, Zhejiang, China
| | - Zhen Cai
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 310000, China
- Institute of Hematology, Zhejiang University, Hangzhou, 310000, Zhejiang, China
- Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou, 310000, China
| | - Yi Zhao
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 310000, China.
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5
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Abstract
Waldenström macroglobulinemia (WM) is a rare subtype of non-Hodgkin lymphoma characterized by the presence of lymphoplasmacytic lymphoma (LPL) in the bone marrow accompanied by a monoclonal immunoglobulin type M (IgM) in the serum. WM was first described only 80 years ago and became reportable in the US as a malignancy in 1988. Very little systematic research was conducted prior to 2000 to characterize incidence, clinical characteristics, risk factors or diagnostic and prognostic criteria, and there were essentially no WM-specific clinical interventional trials. Since the inaugural meeting of the International Workshop in Waldenström's Macroglobulinemia (IWWM) in 2000, WM has become the focus of a steadily increasing and productive body of research, engaging a growing number of investigators throughout the world. This introductory overview provides summary of the current understanding of the epidemiology of WM/LPL as a backdrop for a series of consensus panel recommendations arising from research presented at the 11th IWWM.
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Affiliation(s)
- Mary L McMaster
- Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Health and Human Services, Commissioned Corps of the United States Public Health Service, Washington, DC.
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6
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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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7
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Viruses and Endocrine Diseases. Microorganisms 2023; 11:microorganisms11020361. [PMID: 36838326 PMCID: PMC9967810 DOI: 10.3390/microorganisms11020361] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/27/2023] [Accepted: 01/29/2023] [Indexed: 02/04/2023] Open
Abstract
Viral infections have been frequently associated with physiological and pathological changes in the endocrine system for many years. The numerous early and late endocrine complications reported during the current pandemic of coronavirus disease 2019 (COVID-19) reinforce the relevance of improving our understanding of the impact of viral infections on the endocrine system. Several viruses have been shown to infect endocrine cells and induce endocrine system disturbances through the direct damage of these cells or through indirect mechanisms, especially the activation of the host antiviral immune response, which may lead to the development of local or systemic inflammation or organ-specific autoimmunity. In addition, endocrine disorders may also affect susceptibility to viral infections since endocrine hormones have immunoregulatory functions. This review provides a brief overview of the impact of viral infections on the human endocrine system in order to provide new avenues for the control of endocrine diseases.
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8
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Mafra A, Laversanne M, Gospodarowicz M, Klinger P, De Paula Silva N, Piñeros M, Steliarova-Foucher E, Bray F, Znaor A. Global patterns of non-Hodgkin lymphoma in 2020. Int J Cancer 2022; 151:1474-1481. [PMID: 35695282 DOI: 10.1002/ijc.34163] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 04/29/2022] [Accepted: 05/10/2022] [Indexed: 11/11/2022]
Abstract
We evaluated the global patterns of non-Hodgkin lymphoma (NHL) in 2020 using the estimates of NHL incidence and mortality in 185 countries that are part of the GLOBOCAN 2020 database, developed by the International Agency for Research on Cancer (IARC). As well as new cases and deaths of NHL, corresponding age-standardized (world) rates (ASR) of incidence and mortality per 100 000 person-years were derived by country and world region. In 2020, an estimated 544 000 new cases of NHL were diagnosed worldwide, and approximately 260 000 people died from the disease. Eastern Asia accounted for a quarter (24.9%) of all cases, followed by Northern America (15.1%) and South-Central Asia (9.7%). Incidence rates were higher in men than in women, with similar geographical patterns. While the incidence rates were highest in Australia and New Zealand, Northern America, Northern Europe and Western Europe (>10/100 000 for both sexes combined), the highest mortality rates (>3/100 000) were found in regions in Africa, Western Asia and Oceania. The large variations and the disproportionately higher mortality in low- and middle-income countries can be related to the underlying prevalence and distribution of risk factors, and to the level of access to diagnostic and treatment facilities.
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Affiliation(s)
- Allini Mafra
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | - Mathieu Laversanne
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | - Mary Gospodarowicz
- Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Paulo Klinger
- Department of Hematology and Cell Therapy, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, University of São Paulo, São Paulo, Brazil
| | - Neimar De Paula Silva
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | - Marion Piñeros
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | | | - Freddie Bray
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | - Ariana Znaor
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
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Mazzaro C, Bomben R, Gragnani L, Visentini M, Pozzato G, Pozzo F, Zucchetto A, Gattei V. Hepatitis C virus-associated B-cell lymphomas: The importance of the new direct antiviral agent therapy. Semin Hematol 2022; 59:177-182. [PMID: 36805885 DOI: 10.1053/j.seminhematol.2022.11.003] [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: 09/23/2022] [Revised: 11/23/2022] [Accepted: 11/27/2022] [Indexed: 11/30/2022]
Abstract
Hepatitis C virus (HCV) is a hepatotropic and lymphotropic virus, responsible for both chronic hepatitis and extra-hepatic manifestations. Multiple epidemiologic, clinical, biological, and molecular studies have suggested that HCV plays a causal role also in the development of several lymphoproliferative disorders, either benign, such as mixed cryoglobulinemia, or malignant, such as B-cell non-Hodgkin lymphomas (NHL). Chronic viral antigenic stimulation of B-lymphocytes plays a fundamental basic role from the onset of lymphoma to its final steps. In the past, several studies demonstrated that the association of pegylated interferon plus ribavirin was able to eradicate HCV, with subsequent regression of indolent B-cell low-grade NHL. Other studies have demonstrated that direct antiviral agents (DAAs) therapy have some efficacy in HCV-associated NHL, particularly in patients with low-grade NHL or marginal zone-lymphoma, but these results need to be confirmed in larger studies with longer follow-up. The response rate of antiviral therapy seems favorable also in high grade NHL when DAAs therapy is administered in combination with chemotherapy and therefore antiviral therapy should be considered as a first-line approach in HCV-related NHL.
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Affiliation(s)
- Cesare Mazzaro
- Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Pordenone, Italy.
| | - Riccardo Bomben
- Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Pordenone, Italy
| | - Laura Gragnani
- MASVE Interdepartmental Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, Firenze, Italy
| | - Marcella Visentini
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Gabriele Pozzato
- Clinical and Surgical Sciences, University of Trieste, Trieste, Italy
| | - Federico Pozzo
- Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Pordenone, Italy
| | - Antonella Zucchetto
- Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Pordenone, Italy
| | - Valter Gattei
- Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Pordenone, Italy
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10
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Scheifer C, Luckina E, Lebrun-Vignes B, Diop AA, Damais-Thabut D, Roos-Weil D, Dechartres A, Lebray P. Acute myeloid leukaemia following direct acting antiviral drugs in HCV-infected patients: A 10 years' retrospective single-center study. Clin Res Hepatol Gastroenterol 2022; 46:102000. [PMID: 35933093 DOI: 10.1016/j.clinre.2022.102000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 07/23/2022] [Accepted: 07/24/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND After several cases of peculiar hematological malignancies following introduction of new oral anti-hepatitis C virus (HCV) treatments in our recent practice, we aimed to systematically identify all cases of hematological malignancies (HM) in patients with chronic HCV infection and to compare them according to the prescription of oral anti-HCV Direct Acting Antivirals (DAA) treatment or not. MATERIAL/METHODS In this single-center retrospective observational study, we included all patients with confirmed HM and chronic HCV infection managed between 2010 and 2019 in the Pitié-Salpêtrière hospital, Paris. Non-inclusion criteria were a benign hematological disorder, an HM preceding chronic HCV infection and HCV acute infection. We compared characteristics of patients who received DAA before HM diagnosis to those with no DAA before HM. RESULTS Over the 10 years, 61 cases of HM among HCV infected patients were identified (female 29%, median age of 58.0 years [IQR 17]). Twenty-one received DAA before the onset of HM (Group DAA+) and 40 did not (Group DAA-) including 22 having received DAA after HM. In the DAA+ group, oral NS5B, NS5A and NS3A inhibitors were used in 90, 76 and 29% respectively. HM developed in the two years following DAA initiation in 76%. Eight (38%) had Non-Hodgkin Lymphoma, 5 (24%) had an Acute Myeloid Leukaemia (AML) including two with a mixed phenotype, 2 each had Hodgkin Lymphoma, Multiple Myeloma or a myeloproliferative disorder and one each had a chronic Lymphocytic Leukaemia or AL Amyloidosis. In the Group DAA-, HM were NHL in 20(50%) patients, Myeloproliferative neoplasms in 7 (17%), Multiple Myeloma in 5, Hodgkin Lymphoma in 3, Myelodysplastic syndrome and AML in 2 (5%) each and Acute Lymphoblastic Leukaemia in one. No significant difference between the groups DAA + and - was found according to age, sex, HCV genotype, viral load, co-infection or type and exposition of previous HCV treatments. AML, liver transplantation and cirrhosis were significantly more frequent in the DAA+ group (p = 0.020, 0.045 and 0.032, respectively). CONCLUSION AML seemed more frequent after using DAA treatments, notably in severe HCV patients including cirrhotic and/or liver transplanted patients. A multicentric observational study is ongoing to confirm and explore the results.
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Affiliation(s)
- Carole Scheifer
- Sorbonne Université, Départment d'Hématologie clinique, Assistance Publique Hôpitaux de Paris, Hospital Pitié-Salpétrière, Paris, France.
| | - Elena Luckina
- Sorbonne Université, Centre Régional de Pharmacovigilance, Assistance Publique Hôpitaux de Paris, Hospital Pitié-Salpétrière, Paris, France
| | - Bénédicte Lebrun-Vignes
- Sorbonne Université, Centre Régional de Pharmacovigilance, Assistance Publique Hôpitaux de Paris, Hospital Pitié-Salpétrière, Paris, France; EpiDermE, Univ Paris Est Créteil, Créteil, France
| | - Abdoul-Aziz Diop
- Sorbonne Université, Département d'information médicale, Assistance Publique Hôpitaux de Paris, Hospital Pitié-Salpétrière, Paris, France
| | - Dominique Damais-Thabut
- Sorbonne Université, Département d'hépatogastroentérologie, Assistance Publique Hôpitaux de Paris, Hospital Pitié-Salpétrière, Paris, France
| | - Damien Roos-Weil
- Sorbonne Université, Départment d'Hématologie clinique, Assistance Publique Hôpitaux de Paris, Hospital Pitié-Salpétrière, Paris, France
| | - Agnès Dechartres
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP.Sorbonne Université, Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi), Paris, France
| | - Pascal Lebray
- Sorbonne Université, Département d'hépatogastroentérologie, Assistance Publique Hôpitaux de Paris, Hospital Pitié-Salpétrière, Paris, France
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11
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Viral Agents as Potential Drivers of Diffuse Large B-Cell Lymphoma Tumorigenesis. Viruses 2022; 14:v14102105. [DOI: 10.3390/v14102105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 09/19/2022] [Indexed: 11/16/2022] Open
Abstract
Among numerous causative agents recognized as oncogenic drivers, 13% of total cancer cases occur as a result of viral infections. The intricacy and diversity of carcinogenic processes, however, raise significant concerns about the mechanistic function of viruses in cancer. All tumor-associated viruses have been shown to encode viral oncogenes with a potential for cell transformation and the development of malignancies, including diffuse large B-cell lymphoma (DLBCL). Given the difficulties in identifying single mechanistic explanations, it is necessary to combine ideas from systems biology and viral evolution to comprehend the processes driving viral cancer. The potential for more efficient and acceptable therapies lies in targeted medicines that aim at viral proteins or trigger immune responses to either avoid infection or eliminate infected or cancerous cells. In this review, we aim to describe the role of viral infections and their mechanistic approaches in DLBCL tumorigenesis. To the best of our knowledge, this is the first review summarizing the oncogenic potential of numerous viral agents in DLBCL development.
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Kawata K, Atsukawa M, Ohta K, Chida T, Noritake H, Arai T, Iwakiri K, Yasuda S, Toyoda H, Okubo T, Hiraoka A, Watanabe T, Uojima H, Nozaki A, Tani J, Morishita A, Kageyama F, Sasada Y, Nagasawa M, Matsushita M, Oyaizu T, Mikami S, Ikegami T, Abe H, Matsuura K, Tanaka Y, Tsubota A. Mac-2-binding protein glycan isomer predicts all malignancies after sustained virological response in chronic hepatitis C. Hepatol Commun 2022; 6:1855-1869. [PMID: 35344290 PMCID: PMC9315127 DOI: 10.1002/hep4.1941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 02/28/2022] [Accepted: 03/06/2022] [Indexed: 11/06/2022] Open
Abstract
Despite reports of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection after achieving sustained virological response (SVR), only few studies have demonstrated the incidence of other (non-HCC) malignancies. This study aimed to clarify the incidence, survival probability, and factors associated with malignancy, especially non-HCC malignancies, in patients with chronic HCV infection after achieving SVR. In this retrospective study, records of 3580 patients with chronic HCV infection who achieved SVR following direct-acting antiviral (DAA) treatment were analyzed. The cumulative post-SVR incidence of non-HCC malignancies was 0.9%, 3.1%, and 6.8% at 1, 3, and 5 years, respectively. The survival probability for patients with non-HCC malignancies was 99.1%, 78.8%, and 60.2% at 1, 3, and 5 years, respectively, and the rate was significantly lower than that for patients with HCC. The Cox proportional hazards regression model identified Mac-2-binding protein glycan isomer (M2BPGi) cutoff index (COI) ≥ 1.90 at baseline and ≥ 1.50 at 12 weeks following DAA treatment as significant and independent factors associated with the post-SVR incidence of non-HCC malignancies. Furthermore, patients with either M2BPGi COI ≥ 1.90 at baseline or M2BPGi COI ≥ 1.50 at SVR12 had a significantly higher risk of post-SVR incidence of non-HCC malignancies than of HCC. Conclusion: M2BPGi measurements at baseline and SVR12 may help predict the post-SVR incidence of non-HCC malignancies in patients with chronic HCV infection who achieved SVR following DAA treatment. Early identification of these patients is critical to prolong patient survival.
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Affiliation(s)
- Kazuhito Kawata
- 12793Hepatology DivisionDepartment of Internal Medicine IIHamamatsu University School of MedicineHamamatsuShizuokaJapan
| | - Masanori Atsukawa
- 26367Division of Gastroenterology and HepatologyDepartment of Internal MedicineNippon Medical SchoolBunkyo-ku, TokyoJapan
| | - Kazuyoshi Ohta
- 12793Hepatology DivisionDepartment of Internal Medicine IIHamamatsu University School of MedicineHamamatsuShizuokaJapan
| | - Takeshi Chida
- 12793Hepatology DivisionDepartment of Internal Medicine IIHamamatsu University School of MedicineHamamatsuShizuokaJapan
| | - Hidenao Noritake
- 12793Hepatology DivisionDepartment of Internal Medicine IIHamamatsu University School of MedicineHamamatsuShizuokaJapan
| | - Taeang Arai
- 26367Division of Gastroenterology and HepatologyDepartment of Internal MedicineNippon Medical SchoolBunkyo-ku, TokyoJapan
| | - Katsuhiko Iwakiri
- 26367Division of Gastroenterology and HepatologyDepartment of Internal MedicineNippon Medical SchoolBunkyo-ku, TokyoJapan
| | - Satoshi Yasuda
- 37124Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgaki, GifuJapan
| | - Hidenori Toyoda
- 37124Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgaki, GifuJapan
| | - Tomomi Okubo
- 38626Division of GastroenterologyNippon Medical School Chiba Hokusoh HospitalInzaiChibaJapan
| | - Atsushi Hiraoka
- Gastroenterology CenterEhime Prefectural Central HospitalMatsuyamaEhimeJapan
| | - Tsunamasa Watanabe
- Division of Gastroenterology and HepatologyDepartment of Internal MedicineSt. Marianna University School of MedicineKawasakiKanagawaJapan
| | - Haruki Uojima
- Department of Gastroenterology, Internal MedicineKitasato University School of MedicineSagamiharaKanagawaJapan
| | - Akito Nozaki
- 26437Gastroenterological CenterYokohama City University Medical CenterYokohamaKanagawaJapan
| | - Joji Tani
- Department of Gastroenterology and NeurologyKagawa University Graduate School of MedicineKita-gunKagawaJapan
| | - Asahiro Morishita
- Department of Gastroenterology and NeurologyKagawa University Graduate School of MedicineKita-gunKagawaJapan
| | - Fujito Kageyama
- 37050Department of GastroenterologyHamamatsu Medical CenterHamamatsuShizuokaJapan
| | - Yuzo Sasada
- 13773Department of GastroenterologyIwata City HospitalIwataShizuokaJapan
| | - Masamichi Nagasawa
- Department of GastroenterologySeirei Hamamatsu General HospitalHamamatsuShizuokaJapan
| | - Masahiro Matsushita
- Department of GastroenterologyShimada Municipal HospitalShimadaShizuokaJapan
| | - Tatsuki Oyaizu
- 26388Department of GastroenterologyShizuoka City Shizuoka HospitalShizuokaShizuokaJapan
| | - Shigeru Mikami
- Division of GastroenterologyDepartment of Internal MedicineKikkoman General HospitalNodaChibaJapan
| | - Tadashi Ikegami
- Department of GastroenterologyIbaraki Medical CenterTokyo Medical UniversityAmiIbarakiJapan
| | - Hiroshi Abe
- Division of Gastroenterology and HepatologyDepartment of Internal MedicineShinmatusdo Central General HospitalMatsudoChibaJapan
| | - Kentaro Matsuura
- Department of Gastroenterology and MetabolismNagoya City University Graduate School of Medical SciencesNagoyaAichiJapan
| | - Yasuhito Tanaka
- 13205Department of Gastroenterology and HepatologyFaculty of Life SciencesKumamoto UniversityKumamotoKumamotoJapan
| | - Akihito Tsubota
- Core Research FacilitiesResearch Center for Medical ScienceThe Jikei University School of MedicineMinato-ku, TokyoJapan
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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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Shi X, Zhuo H, Du Y, Nyhan K, Ioannidis J, Wallach JD. Environmental risk factors for non-Hodgkin's lymphoma: umbrella review and comparison of meta-analyses of summary and individual participant data. BMJ MEDICINE 2022; 1:e000184. [PMID: 36936582 PMCID: PMC9978687 DOI: 10.1136/bmjmed-2022-000184] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 05/31/2022] [Indexed: 02/06/2023]
Abstract
Objectives To summarise the range, strength, and validity of reported associations between environmental risk factors and non-Hodgkin's lymphoma, and to evaluate the concordance between associations reported in meta-analyses of summary level data and meta-analyses of individual participant data. Design Umbrella review and comparison of meta-analyses of summary and individual participant level data. Data sources Medline, Embase, Scopus, Web of Science Core Collection, Cochrane Library, and Epistemonikos, from inception to 23 July 2021. Eligibility criteria for selecting studies English language meta-analyses of summary level data and of individual participant data evaluating associations between environmental risk factors and incident non-Hodgkin's lymphoma (overall and subtypes). Data extraction and synthesis Summary effect estimates from meta-analyses of summary level data comparing ever versus never exposure that were adjusted for the largest number of potential confounders were re-estimated using a random effects model and classified as presenting evidence that was non-significant, weak (P<0.05), suggestive (P<0.001 and >1000 cases), highly suggestive (P<0.000001, >1000 cases, largest study reporting a significant association), or convincing (P<0.000001, >1000 cases, largest study reporting a significant association, I2 <50%, 95% prediction interval excluding the null value, and no evidence of small study effects and excess significance bias) evidence. When the same exposures, exposure contrast levels, and outcomes were evaluated in meta-analyses of summary level data and meta-analyses of individual participant data from the International Lymphoma Epidemiology (InterLymph) Consortium, concordance in terms of direction, level of significance, and overlap of 95% confidence intervals was examined. Methodological quality of the meta-analyses of summary level data was assessed by the AMSTAR 2 tool. Results We identified 85 meta-analyses of summary level data reporting 257 associations for 134 unique environmental risk factors and 10 subtypes of non-Hodgkin's lymphoma nearly all (79, 93%) were classified as having critically low quality. Most associations (225, 88%) presented either non-significant or weak evidence. The 11 (4%) associations presenting highly suggestive evidence were primarily for autoimmune or infectious disease related risk factors. Only one association, between history of coeliac disease and risk of non-Hodgkin's lymphoma, presented convincing evidence. Of 40 associations reported in meta-analyses of summary level data that were also evaluated in InterLymph meta-analyses of individual participant data, 22 (55%) pairs were in the same direction, had the same level of statistical significance, and had overlapping 95% confidence intervals; 28 (70%) pairs had summary effect sizes from the meta-analyses of individual participant data that were more conservative. Conclusion This umbrella review suggests evidence of many meta-analyses of summary level data reporting weak associations between environmental risk factors and non-Hodgkin's lymphoma. Improvements to primary studies as well as evidence synthesis in evaluations of evironmental risk factors and non-Hodgkin's lymphoma are needed. Review registration number PROSPERO CRD42020178010.
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Affiliation(s)
- Xiaoting Shi
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA
| | - Haoran Zhuo
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA
| | - Yuxuan Du
- Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA
| | - Kate Nyhan
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA
- Harvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, CT, USA
| | - John Ioannidis
- Department of Medicine, of Epidemiology and Population Health, of Biomedical Data Science, and of Statistics, and Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, USA
| | - Joshua D Wallach
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA
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15
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Cacoub P, Comarmond C, Vieira M, Régnier P, Saadoun D. HCV-related lymphoproliferative disorders in the direct-acting antiviral era: From mixed cryoglobulinaemia to B-cell lymphoma. J Hepatol 2022; 76:174-185. [PMID: 34600000 DOI: 10.1016/j.jhep.2021.09.023] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 08/31/2021] [Accepted: 09/14/2021] [Indexed: 02/06/2023]
Abstract
HCV has been shown to induce many B-cell lymphoproliferative disorders. B lymphocytes specialise in producing immunoglobulins and, during chronic HCV infection, they can cause manifestations ranging from polyclonal hypergammaglobulinaemia without clinical repercussions, through mixed cryoglobulinaemic vasculitis to B-cell non-Hodgkin lymphoma. This spectrum is supported by substantial epidemiological, pathophysiological and therapeutic data. Many, although not all, of the pathogenic pathways leading from one extreme to another have been decrypted. Chronic viral antigen stimulation of B lymphocytes has a central role until the final steps before overt malignancy. This has direct implications for treatment strategies, which always include the use of direct-acting antivirals sometimes alongside immunosuppressants. The role of direct-acting antivirals has been well established in patients with cryoglobulinaemia vasculitis. However, their positive impact on B-cell non-Hodgkin lymphoma needs to be confirmed in larger studies with longer follow-up.
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Affiliation(s)
- Patrice Cacoub
- AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France; Centre de Référence des Maladies Auto-Immunes Systémiques Rares, Centre de Référence des Maladies Auto-Inflammatoires et de l'Amylose inflammatoire, F-75013, Paris, France; Institut National de la Santé et de la Recherche Médicale, INSERM, UMR_S 959, F-75013, Paris, France; CNRS, FRE3632, F-75005, Paris, France; Sorbonne Université, UPMC Univ Paris 06, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005, Paris, France.
| | - Cloé Comarmond
- AP-HP, Lariboisière Hospital, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Matheus Vieira
- AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France; Centre de Référence des Maladies Auto-Immunes Systémiques Rares, Centre de Référence des Maladies Auto-Inflammatoires et de l'Amylose inflammatoire, F-75013, Paris, France; Institut National de la Santé et de la Recherche Médicale, INSERM, UMR_S 959, F-75013, Paris, France; CNRS, FRE3632, F-75005, Paris, France; Sorbonne Université, UPMC Univ Paris 06, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005, Paris, France
| | - Paul Régnier
- AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France; Centre de Référence des Maladies Auto-Immunes Systémiques Rares, Centre de Référence des Maladies Auto-Inflammatoires et de l'Amylose inflammatoire, F-75013, Paris, France; Institut National de la Santé et de la Recherche Médicale, INSERM, UMR_S 959, F-75013, Paris, France; CNRS, FRE3632, F-75005, Paris, France; Sorbonne Université, UPMC Univ Paris 06, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005, Paris, France
| | - David Saadoun
- AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France; Centre de Référence des Maladies Auto-Immunes Systémiques Rares, Centre de Référence des Maladies Auto-Inflammatoires et de l'Amylose inflammatoire, F-75013, Paris, France; Institut National de la Santé et de la Recherche Médicale, INSERM, UMR_S 959, F-75013, Paris, France; CNRS, FRE3632, F-75005, Paris, France; Sorbonne Université, UPMC Univ Paris 06, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005, Paris, France
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16
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Cingam S, Sidana S. Differential Diagnosis of Waldenström's Macroglobulinemia and Early Management: Perspectives from Clinical Practice. Blood Lymphat Cancer 2022; 12:107-117. [PMID: 36003901 PMCID: PMC9394652 DOI: 10.2147/blctt.s259860] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 07/28/2022] [Indexed: 11/23/2022]
Abstract
Waldenström's Macroglobulinemia (WM) is a clonal B-lymphocyte neoplasm characterized by the presence of IgM monoclonal protein and ≥10% bone marrow involvement with lymphoplasmacytic cells. Several mature B-cell and plasma cell disorders can potentially produce monoclonal IgM immunoglobulin and hence, careful consideration of the differential diagnosis is vital. Clinico-pathological features, immunophenotype, and MYD88 mutation status help distinguish WM from other plasma cell and lymphoproliferative disorders. Treatment is only indicated in patients symptomatic from adenopathy or organomegaly, neuropathy, hyper viscosity, cryoglobulinemia, cold agglutinin disease, cytopenia's or amyloidosis. Alkylators (cyclophosphamide, bendamustine) in combination with anti-CD20 antibodies and novel targeted agents including Bruton tyrosine kinase (BTK) inhibitors like ibrutinib are the mainstay of frontline treatment in symptomatic WM.
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Affiliation(s)
- Shashank Cingam
- Division of Hematology and Oncology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, 87102, USA
| | - Surbhi Sidana
- Division of BMT and Cell Therapy, Stanford University School of Medicine, Stanford, CA, 94305, USA
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17
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Wang H, Liu Y, Zhao Y. The association of hepatitis C virus infection and thyroid disease: A systematic review and meta-analysis. Int J Biol Markers 2021; 36:3-9. [PMID: 34825832 DOI: 10.1177/17246008211056959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Previous studies have reported that hepatitis C virus (HCV) infection may increase the risk of thyroid disease (TD) even thyroid cancer (TC), but quantitative assessments of risk were rare and the results were not consistent. The purpose of this study was to evaluate the impact of HCV infection on TD and TC, and provide clues to explore the relationship between HCV infection and TD and TC. The literature retrieval was performed up to August 20th, 2021 in the database of PubMed, Cochrane library, Web of Science, China National Knowledge Infrastructure and Wang Fang. The risk of HCV for TD or TC was expressed with odds ratio (OR) and 95% confidence intervals (CI). Subgroup analysis was used to explore the source of heterogeneity. Six articles (three studies published as article and three studies published as abstract) were included in this meta-analysis, with a total of 5398 controls and 1925 cases of hepatitis C. The results of meta-analysis found that HCV infection were significantly associated with an increased risk of TD (sum OR = 1.80, 95% CI = 1.54-2.10, P < 0.001, I2 = 74.3%) and TC (sum OR = 16.36, 95% CI = 4.65-57.62, P < 0.001, I2 = 0%). HCV infection may increase the risk of TD and TC. More work is needed in the future to establish a causal role, however an awareness of the possibility of increased risk of TD and TC may lead to earlier diagnosis and better outcomes in patients with hepatitis C.
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Affiliation(s)
- Hongpeng Wang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China
| | - Yixiu Liu
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University Cancer Hospital, Chongqing, China
| | - Yanguang Zhao
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University Cancer Hospital, Chongqing, China
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18
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Mullen CJR, Volesky KD, Greenwald ZR, El-Zein M, Franco EL. Is Hodgkin Lymphoma Associated with Hepatitis B and C Viruses? A Systematic Review and Meta-analysis. Cancer Epidemiol Biomarkers Prev 2021; 30:2167-2175. [PMID: 34548328 DOI: 10.1158/1055-9965.epi-21-0548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 07/19/2021] [Accepted: 09/09/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Apart from the Epstein-Barr virus (EBV), the etiology of the hematologic malignancy Hodgkin lymphoma (HL) is not well defined. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with some lymphoproliferative diseases with similarities to HL. METHODS We performed a systematic review and meta-analysis, by searching Embase, MEDLINE, and Web of Science databases on March 9, 2021, for studies reporting a measure of association for HBV and HL or HCV and HL. We calculated pooled relative risks (RR) and their 95% confidence intervals (CI). RESULTS Pooling nine HBV studies with 1,762 HL cases yielded an RR of 1.39 (95% CI, 1.00-1.94) and pooling 15 HCV studies with 4,837 HL cases resulted in an RR of 1.09 (95% CI, 0.88-1.35). Meta-analyzing by study design, hepatitis detection method, and region revealed two subgroups with statistically significant associations-HCV studies that used hospital-based controls and/or were conducted in the West Pacific. No included study assessed age or EBV tumor status in relation to HL. CONCLUSIONS Although we did not find an association between HBV or HCV and HL, research assessing the impact of age and EBV tumor status was lacking. IMPACT The effect of HBV or HCV infection in the development of HL remains unclear.
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Affiliation(s)
- Callum J R Mullen
- Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada.
| | - Karena D Volesky
- Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada
| | - Zoë R Greenwald
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Mariam El-Zein
- Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada
| | - Eduardo L Franco
- Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada
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19
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Askari E, Rodriguez S, Garcia-Sanz R. Waldenström's Macroglobulinemia: An Exploration into the Pathology and Diagnosis of a Complex B-Cell Malignancy. J Blood Med 2021; 12:795-807. [PMID: 34512060 PMCID: PMC8416181 DOI: 10.2147/jbm.s267938] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 07/19/2021] [Indexed: 12/22/2022] Open
Abstract
After 77 years since the initial description, Waldenström macroglobulinemia (WM) remains as a bone marrow neoplastic disorder with lymphoplasmacytic differentiation oversecreting a monoclonal immunoglobulin M (IgM). However, many biological and genetic aspects of this entity have been unraveled and it is now easy to correctly diagnose patients with this illness. The diagnosis requires the presence of a monoclonal IgM component and bone marrow lymphoid infiltration must be demonstrated. In addition, other small B-cell lymphoid neoplasms with plasma cell differentiation must be discarded. Although the clinical picture is highly heterogeneous, the diagnosis is much easier today compared to the past, since now we can demonstrate the presence of somatic mutations, especially the L265P mutation in the MYD88 gene, highly characteristic of WM (>90% of the patients), followed by the WHIM-like mutations in the CXCR4 gene (~35%). The identification of these mutations is very important, because they can modulate the response to new treatments with Bruton's tyrosine kinase (BTK) inhibitors. Thus, the conventional prognostic factors that predict the outcome of these patients (anemia, thrombopenia, high M component, high B2M, and advanced age), must be complemented with the genetic evaluation of the patient, that can help us in the prediction of the risk of transformation from asymptomatic to symptomatic forms (Del6q) and/or from indolent forms of the disease to aggressive lymphomas (CD79b mutations).
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Affiliation(s)
- Elham Askari
- Hematology Department, Fundación Jiménez Díaz, Centro de Investigación Biomédica en Red-Cáncer (CIBERONC) CB16/12/00369, Madrid, Spain
| | - Sara Rodriguez
- Clinica Universidad de Navarra, Centro de Investigación Medica Aplicada (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Accelerator project, Centro de Investigación Biomédica en Red-Cáncer (CIBERONC) CB16/12/00369, Pamplona, Spain
| | - Ramon Garcia-Sanz
- Haematology Department, University Hospital of Salamanca, Research Biomedical Institute of Salamanca (IBSAL), Accelerator project, Centro de Investigación Biomédica en Red-Cáncer (CIBERONC) CB16/12/00369 and Center for Cancer Research-IBMCC (USAL-CSIC), Salamanca, Spain
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20
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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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21
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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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22
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Levy A, Guidez S, Debiais C, Princet I, Bouyer S, Dindinaud E, Delwail V, Systchenko T, Moya N, Gruchet C, Sabirou F, Bobin A, Gardeney H, Nsiala L, Cailly L, Olivier G, Motard C, Fleck E, Corby A, Roul C, Denis G, Dieval C, Leleu X, Tomowiak C. Waldenström macroglobulinemia and relationship to immune deficiency. Leuk Lymphoma 2021; 62:2665-2670. [PMID: 34085595 DOI: 10.1080/10428194.2021.1907379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Primary or secondary immune deficiency (ID) is a risk factor, although rare, to develop Waldenström macroglobulinemia (WM). We aimed to better understand the incidence of this occurrence in the real-life and the outcome of either entity. We conducted a review of 194 WM in the Poitou-Charentes registry and identified 7 (3.6%) with a prior history of ID. Across the 7 WM with ID, 4 progressed to active WM disease and required treatment for WM with a median time between WM diagnosis and the first treatment of 1.5 years (range 0-3). The median time from ID to WM occurrence was 8 years (1-18). WM could develop from ID, although a rare event. Our first action was to systematically decrease immunosuppression with long-term control of ID. Half of indolent WM remained indolent despite ID and for remaining WM none appeared of poor risk WM.
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Affiliation(s)
- Anthony Levy
- Service d'Hématologie et Thérapie Cellulaire, CHU and Inserm, Poitiers, France
| | - Stéphanie Guidez
- Service d'Hématologie et Thérapie Cellulaire, CHU and Inserm, Poitiers, France
| | - Céline Debiais
- Laboratoire d'Anatomie Pathologie, CHU, Poitiers, France
| | | | | | | | - Vincent Delwail
- Service d'Hématologie et Thérapie Cellulaire, CHU and Inserm, Poitiers, France
| | - Thomas Systchenko
- Service d'Hématologie et Thérapie Cellulaire, CHU and Inserm, Poitiers, France
| | - Niels Moya
- Service d'Hématologie et Thérapie Cellulaire, CHU and Inserm, Poitiers, France
| | - Cécile Gruchet
- Service d'Hématologie et Thérapie Cellulaire, CHU and Inserm, Poitiers, France
| | - Florence Sabirou
- Service d'Hématologie et Thérapie Cellulaire, CHU and Inserm, Poitiers, France
| | - Arthur Bobin
- Service d'Hématologie et Thérapie Cellulaire, CHU and Inserm, Poitiers, France
| | - Hélène Gardeney
- Service d'Hématologie et Thérapie Cellulaire, CHU and Inserm, Poitiers, France
| | - Laly Nsiala
- Service d'Hématologie et Thérapie Cellulaire, CHU and Inserm, Poitiers, France
| | - Laura Cailly
- Service d'Hématologie et Thérapie Cellulaire, CHU and Inserm, Poitiers, France
| | | | | | | | - Anne Corby
- Service d'Onco-Hématologie, La Rochelle, France
| | | | | | | | - Xavier Leleu
- Service d'Hématologie et Thérapie Cellulaire, CHU and Inserm, Poitiers, France
| | - Cécile Tomowiak
- Service d'Hématologie et Thérapie Cellulaire, CHU and Inserm, Poitiers, France
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23
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Chuang YC, Chen YR, Kuo TH. Cryoglobulinemic glomerulonephritis with underlying occult HBV infection and Waldenström macroglobulinemia: A case report. Medicine (Baltimore) 2021; 100:e24792. [PMID: 33607837 PMCID: PMC7899821 DOI: 10.1097/md.0000000000024792] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 01/29/2021] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION Occult hepatitis B virus (HBV) infection, defined as negative hepatitis B surface antigen (HBsAg) but detectable HBV DNA in serum and liver tissue, has very rarely been described in cryoglobulinemia (CG) patients. This case report sheds light on the possible link between occult HBV infection and CG. PATIENT CONCERNS A 76-year-old man presented with rapidly deteriorating renal function within 1 year. DIAGNOSIS Cryoglobulinemic glomerulonephritis was diagnosed through renal biopsy. Initially, the patient tested negative for HBsAg, but a low HBV viral load was later discovered, indicating an occult HBV infection. Further studies also revealed Waldenström macroglobulinemia (WM). INTERVENTIONS We treated the patient as WM using plasma exchange and rituximab-based immunosuppressive therapy. OUTCOMES After 1 cycle of immunosuppressive treatment, there was no improvement of renal function. Shortly after, treatment was discontinued due to an episode of life-threatening pneumonia. Hemodialysis was ultimately required. CONCLUSION Future studies are needed to explore the link between occult HBV infection and CG, to investigate the mediating role of lymphomagenesis, and to examine the effectiveness of anti-HBV drugs in treating the group of CG patients with occult HBV infection. We encourage clinicians to incorporate HBV viral load testing into the evaluation panel for CG patients especially in HBV-endemic areas, and to test HBV viral load for essential CG patients in whom CG cannot be attributed to any primary disease.
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Affiliation(s)
- Yu-Che Chuang
- Education Center, National Cheng Kung University Hospital
| | - Ying-Ren Chen
- Department of Pathology, National Cheng Kung University Hospital
| | - Te-Hui Kuo
- Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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24
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Wang CR, Tsai HW. Human hepatitis viruses-associated cutaneous and systemic vasculitis. World J Gastroenterol 2021; 27:19-36. [PMID: 33505148 PMCID: PMC7789062 DOI: 10.3748/wjg.v27.i1.19] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 12/19/2020] [Accepted: 12/27/2020] [Indexed: 02/06/2023] Open
Abstract
Human hepatitis viruses (HHVs) include hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus, and hepatitis E virus and can cause liver inflammation in their common human host. Usually, HHV is rapidly cleared by the immune system, following acute HHV invasion. The morbidities associated with hepatitis A virus and hepatitis E virus infection occur shortly after their intrusion, in the acute stage. Nevertheless, the viral infectious process can persist for a long period of time, especially in HBV and HCV infection, leading to chronic hepatitis and further progressing to hepatic cirrhosis and liver cancer. HHV infection brings about complications in other organs, and both acute and chronic hepatitis have been associated with clinical presentations outside the liver. Vascular involvement with cutaneous and systemic vasculitis is a well-known extrahepatic presentation; moreover, there is growing evidence for a possible causal relationship between viral pathogens and vasculitis. Except for hepatitis delta virus, other HHVs have participated in the etiopathogenesis of cutaneous and systemic vasculitis via different mechanisms, including direct viral invasion of vascular endothelial cells, immune complex-mediated vessel wall damage, and autoimmune responses with stimulation of autoreactive B-cells and impaired regulatory T-cells. Cryoglobulinemic vasculitis and polyarteritis nodosa are recognized for their association with chronic HHV infection. Although therapeutic guidelines for HHV-associated vasculitis have not yet been established, antiviral therapy should be initiated in HBV and HCV-related systemic vasculitis in addition to the use of corticosteroids. Plasma exchange and/or combined cyclophosphamide and corticosteroid therapy can be considered in patients with severe life-threatening vasculitis manifestations.
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Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
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25
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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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26
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Mert D, Merdin A, Çakar MK, Dal MS, Altuntaş F. Evaluation of HBV, HCV, and HIV seroprevalence in patients with plasma cell disorders. Medicine (Baltimore) 2020; 99:e21799. [PMID: 32846815 PMCID: PMC7447389 DOI: 10.1097/md.0000000000021799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Hepatitis B (HBV) and hepatitis C (HCV) viruses are hepatotropic and lymphotropic viruses that can proliferate either in lymphocytes and monocytes or hepatocytes.The aim of this study was to evaluate the seroprevalence of HBV, HCV, and human immunodeficiency virus (HIV) in patients with plasma cell disorders. We also aimed to compare patients with plasma cell disorders and chronic lymphocytic leukemia (CLL) in terms of HBV, HCV, and HIV seropositivity.This is a retrospective study. The patients who had patient file in the Multiple Myeloma Outpatient Unit of our hospital and were followed in our outpatient unit between January 1, 2012 and September 15, 2019, with diagnoses of either of the plasma cell disorders were included in the study. In addition, 272 CLL patients who were admitted to the Leukemia Outpatient Unit of our hospital were also enrolled in the study. The 2 disease groups were compared in terms of HBV, HCV, and HIV seropositivity.A statistically significant relationship was found between disease groups according to hepatitis B surface antigen (P < .05). Hepatitis B positivity were found to be more common in CLL patients. There was also a statistically significant relationship between the disease groups in terms of hepatitis B e antigen positivity (P = .001).We found that hepatitis B surface antigen positivity rate in CLL patients was higher than in patients with plasma cell disorders. Seroprevalence of HBV, HCV, and HIV was found to be very low in patients with plasma cell disorders.
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Affiliation(s)
- Duygu Mert
- Department of Infectious Diseases and Clinical Microbiology
| | - Alparslan Merdin
- University of Health Sciences Ankara Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital, Hematology Clinic and Bone Marrow Transplantation Unit, Ankara, Turkey
| | - Merih Kizil Çakar
- University of Health Sciences Ankara Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital, Hematology Clinic and Bone Marrow Transplantation Unit, Ankara, Turkey
| | - Mehmet Sinan Dal
- University of Health Sciences Ankara Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital, Hematology Clinic and Bone Marrow Transplantation Unit, Ankara, Turkey
| | - Fevzi Altuntaş
- University of Health Sciences Ankara Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital, Hematology Clinic and Bone Marrow Transplantation Unit, Ankara, Turkey
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27
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Wang S, Guo XZ, Xu SX, Qi XS. Risk and treatment of non-hepatic cancers in patients with cirrhosis. Shijie Huaren Xiaohua Zazhi 2020; 28:655-659. [DOI: 10.11569/wcjd.v28.i15.655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Patients with cirrhosis are at a high risk for hepatocellular carcinoma. However, it remains controversial about whether or not there is a high risk for non-hepatic cancers in patients with liver cirrhosis. Additionally, the management of non-hepatic cancers in cirrhotic patients is a clinical challenge, because the use of surgery and anticancer drugs is often compromised by the presence of liver dysfunction. This editorial aims to briefly summarize the findings on the risk and management of non-hepatic cancers in patients with cirrhosis.
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Affiliation(s)
- Shuo Wang
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China,Postgraduate College, China Medical University, Shenyang 110122, Liaoning Province, China
| | - Xiao-Zhong Guo
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
| | - Shi-Xue Xu
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China,Postgraduate College, China Medical University, Shenyang 110122, Liaoning Province, China
| | - Xing-Shun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
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28
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Davis JS, Ferreira D, Paige E, Gedye C, Boyle M. Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies. Clin Microbiol Rev 2020; 33:e00035-19. [PMID: 32522746 PMCID: PMC7289788 DOI: 10.1128/cmr.00035-19] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.
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Affiliation(s)
- Joshua S Davis
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - David Ferreira
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Emma Paige
- Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC, Australia
| | - Craig Gedye
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
- Department of Oncology, Calvary Mater Hospital, Newcastle, NSW, Australia
| | - Michael Boyle
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
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29
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Hepatitis C: Does Successful Treatment Alter the Natural History and Quality of Life? Gastroenterol Clin North Am 2020; 49:301-314. [PMID: 32389364 DOI: 10.1016/j.gtc.2020.01.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The cure of chronic hepatitis C infection has a major impact on the morbidity and mortality of infected patients. It is now clear that sustained virologic response improves overall survival and significantly reduces the risk of liver failure, fibrosis progression, need of liver transplantation, and incidence of hepatocellular carcinoma. Moreover, hepatitis C eradication improves a broad range of extrahepatic manifestations, such as dermatologic, neoplastic, cardiovascular, and endocrine, and improves quality of life.
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30
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Melenotte C, Mezouar S, Mège JL, Gorvel JP, Kroemer G, Raoult D. Bacterial infection and non-Hodgkin's lymphoma. Crit Rev Microbiol 2020; 46:270-287. [PMID: 32412856 DOI: 10.1080/1040841x.2020.1760786] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
One quarter of all cancers are linked to infectious diseases. The link between viral infection and cancer has been widely studied, but few reports have focused on the carcinogenic role of bacterial infection. Nonetheless, Helicobacter pylori, Chlamydia psittaci, Coxiella burnetii, Borrelia burgdorferi and Campylobacter jejuni are bacteria that can be associated with non-Hodgkin's lymphoma (NHL), the most common haematologic malignancy. Here, we review the evidence in favour of a link between these bacterial infections and NHL. Sero-epidemiological observation makes it possible to identify a link between H. pylori, C. burnetii, B. burgdorferi infection and NHL. Helicobacter pylori, Chlamydia psittaci, Coxiella burnetii, Borrelia burgdorferi and Campylobacter jejuni could be identified in NHL tissue samples at the site of chronic inflammation, where B and T lymphocytes are attracted to participate in follicle formation. Lymphoma remissions have been observed under antimicrobial therapies supporting the carcinogenic contribution of bacteria. If the theory of causality is characterized by the lack of universal criteria for establishing a causal link between two diseases, infection and lymphoma, epidemiological, clinical, and histological evidences reported here, should lead clinicians to pay attention to these infectious agents, to detect early lymphoma transformation.
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Affiliation(s)
- Cléa Melenotte
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Soraya Mezouar
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Jean-Louis Mège
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | | | - Guido Kroemer
- Cell Biology and Metabolomics platforms, Villejuif, France.,INSERM, Paris, France.,Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.,Sorbonne Paris Cité, Université Paris Descartes, Paris, France.,Université Pierre et Marie Curie, Paris, France.,Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.,Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden
| | - Didier Raoult
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
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31
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Villaume MT, Patel D, Lopez C, Patel V, Diggs P, Harmsen H, Thompson MA, Morgan D. Dural Marginal Zone Lymphoma in a Patient With a Hepatitis C Virus Infection. World J Oncol 2020; 11:122-125. [PMID: 32494320 PMCID: PMC7239576 DOI: 10.14740/wjon1285] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 04/21/2020] [Indexed: 12/01/2022] Open
Abstract
Primary dural marginal zone lymphomas (MZLs) are exceptionally rare, with fewer than 100 cases reported to date. While the association between hepatitis C virus (HCV) infection and lymphoma is well established, it is unclear if this association extends to all anatomic sites. Here we report a case of dural MZL in a 61-year-old woman with an HCV infection. To our knowledge, this is the first report of a dural MZL associated with an HCV infection in an immunocompetent patient and was successfully treated with radiotherapy and rituximab. As such, future cases of primary MZL found in the dura should prompt consideration of co-infection with microbials such as HCV and upfront treatment with anti-virals should be considered.
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Affiliation(s)
- Matthew T Villaume
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Dilan Patel
- Department of Hematology and Bone Marrow Transplant, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Christine Lopez
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Vivek Patel
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Pauleatha Diggs
- Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Hannah Harmsen
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Mary Ann Thompson
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - David Morgan
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.,Department of Hematology and Bone Marrow Transplant, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
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Nyberg AH, Sadikova E, Cheetham C, Chiang KM, Shi JX, Caparosa S, Younossi ZM, Nyberg LM. Increased cancer rates in patients with chronic hepatitis C. Liver Int 2020; 40:685-693. [PMID: 31755208 DOI: 10.1111/liv.14305] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 10/31/2019] [Accepted: 11/04/2019] [Indexed: 02/06/2023]
Abstract
AIMS As previous reports show an association of chronic hepatitis C (HCV) with hepatocellular carcinoma (HCC) and non-liver cancers, we examine the association of HCV with liver cancer and non-liver cancers. METHODS Retrospective cross-sectional study at Kaiser Permanente Southern California (KPSC) evaluating HCV and non-HCV patients from 1 January 2008 to 12 December 2012. Cancer diagnoses were obtained from the KPSC-SEER-affiliated registry. Logistic regression analyses were used for rate ratios and time-to-event analyses were performed using Cox proportional hazards models, adjusted for age, gender, race, smoking and cirrhosis. Cancer rate ratios were stratified by tobacco, alcohol abuse, diabetes and body mass index (BMI). RESULTS The initial population and final population of multivariable analysis were N = 5 332 903 and N = 2 080 335 respectively. Cancer burden (all sites) was significantly higher in HCV than in non-HCV patients and HCV patients had a high rate of liver cancer. When liver cancer was excluded, cancer rates remained significantly increased in HCV. Unadjusted cancer rates were significantly higher in HCV compared to non-HCV for oesophageal, stomach, colorectal, pancreas, myeloma, non-Hodgkin's lymphoma, head/neck, lung, renal and prostate cancer. After stratification for alcohol abuse, tobacco, diabetes and BMI, increased cancer rates remained significant for all cancer sites, liver cancer and non-Hodgkin's lymphoma. Multivariable analyses demonstrated a strong correlation between cirrhosis and cancer. Tobacco use and diabetes were also associated with cancer. In the absence of cirrhosis, HCV, tobacco use and diabetes significantly increased the cancer risk. Mediation analyses showed that cirrhosis was responsible for a large proportion on the effect of HCV on cancer risk. CONCLUSION This study supports the concept of HCV as a systemic illness and treating HCV regardless of disease severity and prior to progression to cirrhosis.
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Affiliation(s)
- Anders H Nyberg
- Hepatology Research, Kaiser Permanente Southern California, San Diego, CA, USA
| | | | | | - Kevin M Chiang
- Pharmacy Analytical Services, Kaiser Permanente Southern California, Downey, CA, USA
| | - Jiaxiao X Shi
- Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA
| | - Susan Caparosa
- Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA
| | - Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA
| | - Lisa M Nyberg
- Hepatology Research, Kaiser Permanente Southern California, San Diego, CA, 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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34
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Dalal NH, Dores GM, Curtis RE, Linet MS, Morton LM. Cause-specific mortality in individuals with lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia, 2000-2016. Br J Haematol 2020; 189:1107-1118. [PMID: 32090327 DOI: 10.1111/bjh.16492] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 12/24/2019] [Indexed: 02/07/2023]
Abstract
Data on cause-specific mortality after lymphoplasmacytic lymphoma (LPL) and Waldenström macroglobulinaemia (WM) are lacking. We identified causes of death amongst 7289 adults diagnosed with incident first primary LPL (n = 3108) or WM (n = 4181) during 2000-2016 in 17 USA population-based cancer registries. Based on 3132 deaths, 16-year cumulative mortality was 23·2% for lymphomas, 8·4% for non-lymphoma cancers and 14·7% for non-cancer causes for patients aged <65 years at diagnosis of LPL/WM, versus 33·4%, 11·2% and 48·7%, respectively, for those aged ≥75 years. Compared with the general population, patients with LPL/WM had a 20% higher risk of death due to non-cancer causes (n = 1341 deaths, standardised mortality ratio [SMR] 1·2, 95% confidence interval [CI] 1·1-1·2), most commonly from infectious (n = 188; SMR 1·8, 95% CI 1·6-2·1), respiratory (n = 143; SMR 1·2, 95% CI 1·0-1·4), and digestive (n = 80; SMR 1·8, 95% CI 1·4-2·2) diseases, but no excess mortality from cardiovascular diseases (n = 477, SMR 1·1, 95% CI 1·0-1·1). Risks were highest for non-cancer causes within 1 year of diagnosis (n = 239; SMR<1year 1·3, 95% CI 1·2-1·5), declining thereafter (n = 522; SMR≥5years 1·1, 95% CI 1·1-1·2). Myelodysplastic syndrome/acute myeloid leukaemia deaths were notably increased (n = 46; SMR 4·4, 95% CI 3·2-5·9), whereas solid neoplasm deaths were only elevated among ≥5-year survivors (n = 145; SMR≥5years 1·3, 95% CI 1·1-1·5). This work identifies new areas for optimising care and reducing mortality for patients with LPL/WM.
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Affiliation(s)
- Nicole H Dalal
- Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA.,Duke University School of Medicine, Durham, NC, USA
| | - Graça M Dores
- Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA.,United States Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, MD, USA
| | - Rochelle E Curtis
- Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA
| | - Martha S Linet
- Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA
| | - Lindsay M Morton
- Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA
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35
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Moreno Vanegas YA, Juskevicius R, Dholaria B. Hepatitis C Virus-associated Lymphoplasmacytic Lymphoma With Waldenström Macroglobulinemia: Response to Direct-acting Antiviral Therapy. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2020; 20:e195-e199. [PMID: 32033929 DOI: 10.1016/j.clml.2020.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 12/28/2019] [Accepted: 01/04/2020] [Indexed: 02/07/2023]
Affiliation(s)
| | - Ridas Juskevicius
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN
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36
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Ferrari SM, Fallahi P, Elia G, Ragusa F, Camastra S, Paparo SR, Giusti C, Gonnella D, Ruffilli I, Shoenfeld Y, Antonelli A. Novel therapies for thyroid autoimmune diseases: An update. Best Pract Res Clin Endocrinol Metab 2020; 34:101366. [PMID: 31813786 DOI: 10.1016/j.beem.2019.101366] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
A Th1 immune-preponderance has been shown in the immunopathogenesis of autoimmune thyroiditis (AT), Graves' disease (GD) and Graves' Ophthalmopathy (GO), in which the Th1-chemokines (CXCL9, CXCL10, CXCL11), and their (C-X-C)R3 receptor, have a crucial role. Methimazole, and corticosteroids have been shown to modulate these chemokines; several efforts have been done to modulate the autoimmune reaction with other drugs, i.e. PPAR-γ, or -α ligands, or antibodies, or small molecules directed against CXCL10, or CXCR3. Antigen-specific therapy for GD, by inducing T cell tolerance through an immunization with TSH-R peptides, has been published. Drugs targeting cytokines [anti-TNFα (Etanercept), and anti-IL-6 (Tocilizumab)], and RTX (a chimeric monoclonal antibody vs. CD20) have been used in GO, with promising results. Teprotumumab (a human monoclonal anti-IGF-1R blocking antibody) has been investigated in a trial, showing it was very effective in GO patients. Still, more studies are needed for new therapies targeting autoimmune thyroid disorders.
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Affiliation(s)
| | - Poupak Fallahi
- Department of Translational Research of New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
| | - Giusy Elia
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
| | - Francesca Ragusa
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
| | - Stefania Camastra
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
| | | | - Claudia Giusti
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
| | - Debora Gonnella
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
| | - Ilaria Ruffilli
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
| | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Russia.
| | - Alessandro Antonelli
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
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Hepatitis C virus and risk of extrahepatic malignancies: a case-control study. Sci Rep 2019; 9:19444. [PMID: 31857595 PMCID: PMC6923417 DOI: 10.1038/s41598-019-55249-w] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 08/21/2019] [Indexed: 02/06/2023] Open
Abstract
Epidemiological studies have demonstrated an increased risk of non-Hodgkin lymphoma (NHL) in patients with chronic hepatitis C virus (HCV) infection. Therefore, we investigated the risk of extrahepatic malignancies associated with HCV infection. Inpatients diagnosed with lymphoma, breast, thyroid, kidney, or pancreatic cancer (research group, n = 17,925) as well as inpatients with no malignancies (control group, n = 16,580) matched by gender and age were enrolled from The First Affiliated Hospital of Nanjing Medical University between January 2008 and December 2016. A case-control study was conducted by retrospective analysis. The difference in HCV prevalence was analyzed between the research group and the control group. Also, the research group was compared to the 2006 National Hepatitis C sero-survey in China. A total of 86 cases were positive for anti-HCV in the research group. Compared with the control group (103 cases were anti-HCV positive), no significant associations between extrahepatic malignancies and HCV infection were observed. Meanwhile, compared to the 2006 National Hepatitis C sero-survey, we observed a significant association between the chronic lymphoma leukemia/small lymphocytic lymphoma (CLL/SLL) and HCV seropositivity in females in the research group aged 1–59 years old (OR = 14.69; 95% CI, 1.94–111.01). HCV infection had a potential association with CLL/SLL in females aged 1–59 years old. Our study did not confirm an association between HCV infection and the risk of extrahepatic malignancies. In regions with a low HCV prevalence, the association between HCV infection and extrahepatic malignancies needs further investigation.
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38
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Kim M, Lee YK, Park B, Oh DJ, Choi HG. Hepatitis virus B and C infections are associated with an increased risk of non-Hodgkin lymphoma: A nested case-control study using a national sample cohort. J Med Virol 2019; 92:1214-1220. [PMID: 31825111 DOI: 10.1002/jmv.25653] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Accepted: 12/09/2019] [Indexed: 12/23/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) and hepatitis C virus (HCV) are suspected of being associated with non-Hodgkin lymphoma (NHL); however, persuasive data are lacking. Hence, a nested large-population case-control study was performed to investigate such associations in Koreans. METHODS Data were collected from 929 patients with NHL and 3716 healthy subjects, who were matched 1:4 for age, sex, income, and region of residence, from the Korean Health Insurance Review and Assessment Service-National Sample Cohort. The diagnoses of NHL and HBV/HCV infection were based on the International Classification of Diseases (version 10) codes. Conditional logistic regression models were used to assess odds ratios (ORs) for NHL with respect to HBV or HCV with adjustment for the Charlson comorbidity index. RESULTS HBV and HCV rates were higher in the NHL group (3.3% and 1.3%, respectively) than in the control group (0.9% and 0.3%, respectively; P < .001 for each). The adjusted OR of hepatitis infection in patients with NHL were 3.25 (95% confidence interval [CI] = 1.99-5.31) for HBV and 3.36 (95% CI = 1.51-7.46) for HCV (P < .001 for each). Subgroups categorized by age (<55 vs ≥55 years) or sex showed significantly higher adjusted ORs of HBV for NHL. Moreover, patients with NHL ≥ 55 years of age or those who were female showed significantly higher adjusted ORs of HCV; those <55 years or who were male also tended to have higher ORs of HCV. CONCLUSION Infection with either HBV or HCV is associated with NHL in Koreans.
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Affiliation(s)
- Miyoung Kim
- Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea
| | - Young Kyung Lee
- Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea
| | - Bumjung Park
- Department of Otorhinolaryngology-Head & Neck Surgery, Hallym University College of Medicine, Anyang, Korea
| | - Dong Jun Oh
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyo Geun Choi
- Department of Otorhinolaryngology-Head & Neck Surgery, Hallym University College of Medicine, Anyang, Korea.,Hallym Data Science Laboratory, Hallym University College of Medicine, Anyang, Korea
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Imaging of Waldenström Macroglobulinemia: A Comprehensive Review for the Radiologist in the Era of Personalized Medicine. AJR Am J Roentgenol 2019; 213:W248-W256. [PMID: 31287727 DOI: 10.2214/ajr.19.21493] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Abstract
PURPOSE OF THE REVIEW Cryoglobulins are immunoglobulins with the ability to precipitate at temperatures <37 °C. They are related to hematological disorders, infections [especially hepatitis C virus (HCV)], and autoimmune diseases. In this article, the state of the art on Cryoglobulinemic Vasculitis (CV), in a helpful and schematic way, with a special focus on HCV related Mixed Cryoglobulinemia treatment are reviewed. RECENT FINDINGS Direct - acting antivirals (DAA) against HCV have emerged as an important key in HCV treatment to related Cryoglobulinemic Vasculitis, and should be kept in mind as the initial treatment in non-severe manifestations. On the other hand, a recent consensus panel has published their recommendations for treatment in severe and life threatening manifestations of Mixed Cryoglobulinemias. HCV-Cryoglobulinemic vasculitis is the most frequent form of CV. There are new treatment options in HCV-CV with DAA, with an important number of patients achieving complete response and sustained virologic response (SVR). In cases of severe forms of CV, treatment with Rituximab and PLEX are options. The lack of data on maintenance therapy could impulse future studies in this setting.
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Affiliation(s)
- Alejandro Fuentes
- Departamento de Inmunología clínica y Reumatología, Pontificia Universidad Católica de Chile, Diagonal Paraguay, #362, Santiago, Chile
| | - Claudia Mardones
- Departamento de Inmunología clínica y Reumatología, Pontificia Universidad Católica de Chile, Diagonal Paraguay, #362, Santiago, Chile
| | - Paula I Burgos
- Departamento de Inmunología clínica y Reumatología, Pontificia Universidad Católica de Chile, Diagonal Paraguay, #362, Santiago, Chile.
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Kim D, Adejumo AC, Yoo ER, Iqbal U, Li AA, Pham EA, Cholankeril G, Glenn JS, Ahmed A. Trends in Mortality From Extrahepatic Complications in Patients With Chronic Liver Disease, From 2007 Through 2017. Gastroenterology 2019; 157:1055-1066.e11. [PMID: 31251928 DOI: 10.1053/j.gastro.2019.06.026] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 05/28/2019] [Accepted: 06/17/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Trends of mortality associated with extrahepatic complications of chronic liver disease might be changing. We studied trends in mortality from extrahepatic complications of viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease in the United States. METHODS We performed a population-based study using US Census and the National Center for Health Statistics mortality records from 2007 through 2017. We identified trends in age-standardized mortality using Joinpoint trend analysis with estimates of annual percent change. RESULTS The liver-related mortality among patients with hepatitis C virus (HCV) infection increased from 2007 through 2013 and then decreased once patients began receiving treatment with direct-acting antiviral (DAA) agents, from 2014 through 2017. Among patients with HCV infection, the age-standardized mortality for extrahepatic cancers was 2.6%, for cardiovascular disease was 1.9%, and for diabetes was 3.3%. Among individuals with hepatitis B virus infection, liver-related mortality decreased steadily from 2007 through 2017. During the study, age-standardized mortality from hepatitis B virus-related extrahepatic complications increased by an average of 2.0% each year. Although liver-related mortality from ALD continued to increase, mortality from extrahepatic complications of ALD did not change significantly during the 11-year study. Among patients with nonalcoholic fatty liver disease, the cause of death was most frequently cardiovascular disease, which increased gradually over the study period, whereas liver-related mortality increased rapidly. CONCLUSIONS In an analysis of US Census and the National Center for Health Statistics mortality records, we found that after widespread use of DAA agents for treatment of viral hepatitis, cause-specific mortality from extrahepatic cancers increased, whereas mortality from cardiovascular disease or diabetes increased only among patients with HCV infection. These findings indicate the need to reassess risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals successfully treated for HCV infection with DAA agents.
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Affiliation(s)
- Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California.
| | | | - Eric R Yoo
- Department of Medicine, Santa Clara Valley Medical Center, San Jose, California
| | - Umair Iqbal
- Department of Medicine, Geisinger Medical Center, Danville, Pennsylvania
| | - Andrew A Li
- Department of Medicine, Stanford University School of Medicine, Stanford, California
| | - Edward A Pham
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - George Cholankeril
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Jeffrey S Glenn
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
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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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43
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Ioannou GN, Green PK, Berry K, Graf SA. Eradication of Hepatitis C Virus Is Associated With Reduction in Hematologic Malignancies: Major Differences Between Interferon and Direct-Acting Antivirals. Hepatol Commun 2019; 3:1124-1136. [PMID: 31388632 PMCID: PMC6671776 DOI: 10.1002/hep4.1389] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 05/17/2019] [Indexed: 12/15/2022] Open
Abstract
It is unclear whether eradication of hepatitis C virus (HCV) leads to a reduction in the risk of hematologic malignancies. We aimed to determine the impact of sustained virologic response (SVR) induced by either direct-acting antivirals (DAAs) or interferon (IFN) on the risk of hematologic malignancies. We identified 69,581 patients who initiated antiviral treatment in the Veterans Affairs national health care system from January 1, 1999, to December 31, 2015, including 40,410 (58%) IFN-only regimens, 4,546 (6.5%) DAA + IFN regimens, and 24,625 (35%) DAA-only regimens. We retrospectively followed patients to identify incident cases of hematologic malignancies or monoclonal gammopathy of unknown significance (MGUS), a premalignant precursor of multiple myeloma. Among patients treated with IFN, SVR was significantly associated with a reduction in the risk of lymphoma (adjusted hazard ratio [AHR], 0.70; 95% confidence interval [CI], 0.51-0.97), multiple myeloma (AHR, 0.40; 95% CI, 0.20-0.77), MGUS (AHR, 0.65; 95% CI, 0.42-0.99), or all hematologic malignancies and MGUS combined (AHR, 0.67; 95% CI, 0.53-0.84) over a mean follow-up of 10.6 years. In contrast, among patients treated with DAA, SVR was not associated with the risk of lymphoma, multiple myeloma, MGUS, or all hematologic malignancies and MGUS combined (AHR, 1.08; 95% CI, 0.66-1.78) during a mean follow-up of 2.9 years. Neither IFN-induced SVR nor DAA-induced SVR was associated with risk of colon cancer or prostate cancer, which were chosen a priori as comparison/control malignancies. Conclusion: We describe novel strong associations between IFN-induced SVR and lymphoma, multiple myeloma, MGUS, and all hematologic malignancies combined. Surprisingly, these associations were not observed with DAA-induced SVR.
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Affiliation(s)
- George N. Ioannou
- Division of Gastroenterology, Department of MedicineVeterans Affairs Puget Sound Health Care System and University of WashingtonSeattleWA
- Research and DevelopmentVeterans Affairs Puget Sound Health Care SystemSeattleWA
| | - Pamela K. Green
- Research and DevelopmentVeterans Affairs Puget Sound Health Care SystemSeattleWA
| | - Kristin Berry
- Research and DevelopmentVeterans Affairs Puget Sound Health Care SystemSeattleWA
| | - Solomon A. Graf
- Division of Oncology, Department of MedicineVeterans Affairs Puget Sound Health Care System and University of WashingtonSeattleWA
- Clinical Research DivisionFred Hutch Cancer Research CenterSeattleWA
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Rheumatoid factor and immunoglobulin M mark hepatitis C-associated mixed cryoglobulinaemia: an 8-year prospective study. Clin Microbiol Infect 2019; 26:366-372. [PMID: 31229596 DOI: 10.1016/j.cmi.2019.06.018] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 05/28/2019] [Accepted: 06/13/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The prevalence and factors of hepatitis C virus (HCV) -associated mixed cryoglobulinaemia in Asia remain elusive, and we aimed to investigate these topics. METHODS An 8-year prospective cohort study was conducted in 678 consecutive Taiwanese individuals with chronic HCV infection (438 completed an anti-HCV therapy course). RESULTS Of 678 individuals, 437 (64.5%) had mixed cryoglobulinaemia and 20 (2.9%) had mixed cryoglobulinaemic syndrome. At baseline, IgM (cut-off >122 mg/dL), triglycerides and IgG levels, and HCV genotype 3 were independently associated with mixed cryoglobulinaemia. Rheumatoid factor (RF) levels were associated with mixed cryoglobulinaemic syndrome (cut-off >12.2 IU/mL). At 24 weeks post-therapy, the 362 individuals with a sustained virological response (SVR) had higher cured (106/362 (29.3%) versus 10/76 (13.2%), p = 0.003) and lower persistent (100/362 (27.6%) versus 33/76 (43.4%), p = 0.003) mixed cryoglobulinaemia rates than non-SVR patients. Among SVR patients, compared with baseline levels, RF, IgG and IgM levels decreased, except in individuals with new mixed cryoglobulinaemia. Pre-therapy IgM levels were associated with 24-week post-therapy new (95% CI of OR 1.002-1.023) and persistent (95% CI of OR 1.004-1.015) mixed cryoglobulinaemia in SVR patients. After up to 8 years, 24-week post-therapy IgM levels were associated with mixed cryoglobulinaemia in SVR patients (9/51; 17.64%; 95% CI of HR 1.004-1.011). Among 17 SVR patients with pre-therapy mixed cryoglobulinaemic syndrome, 5 (29.4%) had long-term mixed cryoglobulinaemia and 4 (23.5%) had mixed cryoglobulinaemic syndrome. CONCLUSIONS Over 60% of chronic HCV-infected individuals had mixed cryoglobulinaemia, and 17.64% of SVR patients had mixed cryoglobulinaemia 8 years post-therapy. Pre-therapy RF and IgM levels marked HCV-associated mixed cryoglobulinaemic syndrome and mixed cryoglobulinaemia, respectively.
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45
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El-Serag HB, Christie IC, Puenpatom A, Castillo D, Kanwal F, Kramer JR. The effects of sustained virological response to direct-acting anti-viral therapy on the risk of extrahepatic manifestations of hepatitis C infection. Aliment Pharmacol Ther 2019; 49:1442-1447. [PMID: 30932218 PMCID: PMC6510621 DOI: 10.1111/apt.15240] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 09/24/2018] [Accepted: 03/07/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND Direct-acting anti-viral (DAA) therapy may have a beneficial role in extrahepatic manifestations of hepatitis C virus (HCV) infection. However, the available data are limited. AIM To examine the effects of DAA treatment on the risk of several extrahepatic manifestations of HCV. METHODS We conducted a retrospective cohort study of patients from the US Department of Veterans Affairs Corporate Data Warehouse who had a positive HCV RNA test and received first course of DAAs between 2012 and 2016. We calculated incidence rates by sustained virological response (SVR) status for six extrahepatic manifestations, and effect of SVR on these conditions was evaluated in adjusted Cox regression models. RESULTS Of the 45 260 patients treated with DAA with mean follow-up of 2.01 years, 41 711 (92.2%) experienced SVR. Incidence rates ranged from 0.17/1000 PY for porphyria cutanea tarda to 21.04/1000 PY for diabetes in the SVR group and 0.51/1000 PY for porphyria cutanea tarda to 23.11/1000 PY for diabetes in the no SVR group. The risk was reduced with SVR for mixed cryoglobulinaemia (adjusted HR (aHR) = 0.23; 95% CI 0.10-0.56), glomerulonephritis (aHR = 0.61; 95% CI 0.41-0.90) and lichen planus (aHR = 0.46; 95% CI 0.30-0.70), but not for non-Hodgkin's lymphoma (aHR = 0.86; 95% CI 0.52-1.43) or diabetes (aHR = 0.98; 95% CI 0.81-1.19). Non significant risk reduction was seen for porphyria cutanea tarda (aHR = 0.33; 95% CI 0.11-1.03). CONCLUSIONS Successful DAA treatment resulting in SVR was associated with significant reductions in the risk of mixed cryoglobulinaemia, glomerulonephritis, lichen planus and possibly porphyria cutanea tarda, but not non-Hodgkin's lymphoma or diabetes.
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Affiliation(s)
- Hashem B. El-Serag
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, TX,Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Israel C. Christie
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, TX,Department of Medicine, Baylor College of Medicine, Houston, TX
| | | | - Diana Castillo
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, TX
| | - Fasiha Kanwal
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, TX,Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Jennifer R. Kramer
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, TX,Department of Medicine, Baylor College of Medicine, Houston, TX
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46
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Couronné L, Bachy E, Roulland S, Nadel B, Davi F, Armand M, Canioni D, Michot JM, Visco C, Arcaini L, Besson C, Hermine O. From hepatitis C virus infection to B-cell lymphoma. Ann Oncol 2019; 29:92-100. [PMID: 29045541 DOI: 10.1093/annonc/mdx635] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
In addition to liver disorders, hepatitis C virus (HCV) is also associated with extrahepatic immune manifestations and B-cell non-Hodgkin lymphoma (NHL), especially marginal zone lymphoma, de novo or transformed diffuse large B-cell lymphoma and to a lesser extent, follicular lymphoma. Epidemiological data and clinical observations argue for an association between HCV and lymphoproliferative disorders. The causative role of HCV in NHL has been further supported by the response to antiviral therapy. Pathophysiological processes at stake leading from HCV infection to overt lymphoma still need to be further elucidated. Based on reported biological studies, several mechanisms of transformation seem however to emerge. A strong body of evidence supports the hypothesis of an indirect transformation mechanism by which sustained antigenic stimulation leads from oligoclonal to monoclonal expansion and sometimes to frank lymphoma, mostly of marginal zone subtype. By infecting lymphocytes, HCV could play a direct role in cellular transformation, particularly in de novo large B-cell lymphoma. Finally, HCV is associated with follicular lymphoma in a subset of patients. In this setting, it may be hypothesized that inflammatory cytokines stimulate proliferation and transformation of IgH-BCL2 clones that are increased during chronic HCV infection. Unraveling the pathogenesis of HCV-related B-cell lymphoproliferation is of prime importance to optimize therapeutic strategies, especially with the recent development of new direct-acting antiviral drugs.
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Affiliation(s)
- L Couronné
- Department of Hematology, Assistance Publique-Hôpitaux de Paris (APHP), Necker Hospital, Paris, France.,INSERM UMR 1163, CNRS ERL 8254, Imagine Institute, Paris, France.,Paris Descartes-Sorbonne Paris Cité University, Paris, France
| | - E Bachy
- Cancer Research Center of Lyon, INSERM U1052, CNRS UMR 5286, Lyon, France.,Department of Hematology, Lyon Sud Hospital, Lyon, France
| | - S Roulland
- Center of Immunology of Marseille-Luminy, Aix Marseille University, Marseille, France
| | - B Nadel
- Center of Immunology of Marseille-Luminy, Aix Marseille University, Marseille, France
| | - F Davi
- INSERM U1104, Marseille, France.,CNRS UMR 7280, Marseille, France.,Department of Hematology, Pitié-Salpêtrière Hospital, Pierre et Marie Curie University, Paris, France
| | - M Armand
- INSERM U1104, Marseille, France.,CNRS UMR 7280, Marseille, France.,Department of Hematology, Pitié-Salpêtrière Hospital, Pierre et Marie Curie University, Paris, France
| | - D Canioni
- Department of Pathology, Necker Hospital, AP-HP, Paris Descartes-Sorbonne Paris Cité University, Paris, France
| | - J M Michot
- Department of Hematology and Drug Development, Gustave Roussy Institute, Villejuif; France
| | - C Visco
- Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy
| | - L Arcaini
- Department of Molecular Medicine, University of Pavia, Pavia, Italy.,Departement of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - C Besson
- Department of Hematology and Oncology, Hospital of Versailles, Le Chesnay, France.,University of Versailles Saint Quentin en Yvelines, Paris-Saclay University, Communauté Paris-Saclay, Paris, France.,INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France
| | - O Hermine
- Department of Hematology, Assistance Publique-Hôpitaux de Paris (APHP), Necker Hospital, Paris, France.,INSERM UMR 1163, CNRS ERL 8254, Imagine Institute, Paris, France.,Paris Descartes-Sorbonne Paris Cité University, Paris, France
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47
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Zhu X, Jing L, Li X. Hepatitis C virus infection is a risk factor for non-Hodgkin lymphoma: A MOOSE-compliant meta-analysis. Medicine (Baltimore) 2019; 98:e14755. [PMID: 30882645 PMCID: PMC6426592 DOI: 10.1097/md.0000000000014755] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Previous studies have reached conflicting results regarding the possibility that hepatitis C virus (HCV) infection may increase the risk of non-Hodgkin lymphoma (NHL). We performed a meta-analysis to clarify the relationship between HCV infection and development of NHL. The PubMed, Web of Science, and Embase databases were searched for relevant studies estimating the association between HCV infection and NHL risk through October 31, 2017. Fixed effects or random effects models were used to calculate the pooled odds ratio (OR) and its 95% confidence interval (CI). A total of 18 studies met the inclusion criteria. We found a positive association between HCV infection and NHL (pooled OR 1.69, 95% CI 1.40-2.03, P < .05). In conclusion, our meta-analysis suggested that HCV infection was associated with increased risk of developing NHL.
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48
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Su TH, Liu CJ, Tseng TC, Chou SW, Liu CH, Yang HC, Wu SJ, Chen PJ, Chen DS, Chen CL, Kao JH. Early antiviral therapy reduces the risk of lymphoma in patients with chronic hepatitis C infection. Aliment Pharmacol Ther 2019; 49:331-339. [PMID: 30592071 DOI: 10.1111/apt.15101] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Revised: 01/26/2018] [Accepted: 11/27/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Chronic hepatitis C infection is linked to lymphoma development. AIM To investigate whether antiviral therapy prevents the risk of HCV-related lymphoma. METHODS Patients diagnosed with chronic hepatitis C were retrieved from the Taiwan National Health Insurance Research Database during 2004-2012. We included patients who received pegylated interferon and ribavirin (PegIFN/RBV) antiviral therapy for ≥24 weeks (PegIFN/RBV cohort) or hepatoprotectants for ≥90 days without antiviral therapy (HCV-untreated cohort). Both cohorts were matched by age, sex, and comorbidities through propensity scores and followed for newly diagnosed lymphoma or non-Hodgkin's lymphoma (NHL). RESULTS In total, 24 133 patients were included in both the PegIFN/RBV and HCV-untreated cohort. The lymphoma incidence was significantly higher in the untreated than in the treated cohort (66.48 vs 43.34 per 100 000 person-years, P = 0.029). After adjusting for confounders, the patients who received PegIFN/RBV therapy were at a lower risk of developing lymphoma compared with the untreated patients (hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.43-0.96, P = 0.030). Moreover, this beneficial effect was mainly observed in patients with chronic hepatitis C <60 years old with a relative risk reduction of 51% for all lymphoma (HR: 0.49, 95% CI: 0.29-0.82, P = 0.007) and 48% for non-Hodgkin's lymphoma (HR: 0.52, 95% CI: 0.30-0.91, P = 0.022). The risk of all lymphoma or non-Hodgkin's lymphoma development after antiviral therapy was lowered to that of subjects without HCV. CONCLUSIONS PegIFN/RBV-based antiviral therapy significantly reduced the risk of lymphoma, especially non-Hodgkin's lymphoma; the reduction was mostly among patients <60 years old. Early antiviral therapy for chronic hepatitis C is suggested.
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Affiliation(s)
- Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Wan Chou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shang-Ju Wu
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Ding-Shinn Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Chi-Ling Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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49
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Saleh LM, Canioni D, Shamaa S, El-Zaafarany M, Emarah Z, Abdel-Aziz S, Eladle E, Abdelaziz A, Hermine O, Besson C, Abdel-Ghaffar H. High Prevalence of Hepatitis C Virus among B-Cell Non Hodgkin Lymphoma Patients in Mansoura Region (Egypt), ANRS 12263 Study. Mediterr J Hematol Infect Dis 2019; 11:e2019011. [PMID: 30671217 PMCID: PMC6328034 DOI: 10.4084/mjhid.2019.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Accepted: 11/25/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND The prevalence of Hepatitis C virus in Egypt reaches 15%, which is considered the highest in the world. Genotype 4 represents 93 % of Egyptian HCV infections. Non-Hodgkin lymphoma (NHL) is the 5th most common cancer in Egypt. The association between HCV infection and occurrence of B-cell NHL is well known while data are scarce in Eastern countries. OBJECTIVES We aimed to evaluate the prevalence of HCV infection among patients with B-cell NHL and the clinical characteristics of HCV associated B-cell NHL in the Delta region (Mansoura-Egypt). METHODS Between March 2012 and March 2013, 110 adult patients newly diagnosed with B-cell NHL were enrolled in the current study. This study was carried out at Oncology Center, Mansoura University. Study subjects provided serum for HCV testing. RESULTS The prevalence of HCV infection among these patients was 61% (67/110 patients). Among them, 80% (32/40 tested patients) presented with viremia. In contrast with the histological distribution previously described in Northern regions, the majority of HCV associated lymphomas were DLBCLs (72%) followed by SLL/CLL (13%), follicular lymphomas (7.5%) and marginal zone lymphomas (7.5%). CONCLUSIONS B-cell lymphomas are highly associated with HCV infection in Egypt. Further developments are needed to give access to antiviral treatment for these patients.
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Affiliation(s)
- Layla M. Saleh
- Hematology Laboratory, Oncology Center, Mansoura University, Egypt
- Hematology section, Clinical Pathology Department, Faculty of Medicine, Mansoura University, Egypt
| | - Danielle Canioni
- Department of Pathology, Hôpital Necker Enfants Malades, Paris 5 Descartes University, Paris, France
| | - Sameh Shamaa
- Medical Oncology Department, Oncology Center, Mansoura University, Egypt
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Egypt
| | - Maha El-Zaafarany
- Medical Oncology Department, Oncology Center, Mansoura University, Egypt
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Egypt
| | - Ziad Emarah
- Medical Oncology Department, Oncology Center, Mansoura University, Egypt
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Egypt
| | - Sherin Abdel-Aziz
- Hematology Laboratory, Oncology Center, Mansoura University, Egypt
- Hematology section, Clinical Pathology Department, Faculty of Medicine, Mansoura University, Egypt
| | - Entsar Eladle
- Pathology Department, Faculty of Medicine, Mansoura University, Egypt
| | - Alsaeed Abdelaziz
- Internal fellowship, Mansoura University Hospital, Mansoura University, Egypt
| | - Olivier Hermine
- Department of Adult Hematology, Paris 5 Descartes University, Paris, France
- Imagine Institute, Université Sorbonne Paris Cité, Paris, France
| | - Caroline Besson
- Service d’Hématologie-Oncologie, Centre Hospitalier de Versailles, Le Chesnay, France; Université Versailles Saint Quentin en Yvelines, Université Paris-Saclay.; INSERM U 1018, Villejuif, France
| | - Hasan Abdel-Ghaffar
- Hematology Laboratory, Oncology Center, Mansoura University, Egypt
- Hematology section, Clinical Pathology Department, Faculty of Medicine, Mansoura University, Egypt
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50
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Gallipani A, Cha A, Berkowitz L, Bakshi A. Concomitant Treatment of Hepatitis C Virus and Diffuse Large B-Cell Lymphoma with Direct-Acting Antivirals in HIV Coinfection: A Case Report. J Int Assoc Provid AIDS Care 2019; 18:2325958218822062. [PMID: 30798652 PMCID: PMC6748524 DOI: 10.1177/2325958218822062] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
This report describes a case of concomitant treatment of advanced diffuse large B-cell lymphoma with chemoimmunotherapy along with direct-acting antivirals for hepatitis C virus in a patient coinfected with HIV. The patient tolerated gemcitabine, dexamethasone, cisplatin, and rituximab and achieved sustained virologic response after treatment with ledipasvir/sofosbuvir.
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Affiliation(s)
| | - Agnes Cha
- Arnold & Marie Schwartz College of Pharmacy, Brooklyn, NY, USA
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