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Tsutsumi Y, Ito S, Shiratori S, Teshima T. Hepatitis C Virus (HCV)-Ribonucleic Acid (RNA) As a Biomarker for Lymphoid Malignancy with HCV Infection. Cancers (Basel) 2023; 15:2852. [PMID: 37345190 DOI: 10.3390/cancers15102852] [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: 04/25/2023] [Revised: 05/15/2023] [Accepted: 05/15/2023] [Indexed: 06/23/2023] Open
Abstract
The hepatitis C virus (HCV) is potentially associated with liver cancer, and advances in various drugs have led to progress in the treatment of hepatitis C and attempts to prevent its transition to liver cancer. Furthermore, reactivation of HCV has been observed in the treatment of lymphoma, during which the immortalization and proliferation of lymphocytes occur, which leads to the possibility of further stimulating cytokines and the like and possibly to the development of lymphoid malignancy. There are also cases in which the disappearance of lymphoid malignancy has been observed by treating HCV and suppressing HCV-Ribonucleic acid (RNA), as well as cases of recurrence with an increase in HCV-RNA. While HCV-associated lymphoma has a poor prognosis, improving the prognosis with Direct Acting Antivirals (DAA) has recently been reported. The reduction and eradication of HCV-RNA by means of DAA is thus important for the treatment of lymphoid malignancy associated with HCV infection, and HCV-RNA can presumably play a role as a biomarker. This review provides an overview of what is currently known about HCV-associated lymphoma, its epidemiology, the mechanisms underlying the progression to lymphoma, its treatment, the potential and limits of HCV-RNA as a therapeutic biomarker, and biomarkers that are expected now that DAA therapy has been developed.
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Affiliation(s)
- Yutaka Tsutsumi
- Department of Hematology, Hakodate Municipal Hospital, Hakodate, 1-10-1, Minato-cho, Hakodate 041-8680, Japan
| | - Shinichi Ito
- Department of Hematology, Hakodate Municipal Hospital, Hakodate, 1-10-1, Minato-cho, Hakodate 041-8680, Japan
| | - Souichi Shiratori
- Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Takanori Teshima
- Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
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Arcari A, Tabanelli V, Merli F, Marcheselli L, Merli M, Balzarotti M, Zilioli VR, Fabbri A, Cavallo F, Casaluci GM, Tucci A, Puccini B, Pennese E, Di Rocco A, Zanni M, Flenghi L, Gini G, Sartori R, Chiappella A, Usai SV, Tani M, Marino D, Arcaini L, Vallisa D, Spina M. Biological features and outcome of diffuse large B-cell lymphoma associated with hepatitis C virus in elderly patients: Results of the prospective 'Elderly Project' by the Fondazione Italiana Linfomi. Br J Haematol 2023; 201:653-662. [PMID: 36733229 DOI: 10.1111/bjh.18678] [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: 10/21/2022] [Revised: 12/23/2022] [Accepted: 01/18/2023] [Indexed: 02/04/2023]
Abstract
Up to 10%-15% of diffuse large B-cell lymphoma (DLBCL) are related to hepatitis C virus (HCV) infection, in particular in elderly patients. The Fondazione Italiana Linfomi has recently published a multicentre prospective observational study, the 'Elderly Project', on the outcome of DLBCL in patients aged ≥65 years, evaluated using a simplified comprehensive geriatric assessment. The aim of this study was to compare biological and clinical features of HCV positive (HCV+) with HCV negative (HCV-) cases. A total of 89 HCV+ patients were identified out of 1095 evaluated for HCV serology (8.1%). The HCV+ patients were older, less fit, and had frequent extranodal involvement. The cell-of-origin determination by Nanostring showed that HCV+ cases less frequently had an activated B-cell profile compared to HCV- patients (18% vs. 43%). In all, 86% of HCV+ patients received rituximab-cyclophosphamide, doxorubicin, vincristine (Oncovin) and prednisone (R-CHOP)-like immunochemotherapy. Grade 3-4 liver toxicity occurred in 3% of cases. Among centrally reviewed cases confirmed as DLBCL, the 3-year overall survival of HCV+ patients was very similar to HCV- (63% vs. 61%, p = 0.926). In all, 20 HCV+ patients were treated with direct-acting antiviral agents (DAAs), with good tolerance and sustained virological response in all cases. The 3-year progression-free survival for this subgroup was excellent (77%), suggesting DAAs' possible role in reducing the risk of relapse by eliminating the viral trigger.
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Affiliation(s)
- Annalisa Arcari
- Hematology Unit, Ospedale Guglielmo da Saliceto, Piacenza, Italy
| | - Valentina Tabanelli
- Division of Haematopathology, European Institute of Oncology IRCCS, Milan, Italy
| | - Francesco Merli
- Hematology Unit, Azienda Unità Sanitaria Locale-IRCCS, Reggio Emilia, Italy
| | | | - Michele Merli
- Division of Hematology, Ospedale di Circolo and Fondazione Macchi, University of Insubria, Varese, Italy
| | - Monica Balzarotti
- Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy
| | | | - Alberto Fabbri
- Unit of Hematology, Azienda Ospedaliera Universitaria Senese, Siena, Italy
| | - Federica Cavallo
- Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino/AOU Città della Salute e della Scienza di Torino, Torino, Italy
| | - Gloria Margiotta Casaluci
- Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
| | | | - Benedetta Puccini
- Hematology Department, University of Florence and AOU Careggi, Florence, Italy
| | - Elsa Pennese
- Lymphoma Unit, Department of Hematology, Ospedale Spirito Santo, Pescara, Italy
| | - Alice Di Rocco
- Department of Traslational and Precision Medicine, Sapienza University, Rome, Italy
| | - Manuela Zanni
- Division of Hematology, A.O. SS Antonio e Biagio and Cesare Arrigo, Alessandria, Italy
| | - Leonardo Flenghi
- Division of Hematology, S. Maria della Misericordia Hospital, Perugia, Italy
| | - Guido Gini
- Clinic of Hematology, Azienda Ospedaliera Universitaria Ospedali Riuniti, Ancona, Italy
| | - Roberto Sartori
- Onco Hematology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
| | | | - Sara Veronica Usai
- Division of Hematology, Ospedale Oncologico Armando Businco, Cagliari, Italy
| | - Monica Tani
- Hematology Unit, Santa Maria delle Croci Hospital, Ravenna, Italy
| | - Dario Marino
- Department of Clinical and Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS Padova, Padova, Italy
| | - Luca Arcaini
- Department of Molecular Medicine, University of Pavia and Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Daniele Vallisa
- Hematology Unit, Ospedale Guglielmo da Saliceto, Piacenza, Italy
| | - Michele Spina
- Division of Medical Oncology and Immunerelated tumors, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
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Peters A, Keating MM, Nikonova A, Doucette S, Prica A. Management of Marginal Zone Lymphoma: A Canadian Perspective. Curr Oncol 2023; 30:1745-1759. [PMID: 36826096 PMCID: PMC9955247 DOI: 10.3390/curroncol30020135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 01/25/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023] Open
Abstract
Marginal zone lymphomas (MZL) are a rare, heterogenous group of lymphomas, accounting for 5-17% of indolent non-Hodgkin lymphomas in the western world. They can be further divided into three subtypes: extranodal MZL, splenic MZL, and nodal MZL. These subtypes differ in clinical presentation and behavior, which influences how they are managed. There is currently no standard of care for the treatment of MZL, owing to the difficulty in conducting phase 3 randomized trials in MZL, and the fact that there are limited data on the efficacy of therapy in individual subtypes. Treatment practices are thus largely borrowed from other indolent lymphomas and are based on patient and disease characteristics, as well as access to therapy. This review summarizes the Canadian treatment landscape for MZL and how these therapies may be sequenced in practice.
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Affiliation(s)
- Anthea Peters
- Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada
- Correspondence:
| | - Mary-Margaret Keating
- Division of Hematology, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS B3H 2Y9, Canada
| | - Anna Nikonova
- Division of Hematology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
| | | | - Anca Prica
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON M5G 2C1, Canada
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Kadry DY, Elbahnasawy MA, Mansour MTM, EL Gebaly OK, Aziz H, Kamel MM, Abdel-Moneim AS, Radwan S. The impact of hepatitis B virus and hepatitis C virus infections in patients with Hodgkin's and non-Hodgkin's lymphoma. Int J Immunopathol Pharmacol 2023; 37:3946320231207342. [PMID: 37859403 PMCID: PMC10588407 DOI: 10.1177/03946320231207342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 09/24/2023] [Indexed: 10/21/2023] Open
Abstract
BACKGROUND This study aimed to determine the prevalence of HCV and occult HBV among newly diagnosed pre-treatment Egyptian lymphoma patients and evaluate patients' outcomes based on the presence of the viral infections. METHODS The study included 80 therapy-naïve lymphoma patients including 71 non-Hodgkin lymphoma (NHL) and 9 Hodgkin lymphoma disease (HD) in addition to 100 healthy volunteers. HBV screening using HBsAg and anti-HBc IgM and HCV using AB/Ag ELISA and real-time RT-PCR were screened in tested and control groups. The diagnosis was confirmed by histopathology. Overall survival (OS) and progression-free survival (PFS) were conducted to diseased patients. RESULTS Healthy patients showed 4/100, (4%) active HCV infection and 1/100, (1%) active HBV infection and no occult HBV infection. Among NHL patients, 28 were positive for HBV (6 active and 22 occult HBV infection). Occult HBV was also detected in 5/9 HD patients. HCV was detected in (30/71, 42.3%) of NHL patients and in a single HD patient. Ten occult HBV NHL patients showed a mixed infection with HCV. The incidence of both HCV and HBV are higher in NHL than HL patients. After antitumor treatment, complete remission for lymphoma was achieved in 45% of patients. Both overall survival (OS) and progression-free survival (PFS) were correlated and significantly associated with patients' LDH levels. CONCLUSIONS Our findings claim the suggestive role of HCV and occult HBV infections in NHL but not HL patients in comparison to healthy control, suggesting pre-screening of related factors including occult HBV in for potential better therapy response.
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Affiliation(s)
- Dalia Y Kadry
- Clinical Pathology Department and Microbiology Lab, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Mostafa A Elbahnasawy
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo, Egypt
| | - Mohamed TM Mansour
- Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Omnia K EL Gebaly
- Clinical Pathology Department and Microbiology Lab, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Hala Aziz
- Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Mahmoud M Kamel
- Clinical Pathology Department and Microbiology Lab, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Ahmed S Abdel-Moneim
- Microbiology Department, College of Medicine, Taif University, Al-Taif, Saudi Arabia
| | - Samah Radwan
- Clinical Pathology Department and Microbiology Lab, National Cancer Institute, Cairo University, Cairo, Egypt
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5
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Rosenbloom BE, Cappellini MD, Weinreb NJ, Dragosky M, Revel‐Vilk S, Batista JL, Sekulic D, Mistry PK. Cancer risk and gammopathies in 2123 adults with Gaucher disease type 1 in the International Gaucher Group Gaucher Registry. Am J Hematol 2022; 97:1337-1347. [PMID: 36054609 PMCID: PMC9541044 DOI: 10.1002/ajh.26675] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 07/27/2022] [Accepted: 07/28/2022] [Indexed: 01/24/2023]
Abstract
There are numerous reports of cancers in Gaucher disease (GD) from mostly small single-center studies; however, precise risk estimates and cancer types involved have not been delineated. We conducted a study involving 2123 patients with GD type 1 (GD1) to assess the incidence of hematological malignancies, gammopathies, and solid tumors in an international observational study, the International Cooperative Gaucher Group Gaucher Registry (Clinicaltrials.gov: NCT00358943). Risk for cancer overall and for each type of malignancy was compared to the United States (US) population using the Surveillance, Epidemiology, and End Results database. Natural history of gammopathy was determined through assessing the progression from a diagnosis of monoclonal gammopathy of unknown significance (MGUS) to multiple myeloma (MM). Risk for hematological malignancies was more than four times higher than expected compared to the general population: non-Hodgkin lymphoma was approximately three times higher; MM was approximately nine times higher. Age-specific incidence rates of MGUS were unexpectedly high among younger patients. The 10-year cumulative incidence of MM after diagnosis of MGUS was 7.9%, comparable to the general population. Compared to the general US population, GD1 patients were at higher risk for solid malignancies of liver (2.9 times), kidney (2.8 times), melanoma (2.5 times), and breast (1.4 times). Colorectal, prostate, and lung cancer risks were lower than expected. These findings help advance care of patients with GD1 by supporting recommendations for individualized monitoring for malignancies and antecedents such as MGUS for MM and provoke important questions of the role of glucosylceramide and related sphingolipids in cancer biology.
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Affiliation(s)
| | - Maria Domenica Cappellini
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico MilanoMilanItaly
- Department of Internal MedicineUniversity of MilanMilanItaly
| | - Neal J. Weinreb
- Division of Hematology, Department of Internal MedicineUniversity of Miami Miller School of MedicineMiamiFloridaUSA
- Division of Clinical Genetics, Department of Human GeneticsUniversity of Miami Miller School of MedicineMiamiFloridaUSA
| | - Marta Dragosky
- Department of HematologyHenry Moore InstituteBuenos AiresArgentina
| | - Shoshana Revel‐Vilk
- Department of Pediatric Hematology, School of MedicineHebrew UniversityJerusalemIsrael
- Gaucher Unit, Shaare Zedek Medical CenterJerusalemIsrael
| | - Julie L. Batista
- Department of Epidemiology and BiostatisticsSanofiCambridgeMassachusettsUSA
| | - Davorka Sekulic
- Global Medical Affairs Hematology, Sanofi, CambridgeMassachusettsUSA
| | - Pramod K. Mistry
- Department of Internal MedicineYale University School of MedicineNew HavenConnecticutUSA
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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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7
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Kondili LA, Monti M, Quaranta MG, Gragnani L, Panetta V, Brancaccio G, Mazzaro C, Persico M, Masarone M, Gentile I, Andreone P, Madonia S, Biliotti E, Filomia R, Puoti M, Fracanzani AL, Laccabue D, Ieluzzi D, Coppola C, Rumi MG, Benedetti A, Verucchi G, Coco B, Chemello L, Iannone A, Ciancio A, Russo FP, Barbaro F, Morisco F, Chessa L, Massari M, Blanc P, Zignego AL. A prospective study of direct-acting antiviral effectiveness and relapse risk in HCV cryoglobulinemic vasculitis by the Italian PITER cohort. Hepatology 2022; 76:220-232. [PMID: 34919289 PMCID: PMC9305531 DOI: 10.1002/hep.32281] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 10/27/2021] [Accepted: 12/08/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Mixed cryoglobulinemia is the most common HCV extrahepatic manifestation. We aimed to prospectively evaluate the cryoglobulinemic vasculitis (CV) clinical profile after a sustained virologic response (SVR) over a medium-term to long-term period. APPROACH AND RESULTS Direct-acting antiviral-treated cryoglobulinemic patients, consecutively enrolled in the multicentric Italian Platform for the Study of Viral Hepatitis Therapy cohort, were prospectively evaluated. Cumulative incidence Kaplan-Meier curves were reported for response, clinical deterioration, relapse and relapse-free survival rates. Cox regression analysis evaluated factors associated with different outcomes. A clinical response was reported in at least one follow-up point for 373 of 423 (88%) patients with CV who achieved SVR. Clinical response increased over time with a 76% improvement rate at month 12 after the end of treatment. A full complete response (FCR) was reached by 164 (38.8%) patients in at least one follow-up point. CV clinical response fluctuated, with some deterioration of the initial response in 49.6% of patients (median time of deterioration, 19 months). In patients who achieved FCR and had an available follow-up (137 patients) a relapse was observed in 13% and it was transient in 66.7% of patients. The rate of patients without any deterioration was 58% and 41% at 12 and 24 months, respectively. After achieving SVR, a clinical nonresponse was associated with older age and renal involvement; a clinical deterioration/relapse was associated with high pretreatment rheumatoid factor values, and FCR was inversely associated with age, neuropathy, and high cryocrit levels. CONCLUSION In patients with CV, HCV eradication may not correspond to a persistent clinical improvement, and clinical response may fluctuate. This implies an attentive approach to post-SVR evaluation through prognostic factors and tailored treatment.
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Affiliation(s)
| | - Monica Monti
- Center for Systemic Manifestations of Hepatitis VirusesDepartment of Experimental and Clinical MedicineUniversity of FlorenceFlorenceItaly
| | | | - Laura Gragnani
- Center for Systemic Manifestations of Hepatitis VirusesDepartment of Experimental and Clinical MedicineUniversity of FlorenceFlorenceItaly
| | - Valentina Panetta
- L'altrastatistica srlConsultancy & Training, Biostatistics officeRomeItaly
| | | | - Cesare Mazzaro
- Clinical and Experimental Onco‐Haematology UnitIRCCS Centro di Riferimento OncologicoAviano, PordenoneItaly
| | - Marcello Persico
- Internal Medicine and Hepatology UnitSalerno UniversitySalernoItaly
| | - Mario Masarone
- Internal Medicine and Hepatology UnitSalerno UniversitySalernoItaly
| | - Ivan Gentile
- Department of Clinical Medicine and SurgeryUniversity of Naples Federico IINaplesItaly
| | - Pietro Andreone
- Department of Internal MedicineUniversity of Modena and Reggio EmiliaModenaItaly
| | - Salvatore Madonia
- Department of Internal MedicineVilla Sofia‐Cervello HospitalPalermoItaly
| | - Elisa Biliotti
- Infectious and Tropical Diseases UnitUmberto I Hospital‐“Sapienza” UniversityRomeItaly
| | - Roberto Filomia
- Department of Internal MedicineUniversity Hospital of MessinaMessinaItaly
| | | | - Anna Ludovica Fracanzani
- General Medicine and Metabolic DiseasesFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoUniversità degli Studi di MilanoMilanItaly
| | - Diletta Laccabue
- Laboratory of Viral Immunopathology, Unit of Infectious Diseases and HepatologyAzienda Ospedaliero‐Universitaria di ParmaUniversity of ParmaParmaItaly
| | | | - Carmine Coppola
- Department of HepatologyGragnano HospitalGragnano, NaplesItaly
| | | | - Antonio Benedetti
- Clinic of Gastroenterology and HepatologyUniversità Politecnica delle MarcheAnconaItaly
| | - Gabriella Verucchi
- Clinic of Infectious Diseases and Microbiology UnitAlma Mater Studiorum Bologna UniversityBolognaItaly
| | - Barbara Coco
- Hepatology and Liver Physiopathology Laboratory and Internal MedicineDepartment of Clinical and Experimental MedicineUniversity Hospital of PisaPisaItaly
| | - Liliana Chemello
- Unit of Internal Medicine and Hepatology–Clinica Medica 5Department of Medicine‐DIMEDUniversity of PaduaPaduaItaly
| | | | - Alessia Ciancio
- Gastroenterology UnitCittà della Salute e della Scienza of TurinUniversity HospitalTurinItaly
| | - Francesco Paolo Russo
- Gastroenterology UnitDepartment of Surgery, Oncology and GastroenterologyUniversity of PaduaPaduaItaly
| | | | | | | | - Marco Massari
- Infectious Diseases UnitAzienda Unità Sanitaria Locale–IRCCS di Reggio EmiliaReggio EmiliaItaly
| | - Pierluigi Blanc
- Infectious Disease UnitSanta Maria Annunziata HospitalFlorenceItaly
| | - Anna Linda Zignego
- Center for Systemic Manifestations of Hepatitis VirusesDepartment of Experimental and Clinical MedicineUniversity of FlorenceFlorenceItaly
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Tsai YF, Liu YC, Yang CI, Chuang TM, Ke YL, Yeh TJ, Gau YC, Du JS, Wang HC, Cho SF, Hsu CM, Wu PF, Huang CI, Huang CF, Yu ML, Dai CY, Hsiao HH. Poor Prognosis of Diffuse Large B-Cell Lymphoma with Hepatitis C Infection. J Pers Med 2021; 11:844. [PMID: 34575621 PMCID: PMC8465128 DOI: 10.3390/jpm11090844] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 08/24/2021] [Accepted: 08/25/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) in diffuse large B-cell lymphoma (DLBCL) is associated with a higher prevalence and distinctive clinical characteristics and outcomes. METHODS A retrospective analysis of adult DLBCL patients from 2011 to 2015 was studied. RESULTS A total of 206 adult DLBCL were enrolled with 22 (10.7%) HCV-positive patients. Compared to HCV-negative patients, the HCV-positive group had a poor performance status (p = 0.011), lower platelet count (p = 0.029), and higher spleen and liver involvement incidences (liver involvement, p = 0.027, spleen involvement, p = 0.026), and they received fewer cycles of chemotherapy significantly due to morbidity and mortality (p = 0.048). Overall survival was shorter in HCV-positive DLBCL (25.3 months in HCV-positive vs. not reached (NR), p = 0.049). With multivariate analysis, poor performance status (p < 0.001), advanced stage (p < 0.001), less chemotherapy cycles (p < 0.001), and the presence of liver toxicity (p = 0.001) contributed to poor OS in DLBCL. Among HCV-positive DLBCL, the severity of liver fibrosis was the main risk factor related to death. CONCLUSION Inferior survival of HCV-positive DLBCL was observed and associated with poor performance status, higher numbers of complications, and intolerance of treatment, leading to fewer therapy. Therefore, anti-HCV therapy, such as direct-acting antiviral agents, might benefit these patients in the future.
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Affiliation(s)
- Yu-Fen Tsai
- Department of Hematology & Oncology, E-Da Cancer Hospital, Kaohsiung 824, Taiwan;
- School of Chinese Medicine for Post Baccalaureate, College of Medicine, I-Shou University, Kaohsiung 824, Taiwan
| | - Yi-Chang Liu
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
| | - Ching-I Yang
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
- Specialist Nurse and Surgical Nurse Practitioner Office, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Tzer-Ming Chuang
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
| | - Ya-Lun Ke
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
| | - Tsung-Jang Yeh
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
| | - Yuh-Ching Gau
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
| | - Jeng-Shiun Du
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
| | - Hui-Ching Wang
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
| | - Shih-Feng Cho
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
| | - Chin-Mu Hsu
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
| | - Pey-Fang Wu
- Division of Hepatobiliary Ward, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan;
| | - Ching-I Huang
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
- Division of Hepatobiliary Ward, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan;
| | - Chung-Feng Huang
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
- Division of Hepatobiliary Ward, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan;
| | - Ming-Lung Yu
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
- Division of Hepatobiliary Ward, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan;
| | - Chia-Yen Dai
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
- Division of Hepatobiliary Ward, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan;
| | - Hui-Hua Hsiao
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
- Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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9
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Gragnani L, Lorini S, Marri S, Vacchi C, Madia F, Monti M, Ferri C, Zignego AL. Predictors of long-term cryoglobulinemic vasculitis outcomes after HCV eradication with direct-acting antivirals in the real-life. Autoimmun Rev 2021; 21:102923. [PMID: 34419670 DOI: 10.1016/j.autrev.2021.102923] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 08/14/2021] [Indexed: 12/21/2022]
Abstract
Cryoglobulinemic vasculitis (CV) is the most frequent extrahepatic manifestation during HCV-chronic infection. An effective Direct Acting Antiviral-treatment leads to CV clinical response in the majority of CV-patients although symptoms may persist/recur despite a sustained virological response. At present, no standardized clinical predictive factors for disease maintenance/recurrence were proposed, as emerged from a complete literature review we performed and reported. Here we provided a detailed descriptive analysis of a wide population of CV patients treated with DAA-based regimes and followed-up after therapy completion for longer than 72 weeks, in order to identify clinical or laboratory predictors of disease outcome and to optimize the patient management. Together with some baseline symptoms (neuropathy, weakness and sicca syndrome), two newly created scores, CV- and Global Severity Index, emerged as reliable and standardized tools to predict CV clinical response before initiating an antiviral therapy. In addition to predictive parameters previously proposed in the world literature, these novel Indexes could fill an unmet gap in the clinical management of the complex HCV-related CV.
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Affiliation(s)
- Laura Gragnani
- MASVE Interdepartmental Hepatology Center, Department of Experimental and clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, AOU Careggi, Florence, Italy
| | - Serena Lorini
- MASVE Interdepartmental Hepatology Center, Department of Experimental and clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, AOU Careggi, Florence, Italy
| | - Silvia Marri
- MASVE Interdepartmental Hepatology Center, Department of Experimental and clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, AOU Careggi, Florence, Italy
| | - Caterina Vacchi
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Italy
| | - Francesco Madia
- MASVE Interdepartmental Hepatology Center, Department of Experimental and clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, AOU Careggi, Florence, Italy
| | - Monica Monti
- MASVE Interdepartmental Hepatology Center, Department of Experimental and clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, AOU Careggi, Florence, Italy
| | - Clodoveo Ferri
- Rheumatology Unit, University of Modena and Reggio Emilia, School of Medicine, Modena, Italy.
| | - Anna Linda Zignego
- MASVE Interdepartmental Hepatology Center, Department of Experimental and clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, AOU Careggi, Florence, Italy
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10
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Lotfi AA, Mohamed AE, Shalaby NA, Eissa DS, El-Dabaa E, Sallam AM, Kamel MM, Abdelaziz H, El-Afifi AM, Abdel-Moneim AS. Occult hepatitis C virus infection in patients with malignant lymphoproliferative disorders. Int J Immunopathol Pharmacol 2021; 34:2058738420961202. [PMID: 33045856 PMCID: PMC7557643 DOI: 10.1177/2058738420961202] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Despite the link between HCV and malignant lymphoproliferative disorders has been established, the association between occult hepatitis C virus infection and malignant lymphoproliferative disorders remains obscure. The present study intended to identify the possible association between occult HCV infection and malignant lymphoproliferative disorders. Newly diagnosed patients with LPDs were screened for the presence of HCV-RNA in both plasma and PBMCs. PBMCs of the subjects were also, examined by transmission and immuno-electron microscopy. LPD patients showed a high percentage of HCV infection (71.9%): OCI-HCV (37.5%) and HCV (34.38%). Meanwhile, 28.13% of LPD patients did not show any evidence of HCV infection. Ultrastructural examination of PBMCs revealed the presence of intracytoplasmic vacuoles enclosing viral like particles, which were less prominent in occult HCV patients. The possibility of occult HCV should be considered in patients with LPDs which can be helpful in the management of the treatment protocol in order to set up a balance between the control of the tumor progression and minimizing post chemotherapy complications related to HCV infection.
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Affiliation(s)
- Abeya A Lotfi
- Clinical and Chemical Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Asmaa E Mohamed
- Clinical and Chemical Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Nahela A Shalaby
- Clinical and Chemical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Deena S Eissa
- Clinical and Chemical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ehab El-Dabaa
- Biochemistry and Molecular biology department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Ayman M Sallam
- Biochemistry and Molecular biology department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Mahmoud M Kamel
- Clinical Pathology Department, National Cancer Institute, Cairo University, Giza, Egypt
| | - Hisham Abdelaziz
- Clinical Pathology Department, National Cancer Institute, Cairo University, Giza, Egypt
| | - Amal M El-Afifi
- Department of Clinical hematology and transplantation, Ain shams University, Cairo, Egypt
| | - Ahmed S Abdel-Moneim
- Microbiology Department, College of Medicine, Taif University, Taif, Saudi Arabia.,Virology Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt
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11
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Sima A, Hollander P, Baecklund E, Smedby KE, Enblad G, Amini RM. Superior outcome for splenectomised patients in a population-based study of splenic marginal zone lymphoma in Sweden. Br J Haematol 2021; 194:568-579. [PMID: 34109612 DOI: 10.1111/bjh.17577] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 05/06/2021] [Indexed: 12/11/2022]
Abstract
Splenic marginal zone lymphoma (SMZL) is a rare low-grade B-cell lymphoma where associations with viral hepatitis and autoimmune and inflammatory diseases (AID) have been indicated. We aimed at assessing the prevalence of viral hepatitis and AID at SMZL diagnosis and outcome by treatment in a Swedish population-based study. A total of 277 SMZL patients registered in the Swedish Lymphoma Register in 2007-2017 were included. A history of viral hepatitis was reported in five (2%) patients and AID prior to SMZL in 72/240 (30%) patients. Treatment was given up front for 207 (75%) patients. Splenectomy with or without systemic treatment was performed in 119 (57%) and was associated with statistically significantly better overall survival [hazard ratio, HR = 0·47 (95% confidence interval, CI: 0·23-0·93), P = 0·03] and progression-free survival (HR = 0·55, 95% CI: 0·35-0·86, P = 0·008) compared to non-splenectomised patients in multivariable analyses. The up-front splenectomised group was younger and generally had a lower Ann Arbor stage, but also more frequently B symptoms and high lactate dehydrogenase than the non-splenectomised group. Viral hepatitis and AID history did not affect SMZL outcome. We report high incidence of AIDs and low incidence of viral hepatitis in this population-based study of SMZL. Splenectomy up front was associated with a favourable outcome.
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Affiliation(s)
- Andreea Sima
- Clinical and Experimental Pathology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden
| | - Peter Hollander
- Clinical and Experimental Pathology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden
| | - Eva Baecklund
- Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden
| | - Karin E Smedby
- Division of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Gunilla Enblad
- Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden
| | - Rose-Marie Amini
- Clinical and Experimental Pathology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden
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12
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Impact of DAA-Based Regimens on HCV-Related Extra-Hepatic Damage: A Narrative Review. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1323:115-147. [PMID: 33326112 DOI: 10.1007/5584_2020_604] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Two-third of patients with chronic hepatitis C show extrahepatic manifestations due to HCV infection of B lymphocytes, such as mixed cryoglobulinemia and non-Hodgkin B-cell lymphoma, or develop a chronic inflammatory status that may favor the development of adverse cardiovascular events, kidney diseases or metabolic abnormalities.DAAs treatments induce HCV eradication in 95% of treated patients, which also improves the clinical course of extrahepatic manifestations, but with some limitations. After HCV eradication a good compensation of T2DM has been observed, but doubts persist about the possibility of obtaining a stable reduction in fasting glucose and HbA1c levels.Chronic HCV infection is associated with low total and LDL cholesterol serum levels, which however increase significantly after HCV elimination, possibly due to the disruption of HCV/lipid metabolism interaction. Despite this adverse effect, HCV eradication exerts a favorable action on cardiovascular system, possibly by eliminating numerous other harmful effects exerted by HCV on this system.DAA treatment is also indicated for the treatment of patients with mixed cryoglobulinemia syndrome, since HCV eradication results in symptom reduction and, in particular, is effective in cryoglobulinemic vasculitis. Furthermore, HCV eradication exerts a favorable action on HCV-related lymphoproliferative disorders, with frequent remission or reduction of clinical manifestations.There is also evidence that HCV clearance may improve impaired renal functions, but same conflicting data persist on the effect of some DAAs on eGFR.
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13
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Evans MG, Mueller MA, Chen F, Nichter LS. Splenic marginal zone B-cell lymphoma associated with ruptured breast implants: case report and review of the literature. CASE REPORTS IN PLASTIC SURGERY AND HAND SURGERY 2021; 8:46-49. [PMID: 33898650 PMCID: PMC8023617 DOI: 10.1080/23320885.2021.1891903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
We describe splenomegaly and bilateral grade 2 Baker breast capsular contracture in a woman who had undergone augmentation mammoplasty. This case represents the first documented instance of splenic marginal zone lymphoma, and is among the rare reports of B-cell lymphoma, arising in a patient with breast implants.
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Affiliation(s)
- Mark G Evans
- Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA
| | - Melissa A Mueller
- Division of Plastic Surgery, Department of Surgery, University of Indiana, Indianapolis, IN, USA
| | - Frederik Chen
- Department of Radiology, Mayo Clinic, Phoenix, AZ, USA
| | - Larry S Nichter
- Department of Plastic Surgery, University of California, Irvine, CA, USA.,Pacific Center for Plastic Surgery & Mission Plasticos, Newport Beach, CA, USA
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14
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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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15
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Zhang XY, Wang ZM. Relevance on the diagnosis of malignant lymphoma of the salivary gland. World J Clin Cases 2020; 8:2717-2726. [PMID: 32742982 PMCID: PMC7360714 DOI: 10.12998/wjcc.v8.i13.2717] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 04/13/2020] [Accepted: 06/10/2020] [Indexed: 02/05/2023] Open
Abstract
Malignant lymphoma originates from the lymphohematopoietic system. It can occur in any lymphoid tissue. Malignant lymphoma of the salivary gland is rare, but its incidence has increased in recent years. Its clinical- presentations are non-specific, and it is often manifested as a painless mass in a salivary gland, which can be accompanied by multiple swollen cervical lymph nodes. Confirmation of the diagnosis before an invasive procedure is difficult. Clinically, malignant lymphoma of the salivary gland tends to be misdiagnosed, leading to an inappropriate treatment plan and the ultimate delay in the optimal treatment of the disease. This article reviews the pathogenesis, clinical features, imaging findings, diagnosis, treatment and prognosis of malignant lymphoma of the salivary gland.
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Affiliation(s)
- Xin-Yue Zhang
- Department of Stomatology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Zhi-Ming Wang
- Department of Stomatology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
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16
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Merli M, Defrancesco I, Visco C, Besson C, Di Rocco A, Arcari A, Sica A, Cencini E, Tisi MC, Frigeni M, Grossi P, Bianchi B, Mora B, Bertù L, Bruno R, Passamonti F, Arcaini L. Direct-acting antivirals in relapsed or refractory hepatitis C virus-associated diffuse large B-cell lymphoma. Leuk Lymphoma 2020; 61:2122-2128. [PMID: 32343165 DOI: 10.1080/10428194.2020.1755859] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Recent studies have demonstrated feasibility and substantial benefit of direct-acting antivirals (DAAs) administration during or after first-line immune-chemotherapy (I-CT) in patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphomas (DLBCL). However, data on DAAs used during or after salvage treatments are still lacking. In this study we assessed clinical and virological outcome in 11 patients with relapsed (n = 7) or refractory (n = 4) HCV-positive DLBCL. DAAs were given either concurrently (n = 3) or subsequent (n = 8) to salvage I-CT. Most patients (10 of 11) received sofosbuvir-based regimens. All patients completed their planned courses of DAAs and achieved sustained virological response. DAAs were well tolerated, with no grade ≥2 adverse events. At a median follow-up of 3.6 years four patients died (4-year OS: 76%). In conclusion, we provide evidence that DAAs in HCV-positive relapsed/refractory DLBCL are extremely safe and effective, suggesting that they should be used if HCV eradication was not instituted before.
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Affiliation(s)
- Michele Merli
- Department of Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi -ASST Sette Laghi, University of Insubria, Varese, Italy
| | | | - Carlo Visco
- Department of Medicine, Section of Hematology, University of Verona, Verona, Italy
| | - Caroline Besson
- Unit of Hematology-Oncology, Centre Hospitalier de Versailles, Le Chesnay, France
| | - Alice Di Rocco
- Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy
| | - Annalisa Arcari
- Hematology Unit, Department of Onco-Hematology, Guglielmo da Saliceto Hospital, Piacenza, Italy
| | - Antonello Sica
- Department of Oncology and Hematology, AOU "Luigi Vanvitelli", Naples, Italy
| | - Emanuele Cencini
- Department of Hematology, Azienda Ospedaliera Senese, University of Siena, Siena, Italy
| | - Maria Chiara Tisi
- Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy
| | - Marco Frigeni
- Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Paolo Grossi
- Department of Infectious and Tropical Diseases, University Hospital Ospedale di Circolo e Fondazione Macchi - ASST Sette Laghi, University of Insubria, Varese, Italy
| | - Benedetta Bianchi
- Department of Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi -ASST Sette Laghi, University of Insubria, Varese, Italy
| | - Barbara Mora
- Department of Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi -ASST Sette Laghi, University of Insubria, Varese, Italy
| | - Lorenza Bertù
- Department of Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi -ASST Sette Laghi, University of Insubria, Varese, Italy
| | - Raffaele Bruno
- Department of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Francesco Passamonti
- Department of Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi -ASST Sette Laghi, University of Insubria, Varese, Italy
| | - Luca Arcaini
- Department of Molecular Medicine, University of Pavia, Pavia, Italy.,Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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17
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Abstract
Vasculitis, characterized by inflammation and necrosis, manifests a wide spectrum of presentation by involving a vasculature of various sizes and locations. A definitive diagnosis of vasculitis invariably requires histologic confirmation since there are no diagnostic clinical, imaging, or laboratory findings. The most widely adopted vasculitis classification is the Chapel Hill Consensus Conference (CHCC) nomenclature of systemic vasculitis which integrated clinical symptoms, histopathologic features, and laboratory findings. This classification accounts for the size of the involved vessels. This chapter outlines the clinical and histologic features of the small-vessel vasculitis including the immune complex vasculitis and antineutrophil cytoplasmic antibody-associated vasculitis; medium-vessel vasculitis such as polyarteritis nodosa and Kawasaki disease; large-vessel vasculitis, namely, giant cell arteritis and Takayasu arteritis; variable-vessel vasculitis such as Behcet disease and Cogan syndrome; and vasculitis associated with systemic diseases including rheumatoid arthritis, lupus vasculitis, and sarcoid vasculitis. Vasculitis can also be secondary to drugs, infection, underlying systemic disease, or trauma. Therefore, a diagnosis of vasculitis cannot be based on histologic ground alone. Clinical pathologic correlation is necessary.
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Affiliation(s)
- Mai P. Hoang
- Professor of Pathology, Harvard Medical School, Director of Dermatopathology, Massachusetts General Hospital, Boston, MA USA
| | - Maria Angelica Selim
- Professor of Pathology and Dermatology, Director, Dermatopathology Unit, Duke University Medical Center, Durham, NC USA
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18
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Defrancesco I, Zerbi C, Rattotti S, Merli M, Bruno R, Paulli M, Arcaini L. HCV infection and non-Hodgkin lymphomas: an evolving story. Clin Exp Med 2020; 20:321-328. [PMID: 32052244 DOI: 10.1007/s10238-020-00615-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Accepted: 02/07/2020] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus infection represents a global health problem with 3% of population infected worldwide. Several epidemiological studies have shown an increased risk of B cell non-Hodgkin lymphomas in HCV-infected subjects with a wide geographic variability. The observation that HCV eradication by antiviral treatment is associated with successful lymphoma response provided the most convincing evidence for the causal role of HCV in lymphoma's development. According to the most accepted model, HCV-driven chronic antigenic stimulation may represent the major stimulus for lymphoma growth. Several evidences have led to recommend antiviral therapy (in the past interferon-based, now the new direct-acting antiviral agents) in the setting of asymptomatic indolent B cell lymphomas not requiring an immediate systemic treatment. The favourable profile of direct-acting antiviral agents supports the HCV eradication also in the setting of HCV-positive diffuse large B cell lymphoma; however, further studies are needed to assess the appropriate timing of these drugs in the treatment of aggressive lymphomas. Multidisciplinary management involving expert hepatologists is highly warranted.
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Affiliation(s)
| | - Caterina Zerbi
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Sara Rattotti
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100, Pavia, Italy
| | - Michele Merli
- Division of Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi-Azienda Socio-Sanitaria Territoriale Sette Laghi, University of Insubria, Varese, Italy
| | - Raffaele Bruno
- Division of Infectious Diseases Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.,Department of Medical, Surgical, Diagnostic and Paediatric Science, University of Pavia, Pavia, Italy
| | - Marco Paulli
- Department of Molecular Medicine, University of Pavia, Pavia, Italy.,Anatomic Pathology Section, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Luca Arcaini
- Department of Molecular Medicine, University of Pavia, Pavia, Italy. .,Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100, Pavia, Italy.
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19
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Response to Interferon-Free Direct Antivirals (DAAS) Treatment in Hcv-Related Subcutaneous Marginal Zone B-Cell Lymphoma with Lipoma-Like Presentation: Report of Two Cases. Mediterr J Hematol Infect Dis 2019; 11:e2019053. [PMID: 31528319 PMCID: PMC6736227 DOI: 10.4084/mjhid.2019.053] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 08/10/2019] [Indexed: 12/26/2022] Open
Abstract
Many epidemiological, biological and therapeutic studies have extensively investigated the etiological link between HCV infection and B-cell Non-Hodgkin Lymphoma (NHL). Large experiences in the literature demonstrated HCV-related indolent NHL regression after antiviral therapy. While the response to interferon-ribavirin-based antiviral therapy is well documented, evidence of the efficacy of interferon-free Direct-Acting Antivirals (DAAs) in this subset of lymphoma is also currently increasing. Splenic and Nodal Marginal zone Lymphoma (MZL) are frequently associated with HCV chronic infection. In this article we report two cases of HCV-related MZL with an unusual presentation, subcutaneous “lipoma-like” nodules, treated with DAAs. Both patients, a 59-years-old woman and a 72-years-old man, were affected by HCV chronic infection since several years and were referred to our Institute for a diagnosis of MZL with subcutaneous presentation. Given the possible etiological link with HCV infection, both patients were treated with DAAS. A Sustained virological response (SVR) was reached after few weeks of therapy and at the end of treatment a clinically and radiologically documented reduction of MZL localizations, persisting to date, were obtained in both patients. The two clinical cases presented in this article confirm the efficacy of DAA’s as first-line treatment in HCV related NHL, also in this rare entity of MZL with subcutaneous presentation.
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Merli M, Frigeni M, Alric L, Visco C, Besson C, Mannelli L, Di Rocco A, Ferrari A, Farina L, Pirisi M, Piazza F, Loustaud-Ratti V, Arcari A, Marino D, Sica A, Goldaniga M, Rusconi C, Gentile M, Cencini E, Benanti F, Rumi MG, Ferretti VV, Grossi P, Gotti M, Sciarra R, Tisi MC, Cano I, Zuccaro V, Passamonti F, Arcaini L. Direct-Acting Antivirals in Hepatitis C Virus-Associated Diffuse Large B-cell Lymphomas. Oncologist 2019; 24:e720-e729. [PMID: 30552159 PMCID: PMC6693710 DOI: 10.1634/theoncologist.2018-0331] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 11/06/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND International guidelines suggest hepatitis C virus (HCV) eradication by direct-acting antivirals (DAAs) after first-line immunochemotherapy (I-CT) in patients with HCV-positive diffuse large B-cell lymphoma (DLBCL), although limited experiences substantiate this recommendation. Moreover, only a few data concerning concurrent administration of DAAs with I-CT have been reported. SUBJECTS, MATERIALS, AND METHODS We analyzed hematological and virological outcome and survival of 47 consecutive patients with HCV-positive DLBCL treated at 23 Italian and French centers with DAAs either concurrently (concurrent cohort [ConC]: n = 9) or subsequently (sequential cohort [SeqC]: n = 38) to first-line I-CT (mainly rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone [R-CHOP]-like). RESULTS Median age was 61 years, 89% of patients had stage III/IV, and 25% presented evidence of cirrhosis. Genotype was 1 in 56% and 2 in 34% of cases. Overall, 46 of 47 patients obtained complete response to I-CT. All patients received appropriate DAAs according to genotype, mainly sofosbuvir-based regimens (n = 45). Overall, 45 patients (96%) achieved sustained virological response, 8 of 9 in ConC and 37 of 38 in SeqC. DAAs were well tolerated, with only 11 patients experiencing grade 1-2 adverse events. Twenty-three patients experienced hepatic toxicity (grade 3-4 in seven) following I-CT in SeqC, compared to only one patient in ConC. At a median follow-up of 2.8 years, two patients died (2-year overall survival, 97.4%) and three progressed (2-year progression-free survival, 93.1%). CONCLUSION Excellent outcome of this cohort of HCV-positive DLBCL suggests benefit of HCV eradication by DAAs either after or during I-CT. Moreover, concurrent DAAs and R-CHOP administration appeared feasible, effective, and ideally preferable to deferred administration of DAAs for the prevention of hepatic toxicity. IMPLICATIONS FOR PRACTICE Hepatitis C virus (HCV)-associated diffuse large B-cell lymphomas (DLBCLs) represent a great therapeutic challenge, especially in terms of hepatic toxicity during immune-chemotherapy (I-CT) and long-term hepatic complications. The advent of highly effective and toxicity-free direct-acting antivirals (DAAs) created an exciting opportunity to easily eradicate HCV shortly after or in concomitance with first-line immunochemotherapy (usually R-CHOP). This retrospective international study reports the real-life use of the combination of these two therapeutic modalities either in the concurrent or sequential approach (DAAs after I-CT) in 47 patients. The favorable reported results on long-term outcome seem to support the eradication of HCV with DAAs in all patients with HCV-positive DLBCL. Moreover, the results from the concurrent approach were effective and safe and displayed an advantage in preventing hepatic toxicity during I-CT.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Antiviral Agents/therapeutic use
- Cyclophosphamide/administration & dosage
- Disease-Free Survival
- Doxorubicin/administration & dosage
- Female
- Hepacivirus/drug effects
- Hepatitis C, Chronic/drug therapy
- Hepatitis C, Chronic/epidemiology
- Hepatitis C, Chronic/pathology
- Hepatitis C, Chronic/virology
- Humans
- Incidence
- Italy/epidemiology
- Lymphoma, Large B-Cell, Diffuse/drug therapy
- Lymphoma, Large B-Cell, Diffuse/epidemiology
- Lymphoma, Large B-Cell, Diffuse/pathology
- Lymphoma, Large B-Cell, Diffuse/virology
- Male
- Middle Aged
- Prednisone/administration & dosage
- Retrospective Studies
- Rituximab/administration & dosage
- Vincristine/administration & dosage
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Affiliation(s)
- Michele Merli
- Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi-ASST Sette Laghi, University of Insubria, Varese, Italy
| | - Marco Frigeni
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Laurent Alric
- Department of Internal Medicine and Digestive Diseases, University Hospital Toulouse, UMR 152 PharmaDev, IRD Toulouse 3 University, France
| | - Carlo Visco
- Cell Therapy and Hematology, Ospedale San Bortolo, Vicenza, Italy
| | - Caroline Besson
- Unit of Hematology-Oncology, Centre Hospitalier de Versailles, Le Chesnay; Université Versailles Saint Quentin en Yvelines; INSERM U1018, Centre pour la Recherche en Epidemiologie et Sante des Populations (CESP), Equipe Generations et Sante, Gustave Roussy, Villejuif, France
| | - Lara Mannelli
- Hematology, Azienda Ospedaliera Careggi, Florence, Italy
| | - Alice Di Rocco
- Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy
| | - Angela Ferrari
- Hematology Unit, Azienda Unità Sanitaria Locale-IRCCS Reggio Emilia, Italy
| | - Lucia Farina
- Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Mario Pirisi
- Translational Medicine, University of Piemonte Orientale UPO, Novara, Italy
| | | | - Véronique Loustaud-Ratti
- Hepatology, Centre Hospitalier Universitaire de Limoges, U-1248 INSERM, Université de Limoges, Limoges, France
| | | | - Dario Marino
- Department of Clinical and Experimental Oncology, Veneto Institute of Oncology, IOV IRCCS, Padova, Italy
| | - Antonello Sica
- Oncology and Hematology, AOU "Luigi Vanvitelli", Naples, Italy
| | - Maria Goldaniga
- Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Chiara Rusconi
- Hematology and Oncology, Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy
| | - Massimo Gentile
- Onco-Hematology, Hematology Unit, AO of Cosenza, Cosenza, Italy
| | - Emanuele Cencini
- Hematology, Azienda Ospedaliera Senese, University of Siena, Siena, Italy
| | | | - Maria Grazia Rumi
- Hepatology, Ospedale San Giuseppe IRCCS Multimedica, University of Milan, Milan, Italy
| | | | - Paolo Grossi
- Infectious and Tropical Diseases, University Hospital Ospedale di Circolo e Fondazione Macchi - ASST Sette Laghi, University of Insubria, Varese, Italy
| | - Manuel Gotti
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Roberta Sciarra
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Isabel Cano
- Hematology Department, Centre Hospitalier de Versailles, Versailles, France
| | - Valentina Zuccaro
- Infectious and Tropical Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Francesco Passamonti
- Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi-ASST Sette Laghi, University of Insubria, Varese, Italy
| | - Luca Arcaini
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Masarone M, Persico M. Hepatitis C virus infection and non-hepatocellular malignancies in the DAA era: A systematic review and meta-analysis. Liver Int 2019; 39:1292-1306. [PMID: 30983083 DOI: 10.1111/liv.14119] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 03/12/2019] [Accepted: 04/05/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Direct antiviral agents have greatly improved therapeutic options for chronic hepatitis C. Indeed, former "difficult-to-treat" patients can now be treated and can achieve sustained response. Hepatitis C virus (HCV) is associated with hepatocellular carcinoma and with B-cell non-Hodgkin lymphoma (B-NHL). Other malignancies have been reported to be associated with HCV infection albeit with various grades of evidence. Antineoplastic treatment is often reduced or suspended in HCV-positive cancer patients to avoid "HCV reactivation." In this setting, antiviral therapy combined with antineoplastic protocols may improve the outcome. For this reason, we conducted a systematic review and a meta-analysis to update the association between HCV infection and non-hepatocellular malignancies, and to shed light on the effects exerted by antiviral treatment on the natural history of oncological diseases. METHODS Relevant studies were identified by searching PUBMED, EMBASE and MEDLINE up to 1 August 2018. Pooled risk estimates were calculated with random-effects models according to PRISMA guidelines. RESULTS A total of 58 studies were included in the analysis: 27 studies of the association between HCV and B-NHL(OR 3.36; 95% CI 2.40-4.72;P < 0.00001);13 studies of the association between sustained virological response and progression-free survival (PFS) in B-NHL patients(OR 9.34; 95% CI 4.90-17.79; P < 0.00001); 13 studies of the association between HCV and intrahepatic-cholangio-carcinoma (OR 3.95;95% CI 2.25-6.94; P < 0.00001); and 5 studies of the association between HCV infection and pancreatic adeno-carcinoma(OR 1.60; 95% CI:1.25-2.04; P = 0.0002). CONCLUSIONS This study updates the strong association between B-NHL and HCV infection, confirms the association between HCV and non-hepatocellular tumours, and demonstrates a very strong association between viral eradication and a better outcome of HCV-positive B-NHL.
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Affiliation(s)
- Mario Masarone
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| | - Marcello Persico
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
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22
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Occhipinti V, Farina L, Viganò M, Capecchi M, Labanca S, Fanetti I, Corradini P, Rumi M. Concomitant therapy with direct-acting antivirals and chemoimmunotherapy in HCV-associated diffuse large B-cell lymphoma. Dig Liver Dis 2019; 51:719-723. [PMID: 30502232 DOI: 10.1016/j.dld.2018.10.019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 10/11/2018] [Accepted: 10/23/2018] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The association between hepatitis C virus (HCV) infection and B-cell non-Hodgkin's Lymphomas (NHL) is well established. Antiviral therapy (AVT) is the first-line treatment for HCV-related indolent NHL whereas diffuse large B-cell lymphoma (DLBCL) requires immediate start of chemoimmunotherapy (CIT), usually deferring AVT. However, an early HCV elimination may reduce the risk of CIT-induced liver toxicity and consequent CIT interruption or withdrawal. To date few data are available on safety and efficacy of concomitant administration of direct-acting antivirals (DAA) and CIT in HCV-associated DLBCL. METHODS 7 consecutive patients (5 males, median age 65 years) with HCV infection (four genotype 2a/2c, two genotype 1b, one genotype 4; one patient with compensated cirrhosis) and DLBCL received different DAA regimens concurrently with CIT. RESULTS All patients completed the scheduled AVT and CIT with neither interruption nor withdrawal of the latter. One case of neutropenia was observed during concomitant therapy, no liver toxicity occurred. All patients achieved sustained virological response and complete DLBCL response (median follow-up of 12 months). CONCLUSIONS Concomitant administration of DAA and CIT for HCV-associated DLBCL is safe and may prevent CIT-induced liver toxicity. Large, prospective studies are needed to confirm these preliminary data and to assess prognostic implications.
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Affiliation(s)
| | - Lucia Farina
- Hematological Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Mauro Viganò
- Hepatology Unit, San Giuseppe Hospital, University of Milan, Milan, Italy
| | - Marco Capecchi
- Hematological Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Sara Labanca
- Hepatology Unit, San Giuseppe Hospital, University of Milan, Milan, Italy
| | - Ilaria Fanetti
- Hepatology Unit, San Giuseppe Hospital, University of Milan, Milan, Italy
| | - Paolo Corradini
- Hematological Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Mariagrazia Rumi
- Hepatology Unit, San Giuseppe Hospital, University of Milan, Milan, Italy
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23
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Rattotti S, Ferretti VV, Rusconi C, Rossi A, Fogazzi S, Baldini L, Pioltelli P, Balzarotti M, Farina L, Ferreri AJM, Laszlo D, Speziale V, Varettoni M, Sciarra R, Morello L, Tedeschi A, Frigeni M, Defrancesco I, Zerbi C, Flospergher E, Nizzoli ME, Morra E, Arcaini L. Lymphomas associated with chronic hepatitis C virus infection: A prospective multicenter cohort study from the Rete Ematologica Lombarda (REL) clinical network. Hematol Oncol 2019; 37:160-167. [PMID: 30726562 DOI: 10.1002/hon.2575] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2018] [Revised: 01/21/2019] [Accepted: 01/31/2019] [Indexed: 01/16/2023]
Abstract
Chronic hepatitis C virus (HCV) infection is related with an increased risk of non-Hodgkin lymphomas (NHL). In indolent subtypes, regression of NHL was reported after HCV eradication with antiviral therapy (AT). In 2008 in Lombardy, a region of Northern Italy, the "Rete Ematologica Lombarda" (REL, Hematology Network of Lombardy-Lymphoma Workgroup) started a prospective multicenter observational cohort study on NHL associated with HCV infection, named "Registro Lombardo dei Linfomi HCV-positivi" ("Lombardy Registry of HCV-associated non-Hodgkin lymphomas"). Two hundred fifty patients with a first diagnosis of NHL associated with HCV infection were enrolled; also in our cohort, diffuse large B cell lymphoma (DLBCL) and marginal zone lymphoma (MZL) are the two most frequent HCV-associated lymphomas. Two thirds of patients had HCV-positivity detection before NHL; overall, NHL was diagnosed after a median time of 11 years since HCV survey. Our data on eradication of HCV infection were collected prior the recent introduction of the direct-acting antivirals (DAAs) therapy. Sixteen patients with indolent NHL treated with interferon-based AT as first line anti-lymphoma therapy, because of the absence of criteria for an immediate conventional treatment for lymphoma, had an overall response rate of 90%. After a median follow-up of 7 years, the overall survival (OS) was significantly longer in indolent NHL treated with AT as first line (P = 0.048); this confirms a favorable outcome in this subset. Liver toxicity was an important adverse event after a conventional treatment in 20% of all patients, in particular among DLBCL, in which it is more frequent the coexistence of a more advanced liver disease. Overall, HCV infection should be consider as an important co-pathology in the treatment of lymphomas and an interdisciplinary approach should be always considered, in particular to evaluate the presence of fibrosis or necroinflammatory liver disease.
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Affiliation(s)
- Sara Rattotti
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Chiara Rusconi
- Division of Hematology, Ospedale Niguarda Ca' Granda, Milan, Italy
| | - Andrea Rossi
- Division of Hematology, Ospedali Riuniti, Bergamo, Italy
| | | | - Luca Baldini
- Division of Hematology, Fondazione IRCCS Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | | | | | - Lucia Farina
- Division of Hematology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Andrés J M Ferreri
- Unit of Lymphoid Malignancies, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Daniele Laszlo
- Division of Hematology, Istituto Europeo di Oncologia, Milan, Italy
| | - Valentina Speziale
- Division of Internal Medicine, Ospedale Civile di Legnano, Legnano, Italy
| | - Marzia Varettoni
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Roberta Sciarra
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Lucia Morello
- Division of Hematology, Humanitas Cancer Center, Milan, Italy
| | | | - Marco Frigeni
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.,Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | | | - Caterina Zerbi
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | | | | | - Enrica Morra
- Division of Hematology, Ospedale Niguarda Ca' Granda, Milan, Italy
| | - Luca Arcaini
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.,Department of Molecular Medicine, University of Pavia, Pavia, Italy
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Abstract
Cryoglobulinemia is defined as the persistent presence in serum of abnormal immunoglobulins (Igs) that precipitate at low temperatures and dissolve again upon warming. Cryoglobulins may be composed only of a monoclonal Ig (simple type I cryoglobulinemia), of a monoclonal Ig bound to the constant domain of polyclonal Ig heavy chains (mixed type II cryoglobulinemia), or only of polyclonal Igs (mixed type III cryoglobulinemia). The manifestations of type I cryoglobulinemia are often related to intravascular obstruction, whereas those seen in the mixed cryoglobulinemias often originate in true immune complex-mediated vasculitis. The main clinical manifestations affect the skin (purpura, necrotic ulcers), joints, peripheral nervous system, and kidneys (membranoproliferative glomerulonephritis). Patients with type I cryoglobulinemia should be investigated for hematological malignancies (myeloma and B-cell lymphoma). Hepatitis C is the main diagnosis to consider in patients with mixed cryoglobulinemia, followed by connective tissue disease and B-cell non-Hodgkin's lymphoma. The treatment depends mainly on the cause of the cryoglobulinemia. For instance, hepatitis C virus (HCV) eradication is in order in patients with HCV-associated cryoglobulinemia vasculitis, and the underlying hematological malignancy must be treated in patients with type I cryoglobulinemia.
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Clinical practice: hepatitis C virus infection, cryoglobulinemia and cryoglobulinemic vasculitis. Clin Exp Med 2018; 19:1-21. [PMID: 30430284 DOI: 10.1007/s10238-018-0536-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 10/25/2018] [Indexed: 02/06/2023]
Abstract
Cryoglobulins are circulating immunoglobulins that reversibly precipitate at temperatures below 37 °C. Type-II cryoglobulins consist of monoclonal IgM/polyclonal IgG immune complexes (ICs), whereas in type-III cryoglobulins both IgM and IgG are polyclonal. The clinical condition resulting from the presence of cryoglobulins in the blood is called mixed cryoglobulinemia (MC), which can be asymptomatic or manifest as cryoglobulinemic vasculitis (CV). Type-I cryoglobulins, consisting of a single monoclonal isotype, are detected in patients with lymphoproliferative disorders. It is now established that > 90% of MCs are associated with HCV infection. Clinically, the spectrum of symptoms may range in severity from occasional purpuric eruptions to life-threatening features. In addition to the development of liver cirrhosis and hepatocellular carcinoma, the possible progression of HCV-positive CV patients to B-cell non-Hodgkin lymphoma (B-NHL) has been reported. The pathogenetic role played by HCV infection in the onset of B-NHL is suggested by regression of the latter following the achievement of a sustained virologic response (SVR). For several years, interferon-α alone or combined with ribavirin has been the standard of care. However, the rates of clinical, biochemical, and virologic responses have been low, and the occurrence of relapse frequent. The addition of rituximab has resulted in a higher rate of responses. With the advent of direct-acting antiviral agents, SVR has been achieved in ~ 95% of CV patients. However, in a minority of patients, despite SVR, CV may persist or reappear over variable lengths of time from the completion of therapy. The eventual appearance of B-NHL is also possible.
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Liang JH, Gao R, Dai JC, Gale RP, Li W, Fan L, Hu ZB, Xu W, Li JY. The prognostic role of HBV infection in chronic lymphocytic leukemia. J Cancer Res Clin Oncol 2018; 144:1309-1315. [PMID: 29761374 DOI: 10.1007/s00432-018-2663-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Accepted: 05/08/2018] [Indexed: 01/05/2023]
Abstract
PURPOSE We attempt to assess the impact of hepatis-B virus (HBV) status on the prognosis of chronic lymphocytic leukemia (CLL) using a Chinese case cohort. METHODS Five hundred and one consecutive newly diagnosed subjects with CLL were enrolled in this case cohort. HBV infection was defined as hepatitis B surface antigen (HBsAg) positive or hepatitis-B core antibody (HBcAb) positive. Univariate and stepwise multivariate Cox regression analyses were used to screen the prognostic risk factors associated with the end point of time-to-treatment (TTT) or overall survival (OS). Bootstrap re-sampling method was used to evaluate the model's internal validity. The discriminative ability of the models was evaluated using time-dependent receiver-operator characteristic (ROC) curves and corresponding areas under the curve (AUC). RESULTS One hundred and twenty-one subjects (24%) among 501 patients were HBV positive. HBV infection was an independent predictor for the prognosis of TTT (HR = 1.37; 95% CI 1.04-1.80) or OS (HR =2.85; 95% CI 1.80-4.52). The AUCs for HBV infection were 0.62 (95% CI 0.58-0.66) for TTT and 0.69 (95% CI 0.66-0.72) for OS, respectively. When we combined HBV infection with the traditional clinical and biological factors, significant improvements for model's discrimination were observed for TTT [AUC: 0.81 (95% CI: 0.77-0.85) vs. 0.78 (95% CI: 0.74-0.82), P < 0.001] and OS [AUC: 0.81 (95% CI 0.76-0.86) vs. 0.76 (95% CI 0.71-0.82), P < 0.001). Further bootstrap re-sampling method revealed good internal consistence for the final optimal models (Average AUC: 0.78 for TTT and 0.79 for OS based on 1000 bootstraps). CONCLUSIONS Our results indicated that HBV infection should be served as an important risk predictor for prognosis of CLL (TTT and OS).
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Affiliation(s)
- Jin-Hua Liang
- Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
- Key Laboratory of Hematology of Nanjing Medical University, Nanjing, 210029, China
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China
| | - Rui Gao
- Department of Endocrinology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Jun-Cheng Dai
- Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health, Nanjing, 210029, China
| | - Robert Peter Gale
- Division of Experimental Medicine, Department of Medicine, Haematology Research Centre, Imperial College London, London, UK
| | - Wang Li
- Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
- Key Laboratory of Hematology of Nanjing Medical University, Nanjing, 210029, China
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China
| | - Lei Fan
- Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
- Key Laboratory of Hematology of Nanjing Medical University, Nanjing, 210029, China
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China
| | - Zhi-Bin Hu
- Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health, Nanjing, 210029, China
| | - Wei Xu
- Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
- Key Laboratory of Hematology of Nanjing Medical University, Nanjing, 210029, China.
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China.
| | - Jian-Yong Li
- Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
- Key Laboratory of Hematology of Nanjing Medical University, Nanjing, 210029, China.
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China.
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Sonmez M, Bektas O, Yilmaz M, Durmus A, Akdogan E, Topbas M, Erturk M, Ovali E, Omay SB. The Relation of Lymphomaand Hepatitis B Virus/Hepatitis C Virus Infections in the Region of East Black Sea, Turkey. TUMORI JOURNAL 2018; 93:536-9. [DOI: 10.1177/030089160709300603] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Aim and background Hepatitis B virus (HBV) and hepatitis C virus (HCV) are not only hepatotropic, but also lymphotropic viruses. Infections with these viruses induce chronic antigenicity and may stimulate clonal expansion of malignant B-cell neoplasms. Moreover, these viruses can proliferate in lymphatic structures and bone marrow. However, the relationship between lymphomas and HBV/HCV infections is not clear. In our region of the East Black Sea, Turkey (the city of Trabzon), we intended to demonstrate a relation of lymphoma and HBV/HCV infections with a case-controlled study. Methods A total of 109 patients diagnosed with lymphoma between 2002–2005 in the Black Sea Technical University Hospital was investigated. Seventy-one patients had a high-grade and 38 patients a low-grade lymphoma. Hepatitis B surface antigen (HBsAg) and anti-HCV antibodies (anti-HCV Ab) were screened. The control group consisted of patients (n = 551) from other departments with diagnoses other than lymphoma. Results HBsAg was 3.7% and anti-HCV Ab positivity was 2.8% in lymphoma patients, compared with control of 5.3%, 5.1%, respectively. There was no statistically significant difference between two groups ( P = 0.7, OR = 0.69, 95% CI, 0.20–2.10; P = 0.4, OR = 0.53, 95% CI, 0.13–1.86, respectively). Conclusion Our findings suggest that the incidence of HBV and HCV infections in lymphoma patients is no different than that of nonlymphoma patients. Therefore, no direct correlation can be deduced between lymphoma and HBV-HCV infections in our East Black Sea region of Turkey.
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Affiliation(s)
- Mehmet Sonmez
- Department of Haematology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Ozlen Bektas
- Deparment of Internal Medicine, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Mustafa Yilmaz
- Department of Haematology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Ahmet Durmus
- Department of Haematology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Elif Akdogan
- Department of Haematology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Murat Topbas
- Department of Public Health, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Murat Erturk
- Department of Microbiology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Ercument Ovali
- Department of Haematology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Serdar Bedii Omay
- Department of Haematology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
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Hosry J, Miranda RN, Samaniego F, Economides MP, Torres HA. Clinicopathologic characteristics and outcomes of transformed diffuse large B-cell lymphoma in hepatitis C virus-infected patients. Int J Cancer 2017; 142:940-948. [PMID: 29047108 DOI: 10.1002/ijc.31110] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Revised: 09/23/2017] [Accepted: 10/04/2017] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus (HCV) causes a chronic but curable infection associated with the development of marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL). Preliminary data have shown frequent transformation of indolent lymphoma to DLBCL in HCV-infected patients. To compare their clinicopathologic characteristics and oncologic outcomes, we reviewed the medical records and pathology reports of HCV-infected and uninfected patients with DLBCL that transformed from indolent lymphoma seen at The University of Texas MD Anderson Cancer Center (June 2004 to May 2015). To identify predictors of DLBCL relapse, patients with relapse after first-line chemotherapy were compared with those without it using univariate and logistic regression analyses. Compared with the uninfected patients (n = 63), HCV-infected patients (n = 21) were younger (median age =54 years [interquartile range= 49-62 years] vs. 62 years [53-66 years]; p = 0.01) and more often had advanced DLBCL (Ann Arbor stage 3-4; 95% vs. 76%; p = 0.05). Immunophenotypically, more HCV-infected than uninfected patients had CD10-negative B cells (76% vs. 43%; p = 0.008), CD5-positive B cells (39% vs. 7%; p = 0.004) and activated B-cell phenotypes (57% vs. 31%; p = 0.07). Comparison of the patients who had relapse after first-line chemotherapy (n = 42) and those who did not (n = 40) revealed that having CD5-positive B cells was the only factor associated with DLBCL relapse in multivariate analysis (odds ratio= 10.7; p = 0.02). HCV-infected patients with transformed DLBCL have unique clinicopathologic characteristics that make their lymphoma difficult to treat, potentially leading to unfavorable outcome. The impact of HCV eradication should be explored in such patients.
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Affiliation(s)
- Jeff Hosry
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Roberto N Miranda
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Felipe Samaniego
- Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Minas P Economides
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Harrys A Torres
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX.,Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX
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Hepatitis C virus positive diffuse large B-cell lymphomas have distinct molecular features and lack BCL2 translocations. Br J Cancer 2017; 117:1685-1688. [PMID: 28949959 PMCID: PMC5729442 DOI: 10.1038/bjc.2017.345] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Revised: 08/16/2017] [Accepted: 09/01/2017] [Indexed: 01/19/2023] Open
Abstract
Background: The clinical presentation of patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphoma (DLBCL) is different from their HCV-negative counterparts, but the underlying molecular and pathological characteristics are largely under investigated. The virus has a role in lymphomagenesis, as witnessed by the curative potential of antiviral therapy in HCV-related low-grade B-cell lymphomas. Methods: We performed a case-control study including 44 HCV-positive cases of de novo DLBCL, comparing them with 132 HCV-negative patients as controls (ratio 3 to 1). Cases and controls were matched for age, lactate dehydrogenase level and international prognostic index at presentation. Patients were studied by gene expression profiling for cell-of-origin determination and to perform differential expression analysis between groups, fluorescence in-situ hybridisation and immunohistochemistry for MYC, BCL2 and BCL6, TP53 mutations, and diagnostic specimens reviewed to exclude transformation from low-grade lymphoma. Results: Compared to the HCV-negative controls, patients with HCV-positive de novo DLBCL had differential expression of genes that regulate innate immune response and modulate apoptotic pathways, have higher proliferative index, and lack BCL2 translocations. Conclusions: HCV-positive DLBCL have distinct molecular and pathological features compared to the HCV-negative counterparts.
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Esau D. Viral Causes of Lymphoma: The History of Epstein-Barr Virus and Human T-Lymphotropic Virus 1. Virology (Auckl) 2017; 8:1178122X17731772. [PMID: 28983187 PMCID: PMC5621661 DOI: 10.1177/1178122x17731772] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Accepted: 08/17/2017] [Indexed: 01/22/2023] Open
Abstract
In 1964, Epstein, Barr, and Achong published a report outlining their discovery of viral particles in lymphoblasts isolated from a patient with Burkitt lymphoma. The Epstein-Barr virus (EBV) was the first human cancer virus to be described, and its discovery paved the way for further investigations into the oncogenic potential of viruses. In the decades following the discovery of EBV, multinational research efforts led to the discovery of further viral causes of various human cancers. Lymphomas are perhaps the cancer type that is most closely associated with oncogenic viruses: infection with EBV, human T-lymphotropic virus 1 (HTLV-1), human immunodeficiency virus (HIV), Kaposi sarcoma-associated herpesvirus/human herpesvirus 8, and hepatitis C virus have all been associated with lymphomagenesis. Lymphomas have also played an important role in the history of oncoviruses, as both the first human oncovirus (EBV) and the first human retrovirus (HTLV-1) were discovered through isolates taken from patients with unique lymphoma syndromes. The history of the discovery of these 2 key oncoviruses is presented here, and their impact on further medical research, using the specific example of HIV research, is briefly discussed.
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Affiliation(s)
- Daniel Esau
- Department of Medicine, The University of British Columbia, Vancouver, BC, Canada
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31
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Visentini M, Fiorilli M, Casato M. From the pathogenesis to the cure of indolent B-cell lymphoproliferative disorders associated with hepatitis C virus infection: which role for direct-acting antivirals? Expert Rev Hematol 2017; 10:719-727. [PMID: 28675071 DOI: 10.1080/17474086.2017.1349607] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Hepatitis C virus (HCV) causes monoclonal B cell lymphoproliferative disorders ranging from benign, such as in mixed cryoglobulinemia (MC), to indolent or aggressive lymphomas. MC and indolent lymphomas commonly regress when HCV is eradicated with interferon (IFN) therapy; however, sustained virologic response (SVR) to IFN is achieved only in ~50% of patients. The new all oral direct-acting antivirals (DAA), yielding nearly 100% SVR, promise a breakthrough in the treatment of HCV-associated lymphoproliferative disorders, but experience is still scanty. Areas covered: A literature search was performed to summarize current pathogenetic hypotheses in HCV-associated indolent lymphoproliferative disorders and to identify clinical trials focused on the use of antiviral therapy. Hematological outcomes of IFN-based and IFN-free DAA-based regimens were compared. Expert commentary: While MC appears to regress in most patients after DAA therapy, the still very limited experience with indolent lymphomas suggests that hematologic responses might be less than those observed with IFN. Furthermore, anecdotal observations of early progression to aggressive lymphoma after DAA are disquieting. Large studies are needed to determine the values and limits of DAA for treating HCV-associated indolent lymphomas and to identify subgroups at risk of non-response.
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Affiliation(s)
- Marcella Visentini
- a Department of Clinical Medicine , Sapienza University of Rome , Rome , Italy
| | - Massimo Fiorilli
- a Department of Clinical Medicine , Sapienza University of Rome , Rome , Italy
| | - Milvia Casato
- a Department of Clinical Medicine , Sapienza University of Rome , Rome , Italy
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32
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Zignego AL, Ramos-Casals M, Ferri C, Saadoun D, Arcaini L, Roccatello D, Antonelli A, Desbois AC, Comarmond C, Gragnani L, Casato M, Lamprecht P, Mangia A, Tzioufas AG, Younossi ZM, Cacoub P. International therapeutic guidelines for patients with HCV-related extrahepatic disorders. A multidisciplinary expert statement. Autoimmun Rev 2017; 16:523-541. [PMID: 28286108 DOI: 10.1016/j.autrev.2017.03.004] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Accepted: 02/26/2017] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) is both hepatotrophic and lymphotropic virus that causes liver as well extrahepatic manifestations including cryoglobulinemic vasculitis, the most frequent and studied condition, lymphoma, and neurologic, cardiovascular, endocrine-metabolic or renal diseases. HCV-extrahepatic manifestations (HCV-EHMs) may severely affect the overall prognosis, while viral eradication significantly reduces non-liver related deaths. Different clinical manifestations may coexist in the same patient. Due to the variety of HCV clinical manifestations, a multidisciplinary approach along with appropriate therapeutic strategies are required. In the era of interferon-free anti-HCV treatments, international recommendations for the therapeutic management of HCV-EHMs are needed. This implies the need to define the best criteria to use antivirals and/or other therapeutic approaches. The present recommendations, based on qualified expert experience and specific literature, will focus on etiological (antiviral) therapies and/or traditional pathogenetic treatments that still maintain their therapeutic utility.
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Affiliation(s)
- Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
| | - Manuel Ramos-Casals
- Department of Autoimmune Diseases, ICMiD Josep Font Autoimmune Lab, CELLEX-IDIBAPS, Hospital Clinic, Barcelona, Spain
| | - Clodoveo Ferri
- Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
| | - David Saadoun
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Luca Arcaini
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Dario Roccatello
- Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Center of Research of Immunopathology and Rare Diseases, and Nephrology and Dialysis Unit, San G. Bosco Hospital and University of Turin, Italy
| | - Alessandro Antonelli
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, Pisa 56126, Italy
| | - Anne Claire Desbois
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Cloe Comarmond
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Laura Gragnani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Milvia Casato
- Department of Clinical Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185 Rome, Italy.
| | - Peter Lamprecht
- Klinik für Rheumatologie Oberarzt, Ratzeburger Allee 160 (Haus 40), 23538 Lübeck, Germany.
| | - Alessandra Mangia
- Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
| | - Athanasios G Tzioufas
- Department of Pathophysiology, School of Medicine, University of Athens, 75 M. Asias st, Building 16, Room, 32 11527 Athens, Greece.
| | - Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA; Beatty Liver and Obesity Program, Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Patrice Cacoub
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
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Merli M, Rattotti S, Gotti M, Arcaini L. Antiviral therapies for managing viral hepatitis in lymphoma patients. Expert Opin Pharmacother 2017; 18:363-376. [PMID: 28140702 DOI: 10.1080/14656566.2017.1288718] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION In patients with lymphoma the detection of positive hepatitis B or C viruses (HBV and HCV) serology involves crucial therapeutic consequences. In HBV-infected patients the serological profile of active (HBsAg-positive) or resolved (HBsAg-negative/anti-HBcAb-positive) infection is associated to differential risk of viral reactivation during rituximab-based therapy and require appropriate strategies of monitoring and of antiviral prophylaxis. In HCV-associated NHL patients consolidated data demonstrated that interferon (IFN)-based antiviral therapy (AT) is able to induce lymphoma regression strictly related to viral eradication, while preliminary data of the new direct-acting antivirals (DAAs) are very promising. Areas covered: This review summarizes current evidences about HBV reactivation risk in patients undergoing rituximab-based treatments and appropriate options of antiviral prophylaxis with lamivudine, entecavir or tenofovir, as well as pre-emptive strategy in HBsAg-negative/HBcAb-positive patients. Moreover previous experiences with IFN-based AT as well as recent studies with DAAs in HCV-associated indolent lymphomas or diffuse large B-cell lymphoma (DLBCL) are reviewed. Expert opinion: Entecavir or tenofovir prophylaxis is recommended for HBsAg-positive patients, while universal prophilaxis with lamivudine may be preferred in HBsAg-negative/anti-HBc-positive patients. In asymptomatic patients with HCV-associated indolent lymphoma DAA-based AT should be used as first-line option, while in DLBCL its deliver after immunochemotherapy-induced complete remission is suggested.
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Affiliation(s)
- Michele Merli
- a Division of Hematology , University Hospital Ospedale di Circolo & Fondazione Macchi, University of Insubria , Varese , Italy
| | - Sara Rattotti
- b Department of Hematology-Oncology , Fondazione IRCCS Policlinico San Matteo , Pavia , Italy
| | - Manuel Gotti
- b Department of Hematology-Oncology , Fondazione IRCCS Policlinico San Matteo , Pavia , Italy
| | - Luca Arcaini
- b Department of Hematology-Oncology , Fondazione IRCCS Policlinico San Matteo , Pavia , Italy.,c Department of Molecular Medicine , University of Pavia , Pavia , Italy
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34
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Chen CL, Huang JY, Wang CH, Tahara SM, Zhou L, Kondo Y, Schechter J, Su L, Lai MMC, Wakita T, Cosset FL, Jung JU, Machida K. Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2. Nat Commun 2017; 8:13882. [PMID: 28067225 PMCID: PMC5227552 DOI: 10.1038/ncomms13882] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Accepted: 11/08/2016] [Indexed: 12/18/2022] Open
Abstract
B-cell infection by hepatitis C virus (HCV) has been a controversial topic. To examine whether HCV has a genetically determined lymphotropism through a co-receptor specific for the infection by lymphotropic HCV, we established an infectious clone and chimeric virus of hepatotropic and lymphotropic HCV strains derived from an HCV-positive B-cell lymphoma. The viral envelope and 5'-UTR sequences of the lymphotropic HCV strain were responsible for the lymphotropism. Silencing of the virus sensor, RIGI, or overexpression of microRNA-122 promoted persistent viral replication in B cells. By cDNA library screening, we identified an immune cell-specific, co-stimulatory receptor B7.2 (CD86) as a co-receptor of lymphotropic HCV. Infection of B cells by HCV inhibited the recall reaction to antigen stimulation. Together, a co-receptor B7.2 enabled lymphotropic HCV to infect memory B cells, leading to inhibition of memory B-cell function and persistent HCV infection in HCV-infected hosts.
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Affiliation(s)
- Chia-Lin Chen
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA
| | - Jeffrey Y. Huang
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA
| | - Chun-Hsiang Wang
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA
| | - Stanley M Tahara
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA
| | - Lin Zhou
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA
| | - Yasuteru Kondo
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA
| | - Joel Schechter
- Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA
| | - Lishan Su
- Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7290, USA
| | - Michael M C. Lai
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA
- Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan
| | - Takaji Wakita
- Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
| | - François-Loïc Cosset
- International Center for Infectiology Research, Team EVIR, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, F-69007 Lyon, France
| | - Jae U Jung
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA
| | - Keigo Machida
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA
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Kalpadakis C, Pangalis GA, Angelopoulou MK, Vassilakopoulos TP. Treatment of splenic marginal zone lymphoma. Best Pract Res Clin Haematol 2016; 30:139-148. [PMID: 28288709 DOI: 10.1016/j.beha.2016.07.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Accepted: 07/05/2016] [Indexed: 01/06/2023]
Abstract
Splenic marginal zone lymphoma (SMZL) is a distinct lymphoma entity characterized by an indolent clinical course and prolonged survival. Treatment is not standardized, since there are no prospective randomized trials in large series of SMZL patients. Splenectomy and rituximab represent the most effective treatment strategies used so far. The addition of chemotherapy to rituximab has not further improved the outcome, although this issue requires further investigation. Rituximab monotherapy has been associated with high response rates (∼90%), with approximately half of these responses being complete, even at the molecular level. More importantly, many of these responses are long-lasting, with a reported 7-year progression-free survival (PFS) at the rate of 69%. Maintenance rituximab treatment has been associated with further improvement of the quality of response as well as longer response duration in studies derived from one group of investigators. Based on its high efficacy and the good safety profile, rituximab represent one of the best treatment options for SMZL patients. Moreover, rituximab retains its efficacy in the relapse setting in most cases. Splenectomy is a meaningful alternative to rituximab in patients with bulky splenomegaly and cytopenias, without extensive bone marrow infiltration, who are fit for surgery. However splenectomy cannot completely eradicate the disease and it is also associated with greater morbidity or even mortality compared to rituximab. The choice of one of these two treatment approaches (rituximab or splenectomy) should mainly be based on patient's characteristics and on the disease burden. Novel agents are currently testing in low grade lymphomas including a small number of SMZL patients with promising results.
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Affiliation(s)
- Christina Kalpadakis
- Department of Haematology, Heraklion University Hospital, 71001, University of Crete, Heraklion, Crete, Greece.
| | - Gerassimos A Pangalis
- Department of Haematology, Athens Medical Center-Psychikon Branch, 11525, Athens, Greece.
| | - Maria K Angelopoulou
- Department of Haematology, National and Kapodistrian University, Laikon General Hospital, Athens, Greece.
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36
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Gragnani L, Visentini M, Fognani E, Urraro T, De Santis A, Petraccia L, Perez M, Ceccotti G, Colantuono S, Mitrevski M, Stasi C, Del Padre M, Monti M, Gianni E, Pulsoni A, Fiorilli M, Casato M, Zignego AL. Prospective study of guideline-tailored therapy with direct-acting antivirals for hepatitis C virus-associated mixed cryoglobulinemia. Hepatology 2016; 64:1473-1482. [PMID: 27483451 DOI: 10.1002/hep.28753] [Citation(s) in RCA: 146] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Revised: 07/15/2016] [Accepted: 07/22/2016] [Indexed: 02/06/2023]
Abstract
UNLABELLED Hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) vasculitis commonly regresses upon virus eradication, but conventional therapy with pegylated interferon and ribavirin yields approximately 40% sustained virologic responses (SVR). We prospectively evaluated the efficacy and safety of sofosbuvir-based direct-acting antiviral therapy, individually tailored according to the latest guidelines, in a cohort of 44 consecutive patients with HCV-associated MC. In two patients MC had evolved into an indolent lymphoma with monoclonal B-cell lymphocytosis. All patients had negative HCV viremia at week 12 (SVR12) and at week 24 (SVR24) posttreatment, at which time all had a clinical response of vasculitis. The mean (±standard deviation) Birmingham Vasculitis Activity Score decreased from 5.41 (±3.53) at baseline to 2.35 (±2.25) (P < 0.001) at week 4 on treatment to 1.39 (±1.48) (P < 0.001) at SVR12 and to 1.27 (±1.68) (P < 0.001) at SVR24. The mean cryocrit value fell from 7.2 (±15.4)% at baseline to 2.9 (±7.4)% (P < 0.01) at SVR12 and to 1.8 (±5.1)% (P < 0.001) at SVR24. Intriguingly, in the 2 patients with MC and lymphoma there was a partial clinical response of vasculitis and ∼50% decrease of cryocrit, although none experienced a significant decrease of monoclonal B-cell lymphocytosis. Adverse events occurred in 59% of patients and were generally mild, with the exception of 1 patient with ribavirin-related anemia requiring blood transfusion. CONCLUSION Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for HCV-associated MC patients; the overall 100% rate of clinical response of vasculitis, on an intention-to-treat basis, opens the perspective for curing the large majority of these so far difficult-to-treat patients. (Hepatology 2016;64:1473-1482).
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Affiliation(s)
- Laura Gragnani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Marcella Visentini
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Elisa Fognani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Teresa Urraro
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Adriano De Santis
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Luisa Petraccia
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Marie Perez
- Istituto Dermopatico Dell'Immacolata IRCCS, Rome, Italy
| | - Giorgia Ceccotti
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | | | - Milica Mitrevski
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Cristina Stasi
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Martina Del Padre
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Monica Monti
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Elena Gianni
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Alessandro Pulsoni
- Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Italy
| | - Massimo Fiorilli
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Milvia Casato
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
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Tajima K, Takahashi N, Ishizawa K, Murai K, Akagi T, Noji H, Sasaki O, Wano M, Itoh J, Kato Y, Shichishima T, Harigae H, Ishida Y. Clinicopathological characteristics of malignant lymphoma in patients with hepatitis C virus infection in the Tohoku district in Eastern Japan. Leuk Lymphoma 2016; 58:1509-1511. [DOI: 10.1080/10428194.2016.1236376] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Katsushi Tajima
- Department of Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba, Japan
- Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Yamagata University School of Medicine, Yamagata, Japan
| | - Naoto Takahashi
- Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan
| | - Kenichi Ishizawa
- Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kazunori Murai
- Department of Hematology/Oncology, Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Tomoaki Akagi
- Department of Hematology, Aomori Prefectural Central Hospital, Aomori, Japan
| | - Hideyoshi Noji
- Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan
| | - Osamu Sasaki
- Division of Hematology, Department of Internal Medicine, Miyagi Cancer Center, Natori, Japan
| | - Masaharu Wano
- Department of Hematology, Iwate Prefectural Hospital, Morioka, Japan
| | - Jugoh Itoh
- Department of Medical Oncology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Yuichi Kato
- Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Yamagata University School of Medicine, Yamagata, Japan
| | - Tsutomu Shichishima
- Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan
| | - Hideo Harigae
- Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yoji Ishida
- Department of Hematology/Oncology, Internal Medicine, Iwate Medical University, Morioka, Japan
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Högfeldt T, Jaing C, Loughlin KM, Thissen J, Gardner S, Bahnassy AA, Gharizadeh B, Lundahl J, Österborg A, Porwit A, Zekri ARN, Khaled HM, Mellstedt H, Moshfegh A. Differential expression of viral agents in lymphoma tissues of patients with ABC diffuse large B-cell lymphoma from high and low endemic infectious disease regions. Oncol Lett 2016; 12:2782-2788. [PMID: 27698858 PMCID: PMC5038175 DOI: 10.3892/ol.2016.5012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Accepted: 05/23/2016] [Indexed: 12/11/2022] Open
Abstract
Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin's lymphoma (NHL) in adults, accounts for approximately 30-40% of newly diagnosed lymphomas worldwide. Environmental factors, such as viruses and bacteria, may contribute to cancer development through chronic inflammation and the integration of oncogenes, and have previously been indicated in cervical cancer, hepatocellular carcinoma, gastric cancer and lymphoproliferative disorders. In the present study, the presence of microbial agents was analyzed in the lymphoma tissue of patients with activated B-cell like (ABC) DLBCL. The present study compared two groups of patients from geographically varied regions that possess a difference in the prevalence of viral and other microbial agents. The patient populations were from Sweden (a low endemic infectious disease region) and Egypt (a high endemic infectious disease region). A differential expression of several viruses in lymphoma tissues was noted when comparing Swedish and Egyptian patients. JC polyomavirus (JCV) was detected in Swedish and Egyptian patients and, uniquely, the complete hepatitis B virus (HBV) genome was detected only in Egyptian lymphoma patients. None of these viruses were detected in control lymph tissues from Sweden or Egypt. In total, 38% of the Egyptian patients were found to have HBV surface antigens (HBsAgs) in their serum; however, HBsAgs were not found in any of the Swedish patients. The percentage of serum HBsAgs in Egyptian patients with ABC DLBCL was significantly increased compared with the general Egyptian population (P<0.05). The present study may support a notion that viral agents, including JCV and HBV, may be involved in the tumorigenesis of DLBCL in regions of high infectious disease.
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Affiliation(s)
- Therese Högfeldt
- Department of Oncology and Pathology, Karolinska Institute, 171 77 Stockholm, Sweden
| | - Crystal Jaing
- Chemistry, Materials, Earth and Life Sciences, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
| | - Kevin Mc Loughlin
- Computation, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
| | - James Thissen
- Chemistry, Materials, Earth and Life Sciences, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
| | - Shea Gardner
- Computation, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
| | - Abeer A. Bahnassy
- Department of Pathology, National Cancer Institute, Cairo University, Cairo 11796, Egypt
| | - Baback Gharizadeh
- Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304, USA
| | - Joachim Lundahl
- Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, 171 76 Stockholm, Sweden
| | - Anders Österborg
- Department of Oncology and Pathology, Karolinska Institute, 171 77 Stockholm, Sweden
| | - Anna Porwit
- Department of Oncology and Pathology, Karolinska Institute, 171 77 Stockholm, Sweden
| | - Abdel-Rahman N. Zekri
- Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11796, Egypt
| | - Hussein M. Khaled
- Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo 11796, Egypt
| | - Håkan Mellstedt
- Department of Oncology and Pathology, Karolinska Institute, 171 77 Stockholm, Sweden
| | - Ali Moshfegh
- Department of Oncology and Pathology, Karolinska Institute, 171 77 Stockholm, Sweden
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39
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Inflammatory myopathies and lymphoma. J Neurol Sci 2016; 369:377-389. [PMID: 27653927 DOI: 10.1016/j.jns.2016.08.060] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Revised: 08/28/2016] [Accepted: 08/29/2016] [Indexed: 12/18/2022]
Abstract
The inflammatory myopathies comprise a group of immune-mediated muscle diseases. Lymphoma is a term for a variety of lymphatic system malignancies. Autoimmune diseases and lymphoproliferative malignancies share a complex bidirectional relationship. A causal relationship between inflammatory mypathies and lymphoma has not been established. The diagnosis/treatment of inflammatory myopathy usually precedes the detection/diagnosis of lymphoma. Immune system dysregulation presumably underlies the evolution of lymphoma in patients with inflammatory myopathies. Inflammatory activity with chronic B-cell activation and/or antigen stimulation is deemed the major risk factor for lymphoma in patients with autoimmunity. A "paraneoplastic" phenomenon or the effects of immunosuppressive therapy may be alternative immune-based mechanisms. In chronic lymphocytic leukemia immune system disturbance rarely results in non-hematological autoimmune disease, including inflammatory myopathies.
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40
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Hosry J, Mahale P, Turturro F, Miranda RN, Economides MP, Granwehr BP, Torres HA. Antiviral therapy improves overall survival in hepatitis C virus-infected patients who develop diffuse large B-cell lymphoma. Int J Cancer 2016; 139:2519-28. [PMID: 27501007 DOI: 10.1002/ijc.30372] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Revised: 07/07/2016] [Accepted: 07/29/2016] [Indexed: 12/13/2022]
Abstract
Chronic Hepatitis C virus (HCV) infection is associated with increased incidence of non-Hodgkin lymphoma. Several studies have demonstrated regression of indolent lymphoma with antiviral therapy (AVT) alone. However, the role of AVT in HCV-infected patients with diffuse large B-cell lymphoma (DLBCL) is unclear. We therefore analyzed AVT's impact on oncologic outcomes of HCV-infected patients (cases) who developed DLBCL. Cases seen at our institution (June 2004-May 2014) were matched with uninfected counterparts (controls) and then divided according to prior AVT consisting of interferon-based regimens. We studied 304 patients (76 cases and 228 controls). More cases than controls had extranodal (79% vs. 72%; p = 0.07) and upper gastrointestinal (GI; 42% vs. 24%; p = 0.004) involvement. Cases never given AVT had DLBCL more refractory to first-line chemotherapy than that in the controls (33% vs. 17%; p = 0.05) and exhibited a trend toward more progressive lymphoma at last examination compared to controls (50% vs. 32%; p = 0.09) or cases given AVT (50% vs. 27%; p = 0.06). Cases never given AVT had worse 5-year overall survival (OS) rates than did the controls (HR, 2.3 [95% CI, 1.01-5.3]; p = 0.04). Furthermore, AVT improved 5-year OS rates among cases in both univariate (median [Interquartile range]: 39 [26-56] vs. 16 [6-41] months, p = 0.02) and multivariate analyses (HR = 0.21 [95% CI, 0.06-0.69]; p = 0.01). This study highlights the negative impact of chronic HCV on survival of DLBCL patients and shows that treatment of HCV infection is associated with a better cancer response to chemotherapy and improves 5-year OS.
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Affiliation(s)
- Jeff Hosry
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Parag Mahale
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Francesco Turturro
- Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Roberto N Miranda
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Minas P Economides
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Bruno P Granwehr
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Harrys A Torres
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX.
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41
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Perrone S, D’Elia GM, Annechini G, Ferretti A, Tosti ME, Foà R, Pulsoni A. Splenic marginal zone lymphoma: Prognostic factors, role of watch and wait policy, and other therapeutic approaches in the rituximab era. Leuk Res 2016; 44:53-60. [DOI: 10.1016/j.leukres.2016.03.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Revised: 03/09/2016] [Accepted: 03/21/2016] [Indexed: 02/07/2023]
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42
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Mallet V, van Bömmel F, Doerig C, Pischke S, Hermine O, Locasciulli A, Cordonnier C, Berg T, Moradpour D, Wedemeyer H, Ljungman P. Management of viral hepatitis in patients with haematological malignancy and in patients undergoing haemopoietic stem cell transplantation: recommendations of the 5th European Conference on Infections in Leukaemia (ECIL-5). THE LANCET. INFECTIOUS DISEASES 2016; 16:606-617. [PMID: 27599653 DOI: 10.1016/s1473-3099(16)00118-3] [Citation(s) in RCA: 103] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Revised: 02/11/2016] [Accepted: 02/12/2016] [Indexed: 12/24/2022]
Abstract
Viral hepatitis affects millions of people worldwide, and host immunity is the key determinant of patient outcome. Viral hepatitis can be life threatening in patients with haematological malignancy, including haemopoietic stem cell transplant recipients, because of the virus itself, or through a need to decrease the dose of chemotherapy. A past or currently infected haemopoietic stem cell donor could also transmit viral hepatitis. The burden of viral hepatitis in patients with haematological malignancies and the weak evidence on which previous guidelines are based has prompted the European Conference on Infection in Leukaemia (ECIL-5) to convene a group of experts in the fields of viral hepatitis and of haematological malignancy to specifically address previously unconsidered issues and grade the available quality of evidence according to the Infectious Diseases Society of America grading system. The group recommends that all patients should be screened for hepatotropic viruses before haematological treatment and that patients or haemopoietic stem cell donors with markers of past or current viral hepatitis should be assessed by an expert. Screening, vaccination, and treatment rules are reported in this Review.
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Affiliation(s)
- Vincent Mallet
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Institut Pasteur, Institut National de la Santé et de la Recherche Médicale Unité 1223, Paris, France; Hepatology Service, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Cochin Port-Royal, Paris, France.
| | | | - Christopher Doerig
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Sven Pischke
- University Medical Center Hamburg-Eppendorf, First Department of Medicine, Hamburg, Germany
| | - Olivier Hermine
- Department of Haematology, Paris Descartes University, Imagine Institute, Necker Hospital, Paris, France
| | - Anna Locasciulli
- Ematologia e Trapianto di Midollo, Ospedale SanCamillo, Roma, Italia
| | - Catherine Cordonnier
- Haematology Department, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, and Paris-Est Créteil University, Créteil, France
| | - Thomas Berg
- Hepatology Section, University Hospital Leipzig, Leipzig, Germany
| | - Darius Moradpour
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | | | - Per Ljungman
- Karolinska University Hospital, Department of Haematology and Karolinska Institutet, Department of Medicine, Huddinge, Stockholm, Sweden
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Ameri MD, Parekh TM, Qian YW, Elghetany MT, Schnadig V, Nawgiri R. A case of peripheral T-cell lymphoma, not otherwise specified in a HCV and HTLV-II-positive patient, diagnosed by abdominal fluid cytology. J Gastrointest Oncol 2016; 7:S96-9. [PMID: 27034820 DOI: 10.3978/j.issn.2078-6891.2015.054] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a rare neoplasm that typically presents as generalized lymphadenopathy. PTCL, NOS presenting as malignant ascites is rare. METHODS A 61-year-old African-American man with past medical history of HCV, cryoglobulinemia, and cryptococcal pneumonia was admitted for dyspnea on exertion over a period of 1 month and new onset of abdominal distension. RESULTS Ascites, splenomegaly, hepatomegaly and extensive lymphadenopathy were found by imaging. Paracentesis obtained 1.3 liter of abdominal fluid, the cytologic evaluation showed a monomorphic population of intermediate-sized lymphoid cells with irregular to convoluted nuclear contours. Fluid sent for flow cytometry showed an abnormal T-lymphocyte population expressing CD4, weak surface CD3 and absence of CD7. PCR studies of ascitic fluid detected a clonal T-lymphocyte population with T-cell receptor gamma gene rearrangement. Serologic testing for human T lymphotropic virus (HTLV) was positive for HTLV-II. Subsequent bone marrow biopsy revealed lymphomatous involvement. CD30 and ALK-1 immunostaining were negative. This case was classified as PTCL, NOS. CONCLUSIONS PTCL, NOS can have unusual clinical presentation such as ascites and pleural effusion, and may also occur as a complication of immunodeficiency state. Further studies are needed to determine if HCV or HTLV-II viral infection is associated with PTCL.
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Affiliation(s)
- Maryam Dadfarnia Ameri
- 1 Department of Pathology, City of Hope National Medical Center, Duarte, USA ; 2 Department of Internal medicine, 3 Department of Pathology, University of Texas Medical Branch, Galveston, USA ; 4 Department of Pathology & Immunology, Baylor College of Medicine, Houston, USA
| | - Trisha M Parekh
- 1 Department of Pathology, City of Hope National Medical Center, Duarte, USA ; 2 Department of Internal medicine, 3 Department of Pathology, University of Texas Medical Branch, Galveston, USA ; 4 Department of Pathology & Immunology, Baylor College of Medicine, Houston, USA
| | - You-Wen Qian
- 1 Department of Pathology, City of Hope National Medical Center, Duarte, USA ; 2 Department of Internal medicine, 3 Department of Pathology, University of Texas Medical Branch, Galveston, USA ; 4 Department of Pathology & Immunology, Baylor College of Medicine, Houston, USA
| | - M Tarek Elghetany
- 1 Department of Pathology, City of Hope National Medical Center, Duarte, USA ; 2 Department of Internal medicine, 3 Department of Pathology, University of Texas Medical Branch, Galveston, USA ; 4 Department of Pathology & Immunology, Baylor College of Medicine, Houston, USA
| | - Vicki Schnadig
- 1 Department of Pathology, City of Hope National Medical Center, Duarte, USA ; 2 Department of Internal medicine, 3 Department of Pathology, University of Texas Medical Branch, Galveston, USA ; 4 Department of Pathology & Immunology, Baylor College of Medicine, Houston, USA
| | - Ranjina Nawgiri
- 1 Department of Pathology, City of Hope National Medical Center, Duarte, USA ; 2 Department of Internal medicine, 3 Department of Pathology, University of Texas Medical Branch, Galveston, USA ; 4 Department of Pathology & Immunology, Baylor College of Medicine, Houston, USA
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44
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The expanding spectrum of HCV-related cryoglobulinemic vasculitis: a narrative review. Clin Exp Med 2016; 16:233-42. [PMID: 26935415 DOI: 10.1007/s10238-016-0410-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Accepted: 02/10/2016] [Indexed: 02/06/2023]
Abstract
Cryoglobulinemic vasculitis (CV) is a small-to-medium-vessel vasculitis that appears in 10-15 % of patients chronically infected with hepatitis C virus (HCV). The classic symptom triad of CV, purpura/asthenia/arthralgia, is accompanied by clinical features that include glomerulonephritis, neuropathy, interstitial pneumonitis, and cardiomyopathy, ranging in their severity from mild to life threatening. The risk of developing non-Hodgkin lymphoma is also higher. The cumulative 10-year survival rate of CV patients is significantly lower than in the age- and sex-matched general population, with death typically caused by nephropathy, malignancies, liver involvement, and severe infections. Unfailing serological stigmata include both a cryoglobulin IgM fraction with rheumatoid factor activity and decreased complement C4 levels. On peripheral B cells, the expression of the CD81 B cell receptor is reduced while that of the CD19 receptor is increased. A monoclonal B cell lymphocytosis develops in almost one-third of patients. HCV-related proteins (but not HCV-RNA genomic sequences) can be detected on biopsy samples by immunofluorescence and immunohistochemistry and involve the vessel lumen, vessel walls, and the perivascular spaces of the skin, kidney, and peripheral nerves, supporting the pathogenetic role of HCV in the onset of a widespread microvasculitis. Based on the demonstration of HCV infection in the large majority of CV patients, a therapeutic regimen consisting of once-weekly pegylated interferon-α and the daily administration of ribavirin results in a sustained virologic response in ~50 % of patients. In those with refractory and relapsing disease, addition of the anti-CD20 monoclonal antibody rituximab has significantly increased the overall response rates. The extension to CV of latest-generation direct-acting antivirals, strikingly successful in non-CV HCV-positive patients, has yielded high complete response rates according to the few studies published thus far.
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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. Hepatitis C viral infection increases the risk of lymphoid-neoplasms: A population-based cohort study. Hepatology 2016; 63:721-30. [PMID: 26662347 DOI: 10.1002/hep.28387] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 12/04/2015] [Indexed: 12/16/2022]
Abstract
UNLABELLED Chronic hepatitis C viral (HCV) infection has been associated with non-Hodgkin's lymphoma (NHL); however, the results are inconsistent among regions with different HCV prevalence rates. The temporal relationship, risk estimates, and association between HCV and lymphoid-neoplasms remain unclear. This study investigated the temporal relationship between HCV infection and lymphoid-neoplasms using a nationwide population-based cohort. Patients with chronic HCV infection were retrieved from the Taiwan National Health Insurance Research Database during 2001-2005 and designated as the HCV cohort. Those with prior malignancies or coinfected with hepatitis B or human immunodeficiency virus were excluded. The age, sex, and comorbidities, including rheumatological disorders and diabetes, were matched by propensity scores to another non-HCV cohort. Both cohorts were followed longitudinally until 2009 for a new diagnosis of any lymphoid-neoplasms or NHL. A total of 11,679 HCV and 46,716 non-HCV patients were included and followed for 8 years. The incidence rates of any lymphoid-neoplasms and NHL were significantly greater in the HCV cohort than the non-HCV cohort (48.4 versus 22.1, and 37.0 versus 17.5 per 100,000 person-years, respectively, both P < 0.001), even after we excluded lymphoid-neoplasms developed within the first year of follow-up. Cox proportional hazards regression analysis (after adjustment for age, sex, numbers of annual medical visits during follow-up, and comorbidities) indicated that HCV infection was associated with an increased risk of either any lymphoid-neoplasms (hazard ratio = 2.30, 95% confidence interval 1.55-3.43, P < 0.0001) or NHL (hazard ratio = 2.00, 95% confidence interval 1.27-3.16, P = 0.003). CONCLUSION After adjustment for confounders and biases, chronic HCV infection is temporally associated with a two-fold increased risk of lymphoid-neoplasms, especially NHL, in Asian patients; additional large studies are needed to explore whether HCV eradication can reduce the incidence of lymphoid-neoplasms.
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Affiliation(s)
- Tung-Hung Su
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,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
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,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, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taipei, Taiwan
| | - Shih-Wan Chou
- National Taiwan University Health Data Research Center, Taipei, Taiwan
| | - Chen-Hua Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,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
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,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
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Ding-Shinn Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, 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
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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Infectious Aetiology of Marginal Zone Lymphoma and Role of Anti-Infective Therapy. Mediterr J Hematol Infect Dis 2016; 8:e2016006. [PMID: 26740867 PMCID: PMC4696464 DOI: 10.4084/mjhid.2016.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Accepted: 11/16/2015] [Indexed: 02/08/2023] Open
Abstract
Marginal zone lymphomas have been associated with several infectious agents covering both viral and bacterial pathogens and in some cases a clear aetiological role has been established. Pathogenetic mechanisms are currently not completely understood. However, the role of chronic stimulation of the host immune response with persistent lymphocyte activation represents the most convincing explanation for lymphoproliferation. Gastric MALT lymphoma is strictly associated with Helicobacter pylori infection and various eradicating protocols, developed due to increasing antibiotic resistance, represent the first line therapy for gastric MALT. The response rate to eradication is good with 80% of response at 1 year; this finding is also noteworthy because it recapitulates cancer cured only by the antibacterial approach and it satisfies the Koch postulates of causation, establishing a causative relationship between Hp and gastric MALT lymphoma. Patients with chronic HCV infection have 5 times higher risk to develop MZL, in particular, an association with splenic and nodal MZL has been shown in several studies. Moreover, there is evidence of lymphoma regression after antiviral therapy with interferon+ribavirin, thus raising hope that newly available drugs, extremely efficient against HCV replication, could improve outcome also in HCV-driven lymphomas. Another case-study are represented by those rare cases of MZL localized to orbital fat and eye conjunctivas that have been associated with Chlamydophila psittaci infection carried by birds. Efficacy of antibacterial therapy against C. psittaci are conflicting and generally poorer than gastric MALT. Finally, some case reports will cover the relationship between primary cutaneous B-cell Lymphomas and Borrelia Burgdorferi.
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Fiorino S, Bacchi-Reggiani L, de Biase D, Fornelli A, Masetti M, Tura A, Grizzi F, Zanello M, Mastrangelo L, Lombardi R, Acquaviva G, di Tommaso L, Bondi A, Visani M, Sabbatani S, Pontoriero L, Fabbri C, Cuppini A, Pession A, Jovine E. Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma: A systematic review. World J Gastroenterol 2015; 21:12896-12953. [PMID: 26668515 PMCID: PMC4671046 DOI: 10.3748/wjg.v21.i45.12896] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2015] [Revised: 08/05/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To summarize the current knowledge about the potential relationship between hepatitis C virus (HCV) infection and the risk of several extra-liver cancers.
METHODS: We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews: (1) HCV and haematopoietic malignancies; (2) HCV and cholangiocarcinoma; (3) HCV and pancreatic cancer; (4) HCV and breast cancer; (5) HCV and kidney cancer; (6) HCV and skin or oral cancer; and (7) HCV and thyroid cancer.
RESULTS: According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with: (1) a higher incidence of some B-cell Non-Hodgkin-Lymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%; (2) an increased risk of intra-hepatic cholangiocarcinoma; and (3) a correlation between HCV prevalence and pancreatic cancer (PAC) incidence.
CONCLUSION: To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are required to confirm or deny this association.
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Abstract
Chronic infection with the hepatitis C virus (HCV) is a major cause of liver disease worldwide and is also responsible for extrahepatic manifestations (EHMs) involving the skin, kidneys, salivary glands, eyes, thyroid, and immune system. Mixed cryoglobulinemia is the prototype EHM related to HCV infection. Although these HCV-related EHMs may contribute to significant rates of morbidity affecting patient's quality of life and survival, most of these complications can reverse after HCV eradication by interferon therapy. This notwithstanding, individual patients may have an irreversible injury in various organs that is not reversed by a cure of the HCV infection.
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Affiliation(s)
- Mauro Viganò
- Hepatology Division, Ospedale San Giuseppe, Università degli Studi di Milano, Via San Vittore 12, Milan 20122, Italy
| | - Massimo Colombo
- Division of Gastroenterology and Hepatology, "A. M. and A. Migliavacca" Center for Liver Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via F. Sforza 35, Milan 20122, Italy.
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Carrier P, Jaccard A, Jacques J, Tabouret T, Debette-Gratien M, Abraham J, Mesturoux L, Marquet P, Alain S, Sautereau D, Essig M, Loustaud-Ratti V. HCV-associated B-cell non-Hodgkin lymphomas and new direct antiviral agents. Liver Int 2015; 35:2222-7. [PMID: 26104059 DOI: 10.1111/liv.12897] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2015] [Accepted: 06/11/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Hepatitis C virus-related B-cell proliferation is a model of virus-driven autoimmune/neoplastic disorder leading to mixed cryoglobulinaemia and/or B-cell non-Hodgkin lymphoma. These lymphomas are often marginal zone lymphomas or diffuse large B-cell lymphomas. Peginterferon/Ribavirin therapy has proved its crucial role in the cure of these non-Hodgkin lymphomas, but data are lacking concerning new direct anti-viral agents. METHODS We report five cases of Hepatitis C virus-associated B-cell non-Hodgkin lymphoma treated with direct anti-viral agents: two marginal zone lymphomas received direct anti-viral agents alone (one with a leukaemic phase only, one with splenic and deep lymph nodes localizations); one renal marginal zone lymphoma with renal insufficiency received direct anti-viral agents and four rituximab infusions simultaneously; two diffuse large B-cell lymphomas were treated with direct ant-viral agents following chemotherapy. RESULTS Sustained virological response was obtained in all patients, and complete remission of NHL was noted 6 months after cessation of any treatment except for one patient with a persistent small leukaemic phase. CONCLUSION Direct anti-viral agents might be proposed as a first-line treatment in marginal zone lymphomas in the case of no life-threatening complications with the precaution of a long-term follow-up. In the setting of diffuse large B-cell lymphomas, well-tolerated direct anti-viral agents could potentially be introduced very early not only to prevent relapse of these lymphomas but also to limit the liver toxicity of chemotherapy and rituximab by preventing outbreaks of viral load. New observations and trials should support these assumptions.
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Affiliation(s)
- Paul Carrier
- Service d'Hépato-gastroentérologie, CHU Limoges, Limoges, France.,U850 INSERM, Univ. Limoges, CHU Limoges, Limoges, France
| | - Arnaud Jaccard
- Service d'Hématologie Clinique CHU Limoges, Limoges, France
| | - Jérémie Jacques
- Service d'Hépato-gastroentérologie, CHU Limoges, Limoges, France
| | - Tessa Tabouret
- Service d'Hépato-gastroentérologie, CHU Limoges, Limoges, France
| | - Marilyne Debette-Gratien
- Service d'Hépato-gastroentérologie, CHU Limoges, Limoges, France.,U850 INSERM, Univ. Limoges, CHU Limoges, Limoges, France
| | - Julie Abraham
- Service d'Hématologie Clinique CHU Limoges, Limoges, France
| | | | - Pierre Marquet
- U850 INSERM, Univ. Limoges, CHU Limoges, Limoges, France.,Service de Pharmacologie, CHU Limoges, Limoges, France
| | - Sophie Alain
- U850 INSERM, Univ. Limoges, CHU Limoges, Limoges, France.,U1092 INSERM, Univ. Limoges, CHU Limoges, Limoges, France
| | - Denis Sautereau
- Service d'Hépato-gastroentérologie, CHU Limoges, Limoges, France
| | - Marie Essig
- U850 INSERM, Univ. Limoges, CHU Limoges, Limoges, France.,Service de Néphrologie Dialyse Transplantation, CHU de Limoges, Limoges, France
| | - Véronique Loustaud-Ratti
- Service d'Hépato-gastroentérologie, CHU Limoges, Limoges, France.,U850 INSERM, Univ. Limoges, CHU Limoges, Limoges, France
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Zignego AL, Gragnani L, Piluso A, Sebastiani M, Giuggioli D, Fallahi P, Antonelli A, Ferri C. Virus-driven autoimmunity and lymphoproliferation: the example of HCV infection. Expert Rev Clin Immunol 2015; 11:15-31. [PMID: 25534977 DOI: 10.1586/1744666x.2015.997214] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
HCV chronic infection is characterized by possible development of both hepatic and extrahepatic manifestations. The infection by this both hepatotropic and lymphotropic virus is responsible for polyoligoclonal B-lymphocyte expansion, leading to several immune-mediated disorders. Mixed cryoglobulinemia syndrome that in some cases may evolve to frank B-cell non-Hodgkin's lymphoma is the prototype of HCV-driven autoimmune and lymphoproliferative disorders. The HCV oncogenic potential has been suggested by several clinicoepidemiological and laboratory studies; it includes hepatocellular carcinoma, B-cell non-Hodgkin's lymphoma and papillary thyroid cancer. The definition HCV syndrome refers to the complex of HCV-driven diseases; these latter are characterized by heterogeneous geographical distribution, suggesting a role of other important genetic and/or environmental cofactors. The natural history of HCV syndrome is the result of a multifactorial and multistep pathogenetic process, which may evolve from mild manifestations to systemic autoimmune disorders, and less frequently to malignant neoplasias. The present updated review analyzes the clinical and pathogenetic aspects of the main HCV-associated diseases.
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Affiliation(s)
- Anna Linda Zignego
- Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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