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Motomura Y, Yoshifuji K, Tanaka K, Sakashita C, Umezawa Y, Nagao T, Nitta S, Asahina Y, Mori T, Yamamoto M. Hepatitis C virus-related hepatitis flare after immunochemotherapy in a patient with follicular lymphoma. J Clin Exp Hematop 2024; 64:313-317. [PMID: 39603635 PMCID: PMC11786155 DOI: 10.3960/jslrt.24042] [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: 08/02/2024] [Revised: 09/24/2024] [Accepted: 10/03/2024] [Indexed: 11/29/2024] Open
Abstract
Reactivation of hepatitis viruses during chemotherapy can be problematic in the treatment of malignant lymphomas. However, studies on reactivation of chronic hepatitis C virus (HCV) infection are limited. A 43-year-old woman presented with generalized lymphadenopathy and multiple liver tumors, and she was diagnosed with follicular lymphoma (grade 3a; clinical stage IV). Chronic HCV infection was clinically diagnosed. Immunochemotherapy (ICT), including bendamustine and obinutuzumab, was initiated with close liver function monitoring without specific treatment for hepatitis C. However, liver dysfunction worsened 17 days after ICT initiation, and ICT was interrupted. HCV-RNA and transaminase levels continued to elevate. Liver biopsy results confirmed acute exacerbation of chronic hepatitis C. Direct active antiviral (DAA) therapy was started and effective. She has maintained a sustained virologic response since DAA therapy ended. With regard to lymphoma, complete metabolic response was maintained for 4 years without additional treatment. Physicians should be aware of HCV reactivation with hepatitis flare after ICT for lymphoma and consider the indication and timing of DAA therapy for hepatitis C in this setting.
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Li X, Song D, Hao Y, Ren M, Guo Y, Zhao H, Wang Y, Tang L. Efficacy and safety of rituximab in patients with PLA2R associated membranous nephropathy and resolved HCV infection. Sci Rep 2024; 14:20981. [PMID: 39251782 PMCID: PMC11383943 DOI: 10.1038/s41598-024-72082-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 09/03/2024] [Indexed: 09/11/2024] Open
Abstract
Rituximab occasionally induces reactivation of hepatitis C virus (HCV) in patients with resolved HCV infection, sometimes with fatal consequences. As rituximab has become one of the first-line therapies for the treatment of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) and is more widely used, there is a lack of studies reporting the effectiveness and safety of rituximab in patients with PLA2R-associated MN and resolved HCV infection. A single-center retrospective study was conducted on PLA2R-associated membranous nephropathy (MN) patients who were HCVAb positive but HCV-RNA negative and treated with rituximab. A total of 598 adult patients with PLA2R-associated MN who underwent rituximab therapy were screened. General clinical information, including gender, age, pathological data, and previous treatment plans, was collected from medical records. Routine blood tests, liver and kidney function assessments, blood lipid profiles, 24-h urine protein levels, anti-PLA2R antibody titers, circulating B-cell counts, and HCV viral loads were measured at the time of rituximab infusion and repeated at intervals of 1-3 months post-rituximab administration. A total of 8 patients were enrolled, with a median follow-up period of 19.00 (range: 16.00-25.25) months. Among the 8 patients, 5 were male, and the mean age was 50.13 ± 4.29 years. Histological findings indicated that tubuloreticular inclusions, mesangial deposits, intramembranous deposits, and subendothelial deposits were not observed in any of the 8 patients. The overall 1-year remission rate for these patients was 75%, accompanied by a significant reduction in proteinuria. Additionally, blood albumin levels increased significantly, and renal function remained stable. No increase in HCV viral load and stable liver function tests were observed throughout the entire follow-up period. This study suggested that on the basis of successful eradication of HCV virus with antiviral drugs, rituximab can effectively induce clinical remission of patients with PLA2R associated MN and resolved HCV infection, and does not lead to a significant increase in HCV virus load. However, this finding is based on a very small sample size and should be confirmed in larger clinical trials.
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Affiliation(s)
- Xiaodan Li
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China
| | - Dongxu Song
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China
| | - Yingxuan Hao
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China
| | - Mingjing Ren
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China
| | - Yanhong Guo
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China
| | - Huayan Zhao
- Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China
| | - Yulin Wang
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China
| | - Lin Tang
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China.
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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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Kanda T, Matsumoto N, Ishii T, Arima S, Shibuya S, Honda M, Sasaki-Tanaka R, Masuzaki R, Kanezawa S, Nishizawa T, Gon Y, Ogawa M, Kogure H. Chronic Hepatitis C: Acute Exacerbation and Alanine Aminotransferase Flare. Viruses 2023; 15:183. [PMID: 36680223 PMCID: PMC9861769 DOI: 10.3390/v15010183] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 01/05/2023] [Indexed: 01/11/2023] Open
Abstract
The hepatitis C virus (HCV) causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma, as well as extrahepatic manifestations such as malignant lymphoma. Currently, direct-acting antiviral agents (DAAs) against HCV infection can lead to a sustained virological response (SVR) in almost all HCV-infected patients. In this review article, we discuss acute exacerbation and alanine aminotransferase (ALT) flare in patients with chronic HCV infection. Although acute liver failure caused by HCV infection is rare, careful attention should be paid to the cases with ALT elevation during the natural course of chronic HCV infection. HCV genotype 2 infection, the use of rituximab, and a higher dose of corticosteroid are factors associated with HCV acute exacerbation and ALT flare. Treatment regimens for cancer have been interrupted or changed due to ALT flare due to HCV infection in some patients undergoing chemotherapy for cancer. The pathogenesis of HCV acute exacerbation and ALT flare could involve cellular as well as humoral immune responses. In the DAA era, the earlier introduction of DAAs may prevent chronic HCV-infected patients with acute exacerbation and ALT flare from developing into a more severe form, although DAAs may not be effective for all of them.
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Affiliation(s)
- Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Naoki Matsumoto
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Tomotaka Ishii
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Shuhei Arima
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Shinji Shibuya
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Masayuki Honda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Reina Sasaki-Tanaka
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Ryota Masuzaki
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Shini Kanezawa
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Tsukasa Nishizawa
- Division of Respiratory Medicine, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Yasuhiro Gon
- Division of Respiratory Medicine, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Masahiro Ogawa
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Hirofumi Kogure
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
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Jelicic J, Larsen TS, Fialla AD, Bukumiric Z, Andjelic B. Clinical Characteristics and Management of Patients With Concomitant Liver Cirrhosis and Lymphoma: A Systematic Review. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2022; 22:e981-e991. [PMID: 35948478 DOI: 10.1016/j.clml.2022.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 07/07/2022] [Accepted: 07/14/2022] [Indexed: 06/15/2023]
Abstract
Over the years, a rising incidence of liver cirrhosis and lymphoma has been observed. Therefore, the risk of having cirrhosis as a comorbidity increases, thus challenging treatment approaches as data on the management of these patients is lacking. We performed a systematic review to summarize papers that analyzed patients with liver cirrhosis that occurred before and/or concomitantly to lymphoma. We identified 153 papers (230 patients) through Pubmed and/or Embase search. Publications comprised predominantly of case reports and/or case series. Most patients had HCV-related cirrhosis (62.6%), and aggressive lymphoma histology (59.6%). Data on liver status was available in 55.7% of all patients, with 46.1% having decompensated liver cirrhosis. These patients experienced more often treatment reductions and/or modifications, treatment side effects, and inferior survival than those with compensated cirrhosis (median 18 months vs. median not reached). Dose reductions and/or treatment modifications primarily due to concomitant liver disease were common. Moreover, liver toxicity was observed in 33.6% of patients with provided information on treatment side effects, ranging from mild toxicity to liver failure with fatal outcomes. Again, despite treatment modification/reduction, patients with decompensated liver cirrhosis developed hepatic toxicity more frequently than patients with compensated liver disease. Although patients suffering from cirrhosis and lymphoma can tolerate standard chemoimmunotherapy, a cautious multidisciplinary approach is needed to evaluate the risks and benefits.
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Affiliation(s)
- Jelena Jelicic
- Department of Hematology, Sygehus Lillebaelt, Vejle, Denmark; Department of Hematology, Odense University Hospital, Odense, Denmark.
| | - Thomas Stauffer Larsen
- Department of Hematology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Annette Dam Fialla
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Zoran Bukumiric
- Department of Statistics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Bosko Andjelic
- Department of Hematology, Blackpool Victoria Hospital, Lancashire Haematology Centre, Blackpool
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7
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Szpakowski JL, Tucker LY, Baer DM, Pauly MP. Hepatotoxicity during legacy cancer chemotherapy in patients infected with hepatitis C virus: A retrospective cohort study. CANADIAN LIVER JOURNAL 2022; 5:43-60. [PMID: 35990784 PMCID: PMC9231429 DOI: 10.3138/canlivj-2021-0018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 08/13/2021] [Indexed: 11/04/2023]
Abstract
BACKGROUND The rates and causes of significant hepatotoxicity with cancer chemotherapy (CCT) in patients infected with hepatitis C virus (HCV) are incompletely characterized. METHODS We compared rates of grade 3 or 4 hepatotoxicity, defined as elevated transaminases, during CCT in patients who are mono-infected with HCV compared with rates in controls matched on demographics, diagnosis, and rituximab use. We excluded patients with hepatobiliary cancers, hepatitis B virus or human immunodeficiency virus infection. Hepatotoxicity was attributed to a medical cause, cancer progression, or CCT, including HCV flare. RESULTS Patients with HCV (n = 196) had a higher rate of cirrhosis than the 1,130 matched controls (21.9% versus 4%; P <0.001). Their higher rate of overall hepatotoxicity (8.7% versus 4.5% of controls, P = 0.01) was due to higher rate of CCT-related hepatotoxicity (4.1% versus 1.2%, P = 0.01). On multivariable analysis, the largest risk factor for overall hepatotoxicity was cirrhosis, and the only risk factor for CCT-related hepatotoxicity was HCV infection. Among those with HCV, the only significant risk factor for hepatotoxicity was rituximab use. Hepatotoxicity caused by CCT delayed or altered treatment in only 3 HCV patients and 1 control (1.5% versus 0.1%, P = 0.01). CONCLUSIONS Most patients with HCV can safely be treated with cancer chemotherapy. Cirrhosis and HCV infection contributed to increased hepatotoxicity in subjects on CCT. Among HCV patients, rituximab use was the major risk factor for increased hepatotoxicity. Hepatotoxicity due to CCT itself rarely altered or delayed CCT. Nonetheless, HCV-positive patients should be monitored carefully during CCT.
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Affiliation(s)
| | - Lue-Yen Tucker
- Division of Research, Kaiser Permanente, Oakland, California, USA
| | - David M Baer
- Kaiser Permanente Medical Center, Oakland, California, USA
| | - Mary Pat Pauly
- Kaiser Permanente Medical Center, Sacramento, California, USA
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Robbins M, Doucette K. Hepatitis Viruses. INFECTIOUS COMPLICATIONS IN BIOLOGIC AND TARGETED THERAPIES 2022:431-450. [DOI: 10.1007/978-3-031-11363-5_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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9
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Zhang M, Gao F, Peng L, Shen L, Zhao P, Ni B, Hou J, Huang H. Distinct clinical features and prognostic factors of hepatitis C virus-associated non-Hodgkin's lymphoma: a systematic review and meta-analysis. Cancer Cell Int 2021; 21:524. [PMID: 34627251 PMCID: PMC8502277 DOI: 10.1186/s12935-021-02230-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 09/27/2021] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Increasing evidence suggests that hepatitis C virus (HCV) infection is associated with non-Hodgkin's lymphoma (NHL). However, no clear consensus has been reached about the clinical features and effective treatment of HCV-associated NHL patients. We therefore performed a systematic review and meta-analysis to explore the clinical characteristics and effectiveness of antiviral treatment or rituximab administration among NHL patients with HCV infection. METHODS Eight electronic databases, including PubMed, OVID, EMBASE, Cochrane Library, ClinicalTrials, WANFANG, CNKI, and VIP, were searched for eligible studies up to July 31, 2021. The hazard ratio (HR) or odds ratio (OR) corresponding to the 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by Egger's and Begg's tests. Statistical analysis was performed with RevMan 5.4 software and Stata version 15. RESULTS There were 27 shortlisted articles out of a total of 13,368 NHL patients included in the current meta-analysis. Our results demonstrated that NHL patients with HCV infection had a significantly shorter overall survival (OS: HR 1.89; 95% CI 1.42-2.51, P < 0.0001) and progression-free survival (PFS: HR 1.58; 95% CI 1.26-1.98, P < 0.0001), a lower overall response rate (ORR: OR 0.58, 95% CI 0.46-0.73, P < 0.00001) and a higher incidence of hepatic dysfunction during chemotherapy (OR 5.96; 95% CI 2.61-13.62, P < 0.0001) than NHL patients without HCV infection. HCV-positive NHL patients exhibited an advanced disease stage, an elevated level of LDH, a high-intermediate and high IPI/FLIPI risk as well as a higher incidence of spleen and liver involvement. Moreover, antiviral treatment prolonged survival (OS: HR 0.38; 95% CI 0.24-0.60, P < 0.0001), reduced disease progression [PFS/DFS (disease-free survival): HR 0.63; 95% CI 0.46-0.86, P = 0.003] and reinforced the treatment response (ORR: OR 2.62; 95% CI 1.34-5.11, P = 0.005) among the HCV-infected NHL patients. Finally, rituximab administration was associated with a favourable OS, while liver cirrhosis and low levels of albumin predicted a poor OS for HCV-positive NHL patients. CONCLUSIONS The current study provided compelling evidence about an inferior prognosis and distinct clinical characteristics among HCV-associated NHL patients. Antiviral treatment and rituximab-containing regimens were shown to be efficacious in improving the clinical outcomes of NHL patients with HCV infection.
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Affiliation(s)
- Minyue Zhang
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.,Division of Chinese Medicine, M.D. Prefectural People's Hospital, Chuxiong Yi Autonomous Prefecture, 675500, China
| | - Fei Gao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, 611730, China
| | - Ling Peng
- Division of Chinese Medicine, M.D. Prefectural People's Hospital, Chuxiong Yi Autonomous Prefecture, 675500, China
| | - Lijing Shen
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Peng Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, 611730, China
| | - Beiwen Ni
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Jian Hou
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
| | - Honghui Huang
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
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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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11
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Elbedewy TA, Elashtokhy HEA, Abd-Elsalam S, Suliman MA. Hepatitis C Virus Infection and Treatment as Independent Prognostic Factors in Diffuse Large B-Cell Lymphoma Egyptian Patients. Curr Cancer Drug Targets 2021; 20:638-645. [PMID: 32392114 DOI: 10.2174/1568009620666200511084731] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 02/28/2020] [Accepted: 03/17/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Egypt is one of the highest hepatitis C virus (HCV) endemic areas. Chronic HCV infection has extra-hepatic manifestations, including non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is commonly associated with HCV infection. The prognostic value of HCV infection and HCV treatment in patients with DLBCL remains unclear until now. OBJECTIVE The aim of our study is to evaluate the impact of HCV infection and HCV treatment as independent prognostic factors on the event-free survival (EFS) and overall survival (OS) in Egyptian patients with HCV associated DLBCL. METHODS This study included 353 patients with DLBCL, collected retrospectively. While 34 patients with HCV who received HCV antiviral therapy were collected prospectively. Patient's characteristics were collected from the patient records at the time of diagnosis. The status of the patients about HCV infection and HCV treatment were also recorded. Disease progression, relapse, retreatment or deaths were also verified through medical records. EFS and OS were calculated. RESULTS EFS and OS significantly decrease in HCV infected and HCV non-treated patients when compared with HCV non-infected and HCV treated patients, respectively. HCV infection but not HCV treatment was independently associated with EFS and OS using univariate and multivariate analysis. CONCLUSION Hepatitis C virus infection is an independent prognostic factor for EFS and OS in diffuse large B-cell lymphoma. HCV treatment is associated with higher EFS and OS but can not be considered as an independent prognostic factor.
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Affiliation(s)
- Tamer A Elbedewy
- Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | | | | | - Marwa A Suliman
- Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Suez Canal University, Al Ismailia, Egypt
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12
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Miyashita K, Hongo Y, Nakashima A, Kato S, Kusano H, Morizono S, Higashi N. Fatal Hepatitis C after Chemotherapy in a Patient with Malignant Lymphoma: Possible Reactivation of Seronegative Occult Hepatitis C Virus Infection Due to Chemotherapy. Intern Med 2021; 60:1533-1539. [PMID: 33191319 PMCID: PMC8188017 DOI: 10.2169/internalmedicine.4768-20] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
A 79-year-old man with lymphoma who tested negative for anti-hepatitis C virus (HCV) antibody received rituximab-containing chemotherapy. Liver dysfunction of unknown cause had persisted since the second cycle of chemotherapy. Ten months after treatment, he rapidly developed massive ascites and atrophy of the liver, and we detected HCV RNA in his serum using real time polymerase chain reaction. Furthermore, medical interviews showed that the patient had no episodes for acute HCV infection, but he did have a history of unspecified liver dysfunction. These findings support the possibility of the reactivation of seronegative occult HCV infection due to chemotherapy in a cancer patient.
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Affiliation(s)
- Kaname Miyashita
- Department of Haematology, Saiseikai Fukuoka General Hospital, Japan
- Department of Hematology, National Hospital Organization Kyushu Cancer Center, Japan
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Yui Hongo
- Department of Diabetes and Endocrinology, Saiseikai Fukuoka General Hospital, Japan
| | | | - Seiya Kato
- Division of Pathology, Saiseikai Fukuoka General Hospital, Japan
| | - Hironori Kusano
- Department of Pathology, Kurume University School of Medicine, Japan
| | - Shusuke Morizono
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Japan
- Department of Hepatology, Saiseikai Fukuoka General Hospital, Japan
| | - Nobuhiko Higashi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Japan
- Department of Hepatology, Saiseikai Fukuoka General Hospital, Japan
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13
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Ciancio A. Impact of Direct Antiviral Agents (DAAs) on B-cell Non Hodgkin's Lymphoma in patients with chronic hepatitis C. Minerva Gastroenterol (Torino) 2021; 67:227-233. [PMID: 33856146 DOI: 10.23736/s2724-5985.21.02834-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The relationship between HCV infection and extrahepatic manifestations has been demonstrated by epidemiological, clinical, immunological and pathological studies. Patients with HCV infection have an increased risk of morbidity and mortality related to these non-liver diseases. For these reasons, HCV chronic infection should be considered a systemic disease in which extrahepatic manifestations increase the severity of the disease. HCV-extrahepatic manifestations may severely affect the overall prognosis, while viral eradication significantly reduces non-liver related deaths. Over the past 5 years, treatment of chronic HCV infection in patients with hematologic malignancies has evolved rapidly and effective and safe direct-acting antivirals (DAAs) have become the standardof-care treatment. The choice of regimens with DAAs should be individualized after thorough assessment for potential hematologic toxic effects and drug-drug interactions. Elimination of HCV from infected cancer patients confers virologic, hepatic, and oncologic benefits.
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Affiliation(s)
- Alessia Ciancio
- Dipartimento di Scienze Mediche, Scuola di Medicina, Università degli Studi di Torino, Turin, Italy -
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14
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Giannotta JA, Fattizzo B, Cavallaro F, Barcellini W. Infectious Complications in Autoimmune Hemolytic Anemia. J Clin Med 2021; 10:E164. [PMID: 33466516 PMCID: PMC7796467 DOI: 10.3390/jcm10010164] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 12/29/2020] [Accepted: 12/31/2020] [Indexed: 12/16/2022] Open
Abstract
Autoimmune hemolytic anemia (AIHA) may be frequently challenged by infectious complications, mainly as a result of immunosuppressive treatments administered. Furthermore, infectious agents are known triggers of AIHA onset and relapse. Although being risk factors for mortality, infections are an underestimated issue in AIHA. This review will collect the available evidence on the frequency and type of infectious complications in AIHA, detailing the risk related to each treatment (i.e., steroids, rituximab, splenectomy, classic immunosuppressive agents, and new target drugs). Moreover, we will briefly discuss the infectious complications in AIHA secondary to other diseases that harbor an intrinsic infectious risk (e.g., primary immunodeficiencies, systemic autoimmune diseases, lymphoproliferative disorders, solid organ and hematopoietic stem cell transplants). Finally, viral and bacterial reactivations during immune suppressive therapies will be discussed, along with suggested screening and prophylactic strategies.
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Affiliation(s)
- Juri Alessandro Giannotta
- Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20100 Milan, Italy; (B.F.); (F.C.); (W.B.)
| | - Bruno Fattizzo
- Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20100 Milan, Italy; (B.F.); (F.C.); (W.B.)
- Department of Oncology and Oncohematology, University of Milan, Via Festa del Perdono 7, 20100 Milan, Italy
| | - Francesca Cavallaro
- Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20100 Milan, Italy; (B.F.); (F.C.); (W.B.)
- Department of Oncology and Oncohematology, University of Milan, Via Festa del Perdono 7, 20100 Milan, Italy
| | - Wilma Barcellini
- Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20100 Milan, Italy; (B.F.); (F.C.); (W.B.)
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15
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Davis JS, Ferreira D, Paige E, Gedye C, Boyle M. Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies. Clin Microbiol Rev 2020; 33:e00035-19. [PMID: 32522746 PMCID: PMC7289788 DOI: 10.1128/cmr.00035-19] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.
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Affiliation(s)
- Joshua S Davis
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - David Ferreira
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Emma Paige
- Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC, Australia
| | - Craig Gedye
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
- Department of Oncology, Calvary Mater Hospital, Newcastle, NSW, Australia
| | - Michael Boyle
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
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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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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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18
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Qureini A, Asif S, Harry S, Madhusudhana S. A Case of Rituximab-Induced Acute Thrombocytopenia in a Patient with Splenic Marginal Zone Lymphoma and Chronic Hepatitis C Virus Infection. AMERICAN JOURNAL OF CASE REPORTS 2019; 20:1394-1397. [PMID: 31541071 PMCID: PMC6767946 DOI: 10.12659/ajcr.917644] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Patient: Female, 46 Final Diagnosis: Rituximab induced acute thrombocytopenia Symptoms: Abdominal discomfort Medication:— Clinical Procedure: — Specialty: Hematology
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Affiliation(s)
- Aref Qureini
- Department of Internal Medicine, University of Missouri School of Medicine, Kansas City, MO, USA
| | - Samia Asif
- Department of Internal Medicine, University of Missouri School of Medicine, Kansas City, MO, USA
| | - Stephanie Harry
- Department of Hematology and Oncology, University of Missouri School of Medicine, Kansas City, MO, USA
| | - Sheshadri Madhusudhana
- Department of Hematology and Oncology, University of Missouri School of Medicine, Kansas City, MO, USA
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19
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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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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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21
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Shimono J, Miyoshi H, Arakawa F, Yamada K, Sugio T, Miyawaki K, Eto T, Miyagishima T, Kato K, Nagafuji K, Akashi K, Teshima T, Ohshima K. Clinicopathological features of HCV-positive splenic diffuse large B cell lymphoma. Ann Hematol 2019; 98:1197-1207. [PMID: 30729289 DOI: 10.1007/s00277-019-03628-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 01/29/2019] [Indexed: 11/26/2022]
Abstract
The hepatitis C virus (HCV) is a single-stranded RNA virus which is thought to be involved in the onset of B cell lymphoma. HCV-positive diffuse large B cell lymphoma (DLBCL) has been reported to clinically manifest in extranodal lesions (e.g., in the liver, spleen, and stomach). Here, we investigated HCV-positive and -negative primary splenic DLBCL (p-spDLBCL) and non-primary splenic DLBCL (ordinary DLBCL). Furthermore, to examine HCV lymphomagenesis, RNA in situ hybridization (ISH), RT-PCR (reverse-transcription polymerase chain reaction), and NS3 immunostaining of HCV viral nonstructural proteins were performed. HCV-positive p-spDLBCL patients presented fewer B symptoms (asymptomatic) and better performance status, with elevated presence of splenic macronodular lesions and more germinal center B cell (GCB) sub-group cases than HCV-negative p-spDLBCL patients. However, HCV-positive ordinary DLBCL patients were found to have more non-GCB sub-group cases than HCV-negative ordinary DLBCL patients. HCV-positive DLBCL patients showed 20.6% (7/34) NS3 positivity, 16.7% (1/6) HCV-RNA in situ positivity, and 22.2% (2/9) detection of HCV-RNA in tumor tissue by RT-PCR. Splenic samples were found to have a higher frequency of HCV detection than lymph node samples, thus suggesting that HCV may be closely related to lymphomagenesis, especially in splenic lymphoma.
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Affiliation(s)
- Joji Shimono
- Department of Pathology, Kurume University, School of Medicine, Asahimachi 67, Kurume, Fukuoka, 830-0011, Japan
- Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Hiroaki Miyoshi
- Department of Pathology, Kurume University, School of Medicine, Asahimachi 67, Kurume, Fukuoka, 830-0011, Japan.
| | - Fumiko Arakawa
- Department of Pathology, Kurume University, School of Medicine, Asahimachi 67, Kurume, Fukuoka, 830-0011, Japan
| | - Kyohei Yamada
- Department of Pathology, Kurume University, School of Medicine, Asahimachi 67, Kurume, Fukuoka, 830-0011, Japan
| | - Takeshi Sugio
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Kohta Miyawaki
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Tetsuya Eto
- Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
| | | | - Koji Kato
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Koji Nagafuji
- Department of Hematology, Kurume University, School of Medicine, Kurume, Japan
| | - Koichi Akashi
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Takanori Teshima
- Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Koichi Ohshima
- Department of Pathology, Kurume University, School of Medicine, Asahimachi 67, Kurume, Fukuoka, 830-0011, Japan
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22
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AISF position paper on HCV in immunocompromised patients. Dig Liver Dis 2019; 51:10-23. [PMID: 30366813 DOI: 10.1016/j.dld.2018.09.022] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Revised: 09/17/2018] [Accepted: 09/18/2018] [Indexed: 02/06/2023]
Abstract
This report summarizes the clinical features and the indications for treating HCV infection in immunocompromised and transplanted patients in the Direct Acting Antiviral drugs era.
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23
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Liao TL, Hsieh SL, Chen YM, Chen HH, Liu HJ, Lee HC, Chen DY. Rituximab May Cause Increased Hepatitis C Virus Viremia in Rheumatoid Arthritis Patients Through Declining Exosomal MicroRNA-155. Arthritis Rheumatol 2018; 70:1209-1219. [PMID: 29575671 DOI: 10.1002/art.40495] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2017] [Accepted: 03/08/2018] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Several studies have shown that rituximab may enhance hepatitis C virus (HCV) activity. MicroRNAs (miRNAs) have been implicated in modulating the host immune response in HCV infection; miRNAs can be packaged into the exosomes and then shuttled by the exosomes to aid biologic functions. However, the role of exosomal miRNAs (exo-miRNAs) in rituximab-related HCV activity enhancement remains unclear. METHODS The association between rituximab and increased HCV activity was examined using an in vitro cell-based assay. Purified exosomes were confirmed using immunoblotting and flow cytometry and quantified using enzyme-linked immunosorbent assay. Exosomal miRNA-155 (exo-miR-155) levels were measured using quantitative reverse transcription-polymerase chain reaction. RESULTS In vitro data showed that B cell-derived miR-155 could inhibit HCV replication in hepatocytes through exosome transmission. Rituximab could both induce B cell depletion and affect intracellular miR-155 production as well as exo-miR-155 transmission and then enhance HCV activity in hepatocytes (P < 0.005). Serum exosome levels were increased in rheumatoid arthritis (RA) patients with HCV infection compared with the levels in RA patients without HCV infection (P < 0.01). The exo-miR-155 levels were significantly increased in RA patients with HCV infection compared with those without infection (P < 0.01). A significantly greater decrement of exo-miR-155 expression was observed after rituximab therapy compared with those observed before therapy (P < 0.01), and hepatitis C viral loads increased simultaneously (P < 0.05). CONCLUSION Circulating exo-miR-155 levels were negatively correlated with hepatitis C viral loads and subsequently associated with rituximab-related HCV activity enhancement in RA patients. Exo-miR-155 may become a potential diagnostic biomarker or therapeutic target.
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Affiliation(s)
- Tsai-Ling Liao
- Taichung Veterans General Hospital and National Chung Hsing University, Taichung, Taiwan
| | - Shie-Liang Hsieh
- Genomics Research Center, Academia Sinica and National Yang Ming University, Taipei, Taiwan
| | - Yi-Ming Chen
- Taichung Veterans General Hospital and National Chung Hsing University, Taichung, Taiwan, and National Yang Ming University, Taipei, Taiwan
| | - Hsin-Hua Chen
- Taichung Veterans General Hospital and National Chung Hsing University, Taichung, Taiwan, and National Yang Ming University, Taipei, Taiwan
| | - Hung-Jen Liu
- National Chung Hsing University, Taichung, Taiwan
| | - Hsiu-Chin Lee
- Taichung Veterans General Hospital, Taichung, Taiwan
| | - Der-Yuan Chen
- Taichung Veterans General Hospital, China Medical University Hospital, and China Medical University, Taichung, Taiwan
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24
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Lee HL, Bae SH, Jang B, Hwang S, Yang H, Nam HC, Sung PS, Lee SW, Jang JW, Choi JY, Han NI, Song BJ, Lee JW, Yoon SK. Reactivation of Hepatitis C Virus and Its Clinical Outcomes in Patients Treated with Systemic Chemotherapy or Immunosuppressive Therapy. Gut Liver 2018; 11:870-877. [PMID: 28750484 PMCID: PMC5669604 DOI: 10.5009/gnl16434] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Revised: 01/14/2017] [Accepted: 02/26/2017] [Indexed: 12/11/2022] Open
Abstract
Background/Aims According to the results of several studies, the outcome of hepatitis C virus (HCV) reactivation is not as severe as the outcome of hepatitis B virus reactivation. The aim of this study was to evaluate the effect of pharmacological immunosuppression on HCV reactivation. Methods The medical records of patients who underwent systemic chemotherapy, corticosteroid therapy, or other immunosuppressive therapies between January 2008 and March 2015 were reviewed. Subsequently, 202 patients who were seropositive for the anti-HCV antibody were enrolled. Exclusion criteria were: unavailability of data on HCV RNA levels, a history of treatment for chronic hepatitis C, and the presence of liver diseases other than a chronic HCV infection. Results Among the 120 patients enrolled in this study, hepatitis was present in 46 patients (38%). None of the patients were diagnosed with severe hepatitis. Enhanced replication of HCV was noted in nine (27%) of the 33 patients who had data available on both basal and follow-up HCV RNA loads. Reappearance of the HCV RNA from an undetectable state did not occur after treatment. The cumulative rate of enhanced HCV replication was 23% at 1 year and 30% at 2 years. Conclusions Although enhanced HCV replication is relatively common in HCV-infected patients treated with chemotherapy or immunosuppressive therapy, it does not lead to serious sequelae.
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Affiliation(s)
- Hae Lim Lee
- Division of Hepatology, Department of Internal Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Bucheon, Korea
| | - Si Hyun Bae
- Division of Hepatology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Bohyun Jang
- Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Seawon Hwang
- Division of Hepatology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Hyun Yang
- Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Hee Chul Nam
- Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Pil Soo Sung
- Division of Hepatology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Sung Won Lee
- Division of Hepatology, Department of Internal Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Bucheon, Korea
| | - Jeong Won Jang
- Division of Hepatology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jong Young Choi
- Division of Hepatology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Nam Ik Han
- Division of Hepatology, Department of Internal Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Bucheon, Korea
| | - Byung Joo Song
- Department of Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jong Wook Lee
- Division of Hematology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Seung Kew Yoon
- Division of Hepatology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
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Abstract
Infectious agents, such as HCV, account for ∼15% of human cancers. HCV infects not only hepatocytes but also extrahepatic cells. Chronic HCV infection can induce chronic inflammation with qualitative and quantitative alterations of the immune repertoire and tissue microenvironment, which could induce various neoplasias. Epidemiological studies and meta-analyses suggest an increased rate of extrahepatic cancers in patients with chronic HCV infection along with a higher risk of intrahepatic cholangiocarcinoma, pancreatic cancer and non-Hodgkin lymphoma (NHL), highlighting the need to screen for HCV infection in patients with these cancers. Development of B cell NHL has been associated with HCV infection, with a relative risk of ∼1.5. Direct transformation related to the presence of the virus and chronic antigenic stimulation are the two major non-exclusive mechanisms involved in HCV-related lymphomagenesis. HCV infection alters survival of patients with lymphoma, and sustained virologic response (SVR) substantially improves prognosis. Antiviral treatments might induce remission of indolent lymphoma when SVR is achieved even without chemotherapy, emphasizing the role of HCV in lymphomagenesis in this context. However, studies are needed to provide prospective evidence of a causal relationship between chronic HCV infection and other extrahepatic cancers and to determine whether the risk of extrahepatic cancers is reduced with SVR. In this Review, we report on recent studies analysing the risk of extrahepatic cancers associated with chronic HCV infection. Although there is no doubt regarding the direct and indirect causality between HCV and NHL, an increased risk of other cancers is less clear, with the exception of cholangiocarcinoma.
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Nicolini LA, Zappulo E, Viscoli C, Mikulska M. Management of chronic viral hepatitis in the hematological patient. Expert Rev Anti Infect Ther 2018; 16:227-241. [PMID: 29415584 DOI: 10.1080/14787210.2018.1438264] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Infection with HBV and HCV represents a growing challenge in the management of patients with hematological malignancies. Recently, hepatitis E (HEV) was recognized as an endemic infection in developed countries and as an emerging health problem in immunocompromised patients. Areas covered: We reviewed the current knowledge on the impact of chronic viral hepatitis in the hematological setting. Epidemiological features, screening strategies and indications for treatment and monitoring have been explored and commented. Expert commentary: Knowing patient's complete HBV serostatus is mandatory in order to choose between treatment, prophylaxis or a pre-emptive approach. Recent guidelines favor treatment with high barrier molecules in all patients with chronic HBV infection and long lasting prophylaxis with those with inactive or resolved one. With regard to HCV, the new direct-acting antiviral agents have been safely administered in the hematological setting. Their use as first-line single treatment in indolent lymphomas, and combined with chemotherapy in aggressive ones, should be considered. Due to the existing risk of chronic HEV infection in the immunocompromised, screening with serum HEV-RNA should be performed in case of signs and symptoms indicative of hepatitis. In the event of HEV infection, reduction of immunosuppression and, if not feasible or unsuccessful, ribavirin treatment should be prescribed.
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Affiliation(s)
- Laura Ambra Nicolini
- a Infectious Diseases Unit, Department of Health Science (DISSAL), Ospedale Policlinico San Martino, IRCCS per l'Oncologia , University of Genoa , Genoa , Italy
| | - Emanuela Zappulo
- a Infectious Diseases Unit, Department of Health Science (DISSAL), Ospedale Policlinico San Martino, IRCCS per l'Oncologia , University of Genoa , Genoa , Italy.,b Division of Infectious Diseases, Department of Clinical Medicine and Surgery , University of Naples Federico II , Naples , Italy
| | - Claudio Viscoli
- a Infectious Diseases Unit, Department of Health Science (DISSAL), Ospedale Policlinico San Martino, IRCCS per l'Oncologia , University of Genoa , Genoa , Italy
| | - Malgorzata Mikulska
- a Infectious Diseases Unit, Department of Health Science (DISSAL), Ospedale Policlinico San Martino, IRCCS per l'Oncologia , University of Genoa , Genoa , Italy
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Kanakry JA, Ambinder RF. Virus-Associated Lymphoma. Hematology 2018. [DOI: 10.1016/b978-0-323-35762-3.00083-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Torres HA, Hosry J, Mahale P, Economides MP, Jiang Y, Lok AS. Hepatitis C virus reactivation in patients receiving cancer treatment: A prospective observational study. Hepatology 2018; 67:36-47. [PMID: 28653760 PMCID: PMC5739995 DOI: 10.1002/hep.29344] [Citation(s) in RCA: 83] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Revised: 06/17/2017] [Accepted: 06/22/2017] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus (HCV) reactivation in patients receiving cancer treatment has been reported in retrospective studies. We sought to determine prospectively the incidence, predictors, and clinical significance of HCV reactivation during cancer treatment. HCV-infected patients receiving cancer treatment at our institution between November 2012 and July 2016 were studied. Reactivation was defined as an increase in HCV-RNA ≥1 log10 IU/mL over baseline and hepatitis flare as an increase in alanine aminotransferase to ≥3 times the upper limit of normal. One hundred patients were studied, 50 with hematologic malignancies and 50 with solid tumors. Reactivation occurred in 23 (23%) patients, including 18 (36%) patients with hematologic malignancies and 5 (10%) patients with solid tumors. In univariate analysis, patients with reactivation were more likely than those without reactivation to have prolonged lymphopenia (median, 95 versus 22 days; P = 0.01) and to have received rituximab (44% versus 9%; P < 0.0001), bendamustine (22% versus 0%; P < 0.001), high-dose steroids (57% versus 21%; P = 0.001), or purine analogs (22% versus 5%; P = 0.02). Rituximab (odds ratio = 9.52; P = 0.001), and high-dose steroids (odds ratio = 5.05; P = 0.01) retained significance in multivariable analysis. Of the 23 patients with reactivation, 10 (43%) had hepatitis flare. No patient with reactivation experienced liver failure or liver-related death within 36 weeks after initiation of cancer treatment. Fourteen patients with hepatitis flare, six of whom had reactivation, required discontinuation or dose reduction of cancer treatment. CONCLUSION HCV reactivation occurred in 23% of HCV-infected patients receiving cancer treatment, and most had an unremarkable clinical course. However, reactivation can affect the cancer treatment plan. Our findings suggest that HCV infection should not contraindicate cancer therapy and infected patients should have access to multiple cancer treatments with close monitoring while receiving regimens associated with HCV reactivation. (Hepatology 2018;67:36-47).
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Affiliation(s)
- Harrys A. Torres
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - 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
| | - Minas P. Economides
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ying Jiang
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Anna S. Lok
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
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Alderuccio JP, Stefanovic A, Dammrich D, Chapman JR, Vega F, Selvaggi G, Tzakis A, Lossos IS. Decreased survival in hepatitis C patients with monomorphic post-transplant lymphoproliferative disorder after liver transplantation treated with frontline immunochemotherapy. Leuk Lymphoma 2017; 59:2096-2104. [PMID: 29252057 DOI: 10.1080/10428194.2017.1413187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Post-transplant lymphoproliferative disorder (PTLD) develops in 1-3% of liver transplant recipients and no consensus exists about therapeutic management. From 2006 to 2016, 1489 liver transplants were performed at our institution with 20 patients (incidence 1.3%) developing PTLD. Hepatitis C virus (HCV) was the leading cause (n = 10) of liver transplant in PTLD patients. Diffuse large B-cell lymphoma was the most frequent histologic subtype (n = 17), and we report our experience in the management of these patients. Patients were treated with frontline immunochemotherapy without immunosuppression reduction. All evaluable patients achieved a complete remission. Statistically significant decreased survival was identified in HCV-positive patients. Six patients (60%) exhibited increases in HCV RNA levels during therapy. Four patients (40%) developed graft failure and three of them (30%) died from liver dysfunction. This is the first study providing evidence of decreased survival in HCV-positive PTLD patients after liver transplant receiving immunochemotherapy.
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Affiliation(s)
- Juan Pablo Alderuccio
- a Department of Medicine, Division of Hematology , University of Miami Miller School of Medicine , Miami , FL , USA
| | - Alexandra Stefanovic
- a Department of Medicine, Division of Hematology , University of Miami Miller School of Medicine , Miami , FL , USA
| | - Daniel Dammrich
- a Department of Medicine, Division of Hematology , University of Miami Miller School of Medicine , Miami , FL , USA
| | - Jennifer R Chapman
- b Department of Pathology and Laboratory Medicine, Division of Hematopathology , University of Miami Miller School of Medicine , Miami , FL , USA
| | - Francisco Vega
- b Department of Pathology and Laboratory Medicine, Division of Hematopathology , University of Miami Miller School of Medicine , Miami , FL , USA
| | - Gennaro Selvaggi
- c Department of Surgery, Division of Transplantation , University of Miami Miller School of Medicine , Miami , FL , USA
| | - Andreas Tzakis
- c Department of Surgery, Division of Transplantation , University of Miami Miller School of Medicine , Miami , FL , USA
| | - Izidore S Lossos
- a Department of Medicine, Division of Hematology , University of Miami Miller School of Medicine , Miami , FL , USA.,d Department of Molecular and Cellular Pharmacology , University of Miami Miller School of Medicine , Miami , FL , USA.,e Sylvester Comprehensive Cancer Center , Miami , FL , USA
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30
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Shimono J, Miyoshi H, Kato T, Sugio T, Miyawaki K, Kamimura T, Miyagishima T, Eto T, Imaizumi Y, Kato K, Nagafuji K, Akashi K, Seto M, Teshima T, Ohshima K. Hepatitis C virus infection is an independent prognostic factor in follicular lymphoma. Oncotarget 2017; 9:1717-1725. [PMID: 29416725 PMCID: PMC5788593 DOI: 10.18632/oncotarget.23138] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Accepted: 11/13/2017] [Indexed: 01/08/2023] Open
Abstract
Hepatitis C virus (HCV) is a single-stranded RNA virus that not only affects hepatocytes, by B cells as well. It is thought that HCV is involved in the onset of B-cell lymphoma. The clinicopathological characteristics of HCV-positive diffuse large B-cell lymphoma (DLBCL) and HCV-positive splenic marginal zone lymphoma (SMZL) are known, but there has been no report on HCV-positive follicular lymphoma (FL). In this study, the clinicopathological characteristics of HCV-positive FL were examined in 263 patients with FL who were classified into a HCV-positive group with HCV antibody and negative groups without one. The number of patients with HCV-positive FL and HCV-negative FL was 10 (3.8%) and 253 (96.2%), respectively. The patients with HCV-positive FL commonly had more than one region of lymphadenopathy, Ann Arbor stage III/IV, hemoglobin <120 g/l, elevated lactate dehydrogenase level, and high-risk categorization of Follicular Lymphoma International Prognostic Index (FLIPI) than in patients with HCV-negative FL. Overall survival and progression-free survival were poorer in patients with HCV-positive FL than in those with HCV-negative FL (p < 0.0001 and 0.006, respectively). Also, multivariate analysis revealed that positive HCV antibody was a poor prognostic factor of OS. In conclusion, HCV-positive FL has unique clinical features and may have a great impact on the overall survival of affected patients.
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Affiliation(s)
- Joji Shimono
- Department of Pathology, Kurume University, School of Medicine, Kurume, Japan.,Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Hiroaki Miyoshi
- Department of Pathology, Kurume University, School of Medicine, Kurume, Japan
| | - Takeharu Kato
- Department of Hematology, Sasebo City General Hospital, Sasebo, Japan.,Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan
| | - Takeshi Sugio
- Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan
| | - Kohta Miyawaki
- Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan
| | | | | | - Tetsuya Eto
- Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
| | - Yoshitaka Imaizumi
- Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan
| | - Koji Kato
- Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan
| | - Koji Nagafuji
- Department of Hematology, Kurume University, School of Medicine, Kurume, Japan
| | - Koichi Akashi
- Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan
| | - Masao Seto
- Department of Pathology, Kurume University, School of Medicine, Kurume, Japan
| | - Takanori Teshima
- Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Koichi Ohshima
- Department of Pathology, Kurume University, School of Medicine, Kurume, Japan
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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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Liu Y, Li ZY, Li X, Wang JN, Huang QA, Huang Y. Liver toxicity of chemotherapy and targeted therapy for breast cancer patients with hepatitis virus infection. Breast 2017; 35:191-195. [PMID: 28800545 DOI: 10.1016/j.breast.2017.08.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 08/05/2017] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Chemotherapy has greatly improved the prognosis of breast cancer patients. However, it may also result in undesirable side effects such as hepatitis virus reactivation. Little information is available on the liver toxicity of chemotherapy and targeted therapy for breast cancer patients with hepatitis virus (HBV/HCV) infection. METHODS We performed a retrospective survey of 835 patients diagnosed with breast cancer between January 2010 and December 2015 at our institution. All patients had been screened for HBV/HCV infection at the time of breast cancer diagnosis. We retrospectively investigated the toxicity of chemotherapy and the changes in HBV/HCV load based on a medical record review. RESULTS 52 patients with positive anti-HBV antibody test and 21 patients with positive anti-HCV antibody tests received chemotherapy. 762 patients without HBV and HCV infection served as the control group. The morbidity of liver toxicity and disruptions in chemotherapy attributable to liver toxicity were not significantly different among control group, HBV group and HCV groups (27.7% vs 34.6% vs 42.9%, P = 0.189 and 5.0% vs 9.6% vs 9.5%, P = 0.173, respectively). No patients presented with HBV/HCV reactivation. CONCLUSION Breast cancer patients with HCV can be treated with chemotherapy and targeted therapy with trastuzumab. Breast cancer patients with HBV who accept antiviral therapy can be treated with chemotherapy and targeted therapy with trastuzumab and patients can benefit from prophylactic antiviral therapy before chemotherapy. However, a multidisciplinary cooperation and closely monitoring liver function during the course of chemotherapy may benefit patients.
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Affiliation(s)
- Yu Liu
- Department of Thyroid and Breast Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510000, China
| | - Zhan-Yi Li
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510000, China
| | - Xi Li
- Department of Thyroid and Breast Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510000, China
| | - Jia-Ni Wang
- Department of Thyroid and Breast Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510000, China
| | - Qun-Ai Huang
- Department of Thyroid and Breast Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510000, China
| | - Yong Huang
- Department of Thyroid and Breast Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510000, China.
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The influence of rituximab-containing chemotherapy on HCV load in patients with HCV-associated non-Hodgkin's lymphomas. Ann Hematol 2017; 96:1501-1507. [PMID: 28669008 DOI: 10.1007/s00277-017-3058-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 06/24/2017] [Indexed: 01/14/2023]
Abstract
Efficacy and safety of rituximab treatment in patients with Hepatitis C virus (HCV) infection associated non-Hodgkin's lymphoma (NHL) are still disputable. The aim of this study was to evaluate the influence of rituximab-containing chemotherapy on HCV load. Fifty-four patients with both HCV infection and NHL were identified between 2000 and 2016 at our institution. We retrospectively analyzed patients' demographic characteristics, treatment, and kinetics of HCV load before and after treatment with rituximab-containing chemotherapy. In the total group of 54 patients, 29 (54%) received rituximab. Both HCV load pre rituximab and maximal HCV load post rituximab were available in 16 patients. Overall, we observed no significant difference between HCV load pre rituximab and the maximal HCV load post rituximab (P = 0.19). In a patient who was treated simultaneously with direct-acting antivirals (DAAs) and rituximab-containing chemotherapy, HCV load decreased below the sensitivity level (≤12 IU/ml) during treatment. When regarding the influence of rituximab-containing chemotherapy alone on HCV load, we observed a significant elevation of HCV load (P = 0.04). Rituximab-containing chemotherapy may lead to an increase of HCV load in patients with HCV-associated NHL. However, this finding is based on small patient cohort and should be confirmed in larger clinical trials.
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34
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Bagacean C, Zdrenghea M, Tempescul A, Cristea V, Renaudineau Y. Anti-CD20 monoclonal antibodies in chronic lymphocytic leukemia: from uncertainties to promises. Immunotherapy 2017; 8:569-81. [PMID: 27140410 DOI: 10.2217/imt-2015-0015] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Over the last two decades, anti-CD20 monoclonal antibody (mAb) therapy has improved patient outcome in B-cell malignancies, and confirmed CD20 as an important target in chronic lymphocytic leukemia (CLL). Until recently, the gold standard was based on the utilization of rituximab combined with chemotherapy (fludarabine and cyclophosphamide), but patients often relapse. Next, with our better understanding of mAb engineering, anti-CD20 mAb therapy has evolved with the development of new mAb permitting significant clinical responses by improving pharmacokinetics, safety, activity and immunogenicity. Last but not least, the development of key tumoral tyrosine kinase inhibitors and their association with anti-CD20 mAb is a work in progress with promising results.
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Affiliation(s)
- Cristina Bagacean
- Research Unit INSERM ESPRI, ERI29/EA2216 Immunotherapy & B Cell Diseases, Réseau épigénétique et Réseau canaux ioniques du Cancéropôle Grand Ouest, Labex IGO, European University of Brittany, Brest, France.,'Iuliu Hatieganu' University of Medicine & Pharmacy, 8 Babes Street, 400012, Cluj-Napoca, Romania
| | - Mihnea Zdrenghea
- 'Iuliu Hatieganu' University of Medicine & Pharmacy, 8 Babes Street, 400012, Cluj-Napoca, Romania.,'Ion Chiricuta' Institute of Oncology, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
| | - Adrian Tempescul
- Research Unit INSERM ESPRI, ERI29/EA2216 Immunotherapy & B Cell Diseases, Réseau épigénétique et Réseau canaux ioniques du Cancéropôle Grand Ouest, Labex IGO, European University of Brittany, Brest, France.,Department of Hematology, CHRU Morvan, Brest, France
| | - Victor Cristea
- 'Iuliu Hatieganu' University of Medicine & Pharmacy, 8 Babes Street, 400012, Cluj-Napoca, Romania
| | - Yves Renaudineau
- Research Unit INSERM ESPRI, ERI29/EA2216 Immunotherapy & B Cell Diseases, Réseau épigénétique et Réseau canaux ioniques du Cancéropôle Grand Ouest, Labex IGO, European University of Brittany, Brest, France.,Laboratory of Immunology & Immunotherapy, CHRU Morvan, Brest, France
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35
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Liu Y, Li ZY, Wang JN, Li X, Huang QA, Huang Y. Effects of hepatitis C virus infection on the safety of chemotherapy for breast cancer patients. Breast Cancer Res Treat 2017; 164:379-383. [PMID: 28447238 DOI: 10.1007/s10549-017-4259-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Accepted: 04/18/2017] [Indexed: 12/14/2022]
Abstract
PURPOSE Hepatitis C virus (HCV) is one of the major pathogens of chronic viral hepatitis, and approximately 38 million patients are infected with HCV in China. However, little information is available on the effect of HCV infection during chemotherapy for breast cancer and the impact of HCV infection on the toxicity of chemotherapy and targeted therapy. METHODS We performed a retrospective survey of 835 patients who were diagnosed with breast cancer between January 2010 and December 2015 at our institution. All patients had been screened for HCV infection at the time of breast cancer diagnosis. We retrospectively investigated the toxicities of chemotherapy and the changes in HCV load based on a review of the medical records. RESULTS A total of 21 patients with positive anti-HCV antibody tests received chemotherapy. The median patient age was 46.3 ± 11.2 years. Four (19.0%) patients exhibited abnormal liver function at baseline. The morbidity of abnormal liver function at baseline was higher in HCV-infected patients (19.0% vs. 0, P = 0.000). Four patients received trastuzumab therapy. Five (23.8%) patients who received chemotherapy developed hepatitis. No patients presented with HCV reactivation. The morbidity of hepatitis and the rate of disruption of chemotherapy were not significantly different between breast cancer patients without HCV infection and those with HCV infection (23.8 vs. 14.2% P = 0.342, 9.5 vs. 5.0% P = 0.619, respectively). CONCLUSION HCV infection had no adverse impact on chemotherapy in breast cancer patients. However, consulting a gastroenterologist and closely monitoring liver function during the course of chemotherapy may benefit patients.
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Affiliation(s)
- Yu Liu
- Department of Thyroid and Breast Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhan-Yi Li
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jia-Ni Wang
- Department of Thyroid and Breast Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xi Li
- Department of Thyroid and Breast Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Qun-Ai Huang
- Department of Thyroid and Breast Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yong Huang
- Department of Thyroid and Breast Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
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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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Clinico-biological characteristics and outcome of hepatitis C virus-positive patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Ann Hematol 2016; 96:405-410. [PMID: 28035434 DOI: 10.1007/s00277-016-2903-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 12/18/2016] [Indexed: 12/14/2022]
Abstract
Diffuse large B cell lymphoma (DLBCL) patients carrying hepatitis C virus (HCV) have higher risk of treatment toxicity and complications. The aim of this study was to assess the impact of HCV in a series of DLBCL patients treated with immunochemotherapy. 321 patients (161 M/160F; median age, 66 years) diagnosed with de novo DLBCL in a single center between 2002 and 2013 were included. Immunodeficiency-related lymphomas were excluded. HCV+ cases were defined by the presence of IgG anti-HCV. Main clinico-biological characteristics and outcome were analyzed according to the viral status. Two hundred ninety patients were HCV- and 31 HCV+. HCV+ patients were older (median age 71 vs. 64 years, P = 0.03), had more often B symptoms (P = 0.013), spleen (P = 0.003), and liver (P = 0.011) involvement, higher rate of early death (<4 months, P = .001), and shorter overall survival (OS). Eleven HCV+ patients had cirrhosis criteria. HCV+ patients with impaired liver function before or during treatment showed inferior OS. Elevated pre-treatment bilirubin correlated also with higher liver toxicity. In a multivariate analysis that included R-IPI score, serum beta2-microglobulin (β2m), HCV status, and presence of cirrhosis, only R-IPI, β2m, and cirrhosis showed independent prognostic impact on OS. The presence of HCV in DLBCL patients entails higher number of complications and early deaths; however, liver impairment and not the hepatitis viral status was the key feature in the outcome of the patients.
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Hepatitis C virus and non-Hodgkin's lymphomas: A minireview. J Adv Res 2016; 8:131-137. [PMID: 28149648 PMCID: PMC5272953 DOI: 10.1016/j.jare.2016.11.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Revised: 11/28/2016] [Accepted: 11/30/2016] [Indexed: 12/14/2022] Open
Abstract
B-cell NHL is strongly associated with HCV that was proved in the last 2 decades. The most common HCV infection related B-NHL subtypes include MZL and DLBCL lymphomas. HCV-positive NHL patients usually present with older age at diagnosis, higher LDH, and more extranodal disease. The standard chemo-immunotherapy tolerance is generally good. Antiviral treatment achieves virological and hematological remission in HCV associated indolent lymphoma. More aggressive lymphoma requires combination of antiviral treatment and chemotherapy. New generation of HCV antiviral drugs is safe and is highly efficacious. Regimens including DAAs appear promising options as they can reduce the HCV-associated NHL incidence by dramatically lowering the HCV chronic carriers.
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Galati G, Rampa L, Vespasiani-Gentilucci U, Marino M, Pisani F, Cota C, Guidi A, Picardi A. Hepatitis C and double-hit B cell lymphoma successfully treated by antiviral therapy. World J Hepatol 2016; 8:1244-1250. [PMID: 27803769 PMCID: PMC5067444 DOI: 10.4254/wjh.v8.i29.1244] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 06/25/2016] [Accepted: 08/16/2016] [Indexed: 02/06/2023] Open
Abstract
B cells lymphoma is one of the most challenging extra-hepatic manifestations of hepatitis C virus (HCV). Recently, a new kind of B-cell lymphoma, named double-hit B (DHL), was characterized with an aggressive clinical course whereas a potential association with HCV was not investigated. The new antiviral direct agents (DAAs) against HCV are effective and curative in the majority of HCV infections. We report the first case, to our knowledge, of DHL and HCV-infection successfully treated by new DAAs. According to our experience, a DHL must be suspected in case of HCV-related lymphoma, and an early diagnosis could direct towards a different hematological management because a worse prognosis might be expected. A possible effect of DAAs on DHL regression should be investigated, but eradicating HCV would avoid life-threatening reactivation of viral hepatitis during pharmacological immunosuppression in onco-haematological diseases.
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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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Lin JW, Chang ML, Hsu CW, Chen YC, Liang KH, Huang YH, Lin CC, Yeh CT. Acute exacerbation of hepatitis C in hepatocellular carcinoma patients receiving chemotherapy. J Med Virol 2016; 89:153-160. [PMID: 27273118 DOI: 10.1002/jmv.24595] [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] [Accepted: 06/05/2016] [Indexed: 02/06/2023]
Abstract
Acute hepatitis C exacerbations can occur in cancer patients carrying hepatitis C virus (HCV) when receiving systemic chemotherapy. However, clinical studies evaluating these complications remain rare due to the lack of clinically proven effective and tolerable anti-HCV treatments at late cancer stages. Furthermore, no data were available regarding hepatitis C exacerbation in advanced hepatocellular carcinoma (HCC) patients receiving chemotherapy. To address this issue, 48 patients with HCV-related advanced HCC, who underwent systemic chemotherapy using 5- fluorouracil, cisplatin, and mitoxantrone from 2008 to 2014 were analyzed. Nine patients developed acute hepatitis exacerbations defined by HCV-RNA elevation ≥10-fold and alanine transaminase (ALT) elevation ≥5-fold of the upper normal limit. Six were genotype 1b and 3 were genotype 2. Three patterns of clinical courses were observed including single episode of exacerbation (n = 5), fluctuated flares (n = 3), and delayed exacerbation (n = 1). Hepatic failure developed in five patients. Patients with acute exacerbations were less likely to have pretreatment ascites (11.1% vs. 53.8%; P = 0.028) and displayed a lower baseline ALT (44.1 ± 28.5 U/L vs. 72.6 ± 19.2 U/L; P = 0.007). Paradoxically, despite a high risk of hepatic failure, occurrence of hepatitis C exacerbation was associated with a favorable overall survival (P = 0.027; 22.8 vs. 5.4 months). In conclusion, hepatitis C exacerbation can occur in HCC patients receiving chemotherapy, leading to liver failure. However, the flare was associated with a better overall survival, possibly due to its association with a better baseline liver function. J. Med. Virol. 89:153-160, 2017. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Ji-Wei Lin
- Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
| | - Ming-Ling Chang
- Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
| | - Chao-Wei Hsu
- Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
| | - Yi-Cheng Chen
- Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
| | - Kung-Hao Liang
- Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
| | - Ya-Hui Huang
- Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
| | - Chen-Chun Lin
- Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
| | - Chau-Ting Yeh
- Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan. .,Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
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Totani H, Kusumoto S, Tanaka Y, Suzuki N, Hagiwara S, Kinoshita S, Iio E, Ito A, Ri M, Ishida T, Komatsu H, Iida S. The value of serum Wisteria floribunda agglutinin-positive human Mac-2-binding protein as a predictive marker for hepatitis C virus-related complications after systemic chemotherapy. Int J Hematol 2016; 104:384-91. [PMID: 27255233 DOI: 10.1007/s12185-016-2033-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Revised: 05/26/2016] [Accepted: 05/26/2016] [Indexed: 12/23/2022]
Abstract
Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA(+)-M2BP) was developed recently as a predictive marker of progression to liver fibrosis and hepatocellular carcinoma (HCC) in patients seropositive for hepatitis C virus (HCV). We retrospectively analyzed 16 HCV-seropositive patients who received systemic chemotherapy for hematologic malignancies to evaluate the usefulness of WFA(+)-M2BP for predicting HCV-related complications. These were defined as the onset of significant liver damage (LD) with increased HCV RNA levels, leading to interrupted or discontinued chemotherapy or the occurrence of HCC after chemotherapy. Baseline WFA(+)-M2BP levels were determined using preserved serum samples. The median level of WFA(+)-M2BP was 1.59 [cutoff index (C.O.I.) value range 0.38-6.66]. With a median follow-up of 623 days (range 120-2404), LD and HCC were observed in three and two patients, respectively. Detectable HCV RNA and WFA(+)-M2BP ≥2.0 C.O.I. at baseline were identified as risk factors for these HCV-related complications (P = 0.034 and P = 0.005, respectively). The sensitivity, specificity, and positive and negative predictive values of the WFA(+)-M2BP level (cutoff point: 2.0 C.O.I.) for the occurrence of HCV-related complications were 100.0, 81.8, 71.4, and 100.0 %, respectively. WFA(+)-M2BP may be a useful marker for the prediction of HCV-related complications in HCV-seropositive patients following systemic chemotherapy.
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Affiliation(s)
- Haruhito Totani
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan
| | - Shigeru Kusumoto
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan.
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Nana Suzuki
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan
| | - Shinya Hagiwara
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan
| | - Shiori Kinoshita
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan
| | - Etsuko Iio
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Asahi Ito
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan
| | - Masaki Ri
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan
| | - Takashi Ishida
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan
| | - Hirokazu Komatsu
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan
| | - Shinsuke Iida
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan
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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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Wang Y, Zhang L, Qian Y, Xu P, Wang L, Li J, Zhao W, Shen Z, Shen Y. [Clinical characteristics and outcome of 216 indolent B cell lymphomas]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2016; 37:61-4. [PMID: 26876256 PMCID: PMC7342303 DOI: 10.3760/cma.j.issn.0253-2727.2016.01.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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46
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Barta SK. Coinfection with Hepatitis B or C in People Living with HIV Undergoing Immunosuppressive Therapy. HIV-ASSOCIATED HEMATOLOGICAL MALIGNANCIES 2016:227-234. [DOI: 10.1007/978-3-319-26857-6_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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47
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Vannata B, Arcaini L, Zucca E. Hepatitis C virus-associated B-cell non-Hodgkin's lymphomas: what do we know? Ther Adv Hematol 2015; 7:94-107. [PMID: 27054025 DOI: 10.1177/2040620715623924] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Epidemiological studies have shown an increased risk of developing B-cell lymphomas in patients with chronic hepatitis C virus (HCV) infection. There is, however, a great geographic variability and it remains unclear whether additional environmental and genetic factors are involved or whether the international discrepancies represent simply a consequence of the variable prevalence of HCV infection in different countries. Other confounding factors may affect the comparability of the different studies, including the method of HCV assessment, the selection of normal controls, the lymphoma classification used and the year of publication. The most convincing evidence for a causal relationship comes from the observation, mainly limited to some indolent subtypes, of B-cell lymphoma regressions after successful HCV eradication with antiviral treatment. Yet, the molecular mechanism of HCV-induced lymphomagenesis are mainly hypothetical. According to most plausible models, lymphoma growth is a consequence of continuous antigenic stimulation induced by the chronic viral infection. This review will summarize the current knowledge on HCV-associated lymphomas and their management.
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Affiliation(s)
- Barbara Vannata
- Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
| | - Luca Arcaini
- Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo and Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Emanuele Zucca
- Lymphoma Unit, Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona 6500, Switzerland
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48
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Kyvernitakis A, Taremi M, Blechacz B, Hwang J, Jiang Y, Mahale P, Torres HA. Impact of hepatitis E virus seropositivity on chronic liver disease in cancer patients with hepatitis C virus infection. Hepatol Res 2015; 45:1146-51. [PMID: 25488194 DOI: 10.1111/hepr.12460] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Revised: 11/17/2014] [Accepted: 12/06/2014] [Indexed: 01/17/2023]
Abstract
AIM Immunocompromised patients can develop chronic hepatitis E virus (HEV) infection and progress to cirrhosis. Hepatitis C virus (HCV)-infected cancer patients who have received chemotherapeutic agents experience accelerated liver fibrosis progression. Our aim was to investigate the prevalence and impact of HEV seropositivity on liver-related outcomes in HCV-infected cancer patients. METHODS As part of a prospective study of HCV-infected cancer patients conducted at our center, we investigate the characteristics associated with progression of their liver disease. RESULTS Of the 115 patients tested, 13 (11%) were positive for HEV immunoglobulin G. HEV seropositivity was associated with advanced age (P = 0.004), race (P = 0.02), place of birth outside the USA (P = 0.021), cirrhosis (P = 0.027), history of reused needles/syringes during massive vaccination campaigns (P = 0.015) and coronary artery disease (P = 0.039). Overall, 47 (41%) of the patients had cirrhosis. Factors independently associated with cirrhosis were male sex (odds ratio [OR], 2.8; P = 0.028) and HEV seropositivity (OR, 4.1; P = 0.032). CONCLUSION HEV seropositivity is present in 11% of HCV-infected cancer patients and seems to be associated with cirrhosis. Our results suggest that HEV screening should be implemented in HCV-infected patients with cancer.
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Affiliation(s)
- Andreas Kyvernitakis
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Mahnaz Taremi
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Boris Blechacz
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jessica Hwang
- Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ying Jiang
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Parag Mahale
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Harrys A Torres
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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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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50
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Mahale P, Turturro F, Romaguera JE, Fowler N, Torres HA. The effect of different rituximab-containing chemotherapy strategies on hepatitis C viremia. Leuk Lymphoma 2015; 57:1487-90. [PMID: 26402559 DOI: 10.3109/10428194.2015.1099649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- Parag Mahale
- a Department of Infectious Diseases , Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center , Houston , TX , USA
| | - Francesco Turturro
- b Department of Lymphoma/Myeloma , The University of Texas MD Anderson Cancer Center , Houston , TX , USA
| | - Jorge E Romaguera
- b Department of Lymphoma/Myeloma , The University of Texas MD Anderson Cancer Center , Houston , TX , USA
| | - Nathan Fowler
- b Department of Lymphoma/Myeloma , The University of Texas MD Anderson Cancer Center , Houston , TX , USA
| | - Harrys A Torres
- a Department of Infectious Diseases , Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center , Houston , TX , USA
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