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George M, Mustafayev K, Ahmed S, Thomas SK, Jiang Y, Patel K, Torres HA. Direct-Acting Antivirals Induce Lymphoproliferative Disease Response in HCV-Infected Patients With Indolent B-Cell Non-Hodgkin's Lymphoma: A Prospective Observational Study. Hematol Oncol 2025; 43:e70044. [PMID: 39921915 DOI: 10.1002/hon.70044] [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: 12/03/2024] [Revised: 01/16/2025] [Accepted: 01/27/2025] [Indexed: 02/10/2025]
Abstract
B-cell non-Hodgkin lymphoma (NHL) in one of the most serious extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. No prospective studies have been conducted in the United States (US) on the impact of direct-acting antivirals (DAAs) in HCV-infected patients with indolent B-cell NHL not requiring chemotherapy. In this prospective study, we evaluated the general characteristics of US patients with HCV-associated indolent B-cell NHL and the oncologic impact of only DAA treatment without systemic cancer therapy in those patients. We enrolled patients seen at our center during 2014-2021; we analyzed only chemotherapy-naïve patients treated with DAAs. Patients who required immediate conventional treatment for lymphoma were excluded from the study. The primary endpoints were sustained virologic response at 12 weeks (SVR12) and lymphoproliferative disease response, classified as complete response, partial response, stable disease, or progressive disease. The secondary endpoints were overall response rate (ORR) of NHL, duration of response (DOR), overall survival (OS), and progression-free survival (PFS). Nine patients met the study criteria and were analyzed. Most patients were male (n = 6), White (n = 6), younger than 65 years (n = 6), and non-cirrhotic (n = 8); had HCV genotype 1 (n = 5); and had been infected for more than 30 years (n = 7). All patients achieved SVR12. Six patients (67%) had complete response, and 3 (33%) had progressive disease. The ORR was 67%. The median DOR was 51 months (range 16-81 months). The 5-year DOR, OS, and PFS rates were 100%, 83%, and 67%, respectively. HCV-associated NHL is a late extrahepatic complication of HCV. Infected patients with indolent NHL have an excellent virologic responses to DAAs and most of them experienced a favorable oncologic response after HCV eradication without chemotherapy.
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Affiliation(s)
- Monica George
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Khalis Mustafayev
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Sairah Ahmed
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Sheeba K Thomas
- Department of Lymphoma and Myeloma, 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
| | - Krina Patel
- Department of Lymphoma and Myeloma, 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
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Kim SY, Koh JY, Lee DH, Kim HD, Choi SJ, Ko YY, Lee HS, Lee JS, Choi IA, Lee EY, Jeong HW, Jung MK, Park SH, Park JY, Kim W, Shin EC. Epigenetic scars in regulatory T cells are retained after successful treatment of chronic hepatitis C with direct-acting antivirals. J Hepatol 2024; 81:806-818. [PMID: 38879170 DOI: 10.1016/j.jhep.2024.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 06/04/2024] [Accepted: 06/05/2024] [Indexed: 08/09/2024]
Abstract
BACKGROUND & AIMS Chronic HCV infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Herein, we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (Treg) cells from patients with chronic HCV infection before, during, and after DAA treatment. METHODS Patients with chronic genotype 1b HCV infection who achieved sustained virologic response by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of Treg cells were investigated through flow cytometry analysis. Moreover, the transcriptomic and epigenetic landscapes of Treg cells were analyzed using RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin with sequencing) analysis. RESULTS The Treg cell population - especially the activated Treg cell subpopulation - was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA sequencing analysis revealed that viral clearance did not abrogate the inflammatory features of these Treg cells, such as Treg activation and TNF signaling. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of Treg cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that Treg cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance. CONCLUSIONS Overall, our results showed that during chronic HCV infection, the expanded Treg cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the Treg cell population after recovery from chronic HCV infection. IMPACT AND IMPLICATIONS During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of direct-acting antivirals has led to high cure rates. Nevertheless, we have demonstrated that inflammatory features of Treg cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection.
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Affiliation(s)
- So-Young Kim
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
| | - June-Young Koh
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; GENOME INSIGHT Inc., Daejeon 34051, Republic of Korea
| | - Dong Hyeon Lee
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul 07061, Republic of Korea
| | - Hyung-Don Kim
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
| | - Seong Jin Choi
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
| | - Yun Yeong Ko
- The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea
| | - Ha Seok Lee
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
| | - Jeong Seok Lee
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; GENOME INSIGHT Inc., Daejeon 34051, Republic of Korea
| | - In Ah Choi
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea
| | - Eun Young Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Hye Won Jeong
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea
| | - Min Kyung Jung
- The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea
| | - Su-Hyung Park
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul 07061, Republic of Korea.
| | - Eui-Cheol Shin
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea.
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Reiberger T, Lens S, Cabibbo G, Nahon P, Zignego AL, Deterding K, Elsharkawy AM, Forns X. EASL position paper on clinical follow-up after HCV cure. J Hepatol 2024; 81:326-344. [PMID: 38845253 DOI: 10.1016/j.jhep.2024.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 04/05/2024] [Indexed: 07/26/2024]
Abstract
Following the advent of direct-acting antivirals (DAAs), hepatitis C virus (HCV) infection can be cured in almost all infected patients. This has led to a number of clinical questions regarding the optimal management of the millions of patients cured of HCV. This position statement provides specific guidance on the appropriate follow-up after a sustained virological response in patients without advanced fibrosis, those with compensated advanced chronic liver disease, and those with decompensated cirrhosis. Guidance on hepatocellular carcinoma risk assessment and the management of extrahepatic manifestations of HCV is also provided. Finally, guidance is provided on the monitoring and treatment of reinfection in at-risk patients. The recommendations are based on the best available evidence and are intended to help healthcare professionals involved in the management of patients after treatment for HCV.
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Affiliation(s)
- Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Sabela Lens
- Liver Unit, Hospital Clinic Barcelona. IDIBAPS. Liver and Digestive Diseases Networking Biomedical Research Centre (CIBERehd). University of Barcelona. Spain
| | - Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Italy
| | - Pierre Nahon
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, Liver Unit, Bobigny; Université Sorbonne Paris Nord, F-93000 Bobigny; Inserm, UMR-1138 "Functional Genomics of Solid Tumors", Centre de Recherche des Cordeliers, Université de Paris, France
| | - Anna Linda Zignego
- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy
| | - Katja Deterding
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School. Germany
| | - Ahmed M Elsharkawy
- Liver Unit, Queen Elizabeth Hospital Birmingham. NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham, United Kingdom
| | - Xavier Forns
- Liver Unit, Hospital Clinic Barcelona. IDIBAPS. Liver and Digestive Diseases Networking Biomedical Research Centre (CIBERehd). University of Barcelona. Spain.
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Merli M, Rattotti S, Spina M, Re F, Motta M, Piazza F, Orsucci L, Ferreri AJ, Perbellini O, Dodero A, Vallisa D, Pulsoni A, Santoro A, Sacchi P, Zuccaro V, Chimienti E, Russo F, Visco C, Zignego AL, Marcheselli L, Passamonti F, Luminari S, Paulli M, Bruno R, Arcaini L. Direct-Acting Antivirals as Primary Treatment for Hepatitis C Virus-Associated Indolent Non-Hodgkin Lymphomas: The BArT Study of the Fondazione Italiana Linfomi. J Clin Oncol 2022; 40:4060-4070. [PMID: 35714311 PMCID: PMC9746784 DOI: 10.1200/jco.22.00668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
PURPOSE We prospectively treated patients with hepatitis C virus (HCV)-associated indolent lymphomas with genotype-appropriate direct-acting antivirals (DAAs) with the aim to evaluate virologic and hematologic outcomes. No prospective studies in this setting have been published so far. METHODS FIL_BArT is a prospective, multicenter, phase II trial that evaluated genotype-appropriate DAAs in untreated HCV-positive patients with indolent lymphomas without criteria for immediate conventional antilymphoma treatment. The primary objective was sustained virologic response, whereas the main secondary objectives were overall response rate of lymphoma and progression-free survival. RESULTS Forty patients were enrolled, including 27 with marginal zone lymphoma. Median age was 68 years. Extranodal sites were involved in 14 cases (35%). Main genotypes were 1 in 16 patients and 2 in 21 patients. All patients received genotype-guided DAAs: 17 ledipasvir/sofosbuvir, eight sofosbuvir plus ribavirin, and 15 sofosbuvir/velpatasvir. All patients achieved sustained virologic response (100%). DAAs were well tolerated, with only two grade 3-4 adverse events. Overall response rate of lymphoma was 45%, including eight patients (20%) achieving complete response and 10 (25%) partial response, whereas 16 exhibited stable disease and six progressed. With a median follow-up of 37 months, two patients died (3-year overall survival 93%; 95% CI, 74 to 98) and three additional patients progressed, with a 3-year progression-free survival of 76% (95% CI, 57 to 87). CONCLUSION HCV eradication by DAAs was achieved in 100% of HCV-positive patients with indolent lymphomas not requiring immediate conventional treatment and resulted in non-negligible rate of lymphoma responses. Treatment with DAAs should be considered as the first-line therapy in this setting.
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Affiliation(s)
- Michele Merli
- Division of Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, University of Insubria, Varese, Italy
| | - Sara Rattotti
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Michele Spina
- Division of Medical Oncology and Immune-related Tumors, Centro di Riferimento Oncologico IRCCS, Aviano, Italy
| | - Francesca Re
- Division of Hematology and BMT Center, Azienda Ospedaliera Universitaria, Parma, Italy
| | - Marina Motta
- Division of Hematology, ASST Spedali Civili, Brescia, Italy
| | - Francesco Piazza
- Hematology and Clinical Immunology Unit, Department of Medicine—DIMED, University of Padova, Padova, Italy
| | - Lorella Orsucci
- Division of Hematology, Città della Salute e della Scienza di Torino, Torino, Italy
| | | | - Omar Perbellini
- Division of Hematology, San Bortolo Hospital, Vicenza, Italy
| | - Anna Dodero
- Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Daniele Vallisa
- Division of Hematology, Ospedale Guglielmo da Saliceto, Piacenza, Italy
| | - Alessandro Pulsoni
- Department of Translational and Precision Medicine, Sapienza University of Roma, Roma, Italy
| | - Armando Santoro
- Department of Biomedical Sciences, Humanitas University, IRCCS Humanitas Research Hospital-Humanitas Cancer Center, Milano, Italy
| | - Paolo Sacchi
- Division of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Valentina Zuccaro
- Division of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Emanuela Chimienti
- Division of Medical Oncology and Immune-related Tumors, Centro di Riferimento Oncologico IRCCS, Aviano, Italy
| | - Filomena Russo
- Division of Hematology and BMT Center, Azienda Ospedaliera Universitaria, Parma, Italy
| | - Carlo Visco
- Department of Medicine, Section of Hematology, University of Verona, Verona, Italy
| | - Anna Linda Zignego
- Department of Clinical and Experimental Medicine, Interdepartmental Hepatology Center MASVE, University of Firenze, Firenze, Italy
| | | | - Francesco Passamonti
- Division of Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, University of Insubria, Varese, Italy,Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Stefano Luminari
- Surgical, Medical and Dental Department of Morphological Sciences related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy,Division of Hematology, Azienda Unità Sanitaria Locale-IRCCS, Reggio Emilia, Italy
| | - Marco Paulli
- Unit of Anatomic Pathology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy,Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Raffaele Bruno
- Division of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy,Department of Clinical, Surgical, Diagnostic, and Paediatric Sciences, University of Pavia, Pavia, Italy
| | - Luca Arcaini
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy,Department of Molecular Medicine, University of Pavia, Pavia, Italy,Luca Arcaini, MD, Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100 Pavia, Italy; e-mail:
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Mazzaro C, Dal Maso L, Visentini M, Ermacora A, Andreone P, Gattei V, Pozzato G. Hepatitis C virus-associated indolent B-cell lymphomas: A review on the role of the new direct antiviral agents therapy. Hematol Oncol 2021; 39:439-447. [PMID: 34477233 DOI: 10.1002/hon.2862] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 02/23/2021] [Accepted: 03/06/2021] [Indexed: 12/11/2022]
Abstract
Several studies have suggested that hepatitis C virus (HCV) may be the causative agent of some B-cell non-Hodgkin lymphomas (B-NHL). Several authors have demonstrated that pegylated interferon (Peg-IFN) plus ribavirin (RBV) can revert indolent low-grade B-NHL by inducing HCV eradication. Presently, the combination therapy (IFN plus RBV) has been abandoned since the direct antiviral agents (DAAs) have shown very high efficacy in achieving sustained virologic response (SVR) (range: 95%-100%). This review analyzed DAAs efficacy in HCV-associated indolent low-grade NHL, providing a detailed literature review. Overall, 122 B-cell NHL patients were treated with DAAs: complete/partial hematological response, particularly in those with marginal zone lymphoma, was obtained in most cases. Hematological response, obtained either with DAAs or IFN-based therapy, was similar. Nonetheless, DAAs therapy showed better tolerability and higher SVR. A fraction of the patients, despite SVR, underwent hematologic relapse or progression. In these cases, a recovery treatment with immunotherapy, or chemoimmunotherapy, had to be planned. In conclusion, data obtained from published studies mostly agree that HCV eradication with DAAs should be considered as the first-line treatment in HCV-related NHL. In fact, the chronic viral stimulation of the immune system might be the primary pathogenic mechanism in disease development and progression.
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Affiliation(s)
- Cesare Mazzaro
- Clinical of Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano (PN), Italy
| | - Luigino Dal Maso
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano (PN), Italy
| | - Marcella Visentini
- Department of Clinical Medicine, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Roma, Italy
| | - Anna Ermacora
- Department of Internal Medicine, Pordenone General Hospital, Pordenone, Italy
| | - Pietro Andreone
- Clinical and Surgical Sciences, University of Trieste, Trieste, Italy
| | - Valter Gattei
- Clinical of Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano (PN), Italy
| | - Gabriele Pozzato
- Department of SMECHIMAI, University of Modena and Reggio Emilia, Modena, Italy
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Impact of DAA-Based Regimens on HCV-Related Extra-Hepatic Damage: A Narrative Review. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1323:115-147. [PMID: 33326112 DOI: 10.1007/5584_2020_604] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Two-third of patients with chronic hepatitis C show extrahepatic manifestations due to HCV infection of B lymphocytes, such as mixed cryoglobulinemia and non-Hodgkin B-cell lymphoma, or develop a chronic inflammatory status that may favor the development of adverse cardiovascular events, kidney diseases or metabolic abnormalities.DAAs treatments induce HCV eradication in 95% of treated patients, which also improves the clinical course of extrahepatic manifestations, but with some limitations. After HCV eradication a good compensation of T2DM has been observed, but doubts persist about the possibility of obtaining a stable reduction in fasting glucose and HbA1c levels.Chronic HCV infection is associated with low total and LDL cholesterol serum levels, which however increase significantly after HCV elimination, possibly due to the disruption of HCV/lipid metabolism interaction. Despite this adverse effect, HCV eradication exerts a favorable action on cardiovascular system, possibly by eliminating numerous other harmful effects exerted by HCV on this system.DAA treatment is also indicated for the treatment of patients with mixed cryoglobulinemia syndrome, since HCV eradication results in symptom reduction and, in particular, is effective in cryoglobulinemic vasculitis. Furthermore, HCV eradication exerts a favorable action on HCV-related lymphoproliferative disorders, with frequent remission or reduction of clinical manifestations.There is also evidence that HCV clearance may improve impaired renal functions, but same conflicting data persist on the effect of some DAAs on eGFR.
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Primary Hepatic Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue in a Patient with Chronic Hepatitis B Virus Infection: Case Report and Summary of the Literature. ACTA ACUST UNITED AC 2021; 57:medicina57030280. [PMID: 33803501 PMCID: PMC8002959 DOI: 10.3390/medicina57030280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/12/2021] [Accepted: 03/15/2021] [Indexed: 11/17/2022]
Abstract
Background: The incidence of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is low, at 7–8% of all non-Hodgkin lymphoma cases. The most common site of MALT lymphoma occurrence is the stomach. Primary hepatic extranodal marginal zone lymphoma of MALT is classified as a type of non-gastric MALT lymphoma and is considered extremely rare, with no consensus on imaging study findings or treatment due to a limited number of reports. We herein describe a rare case of primary hepatic extranodal marginal zone lymphoma of MALT with underlying hepatitis B infection (HBV) and present useful diagnostic findings of various imaging modalities, including contrast-enhanced ultrasonography (CEUS) with Sonazoid. Case presentation: A 66-year-old woman was diagnosed as being a non-active carrier of HBV at 51 years of age at the time of total hysterectomy and bilateral adnexectomy for uterine cervical cancer. She was admitted to our hospital following the incidental detection of two focal liver lesions on computed tomography. The lesions were considered malignant based on clinical and other radiologic imaging findings. Her CEUS results of hypo-enhancement in the portal and late phases were consistent with those of previously reported cases of hepatic extranodal marginal zone lymphoma of MALT, and histological liver biopsy findings were compatible with the diagnosis. Conclusions: Primary hepatic extranodal marginal zone lymphoma of MALT is a rare condition that can appear in HBV carriers. Characteristic CEUS findings may help in disease diagnosis. Clinicians should bear primary hepatic extranodal marginal zone lymphoma of MALT in mind when encountering patients with focal liver lesions which exhibit image findings different from those of typical hepatocellular carcinoma.
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Pozzato G, Mazzaro C, Gattei V. Hepatitis C virus-associated non-Hodgkin lymphomas: the endless history. Minerva Med 2020; 112:215-227. [PMID: 33263375 DOI: 10.23736/s0026-4806.20.07184-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Hepatitis C virus (HCV) is a global population problem due to its high prevalence worldwide. In the prognosis of patients with HCV not only hepatic but increasingly frequent of extrahepatic HCV manifestations, such as mixed cryoglobulinemia (MC) and non-Hodgkin's lymphoma (NHL), are important. The role of the HCV virus in the pathogenesis of lymphoproliferative diseases is confirmed by a large number of epidemiological studies, as well as by the effectiveness of antiviral therapy in patients with non-Hodgkin's lymphoma (NHL). The purpose of the review was to provide an overview of epidemiological and biological data explaining the role of HCV in the development of NHL. The review also discusses HCV-associated NHL treatment by the traditional antiviral therapy (interferon and ribavirin) and by the new direct antiviral agents.
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Affiliation(s)
- Gabriele Pozzato
- Department of Clinical and Surgical Sciences, Maggiore Hospital, University of Trieste, Trieste, Italy -
| | - Cesare Mazzaro
- Unit of Clinical and Experimental Onco-Hematology, CRO Aviano National Cancer Institute IRCCS, Aviano, Pordenone, Italy
| | - Valter Gattei
- Unit of Clinical and Experimental Onco-Hematology, CRO Aviano National Cancer Institute IRCCS, Aviano, Pordenone, Italy
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Zhang S, Xuan Z, Zhang L, Lu J, Song P, Zheng S. Splenic marginal zone lymphoma: a case report and literature review. World J Surg Oncol 2020; 18:259. [PMID: 33004051 PMCID: PMC7532117 DOI: 10.1186/s12957-020-02030-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 09/16/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Splenic marginal zone lymphoma (SMZL) is a rare non-Hodgkin lymphoma, and much little is known about its clinical characteristics and management strategies. Here we present a case of SMZL and review relevant literature to provide a better recognition of this disease entity. CASE PRESENTATION A 49-year-old Chinese female was admitted to our hospital with complaints of abdominal distension and acid reflux. Physical examinations and imaging investigations suggested the presence of splenomegaly. Laboratory workups revealed mildly reduced white blood cell count otherwise was not remarkable. The patient underwent splenectomy. Histological examination combined with immunohistochemical analysis of the resected spleen confirmed the diagnosis of SMZL. The patient recovered uneventfully during follow-ups. CONCLUSIONS Due to the rarity and unspecific clinical features, SMZL is extremely challenging to be diagnosed preoperatively. Patients with SMZL are generally associated with favorable prognosis. Combining the staging characteristics of non-Hodgkin's lymphoma and splenic primary lymphoma may assist in clinical staging management of SMZL.
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Affiliation(s)
- Shiyu Zhang
- The First Affiliated Hospital, Zhejiang University School of Medicine, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang Province, China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Zhejiang Province, China.,Key Laboratory of the diagnosis and treatment of organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Beijing Province, China.,Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Zhejiang Province, 310003, Hangzhou, China
| | - Zefeng Xuan
- The First Affiliated Hospital, Zhejiang University School of Medicine, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang Province, China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Zhejiang Province, China.,Key Laboratory of the diagnosis and treatment of organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Beijing Province, China.,Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Zhejiang Province, 310003, Hangzhou, China
| | - Liang Zhang
- The First Affiliated Hospital, Zhejiang University School of Medicine, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang Province, China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Zhejiang Province, China.,Key Laboratory of the diagnosis and treatment of organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Beijing Province, China.,Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Zhejiang Province, 310003, Hangzhou, China
| | - Jiahua Lu
- The First Affiliated Hospital, Zhejiang University School of Medicine, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang Province, China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Zhejiang Province, China.,Key Laboratory of the diagnosis and treatment of organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Beijing Province, China.,Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Zhejiang Province, 310003, Hangzhou, China
| | - Penghong Song
- The First Affiliated Hospital, Zhejiang University School of Medicine, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang Province, China. .,NHC Key Laboratory of Combined Multi-organ Transplantation, Zhejiang Province, China. .,Key Laboratory of the diagnosis and treatment of organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Beijing Province, China. .,Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Zhejiang Province, 310003, Hangzhou, China.
| | - Shusen Zheng
- The First Affiliated Hospital, Zhejiang University School of Medicine, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang Province, China. .,NHC Key Laboratory of Combined Multi-organ Transplantation, Zhejiang Province, China. .,Key Laboratory of the diagnosis and treatment of organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Beijing Province, China. .,Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Zhejiang Province, 310003, Hangzhou, China.
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10
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Peveling-Oberhag J, Bankov K, Dultz G, Ballo O, Lohmeyer J, Brunnberg U, Marcu V, Walter D, Zeuzem S, Hansmann ML, Welzel TM, Vermehren J. miRNA-26b downregulation in peripheral blood mononuclear cells of patients with hepatitis C associated lymphomas is restored by successful interferon-free antiviral therapy. Antivir Ther 2020; 24:437-442. [PMID: 31180334 DOI: 10.3851/imp3322] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/28/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND Patients with chronic HCV infection are at increased risk of developing B-cell non-Hodgkin lymphoma (B-NHL). Regression of HCV-associated B-NHL (HCV-NHL) can be achieved through HCV eradication using interferon (IFN). However, only about two-thirds of patients with sustained virological response (SVR) also had a consecutive lymphoma response. miRNA-26b is associated with HCV-NHL response to antiviral therapy. Recent data suggest that IFN-free direct-acting antiviral (DAA) regimens also have anti-lymphoma activity in this patient population. METHODS We report four patients with HCV-NHL who were treated with different IFN-free DAA regimens as oncological monotherapy in our centre between 2015 and 2016. We analysed the virological and lymphoproliferative disease response. Moreover, we analysed miRNA-26b expression in peripheral blood mononuclear cells at different time points during antiviral therapy for all included patients as well as for a total of 10 controls with (n=5) and without (n=5) chronic HCV infection. RESULTS All patients had marginal zone lymphoma subtype and received different DAA regimens for 12-24 weeks. All four patients achieved SVR, but only three patients also had lymphoma response (one complete response, two partial responses). One patient showed progression to a high-grade lymphoma subtype after SVR. miRNA-26b expression was generally decreased in patients with HCV-NHL. Moreover, miRNA-26b expression was restored in those HCV-NHL patients with lymphoma response after 6 months (P=0.009). CONCLUSIONS We have demonstrated that IFN-free DAA treatment of HCV can improve or even cure NHL. miRNA-26b-levels could be a potentially useful biomarker to predict lymphoma response in HCV-NHL patients.
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Affiliation(s)
- Jan Peveling-Oberhag
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany.,Department of Internal Medicine 1, Robert-Bosch-Hospital, Stuttgart, Germany.,Senckenberg Institute for Pathology, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Katrin Bankov
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany.,Senckenberg Institute for Pathology, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Georg Dultz
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Olivier Ballo
- Department of Internal Medicine 2, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Julian Lohmeyer
- Department of Internal Medicine 2, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Uta Brunnberg
- Department of Internal Medicine 2, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Vasile Marcu
- Department of Internal Medicine 2, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Dirk Walter
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Stefan Zeuzem
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Martin-Leo Hansmann
- Senckenberg Institute for Pathology, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Tania M Welzel
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Johannes Vermehren
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany
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11
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Sakai H, Miwa T, Ikoma Y, Hanai T, Nakamura N, Imai K, Kitagawa J, Shirakami Y, Kanemura N, Suetsugu A, Takai K, Shiraki M, Shimizu M. Development of diffuse large B-cell lymphoma after sofosbuvir-ledipasvir treatment for chronic hepatitis C: A case report and literature review. Mol Clin Oncol 2020; 13:1. [PMID: 32754315 PMCID: PMC7391802 DOI: 10.3892/mco.2020.2071] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Accepted: 05/20/2020] [Indexed: 12/11/2022] Open
Abstract
Recently, treatments for chronic hepatitis C virus (HCV) infection have significantly improved by the development of direct-acting antiviral agents (DAAs) and almost all patients with HCV can complete antiviral treatment without apparent adverse events. Malignant lymphoma, particularly B-cell non-Hodgkin's lymphoma, is one of the extrahepatic manifestations associated with chronic HCV infection. The effectiveness of anti-HCV therapy with DAAs for B-cell non-Hodgkin's lymphoma has been demonstrated in recent reports, whereas late-onset B-cell non-Hodgkin's lymphoma after HCV eradication with DAAs has occasionally been reported. In the present study, a 77-year-old man with chronic hepatitis C and intermediate liver cancer risk received sofosbuvir-ledipasvir treatment for 12 weeks. Two months following the end of antiviral therapy, he had achieved sustained virologic response for 8 weeks. However, the patient occasionally found swelling of the right cervical lymph nodes without any subjective symptoms. Lymph node biopsy revealed diffuse large B-cell lymphoma and whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography showed increased FDG uptake in the right cervical, right submandibular, mediastinal and mesenteric lymph nodes. The patient received six courses of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and achieved complete response at 8 months after chemotherapy initiation. Thus, the development of lymphoid malignancies may arise, even after HCV eradication with DAAs. Therefore, clinicians should be aware of such risks during and after antiviral treatment with DAAs.
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Affiliation(s)
- Hiroyasu Sakai
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Takao Miwa
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Yoshikazu Ikoma
- Department of Hematology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Tatsunori Hanai
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Nobuhiko Nakamura
- Department of Hematology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Kenji Imai
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Junichi Kitagawa
- Department of Hematology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Yohei Shirakami
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Nobuhiro Kanemura
- Department of Hematology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Atsushi Suetsugu
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Koji Takai
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Makoto Shiraki
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Masahito Shimizu
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
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12
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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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13
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Ferreira VL, Leonart LP, Rocca AMD, Pontarolo R. Analysis of Safety Outcomes in Chronic Hepatitis C Patients using Interferon-free Treatment: A Systematic Review of Case Reports. CURRENT DRUG THERAPY 2019. [DOI: 10.2174/1574885514666190130162547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:Second generation direct acting-antivirals are safe and effective treatments for chronic hepatitis C patients.Objective:We aimed to conduct a systematic review of case reports and case series to evaluate the safety of the drugs, highlighting a compilation of AE not previously reported in other reviews.Methods:The search was performed in four electronic databases and included only case reports and case series that evaluated interferon-free therapies and provided safety outcomes.Results:Initially 1,235 records were retrieved, and after screening 30 studies were included in the analysis (23 case reports and 7 case series). A total of 39 patients were included, receiving eight different interferon-free treatments. Nineteen patients discontinued treatment (only 8 of these achieved treatment response). Other 19 patients achieved SVR without discontinuation. Rare adverse events were observed, including breast hypertrophy, retinopathy and drug-induced infection. Some patients were in an advanced stage of the disease, and were therefore unable to withstand treatment due to the appearance of complications.Conclusion:In this sense, it is important to monitor the use of these drugs that can favor the appearance of serious AE. (PROSPERO registration number CRD42016051680).
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Affiliation(s)
- Vinicius Lins Ferreira
- Pharmaceutical Sciences Post-Graduate Program, Universidade Federal do Paraná, Curitiba, Brazil
| | - Leticia Paula Leonart
- Pharmaceutical Sciences Post-Graduate Program, Universidade Federal do Paraná, Curitiba, Brazil
| | - Ana Maria Della Rocca
- Pharmaceutical Sciences Post-Graduate Program, Universidade Federal do Paraná, Curitiba, Brazil
| | - Roberto Pontarolo
- Pharmaceutical Sciences Post-Graduate Program, Universidade Federal do Paraná, Curitiba, Brazil
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14
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Okay M, Aslan T, Özdemir E, Üner A, Sağlam A, Güngör E, Uysal A, Alayvaz Aslan N, Yıldızhan E, Ağıt A, Dal MS, Korkmaz S, Namdaroğlu S, Sivgin S, Akgün Çağlıyan G, Demircioğlu S, Barışta İ, Özhamam E, Vural F, Eser B, Özet G, Yıldırım R, Doğu MH, Berber İ, Erkurt MA, Malkan ÜY, Altuntaş F, Büyükaşık Y. Splenic Marginal Zone Lymphoma in Turkey: Association with Hepatitis B Instead of Hepatitis C Virus as an Etiologic and Possible Prognostic Factor - A Multicenter Cohort Study. Turk J Haematol 2019; 37:84-90. [PMID: 31630512 PMCID: PMC7236417 DOI: 10.4274/tjh.galenos.2019.2019.0177] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objective: Chronic antigenic stimulation is frequently blamed in the pathogenesis of extranodal marginal zone lymphomas including splenic marginal zone lymphoma (SMZL). Chronic hepatitis C is frequently observed in SMZL patients in some geographical regions. However, these reports are largely from North America and Europe, and data from other countries are insufficient. In this multicenter study we aimed to identify the clinical characteristics of SMZL patients in Turkey, including viral hepatitis status and treatment details. Materials and Methods: Data were gathered from participating centers from different regions of Turkey using IBM SPSS Statistics 23 for Windows. Hepatitis B virus surface antigen (HBsAg), anti-HBs antibody, anti-HB core antigen antibody (anti-HBcAg), HB viral load, anti-hepatitis C virus (HCV) antibody, HCV viral load results were analyzed. Results: One hundred and four patients were reported. Hepatitis C virus positivity was observed in only one patient. However, hepatitis B virus surface antigen (HBsAg) positivity was observed in 11.2% and HBsAg and/or anti-HB core antigen antibody (anti-HBcAg) positivities were seen in 34.2% of the patients. The median age was 60 years (range=35-87). Median follow-up duration was 21.2 months (range=00.2-212; 23.2 months for surviving patients). Median overall survival was not reached. Estimated 3-year and 10-year survival rates were 84.8% and 68.9%, respectively. Older age, no splenectomy during follow-up, platelet count of <90x103/μL, lower albumin, higher lactate dehydrogenase, higher β2-microglobulin, and HBsAg positivity were associated with increased risk of death. Only albumin remained significant in multivariable analysis. Conclusion: These results indicate that hepatitis B virus may be a possible risk factor for SMZL in our population. It may also be an indirect prognostic factor.
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Affiliation(s)
- Müfide Okay
- Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, Turkey
| | - Tuncay Aslan
- Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, Turkey
| | - Evren Özdemir
- Medicana International Ankara Hospital, Clinic of Medical Oncology, Ankara, Turkey
| | - Ayşegül Üner
- Hacettepe University Faculty of Medicine, Department of Pathology, Ankara, Turkey
| | - Arzu Sağlam
- Hacettepe University Faculty of Medicine, Department of Pathology, Ankara, Turkey
| | - Elif Güngör
- Trakya University Faculty of Medicine, Department of Internal Medicine, Edirne, Turkey
| | - Ayşe Uysal
- University of Health Sciences, Trabzon Kanuni Training and Research Hospital, Division of Hematology, Trabzon, Turkey
| | - Nevin Alayvaz Aslan
- Ondokuz Mayıs University Faculty of Medicine, Department of Hematology, Samsun, Turkey
| | - Esra Yıldızhan
- Erciyes University Faculty of Medicine, Department of Hematology, Kayseri, Turkey
| | - Abdullah Ağıt
- Ankara Numune Training and Research Hospital, Division of Hematology, Ankara, Turkey
| | - Mehmet Sinan Dal
- University of Health Sciences, Ankara Oncology Training and Research Hospital, Clinic of Hematology and BMT Unit, Ankara, Turkey
| | - Serdal Korkmaz
- Kayseri Training and Research Hospital, Division of Hematology, Kayseri, Turkey
| | | | | | | | - Sinan Demircioğlu
- Yüzüncü Yıl University Faculty of Medicine, Department of Hematology, Van, Turkey
| | - İbrahim Barışta
- Hacettepe University Faculty of Medicine, Department of Medical Oncology, Ankara, Turkey
| | - Esra Özhamam
- Ankara Numune Training and Research Hospital, Division of Pathology, Ankara, Turkey
| | - Filiz Vural
- Ege University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, İzmir, Turkey
| | - Bülent Eser
- Erciyes University Faculty of Medicine, Department of Hematology, Kayseri, Turkey
| | - Gülsüm Özet
- Ankara Numune Training and Research Hospital, Division of Hematology, Ankara, Turkey
| | - Rahşan Yıldırım
- Atatürk University Faculty of Medicine, Department of Hematology, Erzurum, Turkey
| | - Mehmet Hilmi Doğu
- İstanbul Training and Research Hospital, Clinic Hematology, İstanbul, Turkey
| | - İlhami Berber
- Malatya Training and Research Hospital, Division of Hematology, Malatya, Turkey
| | - Mehmet Ali Erkurt
- İnönü University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Malatya, Turkey
| | - Ümit Yavuz Malkan
- University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Clinic of Hematology, Ankara, Turkey
| | - Fevzi Altuntaş
- University of Health Sciences, Ankara Oncology Training and Research Hospital, Clinic of Hematology and BMT Unit, Ankara, Turkey,Yıldırım Beyazıt University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, Turkey
| | - Yahya Büyükaşık
- Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, Turkey
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15
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Liu CJ, Tseng KC, Lo CC, Tseng IH, Cheng PN. Limited drug-drug interaction of elbasvir/grazoprevir for chronic hepatitis C. J Formos Med Assoc 2019; 119:933-940. [PMID: 31594667 DOI: 10.1016/j.jfma.2019.09.011] [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: 07/24/2019] [Revised: 08/19/2019] [Accepted: 09/20/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/PURPOSE The assessment of drug-drug interaction (DDI) is important not only for safety but also for maintaining the efficacy of direct acting antivirals in chronic hepatitis C (CHC). This study aims to evaluate DDI before and during elbasvir/grazoprevir (EBR/GZR) treatment. METHODS CHC patients who treated with EBR/GZR in five hospitals were enrolled. The patients' demographic data, comorbidities, concomitant medications taken before and during EBR/GZR were recorded. DDI was evaluated using a tool from the HEP Drug Interactions (www.hep-druginteractions.org) website. In addition to the evaluation of DDI for EBR/GZR, the virtual DDI of ledipasvir/sofosbuvir (LDV/SOF), sofosbuvir/velpatasvir (SOF/VEL) and glecaprevir/pibrentasvir (GLE/PIB) were evaluated. Degrees of DDI were classified as "do not co-administer", "potential interaction", and "potentially weak interaction". RESULTS A total of 460 patients were enrolled. At baseline, 80.1% of patients had one or more comorbidities and 72.8% took one or more medications. Cardiovascular diseases (43.9%), gastrointestinal diseases (37.4%), and metabolic diseases (36.7%) were the three most common comorbidities. The prevalence of DDI before EBR/GZR treatment was 12.8% (59 patients). Among the same population, the prevalence of virtual DDI of SOF/VEL, GLE/PIB, and LDV/SOF were 38.5% (179 patients), 48.8% (220 patients), and 57.0% (262 patients), respectively. During EBR/GZR treatment, 167 patients (36.3%) took newly prescribed medications. One patient (0.2%) and seven patients (1/5%) exhibited do-not-co-administer and potential interaction with EBR/GZR, respectively. CONCLUSION DDI was limited in treatment with EBR/GZR. DDI can occur upon the administering of a new medication during antiviral treatment and attention should be paid to it. TRIAL REGISTRATION NUMBER NCT03706222.
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Affiliation(s)
- Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University, Hospital, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan
| | - Kuo-Chih Tseng
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi; School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Ching-Chu Lo
- Department of Internal Medicine, St. Martin de Porres Hospital, Chia-Yi, Taiwan
| | - I-Hao Tseng
- Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan
| | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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16
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Ioannou GN, Green PK, Berry K, Graf SA. Eradication of Hepatitis C Virus Is Associated With Reduction in Hematologic Malignancies: Major Differences Between Interferon and Direct-Acting Antivirals. Hepatol Commun 2019; 3:1124-1136. [PMID: 31388632 PMCID: PMC6671776 DOI: 10.1002/hep4.1389] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 05/17/2019] [Indexed: 12/15/2022] Open
Abstract
It is unclear whether eradication of hepatitis C virus (HCV) leads to a reduction in the risk of hematologic malignancies. We aimed to determine the impact of sustained virologic response (SVR) induced by either direct-acting antivirals (DAAs) or interferon (IFN) on the risk of hematologic malignancies. We identified 69,581 patients who initiated antiviral treatment in the Veterans Affairs national health care system from January 1, 1999, to December 31, 2015, including 40,410 (58%) IFN-only regimens, 4,546 (6.5%) DAA + IFN regimens, and 24,625 (35%) DAA-only regimens. We retrospectively followed patients to identify incident cases of hematologic malignancies or monoclonal gammopathy of unknown significance (MGUS), a premalignant precursor of multiple myeloma. Among patients treated with IFN, SVR was significantly associated with a reduction in the risk of lymphoma (adjusted hazard ratio [AHR], 0.70; 95% confidence interval [CI], 0.51-0.97), multiple myeloma (AHR, 0.40; 95% CI, 0.20-0.77), MGUS (AHR, 0.65; 95% CI, 0.42-0.99), or all hematologic malignancies and MGUS combined (AHR, 0.67; 95% CI, 0.53-0.84) over a mean follow-up of 10.6 years. In contrast, among patients treated with DAA, SVR was not associated with the risk of lymphoma, multiple myeloma, MGUS, or all hematologic malignancies and MGUS combined (AHR, 1.08; 95% CI, 0.66-1.78) during a mean follow-up of 2.9 years. Neither IFN-induced SVR nor DAA-induced SVR was associated with risk of colon cancer or prostate cancer, which were chosen a priori as comparison/control malignancies. Conclusion: We describe novel strong associations between IFN-induced SVR and lymphoma, multiple myeloma, MGUS, and all hematologic malignancies combined. Surprisingly, these associations were not observed with DAA-induced SVR.
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Affiliation(s)
- George N. Ioannou
- Division of Gastroenterology, Department of MedicineVeterans Affairs Puget Sound Health Care System and University of WashingtonSeattleWA
- Research and DevelopmentVeterans Affairs Puget Sound Health Care SystemSeattleWA
| | - Pamela K. Green
- Research and DevelopmentVeterans Affairs Puget Sound Health Care SystemSeattleWA
| | - Kristin Berry
- Research and DevelopmentVeterans Affairs Puget Sound Health Care SystemSeattleWA
| | - Solomon A. Graf
- Division of Oncology, Department of MedicineVeterans Affairs Puget Sound Health Care System and University of WashingtonSeattleWA
- Clinical Research DivisionFred Hutch Cancer Research CenterSeattleWA
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17
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Masarone M, Persico M. Hepatitis C virus infection and non-hepatocellular malignancies in the DAA era: A systematic review and meta-analysis. Liver Int 2019; 39:1292-1306. [PMID: 30983083 DOI: 10.1111/liv.14119] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 03/12/2019] [Accepted: 04/05/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Direct antiviral agents have greatly improved therapeutic options for chronic hepatitis C. Indeed, former "difficult-to-treat" patients can now be treated and can achieve sustained response. Hepatitis C virus (HCV) is associated with hepatocellular carcinoma and with B-cell non-Hodgkin lymphoma (B-NHL). Other malignancies have been reported to be associated with HCV infection albeit with various grades of evidence. Antineoplastic treatment is often reduced or suspended in HCV-positive cancer patients to avoid "HCV reactivation." In this setting, antiviral therapy combined with antineoplastic protocols may improve the outcome. For this reason, we conducted a systematic review and a meta-analysis to update the association between HCV infection and non-hepatocellular malignancies, and to shed light on the effects exerted by antiviral treatment on the natural history of oncological diseases. METHODS Relevant studies were identified by searching PUBMED, EMBASE and MEDLINE up to 1 August 2018. Pooled risk estimates were calculated with random-effects models according to PRISMA guidelines. RESULTS A total of 58 studies were included in the analysis: 27 studies of the association between HCV and B-NHL(OR 3.36; 95% CI 2.40-4.72;P < 0.00001);13 studies of the association between sustained virological response and progression-free survival (PFS) in B-NHL patients(OR 9.34; 95% CI 4.90-17.79; P < 0.00001); 13 studies of the association between HCV and intrahepatic-cholangio-carcinoma (OR 3.95;95% CI 2.25-6.94; P < 0.00001); and 5 studies of the association between HCV infection and pancreatic adeno-carcinoma(OR 1.60; 95% CI:1.25-2.04; P = 0.0002). CONCLUSIONS This study updates the strong association between B-NHL and HCV infection, confirms the association between HCV and non-hepatocellular tumours, and demonstrates a very strong association between viral eradication and a better outcome of HCV-positive B-NHL.
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Affiliation(s)
- Mario Masarone
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| | - Marcello Persico
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
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18
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El-Serag HB, Christie IC, Puenpatom A, Castillo D, Kanwal F, Kramer JR. The effects of sustained virological response to direct-acting anti-viral therapy on the risk of extrahepatic manifestations of hepatitis C infection. Aliment Pharmacol Ther 2019; 49:1442-1447. [PMID: 30932218 PMCID: PMC6510621 DOI: 10.1111/apt.15240] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 09/24/2018] [Accepted: 03/07/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND Direct-acting anti-viral (DAA) therapy may have a beneficial role in extrahepatic manifestations of hepatitis C virus (HCV) infection. However, the available data are limited. AIM To examine the effects of DAA treatment on the risk of several extrahepatic manifestations of HCV. METHODS We conducted a retrospective cohort study of patients from the US Department of Veterans Affairs Corporate Data Warehouse who had a positive HCV RNA test and received first course of DAAs between 2012 and 2016. We calculated incidence rates by sustained virological response (SVR) status for six extrahepatic manifestations, and effect of SVR on these conditions was evaluated in adjusted Cox regression models. RESULTS Of the 45 260 patients treated with DAA with mean follow-up of 2.01 years, 41 711 (92.2%) experienced SVR. Incidence rates ranged from 0.17/1000 PY for porphyria cutanea tarda to 21.04/1000 PY for diabetes in the SVR group and 0.51/1000 PY for porphyria cutanea tarda to 23.11/1000 PY for diabetes in the no SVR group. The risk was reduced with SVR for mixed cryoglobulinaemia (adjusted HR (aHR) = 0.23; 95% CI 0.10-0.56), glomerulonephritis (aHR = 0.61; 95% CI 0.41-0.90) and lichen planus (aHR = 0.46; 95% CI 0.30-0.70), but not for non-Hodgkin's lymphoma (aHR = 0.86; 95% CI 0.52-1.43) or diabetes (aHR = 0.98; 95% CI 0.81-1.19). Non significant risk reduction was seen for porphyria cutanea tarda (aHR = 0.33; 95% CI 0.11-1.03). CONCLUSIONS Successful DAA treatment resulting in SVR was associated with significant reductions in the risk of mixed cryoglobulinaemia, glomerulonephritis, lichen planus and possibly porphyria cutanea tarda, but not non-Hodgkin's lymphoma or diabetes.
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Affiliation(s)
- Hashem B. El-Serag
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, TX,Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Israel C. Christie
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, TX,Department of Medicine, Baylor College of Medicine, Houston, TX
| | | | - Diana Castillo
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, TX
| | - Fasiha Kanwal
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, TX,Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Jennifer R. Kramer
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, TX,Department of Medicine, Baylor College of Medicine, Houston, TX
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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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20
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Rattotti S, Ferretti VV, Rusconi C, Rossi A, Fogazzi S, Baldini L, Pioltelli P, Balzarotti M, Farina L, Ferreri AJM, Laszlo D, Speziale V, Varettoni M, Sciarra R, Morello L, Tedeschi A, Frigeni M, Defrancesco I, Zerbi C, Flospergher E, Nizzoli ME, Morra E, Arcaini L. Lymphomas associated with chronic hepatitis C virus infection: A prospective multicenter cohort study from the Rete Ematologica Lombarda (REL) clinical network. Hematol Oncol 2019; 37:160-167. [PMID: 30726562 DOI: 10.1002/hon.2575] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2018] [Revised: 01/21/2019] [Accepted: 01/31/2019] [Indexed: 01/16/2023]
Abstract
Chronic hepatitis C virus (HCV) infection is related with an increased risk of non-Hodgkin lymphomas (NHL). In indolent subtypes, regression of NHL was reported after HCV eradication with antiviral therapy (AT). In 2008 in Lombardy, a region of Northern Italy, the "Rete Ematologica Lombarda" (REL, Hematology Network of Lombardy-Lymphoma Workgroup) started a prospective multicenter observational cohort study on NHL associated with HCV infection, named "Registro Lombardo dei Linfomi HCV-positivi" ("Lombardy Registry of HCV-associated non-Hodgkin lymphomas"). Two hundred fifty patients with a first diagnosis of NHL associated with HCV infection were enrolled; also in our cohort, diffuse large B cell lymphoma (DLBCL) and marginal zone lymphoma (MZL) are the two most frequent HCV-associated lymphomas. Two thirds of patients had HCV-positivity detection before NHL; overall, NHL was diagnosed after a median time of 11 years since HCV survey. Our data on eradication of HCV infection were collected prior the recent introduction of the direct-acting antivirals (DAAs) therapy. Sixteen patients with indolent NHL treated with interferon-based AT as first line anti-lymphoma therapy, because of the absence of criteria for an immediate conventional treatment for lymphoma, had an overall response rate of 90%. After a median follow-up of 7 years, the overall survival (OS) was significantly longer in indolent NHL treated with AT as first line (P = 0.048); this confirms a favorable outcome in this subset. Liver toxicity was an important adverse event after a conventional treatment in 20% of all patients, in particular among DLBCL, in which it is more frequent the coexistence of a more advanced liver disease. Overall, HCV infection should be consider as an important co-pathology in the treatment of lymphomas and an interdisciplinary approach should be always considered, in particular to evaluate the presence of fibrosis or necroinflammatory liver disease.
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Affiliation(s)
- Sara Rattotti
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Chiara Rusconi
- Division of Hematology, Ospedale Niguarda Ca' Granda, Milan, Italy
| | - Andrea Rossi
- Division of Hematology, Ospedali Riuniti, Bergamo, Italy
| | | | - Luca Baldini
- Division of Hematology, Fondazione IRCCS Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | | | | | - Lucia Farina
- Division of Hematology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Andrés J M Ferreri
- Unit of Lymphoid Malignancies, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Daniele Laszlo
- Division of Hematology, Istituto Europeo di Oncologia, Milan, Italy
| | - Valentina Speziale
- Division of Internal Medicine, Ospedale Civile di Legnano, Legnano, Italy
| | - Marzia Varettoni
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Roberta Sciarra
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Lucia Morello
- Division of Hematology, Humanitas Cancer Center, Milan, Italy
| | | | - Marco Frigeni
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.,Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | | | - Caterina Zerbi
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | | | | | - Enrica Morra
- Division of Hematology, Ospedale Niguarda Ca' Granda, Milan, Italy
| | - Luca Arcaini
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.,Department of Molecular Medicine, University of Pavia, Pavia, Italy
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21
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Su TH, Liu CJ, Tseng TC, Chou SW, Liu CH, Yang HC, Wu SJ, Chen PJ, Chen DS, Chen CL, Kao JH. Early antiviral therapy reduces the risk of lymphoma in patients with chronic hepatitis C infection. Aliment Pharmacol Ther 2019; 49:331-339. [PMID: 30592071 DOI: 10.1111/apt.15101] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Revised: 01/26/2018] [Accepted: 11/27/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Chronic hepatitis C infection is linked to lymphoma development. AIM To investigate whether antiviral therapy prevents the risk of HCV-related lymphoma. METHODS Patients diagnosed with chronic hepatitis C were retrieved from the Taiwan National Health Insurance Research Database during 2004-2012. We included patients who received pegylated interferon and ribavirin (PegIFN/RBV) antiviral therapy for ≥24 weeks (PegIFN/RBV cohort) or hepatoprotectants for ≥90 days without antiviral therapy (HCV-untreated cohort). Both cohorts were matched by age, sex, and comorbidities through propensity scores and followed for newly diagnosed lymphoma or non-Hodgkin's lymphoma (NHL). RESULTS In total, 24 133 patients were included in both the PegIFN/RBV and HCV-untreated cohort. The lymphoma incidence was significantly higher in the untreated than in the treated cohort (66.48 vs 43.34 per 100 000 person-years, P = 0.029). After adjusting for confounders, the patients who received PegIFN/RBV therapy were at a lower risk of developing lymphoma compared with the untreated patients (hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.43-0.96, P = 0.030). Moreover, this beneficial effect was mainly observed in patients with chronic hepatitis C <60 years old with a relative risk reduction of 51% for all lymphoma (HR: 0.49, 95% CI: 0.29-0.82, P = 0.007) and 48% for non-Hodgkin's lymphoma (HR: 0.52, 95% CI: 0.30-0.91, P = 0.022). The risk of all lymphoma or non-Hodgkin's lymphoma development after antiviral therapy was lowered to that of subjects without HCV. CONCLUSIONS PegIFN/RBV-based antiviral therapy significantly reduced the risk of lymphoma, especially non-Hodgkin's lymphoma; the reduction was mostly among patients <60 years old. Early antiviral therapy for chronic hepatitis C is suggested.
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Affiliation(s)
- Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Wan Chou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shang-Ju Wu
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Ding-Shinn Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Chi-Ling Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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22
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Gallipani A, Cha A, Berkowitz L, Bakshi A. Concomitant Treatment of Hepatitis C Virus and Diffuse Large B-Cell Lymphoma with Direct-Acting Antivirals in HIV Coinfection: A Case Report. J Int Assoc Provid AIDS Care 2019; 18:2325958218822062. [PMID: 30798652 PMCID: PMC6748524 DOI: 10.1177/2325958218822062] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
This report describes a case of concomitant treatment of advanced diffuse large B-cell lymphoma with chemoimmunotherapy along with direct-acting antivirals for hepatitis C virus in a patient coinfected with HIV. The patient tolerated gemcitabine, dexamethasone, cisplatin, and rituximab and achieved sustained virologic response after treatment with ledipasvir/sofosbuvir.
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Affiliation(s)
| | - Agnes Cha
- Arnold & Marie Schwartz College of Pharmacy, Brooklyn, NY, USA
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23
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Ioannou GN, Feld JJ. What Are the Benefits of a Sustained Virologic Response to Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection? Gastroenterology 2019; 156:446-460.e2. [PMID: 30367836 DOI: 10.1053/j.gastro.2018.10.033] [Citation(s) in RCA: 140] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 09/26/2018] [Accepted: 10/03/2018] [Indexed: 02/06/2023]
Abstract
Direct-acting antiviral (DAA) regimens are safe and effective at eradicating hepatitis C virus (HCV) infection. Unfortunately, DAAs remain expensive, so treatment of all HCV-infected patients would substantially affect health care costs. It is therefore important to continue to assess the hepatic and extrahepatic benefits of a DAA-induced sustained virologic response (SVR). A DAA-induced SVR reduces a patient's risk of cirrhosis and hepatocellular carcinoma and extrahepatic manifestations of HCV infection; there are also data to indicate that an SVR can reduce mortality. SVR is a relevant clinical end point, but further analyses are required to confirm its importance among diverse HCV-infected populations and to document the public health benefits of HCV elimination at the population level. We review the evidence for the benefits associated with SVRs in different clinical settings and challenges to data collection.
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Affiliation(s)
- George N Ioannou
- Division of Gastroenterology, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, Washington; Department of Medicine, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, Washington; Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, Washington.
| | - Jordan J Feld
- Toronto Centre for Liver Disease, University Health Network, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Ontario, Canada
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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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25
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Salmon D, Mondelli MU, Maticic M, Arends JE. The benefits of hepatitis C virus cure: Every rose has thorns. J Viral Hepat 2018; 25:320-328. [PMID: 29112304 DOI: 10.1111/jvh.12823] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Accepted: 09/19/2017] [Indexed: 02/06/2023]
Abstract
To examine mid-term benefits on hepatic complications, extrahepatic clinical syndromes and quality of life associated with HCV cure; to review the few safety issues linked to oral direct-acting antivirals (DAAs); and to discuss the potential population benefits of reducing the burden of HCV infection. DAAs cure HCV infection in more than 95% of patients. The halting of liver inflammation and fibrosis progression translates into both hepatic and extrahepatic benefits and reduces the need for liver transplantation. A reduction in the frequency of extrahepatic manifestations such as mixed cryoglobulinaemia and vasculitis and improvements in quality of life and fatigue have also been described. A few safety issues linked to DAAs such as the potential recurrence of aggressive HCC, the flares of hepatitis B virus in patients with overt or occult HBV infection are been discussed. Curing HCV infection also has a high potential to reduce the burden of HCV infection at the population level. With widespread scaling up of HCV treatment, several modeling studies suggest that major reductions in HCV prevalence and incidence are possible, and that elimination of viral hepatitis is an achievable target by 2030.
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Affiliation(s)
- D Salmon
- Division of Infectious Diseases and Immunology, Center for Diagnosis, Paris Centre University Hospitals, APHP, Paris Descartes University, Paris, France
| | - M U Mondelli
- Division of Infectious Diseases and Immunology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - M Maticic
- Faculty of Medicine, Clinic for Infectious Diseases and Febrile Illnesses, University Medical Centre Ljubljana, University of Ljubljana, Ljubljana, Slovenia
| | - J E Arends
- Department of Internal Medicine, Infectious diseases section, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
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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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Hepatic Failure Due to Cholestatic Hepatitis C in an Immunosuppressed Patient Treated With Elbasvir and Grazeprevir. ACG Case Rep J 2018; 5:e6. [PMID: 29392153 PMCID: PMC5772065 DOI: 10.14309/crj.2018.6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 11/15/2017] [Indexed: 11/17/2022] Open
Abstract
Hepatitis C-induced cholestatic hepatitis is a well-known fatal complication of postorthotropic liver transplantation and prolonged immunosuppression. Recent studies on direct-acting antiviral agents have shown promising results in terms of morbidity and mortality of this condition in postorthotropic liver, heart, and renal transplant patients. However, hepatitis C-induced cholestatic hepatitis remains a highly fatal condition in non-transplant patients. We report the first-ever use of the oral direct-acting antiviral combination, elbasvir and grazeprevir, in the treatment of a non-liver transplant patient with cholestatic hepatitis.
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Persico M, Aglitti A, Caruso R, De Renzo A, Selleri C, Califano C, Abenavoli L, Federico A, Masarone M. Efficacy and safety of new direct antiviral agents in hepatitis C virus-infected patients with diffuse large B-cell non-Hodgkin's lymphoma. Hepatology 2018; 67:48-55. [PMID: 28714143 DOI: 10.1002/hep.29364] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Revised: 06/29/2017] [Accepted: 07/07/2017] [Indexed: 12/18/2022]
Abstract
UNLABELLED The association of hepatitis C virus (HCV) with non-Hodgkin's lymphoma (NHL) has been demonstrated throughout the world. The new interferon-free direct antiviral agents (DAAs) showed high efficacy and safety, and preliminary data seem to confirm their activity on low-grade NHL. The question arises as whether or not-and how-to treat the HCV-positive patients suffering from diffuse large B-cell lymphomas (DLBCLs). The aim of this observational study was to evaluate whether DAA antiviral treatment of DLBCL/HCV-infected patients in concomitance with chemotherapy is a safe and effective option. Twenty (13 males and 7 females) HCV genotype 1b-positive subjects, undergoing chemotherapy for DLBCL, were enrolled between June 2015 and December 2015. After informed consent, all patients underwent antiviral therapy (AVT) with sofosbuvir/ledipasvir and chemotherapy (14 rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone and 6 cyclophosphamide, doxorubicin, vincristine, and prednisone) for DLBCL. Complete hematological (Revised European-American Lymphoma classification, Ann Arbor, and International Prognostic Index [IPI] scores) and hepatological (viral markers, liver stiffness, and biochemical parameters) evaluations were made. A historical retrospective cohort of 101 DLBCL/HCV-positive patients not undergoing AVT was enrolled for comparison. DAA-treated and untreated patients were similar for sex distribution, IPI score, and NHL stage, and differed for age (older in treated), chemotherapy and use of AVT. Overall survival (OS) and disease-free survival (DFS) were evaluated among a 52-week of follow-up. No statistical difference was found in OS after 52 weeks (P = 0.122), whereas a statistically significant higher DFS was achieved in treated patients (P = 0.036). At the multivariate analysis, only IPI score and AVT were independently correlated with a better DFS. No differences in adverse events were reported. CONCLUSION DAA treatment in concomitance with chemotherapy was shown to be safe and effective in influencing remission of aggressive lymphomas in HCV patients. (Hepatology 2018;67:48-55).
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Affiliation(s)
- Marcello Persico
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| | - Andrea Aglitti
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| | - Rosa Caruso
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| | - Amalia De Renzo
- Hematology Department, Federico Secondo University of Naples, Naples, Italy
| | | | - Catello Califano
- Hematology Department, Umberto I Hospital, Nocera Inferiore (Salerno), Italy
| | - Ludovico Abenavoli
- Department of Health Sciences, University Magna Graecia, Catanzaro, Italy
| | - Alessandro Federico
- Hepatogastroenterology Division, University of Campania "Luigi Vanvitelli, Naples, Italy
| | - Mario Masarone
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
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van den Brand M, Scheijen B, Hess CJ, van Krieken JHJ, Groenen PJTA. Pathways towards indolent B-cell lymphoma - Etiology and therapeutic strategies. Blood Rev 2017; 31:426-435. [PMID: 28802906 DOI: 10.1016/j.blre.2017.08.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Revised: 05/07/2017] [Accepted: 08/04/2017] [Indexed: 02/06/2023]
Abstract
Although patients with indolent B-cell lymphomas have a relatively good survival rate, conventional chemotherapy is not curative. Disease courses are typically characterized by multiple relapses and progressively shorter response duration with subsequent lines of therapy. There has been an explosion of innovative targeted agents in the past years. This review discusses current knowledge on the etiology of indolent B-cell lymphomas with respect to the role of micro-organisms, auto-immune diseases, and deregulated pathways caused by mutations. In particular, knowledge on the mutational landscape of indolent B-cell lymphomas has strongly increased in recent years and harbors great promise for more accurate decision making in the current wide range of therapeutic options. Despite this promise, only in chronic lymphocytic leukemia the detection of TP53 mutations and/or del17p currently have a direct effect on treatment decisions. Nevertheless, it is expected that in the near future the role of genetic testing will increase for prediction of response to targeted treatment as well as for more accurate prediction of prognosis in indolent B-cell lymphomas.
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MESH Headings
- Animals
- DNA Damage
- Epigenesis, Genetic
- Gene Expression Regulation, Neoplastic
- Humans
- Leukemia, Lymphocytic, Chronic, B-Cell/etiology
- Leukemia, Lymphocytic, Chronic, B-Cell/genetics
- Leukemia, Lymphocytic, Chronic, B-Cell/microbiology
- Leukemia, Lymphocytic, Chronic, B-Cell/therapy
- Lymphoma, B-Cell/etiology
- Lymphoma, B-Cell/genetics
- Lymphoma, B-Cell/microbiology
- Lymphoma, B-Cell/therapy
- Lymphoma, B-Cell, Marginal Zone/etiology
- Lymphoma, B-Cell, Marginal Zone/genetics
- Lymphoma, B-Cell, Marginal Zone/microbiology
- Lymphoma, B-Cell, Marginal Zone/therapy
- Lymphoma, Follicular/etiology
- Lymphoma, Follicular/genetics
- Lymphoma, Follicular/microbiology
- Lymphoma, Follicular/therapy
- Molecular Targeted Therapy/methods
- Mutation
- Signal Transduction
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Affiliation(s)
- Michiel van den Brand
- Department of Pathology, Radboud university medical center, Geert Grooteplein Zuid 10, 6525GA Nijmegen, The Netherlands; Pathology-DNA, location Rijnstate, Wagnerlaan 55, 6815AD Arnhem, The Netherlands.
| | - Blanca Scheijen
- Department of Pathology, Radboud university medical center, Geert Grooteplein Zuid 10, 6525GA Nijmegen, The Netherlands.
| | - Corine J Hess
- Department of Hematology, Radboud university medical center, Geert Grooteplein Zuid 10, 6525GA Nijmegen, The Netherlands.
| | - J Han Jm van Krieken
- Department of Pathology, Radboud university medical center, Geert Grooteplein Zuid 10, 6525GA Nijmegen, The Netherlands.
| | - Patricia J T A Groenen
- Department of Pathology, Radboud university medical center, Geert Grooteplein Zuid 10, 6525GA Nijmegen, The Netherlands.
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Pozzato G, Mazzaro C, Gattei V. Hepatitis C Virus-Associated Non-Hodgkin Lymphomas: Biology, Epidemiology, and Treatment. Clin Liver Dis 2017; 21:499-515. [PMID: 28689589 DOI: 10.1016/j.cld.2017.03.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Eradication of hepatitis C virus (HCV) in indolent non-Hodgkin lymphomas (NHLs), especially in marginal zone lymphomas, determines the regression of the hematologic disorder in a significant fraction of cases. Because direct antiviral agents show an excellent profile in terms of efficacy, safety, and rapid onset of action, these drugs can be used in any clinical situation and in the presence of any comorbidities. To avoid the progression of the NHL, despite HCV eradication, antiviral therapy should be provided as soon as the viral infection is discovered; before that, the chronic antigenic stimulation determines the irreversible proliferation of neoplastic B cells.
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Affiliation(s)
- Gabriele Pozzato
- Department of Clinical and Surgical Sciences, University of Trieste, Ematologia Clinica, Ospedale Maggiore, Piazza Ospedale 1, Trieste 34121, Italy.
| | - Cesare Mazzaro
- Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano 33081, Italy
| | - Valter Gattei
- Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano 33081, Italy
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Abstract
Chronic infection with hepatitis C virus (HCV) is a multifaceted disease characterized by many extrahepatic manifestations (EHMs) that affect outcome and quality of life. HCV eradication by antiviral treatment has been proved beneficial in preventing the development of EHMs and is also able to improve many HCV-related severe disorders and neurocognitive outcomes and quality of life. Until recently, antiviral therapy of EHMs was limited to the presence of interferon-based treatment, and was contraindicated in many patients because of hematologic toxicity or risk of exacerbating immune-mediated disorders. The availability of interferon-free regimens solves this issue allowing for enhanced safety and efficacy to provide universal treatment of HCV-related EHMs.
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Polo ML, Laufer N. Extrahepatic manifestations of HCV: the role of direct acting antivirals. Expert Rev Anti Infect Ther 2017; 15:737-746. [PMID: 28696154 DOI: 10.1080/14787210.2017.1354697] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Hepatitis C virus (HCV) represents a major health concern, as nearly 3 million people become newly infected by this pathogen annually. The majority of infected individuals fail to clear the virus, and chronicity is established. Chronic HCV patients are at high risk for liver disease, ranging from mild fibrosis to cirrhosis and severe hepatocellular carcinoma. Over the last few years, the development of multiple direct acting antivirals (DAA) have revolutionized the HCV infection treatment, demonstrating cure rates higher than 90%, and showing less side effects than previous interferon-based regimens. Areas covered: Besides liver, HCV infection affects a variety of organs, therefore inducing diverse extrahepatic manifestations. This review covers clinical, experimental, and epidemiological publications regarding systemic manifestations of HCV, as well as recent studies focused on the effect of DAA in such conditions. Expert commentary: Though further research is needed; available data suggest that HCV eradication is often associated with the improvement of extrahepatic symptoms. Therefore, the emergence of DAA would offer the opportunity to treat both HCV infection and its systemic manifestations, requiring shorter treatment duration and driving minor adverse effects.
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Affiliation(s)
- María Laura Polo
- a Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS) , Universidad de Buenos Aires- CONICET , Buenos Aires , Argentina
| | - Natalia Laufer
- a Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS) , Universidad de Buenos Aires- CONICET , Buenos Aires , Argentina
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Hattori N, Ikeda H, Nakano H, Matsumoto N, Watanabe T, Shigefuku R, Noguchi Y, Matsunaga K, Sakai H, Okuse C, Yamamoto H, Miura I, Suzuki M, Itoh F. Curative Effects for B-Cell Lymphoma Accomplished by Direct-Acting Antiviral Agents of Hepatitis C. Open Forum Infect Dis 2017; 4:ofx057. [PMID: 28491894 PMCID: PMC5419202 DOI: 10.1093/ofid/ofx057] [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: 01/19/2017] [Accepted: 03/22/2017] [Indexed: 12/11/2022] Open
Abstract
Hepatitis C virus (HCV) is a hepatotropic and lymphotropic virus with the capabilities of tumorigenesis. We present an HCV-infected patient affected with B-cell lymphomas after suffering from hepatocellular carcinoma. The patient exhibited curative effects for lymphomas after treatment with sofosbuvir and ledipasvir, which is shown clearly with a positron emission tomography scanner.
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Affiliation(s)
| | - Hiroki Ikeda
- Divisions of Gastroenterology and Hepatology and
| | | | | | | | | | | | | | - Hirotaka Sakai
- Hematology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Chiaki Okuse
- Division of Gastroenterology and Hepatology, Kawasaki Municipal Tama Hospital, Japan
| | | | - Ikuo Miura
- Hematology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Michihiro Suzuki
- Division of Gastroenterology and Hepatology, Kawasaki Municipal Tama Hospital, Japan
| | - Fumio Itoh
- Divisions of Gastroenterology and Hepatology and
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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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35
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Gragnani L, Visentini M, Fognani E, Urraro T, De Santis A, Petraccia L, Perez M, Ceccotti G, Colantuono S, Mitrevski M, Stasi C, Del Padre M, Monti M, Gianni E, Pulsoni A, Fiorilli M, Casato M, Zignego AL. Prospective study of guideline-tailored therapy with direct-acting antivirals for hepatitis C virus-associated mixed cryoglobulinemia. Hepatology 2016; 64:1473-1482. [PMID: 27483451 DOI: 10.1002/hep.28753] [Citation(s) in RCA: 146] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Revised: 07/15/2016] [Accepted: 07/22/2016] [Indexed: 02/06/2023]
Abstract
UNLABELLED Hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) vasculitis commonly regresses upon virus eradication, but conventional therapy with pegylated interferon and ribavirin yields approximately 40% sustained virologic responses (SVR). We prospectively evaluated the efficacy and safety of sofosbuvir-based direct-acting antiviral therapy, individually tailored according to the latest guidelines, in a cohort of 44 consecutive patients with HCV-associated MC. In two patients MC had evolved into an indolent lymphoma with monoclonal B-cell lymphocytosis. All patients had negative HCV viremia at week 12 (SVR12) and at week 24 (SVR24) posttreatment, at which time all had a clinical response of vasculitis. The mean (±standard deviation) Birmingham Vasculitis Activity Score decreased from 5.41 (±3.53) at baseline to 2.35 (±2.25) (P < 0.001) at week 4 on treatment to 1.39 (±1.48) (P < 0.001) at SVR12 and to 1.27 (±1.68) (P < 0.001) at SVR24. The mean cryocrit value fell from 7.2 (±15.4)% at baseline to 2.9 (±7.4)% (P < 0.01) at SVR12 and to 1.8 (±5.1)% (P < 0.001) at SVR24. Intriguingly, in the 2 patients with MC and lymphoma there was a partial clinical response of vasculitis and ∼50% decrease of cryocrit, although none experienced a significant decrease of monoclonal B-cell lymphocytosis. Adverse events occurred in 59% of patients and were generally mild, with the exception of 1 patient with ribavirin-related anemia requiring blood transfusion. CONCLUSION Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for HCV-associated MC patients; the overall 100% rate of clinical response of vasculitis, on an intention-to-treat basis, opens the perspective for curing the large majority of these so far difficult-to-treat patients. (Hepatology 2016;64:1473-1482).
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Affiliation(s)
- Laura Gragnani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Marcella Visentini
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Elisa Fognani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Teresa Urraro
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Adriano De Santis
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Luisa Petraccia
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Marie Perez
- Istituto Dermopatico Dell'Immacolata IRCCS, Rome, Italy
| | - Giorgia Ceccotti
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | | | - Milica Mitrevski
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Cristina Stasi
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Martina Del Padre
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Monica Monti
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Elena Gianni
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Alessandro Pulsoni
- Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Italy
| | - Massimo Fiorilli
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Milvia Casato
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
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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: 03/24/2016] [Revised: 06/25/2016] [Accepted: 08/15/2016] [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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Affiliation(s)
- Giovanni Galati
- Giovanni Galati, Lorenzo Rampa, Umberto Vespasiani-Gentilucci, Alessandro Guidi, Antonio Picardi, Unit of Internal Medicine and Hepatology, Department of Medicine, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
| | - Lorenzo Rampa
- Giovanni Galati, Lorenzo Rampa, Umberto Vespasiani-Gentilucci, Alessandro Guidi, Antonio Picardi, Unit of Internal Medicine and Hepatology, Department of Medicine, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
| | - Umberto Vespasiani-Gentilucci
- Giovanni Galati, Lorenzo Rampa, Umberto Vespasiani-Gentilucci, Alessandro Guidi, Antonio Picardi, Unit of Internal Medicine and Hepatology, Department of Medicine, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
| | - Mirella Marino
- Giovanni Galati, Lorenzo Rampa, Umberto Vespasiani-Gentilucci, Alessandro Guidi, Antonio Picardi, Unit of Internal Medicine and Hepatology, Department of Medicine, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
| | - Francesco Pisani
- Giovanni Galati, Lorenzo Rampa, Umberto Vespasiani-Gentilucci, Alessandro Guidi, Antonio Picardi, Unit of Internal Medicine and Hepatology, Department of Medicine, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
| | - Carlo Cota
- Giovanni Galati, Lorenzo Rampa, Umberto Vespasiani-Gentilucci, Alessandro Guidi, Antonio Picardi, Unit of Internal Medicine and Hepatology, Department of Medicine, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
| | - Alessandro Guidi
- Giovanni Galati, Lorenzo Rampa, Umberto Vespasiani-Gentilucci, Alessandro Guidi, Antonio Picardi, Unit of Internal Medicine and Hepatology, Department of Medicine, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
| | - Antonio Picardi
- Giovanni Galati, Lorenzo Rampa, Umberto Vespasiani-Gentilucci, Alessandro Guidi, Antonio Picardi, Unit of Internal Medicine and Hepatology, Department of Medicine, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
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Alric L, Besson C, Lapidus N, Jeannel J, Michot JM, Cacoub P, Canioni D, Pol S, Davi F, Rabiega P, Ysebaert L, Bonnet D, Hermine O. Antiviral Treatment of HCV-Infected Patients with B-Cell Non-Hodgkin Lymphoma: ANRS HC-13 Lympho-C Study. PLoS One 2016; 11:e0162965. [PMID: 27749916 PMCID: PMC5066969 DOI: 10.1371/journal.pone.0162965] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Accepted: 08/31/2016] [Indexed: 12/31/2022] Open
Abstract
Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted. METHODS First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL. In a second series, interferon-free regimens using a newly optimal combination therapy with direct-acting antiviral drugs (DAAs) were evaluated in 10 patients with HCV and B-NHL. RESULTS The main lymphoma type was diffuse large B-cell lymphoma (38%) followed by marginal zone lymphoma (31%). In the multivariate analysis, patients with B-NHL treated by Peg-IFN-based therapy exhibited a greater SVR rate compared with controls, 50.8% vs 30.8%, respectively, p<0.01, odds ratio (OR) = 11.2 [2.3, 52.8]. B-NHL response was better (p = 0.02) in patients with SVR (69%) than in patients without SVR (31%). Premature discontinuation of Peg-IFN-based therapy was significantly more frequent in the B-NHL group (19.6%) compared with the control group (6.3%), p<0.02. Overall, survival was significantly enhanced in the controls than in the B-NHL group (hazard ratio = 34.4 [3.9, 304.2], p< 0.01). Using DAAs, SVR was achieved in 9/10 patients (90%). DAAs were both well tolerated and markedly efficient. CONCLUSIONS The virologic response of HCV-associated B-NHL is high. Our study provides a comprehensive evaluation of different strategies for the antiviral treatment of B-NHL associated with HCV infection.
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Affiliation(s)
- Laurent Alric
- Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France
| | - Caroline Besson
- Université Paris sud Faculté de Médecine Kremlin Bicêtre, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, IMVA INSERM U1184, Paris, France
| | - Nathanael Lapidus
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136), Department of Public Health, Hôpital Saint-Antoine, AP-HP, Paris, France
| | - Juliette Jeannel
- Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France
| | - Jean-Marie Michot
- Université Paris sud Faculté de Médecine Kremlin Bicêtre, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, IMVA INSERM U1184, Paris, France
| | - Patrice Cacoub
- Paris 6 Pierre et Marie Curie University, UMR 7211, INSERM, UMR S 959, CNRS, UMR 7211, AP-HP, Department of Internal Medicine, Hôpital Pitié-Salpêtrière, Paris, France
| | - Danielle Canioni
- Paris 5 Descartes University, AP-HP, Department of Pathology, Hôpital Necker, Paris, France
| | - Stanislas Pol
- Université Descartes, Inserm U-318 Institut Pasteur, AP-HP, Department of hepatology, Hôpital Cochin, Paris, France
| | - Frédéric Davi
- Paris 6 Pierre et Marie Curie University, AP-HP, Department of Biological Hematology and Cytogenetic, Hôpital Pitié-Salpêtrière, Paris, France
| | - Pascaline Rabiega
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136), Department of Public Health, Hôpital Saint-Antoine, AP-HP, Paris, France
| | - Loic Ysebaert
- Department of Hematology IUCT oncopole, CHU, Toulouse, France
| | - Delphine Bonnet
- Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France
| | - Olivier Hermine
- Paris 5 Descartes University, AP-HP, INSERM U 1163, CNRS ERL 8254, Department of Adult Hematology and Imagine Institute, Hôpital Necker, Paris, France
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Merli M, Carli G, Arcaini L, Visco C. Antiviral therapy of hepatitis C as curative treatment of indolent B-cell lymphoma. World J Gastroenterol 2016; 22:8447-8458. [PMID: 27784957 PMCID: PMC5064026 DOI: 10.3748/wjg.v22.i38.8447] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 08/02/2016] [Accepted: 08/23/2016] [Indexed: 02/06/2023] Open
Abstract
The association of hepatitis C virus (HCV) and B-cell non-Hodgkin lymphomas (NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by interventional studies demonstrating the capability of antiviral treatment (AT) with interferon (IFN) with or without ribavirin to induce the regression of indolent lymphomas, especially of marginal-zone origin. In the largest published retrospective study (100 patients) the overall response rate (ORR) after first-line IFN-based AT was 77% (44% complete responses) and responses were sustainable (median duration of response 33 mo). These results were confirmed by a recent meta-analysis on 254 patients, demonstrating an ORR of 73%. Moreover this analysis confirmed the highly significant correlation between the achievement of viral eradication sustained virological response (SVR) and hematological responses. Two large prospective studies demonstrated that AT is associated with improved survival and argue in favor of current guidelines’ recommendation of AT as preferential first-line option in asymptomatic patients with HCV-associated indolent NHL. The recently approved direct-acting antiviral agents (DAAs) revolutionized the treatment of HCV infection, leading to SVR approaching 100% in all genotypes. Very preliminary data of IFN-free DAAs therapy in indolent HCV-positive NHL seem to confirm their activity in inducing lymphoma regression.
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39
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Saadoun D, Thibault V, Si Ahmed SN, Alric L, Mallet M, Guillaud C, Izzedine H, Plaisier A, Fontaine H, Costopoulos M, Le Garff-Tavernier M, Hezode C, Pol S, Musset L, Poynard T, Cacoub P. Sofosbuvir plus ribavirin for hepatitis C virus-associated cryoglobulinaemia vasculitis: VASCUVALDIC study. Ann Rheum Dis 2016; 75:1777-82. [PMID: 26567178 DOI: 10.1136/annrheumdis-2015-208339] [Citation(s) in RCA: 123] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Accepted: 10/26/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) is the aetiological agent for most cases of cryoglobulinaemia vasculitis. Interferon-containing regimens are associated with important side effects and may exacerbate the vasculitis. OBJECTIVE To evaluate safety and efficacy of an oral interferon-free regimen, sofosbuvir plus ribavirin, in HCV-cryoglobulinaemia vasculitis. PATIENTS AND METHODS We enrolled 24 consecutive patients (median age of 56.5 years and 46% of women) with HCV-cryoglobulinaemia vasculitis. Sofosbuvir (400 mg/day) was associated with ribavirin (200-1400 mg/day), for 24 weeks. The primary efficacy end point was a complete clinical response of the vasculitis at the end of treatment (week 24). RESULTS Main features of HCV-cryoglobulinaemia vasculitis included purpura and peripheral neuropathy (67%), arthralgia (58%), glomerulonephritis (21%) and skin ulcers (12%). Twenty-one patients (87.5%) were complete clinical response at week 24. Complete clinical response was achieved in six (25%) patients at week 4, four (16.6%) at week 8, seven (29.2%) at week 12, three (12.5%) at week 16 and one (4.2%) at week 20. The cryoglobulin level decreased from 0.35 (0.16-0.83) at baseline to 0.15 (0.05-0.45) g/L at week 24. The C4 serum level increased from 0.10 (0.07-0.19) to 0.17 (0.09-0.23) g/L at week 24. Seventy-four per cent of patients had a sustained virological response at week 12 post treatment. The most common side effects were fatigue, insomnia and anaemia. Two serious adverse events were observed. CONCLUSIONS Sofosbuvir plus ribavirin combination was associated with a high rate of complete clinical response and a low rate of serious adverse events in HCV-cryoglobulinaemia vasculitis.
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Affiliation(s)
- David Saadoun
- Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Sorbonne Universités, UPMC Univ Paris 06, Paris, France INSERM, UMR_S 959, Paris, France CNRS, FRE3632, Paris, France Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, AP-HP, Paris, France
| | - Vincent Thibault
- Groupe Hospitalier Pitié-Salpétrière, Department of Virology, APHP, Paris, France
| | | | - Laurent Alric
- Department of Internal Medicine-Digestive, Centre hospitalier universitaire Purpan, UMR 152 Toulouse 3 University, Toulouse, France
| | - Maxime Mallet
- Groupe Hospitalier Pitié-Salpétrière, Department of Hepatology, AP-HP, Paris, France
| | | | - Hassane Izzedine
- Groupe Hospitalier Pitié-Salpétrière, Department of Nephrology, APHP, Paris, France
| | | | - Hélène Fontaine
- Department of Hepatology, APHP, Hôpital Cochin, Paris, France
| | - Myrto Costopoulos
- Groupe Hospitalier Pitié-Salpétrière, Biological Hematology, APHP, Paris, France
| | | | - Christophe Hezode
- Department of Hepatology, APHP, Hôpital Henri Mondor, Créteil, France
| | - Stanislas Pol
- Department of Hepatology, APHP, Hôpital Cochin, Paris, France
| | - Lucile Musset
- Groupe Hospitalier Pitié-Salpétrière, Department of Immunology, UF d'Immunochimie et d'autoimmunité, APHP, Paris, France
| | - Thierry Poynard
- Groupe Hospitalier Pitié-Salpétrière, Department of Hepatology, AP-HP, Paris, France
| | - Patrice Cacoub
- Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Sorbonne Universités, UPMC Univ Paris 06, Paris, France INSERM, UMR_S 959, Paris, France CNRS, FRE3632, Paris, France Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, AP-HP, Paris, France
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Interferon-free antiviral treatment in B-cell lymphoproliferative disorders associated with hepatitis C virus infection. Blood 2016; 128:2527-2532. [PMID: 27605512 DOI: 10.1182/blood-2016-05-714667] [Citation(s) in RCA: 127] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 08/30/2016] [Indexed: 12/18/2022] Open
Abstract
Regression of hepatitis C virus (HCV)-associated lymphoma with interferon (IFN)-based antiviral treatment supports an etiological link between lymphoma and HCV infection. In addition, a favorable impact of antiviral treatment on overall survival of patients with HCV-related lymphoma has been reported. Data on IFN-free regimens combining direct-acting antivirals (DAAs) in HCV-associated lymphoproliferative disorders are scanty. We analyzed the virological and lymphoproliferative disease response (LDR) of 46 patients with indolent B-cell non-Hodgkin lymphomas (NHLs) or chronic lymphocytic leukemia (CLL) and chronic HCV infection treated with DAAs. The histological distribution was 37 marginal zone lymphomas (MZLs), 2 lymphoplasmacytic lymphomas, 2 follicular lymphomas, 4 CLL/small lymphocytic lymphomas (CLL/SLLs), and 1 low-grade NHL not otherwise specified. Thirty-nine patients received a sofosbuvir-based regimen and 7 patients received other DAAs. The median duration of DAA therapy was 12 weeks (range, 6-24 weeks). A sustained virological response at week 12 after finishing DAAs was obtained in 45 patients (98%); the overall LDR rate was 67%, including 12 patients (26%) who achieved a complete response. The LDR rate was 73% among patients with MZL, whereas no response was observed in CLL/SLL patients. Seven patients cleared cryoglobulins out of 15 who were initially positive. After a median follow-up of 8 months, 1-year progression-free and overall survival rates were 75% (95% confidence interval [CI], 51-88] and 98% [95% CI, 86-100], respectively. DAA therapy induces a high LDR rate in HCV-associated indolent lymphomas. These data provide a strong rationale for prospective trials with DAAs in this setting.
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Mihăilă RG. Hepatitis C virus - associated B cell non-Hodgkin's lymphoma. World J Gastroenterol 2016; 22:6214-6223. [PMID: 27468211 PMCID: PMC4945980 DOI: 10.3748/wjg.v22.i27.6214] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2016] [Revised: 05/26/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
The hepatitis C virus (HCV) infected patients are prone to develop bone marrow or various tissue infiltrates with monoclonal B cells, monoclonal B lymphocytosis or different types of B cell non-Hodgkin’s lymphoma (BCNHL), of which the most common are splenic marginal zone BCNHL, diffuse large BCNHL and follicular lymphoma. The association between chronic HCV infection and non Hodgkin’s lymphoma has been observed especially in areas with high prevalence of this viral infection. Outside the limitations of some studies that have been conducted, there are also geographic, environmental, and genetic factors that contribute to the epidemiological differences. Various microenvironmental signals, such as cytokines, viral antigenic external stimulation of lymphocyte receptors by HCV antigens, and intercellular interactions contribute to B cell proliferation. HCV lymphotropism and chronic antigenic stimulation are involved in B-lymphocyte expansion, as mixted cryoglobulinemia or monoclonal gammopathy of undetermined significance, which can progress to BCNHL. HCV replication in B lymphocytes has oncogenic effect mediated by intracellular HCV proteins. It is also involved in an important induction of reactive oxygen species that can lead to permanent B lymphocyte damage, as DNA mutations, after binding to surface B-cell receptors. Post-transplant lymphoproliferative disorder could appear and it has a multiclonal potentiality that may develop into different types of lymphomas. The hematopoietic stem cell transplant made for lymphoma in HCV-infected patients can increase the risk of earlier progression to liver fibrosis and cirrhosis. HCV infected patients with indolent BCNHL who receive antiviral therapy can be potentially cured. Viral clearance was related to lymphoma response, fact that highlights the probable involvement of HCV in lymphomagenesis. Direct acting antiviral drugs could be a solution for the patients who did not tolerate or respond to interferon, as they seem to be safe and highly effective. The use of chemotherapy in combination with rituximab for the treatment of BCNHL in patients infected with HCV can produce liver dysfunction. The addition of immunotherapy with rituximab can increase the viral replication, and severe complications can occure especially in patients co-infected with hepatitis B virus or immune immunodeficiency virus, in those with hepatocarcinoma, cirrhosis, or liver cytolysis. But the final result of standard immunochemotherapy applied to diffuse large BCNHL patients with HCV infection is not notably worse than in those without this viral infection. The treatment of patients chronically infected with HCV and having BCNHL is complex and requires a multidisciplinary approach and the risk / benefit ratio of rituximab treatment must be evaluated especially in those with liver cytolysis.
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MESH Headings
- Antineoplastic Agents/therapeutic use
- Antiviral Agents/therapeutic use
- B-Lymphocytes/immunology
- Cell Proliferation
- Hematopoietic Stem Cell Transplantation
- Hepatitis C Antigens/immunology
- Hepatitis C, Chronic/immunology
- Hepatitis C, Chronic/therapy
- Humans
- Liver Transplantation
- Lymphoma, B-Cell/immunology
- Lymphoma, B-Cell/therapy
- Lymphoma, B-Cell, Marginal Zone/immunology
- Lymphoma, B-Cell, Marginal Zone/therapy
- Lymphoma, Follicular/immunology
- Lymphoma, Follicular/therapy
- Lymphoma, Large B-Cell, Diffuse/immunology
- Lymphoma, Large B-Cell, Diffuse/therapy
- Lymphoma, Non-Hodgkin/immunology
- Lymphoma, Non-Hodgkin/therapy
- Rituximab/therapeutic use
- Splenic Neoplasms/immunology
- Splenic Neoplasms/therapy
- Virus Replication/immunology
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Tang L, Marcell L, Kottilil S. Systemic manifestations of hepatitis C infection. Infect Agent Cancer 2016; 11:29. [PMID: 27222662 PMCID: PMC4878040 DOI: 10.1186/s13027-016-0076-7] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2015] [Accepted: 05/10/2016] [Indexed: 12/19/2022] Open
Abstract
Chronic hepatitis C (HCV) is a common infection affecting 185 million people worldwide. The most common manifestation of chronic HCV is progressive liver fibrosis, cirrhosis, liver failure and hepatocellular carcinoma. However, several systemic manifestations of HCV have been recognized and reported in the literature. The purpose of this review is to assimilate published literature based on evidence to categorize these extrahepatic manifestations with the likelihood of a causal association with HCV. Exciting recent developments have resulted in simple all oral interferon-free highly effective therapy for HCV. However, this treatment is also expensive and less accessible to most affected individuals as treatment recommendations are based on stage of liver fibrosis. Expanding the scope of HCV therapy to those with extrahepatic manifestations beyond what is currently recommended will significantly reduce the morbidity and mortality in this aging population.
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Affiliation(s)
- Lydia Tang
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, 725 W Lombard St, Room S222, Baltimore, MD USA
| | - Lauren Marcell
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, 725 W Lombard St, Room S222, Baltimore, MD USA
| | - Shyam Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, 725 W Lombard St, Room S222, Baltimore, MD USA
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Splenic marginal zone lymphoma: from genetics to management. Blood 2016; 127:2072-81. [DOI: 10.1182/blood-2015-11-624312] [Citation(s) in RCA: 104] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Accepted: 03/07/2016] [Indexed: 12/16/2022] Open
Abstract
AbstractSplenic marginal zone lymphoma (SMZL) is a rare B-cell malignancy involving the spleen, bone marrow, and frequently the blood. SMZL lymphomagenesis involves antigen and/or superantigen stimulation and molecular deregulation of genes (NOTCH2 and KLF2) involved in the physiological differentiation of spleen marginal zone B cells. Diagnosis requires either spleen histology or, alternatively, the documentation of a typical cell morphology and immunophenotype on blood cells coupled with the detection of intrasinusoidal infiltration by CD20+ cells in the bone marrow. Among B-cell tumors, deletion of 7q and NOTCH2 mutations are almost specific lesions of SMZL, thus representing promising diagnostic biomarkers of this lymphoma. Although the majority of SMZLs show an indolent course with a median survival of approximately 10 years, nearly 30% of patients experience a poor outcome. No randomized trials are reported for SMZL, and few prospective trials are available. A watch-and-wait approach is advisable for asymptomatic patients. Treatment options for symptomatic patients ranges from splenectomy to rituximab alone or combined with chemotherapy. In some geographic areas, a subset of patients with SMZL associates with hepatitis C virus infection, prompting virus eradication as an effective lymphoma treatment. It would be worthwhile to explore deregulated cellular programs of SMZL as therapeutic targets in the future; improved clinical and biological prognostication will be essential for identifying patients who may benefit from novel approaches.
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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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Su TH, Liu CJ, Tseng TC, Chou SW, Liu CH, Yang HC, Wu SJ, Chen PJ, Chen DS, Chen CL, Kao JH. Hepatitis C viral infection increases the risk of lymphoid-neoplasms: A population-based cohort study. Hepatology 2016; 63:721-730. [PMID: 26662347 DOI: 10.1002/hep.28387] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 12/04/2015] [Indexed: 12/16/2022]
Abstract
UNLABELLED Chronic hepatitis C viral (HCV) infection has been associated with non-Hodgkin's lymphoma (NHL); however, the results are inconsistent among regions with different HCV prevalence rates. The temporal relationship, risk estimates, and association between HCV and lymphoid-neoplasms remain unclear. This study investigated the temporal relationship between HCV infection and lymphoid-neoplasms using a nationwide population-based cohort. Patients with chronic HCV infection were retrieved from the Taiwan National Health Insurance Research Database during 2001-2005 and designated as the HCV cohort. Those with prior malignancies or coinfected with hepatitis B or human immunodeficiency virus were excluded. The age, sex, and comorbidities, including rheumatological disorders and diabetes, were matched by propensity scores to another non-HCV cohort. Both cohorts were followed longitudinally until 2009 for a new diagnosis of any lymphoid-neoplasms or NHL. A total of 11,679 HCV and 46,716 non-HCV patients were included and followed for 8 years. The incidence rates of any lymphoid-neoplasms and NHL were significantly greater in the HCV cohort than the non-HCV cohort (48.4 versus 22.1, and 37.0 versus 17.5 per 100,000 person-years, respectively, both P < 0.001), even after we excluded lymphoid-neoplasms developed within the first year of follow-up. Cox proportional hazards regression analysis (after adjustment for age, sex, numbers of annual medical visits during follow-up, and comorbidities) indicated that HCV infection was associated with an increased risk of either any lymphoid-neoplasms (hazard ratio = 2.30, 95% confidence interval 1.55-3.43, P < 0.0001) or NHL (hazard ratio = 2.00, 95% confidence interval 1.27-3.16, P = 0.003). CONCLUSION After adjustment for confounders and biases, chronic HCV infection is temporally associated with a two-fold increased risk of lymphoid-neoplasms, especially NHL, in Asian patients; additional large studies are needed to explore whether HCV eradication can reduce the incidence of lymphoid-neoplasms.
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Affiliation(s)
- Tung-Hung Su
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taipei, Taiwan
| | - Shih-Wan Chou
- National Taiwan University Health Data Research Center, Taipei, Taiwan
| | - Chen-Hua Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shang-Ju Wu
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Ding-Shinn Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Chi-Ling Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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Vannata B, Arcaini L, Zucca E. Hepatitis C virus-associated B-cell non-Hodgkin's lymphomas: what do we know? Ther Adv Hematol 2015; 7:94-107. [PMID: 27054025 DOI: 10.1177/2040620715623924] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Epidemiological studies have shown an increased risk of developing B-cell lymphomas in patients with chronic hepatitis C virus (HCV) infection. There is, however, a great geographic variability and it remains unclear whether additional environmental and genetic factors are involved or whether the international discrepancies represent simply a consequence of the variable prevalence of HCV infection in different countries. Other confounding factors may affect the comparability of the different studies, including the method of HCV assessment, the selection of normal controls, the lymphoma classification used and the year of publication. The most convincing evidence for a causal relationship comes from the observation, mainly limited to some indolent subtypes, of B-cell lymphoma regressions after successful HCV eradication with antiviral treatment. Yet, the molecular mechanism of HCV-induced lymphomagenesis are mainly hypothetical. According to most plausible models, lymphoma growth is a consequence of continuous antigenic stimulation induced by the chronic viral infection. This review will summarize the current knowledge on HCV-associated lymphomas and their management.
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Affiliation(s)
- Barbara Vannata
- Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
| | - Luca Arcaini
- Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo and Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Emanuele Zucca
- Lymphoma Unit, Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona 6500, Switzerland
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Lymphoma Remission by Interferon-Free HCV Eradication Without Chemotherapy. ACG Case Rep J 2015; 3:69-70. [PMID: 26504885 PMCID: PMC4612765 DOI: 10.14309/crj.2015.104] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Accepted: 08/25/2015] [Indexed: 11/19/2022] Open
Abstract
Epidemiologic studies have suggested an association between hepatitis C virus (HCV) infection and antigendriven lymphoproliferative disorders, in particular marginal zone lymphomas. Antiviral therapy has been shown to exert an anti-lymphoma effect in these indolent B-cell lymphoproliferations, with survival gains observed. However, these protocols have traditionally incorporated interferon. We describe a patient with chronic hepatitis C, immune thrombocytopenia, and splenic marginal zone lymphoma who, after eradication of HCV with sofosbuvir and ribavirin, exhibited complete remission of both hematologic conditions. With the numerous new potent drugs currently available, the future looks positive with highly efficacious interferon-free regimens for HCV therapy.
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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; 35:2222-2227. [PMID: 26104059 DOI: 10.1111/liv.12897] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [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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Cholestatic hepatitis C after chemotherapy containing rituximab in diffuse large B cell lymphoma. Ann Hepatol 2015. [DOI: 10.1016/s1665-2681(19)30773-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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