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Saputra LA, Indrawati I, Hardianti MS, Anggorowati N. Correlation Between the Hepatitis C Virus NS3 Protein and CD30 Expression in Diffuse Large B-cell Lymphoma. Cureus 2024; 16:e65108. [PMID: 39171065 PMCID: PMC11338068 DOI: 10.7759/cureus.65108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/22/2024] [Indexed: 08/23/2024] Open
Abstract
INTRODUCTION One of the etiologies of non-Hodgkin lymphoma (NHL) is chronic infection related to lymphoma pathogenesis, with a high prevalence of hepatitis C virus (HCV) infection seen. In determining the treatment and prognosis of NHL, cluster of differentiation 30 (CD30) immunohistochemical staining plays an important role. High levels of CD30 are found in patients with HCV infection. This study aimed to determine the prevalence of CD30 and HCV expression and its correlation with clinicopathological characteristics of Indonesian diffuse large B-cell lymphoma (DLBCL) patients. METHODS A total of 86 formalin-fixed paraffin-embedded (FFPE) samples of DLBCL cases were collected over the course of two years from the Anatomical Pathology department at Dr. Sardjito General Hospital in the special region of Yogyakarta, Indonesia. Immunohistochemistry was performed to detect the two markers (CD30 and HCV). Chi-square tests were used to investigate the correlations between CD30 expression and clinicopathological features in DLBCL patients. RESULTS The positivity rate of CD30 expression in 86 DLBCL samples was 25.6% (22/86) when using a 0% cut-off, and 7.0% (6/86) while using a 20% cutoff. The positivity rate of HCV expression in DLBCL samples was 34.9% (30/86). Positive CD30 expression, HCV expression and clinicopathological features (age, sex, Ann Arbor stage, extranodal involvement, and morphological variations) did not have statistically significant relationships (p>0.05). CONCLUSION There was no statistically significant correlation between CD30 immunoreactivity (cut-off >0% or >20%) and HCV NS3 expression and clinicopathological features (age, sex, Ann Arbor stage, extranodal involvement, lactate dehydrogenase, Eastern Cooperative Oncology Group status and morphological variants) in DLBCL.
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Affiliation(s)
- Lili A Saputra
- Department of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta, IDN
- Department of Anatomical Pathology, Faculty of Medicine, Universitas Kristen Duta Wacana, Yogyakarta, IDN
| | - Indrawati Indrawati
- Department of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, IDN
| | - Mardiah S Hardianti
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta, IDN
| | - Nungki Anggorowati
- Department of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, IDN
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Zhang M, Gao F, Peng L, Shen L, Zhao P, Ni B, Hou J, Huang H. Distinct clinical features and prognostic factors of hepatitis C virus-associated non-Hodgkin's lymphoma: a systematic review and meta-analysis. Cancer Cell Int 2021; 21:524. [PMID: 34627251 PMCID: PMC8502277 DOI: 10.1186/s12935-021-02230-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 09/27/2021] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Increasing evidence suggests that hepatitis C virus (HCV) infection is associated with non-Hodgkin's lymphoma (NHL). However, no clear consensus has been reached about the clinical features and effective treatment of HCV-associated NHL patients. We therefore performed a systematic review and meta-analysis to explore the clinical characteristics and effectiveness of antiviral treatment or rituximab administration among NHL patients with HCV infection. METHODS Eight electronic databases, including PubMed, OVID, EMBASE, Cochrane Library, ClinicalTrials, WANFANG, CNKI, and VIP, were searched for eligible studies up to July 31, 2021. The hazard ratio (HR) or odds ratio (OR) corresponding to the 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by Egger's and Begg's tests. Statistical analysis was performed with RevMan 5.4 software and Stata version 15. RESULTS There were 27 shortlisted articles out of a total of 13,368 NHL patients included in the current meta-analysis. Our results demonstrated that NHL patients with HCV infection had a significantly shorter overall survival (OS: HR 1.89; 95% CI 1.42-2.51, P < 0.0001) and progression-free survival (PFS: HR 1.58; 95% CI 1.26-1.98, P < 0.0001), a lower overall response rate (ORR: OR 0.58, 95% CI 0.46-0.73, P < 0.00001) and a higher incidence of hepatic dysfunction during chemotherapy (OR 5.96; 95% CI 2.61-13.62, P < 0.0001) than NHL patients without HCV infection. HCV-positive NHL patients exhibited an advanced disease stage, an elevated level of LDH, a high-intermediate and high IPI/FLIPI risk as well as a higher incidence of spleen and liver involvement. Moreover, antiviral treatment prolonged survival (OS: HR 0.38; 95% CI 0.24-0.60, P < 0.0001), reduced disease progression [PFS/DFS (disease-free survival): HR 0.63; 95% CI 0.46-0.86, P = 0.003] and reinforced the treatment response (ORR: OR 2.62; 95% CI 1.34-5.11, P = 0.005) among the HCV-infected NHL patients. Finally, rituximab administration was associated with a favourable OS, while liver cirrhosis and low levels of albumin predicted a poor OS for HCV-positive NHL patients. CONCLUSIONS The current study provided compelling evidence about an inferior prognosis and distinct clinical characteristics among HCV-associated NHL patients. Antiviral treatment and rituximab-containing regimens were shown to be efficacious in improving the clinical outcomes of NHL patients with HCV infection.
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Affiliation(s)
- Minyue Zhang
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.,Division of Chinese Medicine, M.D. Prefectural People's Hospital, Chuxiong Yi Autonomous Prefecture, 675500, China
| | - Fei Gao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, 611730, China
| | - Ling Peng
- Division of Chinese Medicine, M.D. Prefectural People's Hospital, Chuxiong Yi Autonomous Prefecture, 675500, China
| | - Lijing Shen
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Peng Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, 611730, China
| | - Beiwen Ni
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Jian Hou
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
| | - Honghui Huang
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
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Tsai YF, Liu YC, Yang CI, Chuang TM, Ke YL, Yeh TJ, Gau YC, Du JS, Wang HC, Cho SF, Hsu CM, Wu PF, Huang CI, Huang CF, Yu ML, Dai CY, Hsiao HH. Poor Prognosis of Diffuse Large B-Cell Lymphoma with Hepatitis C Infection. J Pers Med 2021; 11:844. [PMID: 34575621 PMCID: PMC8465128 DOI: 10.3390/jpm11090844] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 08/24/2021] [Accepted: 08/25/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) in diffuse large B-cell lymphoma (DLBCL) is associated with a higher prevalence and distinctive clinical characteristics and outcomes. METHODS A retrospective analysis of adult DLBCL patients from 2011 to 2015 was studied. RESULTS A total of 206 adult DLBCL were enrolled with 22 (10.7%) HCV-positive patients. Compared to HCV-negative patients, the HCV-positive group had a poor performance status (p = 0.011), lower platelet count (p = 0.029), and higher spleen and liver involvement incidences (liver involvement, p = 0.027, spleen involvement, p = 0.026), and they received fewer cycles of chemotherapy significantly due to morbidity and mortality (p = 0.048). Overall survival was shorter in HCV-positive DLBCL (25.3 months in HCV-positive vs. not reached (NR), p = 0.049). With multivariate analysis, poor performance status (p < 0.001), advanced stage (p < 0.001), less chemotherapy cycles (p < 0.001), and the presence of liver toxicity (p = 0.001) contributed to poor OS in DLBCL. Among HCV-positive DLBCL, the severity of liver fibrosis was the main risk factor related to death. CONCLUSION Inferior survival of HCV-positive DLBCL was observed and associated with poor performance status, higher numbers of complications, and intolerance of treatment, leading to fewer therapy. Therefore, anti-HCV therapy, such as direct-acting antiviral agents, might benefit these patients in the future.
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Affiliation(s)
- Yu-Fen Tsai
- Department of Hematology & Oncology, E-Da Cancer Hospital, Kaohsiung 824, Taiwan;
- School of Chinese Medicine for Post Baccalaureate, College of Medicine, I-Shou University, Kaohsiung 824, Taiwan
| | - Yi-Chang Liu
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
| | - Ching-I Yang
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
- Specialist Nurse and Surgical Nurse Practitioner Office, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Tzer-Ming Chuang
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
| | - Ya-Lun Ke
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
| | - Tsung-Jang Yeh
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
| | - Yuh-Ching Gau
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
| | - Jeng-Shiun Du
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
| | - Hui-Ching Wang
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
| | - Shih-Feng Cho
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
| | - Chin-Mu Hsu
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
| | - Pey-Fang Wu
- Division of Hepatobiliary Ward, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan;
| | - Ching-I Huang
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
- Division of Hepatobiliary Ward, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan;
| | - Chung-Feng Huang
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
- Division of Hepatobiliary Ward, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan;
| | - Ming-Lung Yu
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
- Division of Hepatobiliary Ward, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan;
| | - Chia-Yen Dai
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
- Division of Hepatobiliary Ward, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan;
| | - Hui-Hua Hsiao
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (Y.-C.L.); (C.-I.Y.); (T.-M.C.); (Y.-L.K.); (T.-J.Y.); (Y.-C.G.); (J.-S.D.); (H.-C.W.); (S.-F.C.); (C.-M.H.)
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-I.H.); (C.-F.H.); (M.-L.Y.); (C.-Y.D.)
- Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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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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Elbedewy TA, Elashtokhy HEA, Abd-Elsalam S, Suliman MA. Hepatitis C Virus Infection and Treatment as Independent Prognostic Factors in Diffuse Large B-Cell Lymphoma Egyptian Patients. Curr Cancer Drug Targets 2020; 20:638-645. [PMID: 32392114 DOI: 10.2174/1568009620666200511084731] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 02/28/2020] [Accepted: 03/17/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Egypt is one of the highest hepatitis C virus (HCV) endemic areas. Chronic HCV infection has extra-hepatic manifestations, including non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is commonly associated with HCV infection. The prognostic value of HCV infection and HCV treatment in patients with DLBCL remains unclear until now. OBJECTIVE The aim of our study is to evaluate the impact of HCV infection and HCV treatment as independent prognostic factors on the event-free survival (EFS) and overall survival (OS) in Egyptian patients with HCV associated DLBCL. METHODS This study included 353 patients with DLBCL, collected retrospectively. While 34 patients with HCV who received HCV antiviral therapy were collected prospectively. Patient's characteristics were collected from the patient records at the time of diagnosis. The status of the patients about HCV infection and HCV treatment were also recorded. Disease progression, relapse, retreatment or deaths were also verified through medical records. EFS and OS were calculated. RESULTS EFS and OS significantly decrease in HCV infected and HCV non-treated patients when compared with HCV non-infected and HCV treated patients, respectively. HCV infection but not HCV treatment was independently associated with EFS and OS using univariate and multivariate analysis. CONCLUSION Hepatitis C virus infection is an independent prognostic factor for EFS and OS in diffuse large B-cell lymphoma. HCV treatment is associated with higher EFS and OS but can not be considered as an independent prognostic factor.
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Affiliation(s)
- Tamer A Elbedewy
- Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | | | | | - Marwa A Suliman
- Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Suez Canal University, Al Ismailia, Egypt
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Shimono J, Miyoshi H, Arakawa F, Yamada K, Sugio T, Miyawaki K, Eto T, Miyagishima T, Kato K, Nagafuji K, Akashi K, Teshima T, Ohshima K. Clinicopathological features of HCV-positive splenic diffuse large B cell lymphoma. Ann Hematol 2019; 98:1197-1207. [PMID: 30729289 DOI: 10.1007/s00277-019-03628-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 01/29/2019] [Indexed: 11/26/2022]
Abstract
The hepatitis C virus (HCV) is a single-stranded RNA virus which is thought to be involved in the onset of B cell lymphoma. HCV-positive diffuse large B cell lymphoma (DLBCL) has been reported to clinically manifest in extranodal lesions (e.g., in the liver, spleen, and stomach). Here, we investigated HCV-positive and -negative primary splenic DLBCL (p-spDLBCL) and non-primary splenic DLBCL (ordinary DLBCL). Furthermore, to examine HCV lymphomagenesis, RNA in situ hybridization (ISH), RT-PCR (reverse-transcription polymerase chain reaction), and NS3 immunostaining of HCV viral nonstructural proteins were performed. HCV-positive p-spDLBCL patients presented fewer B symptoms (asymptomatic) and better performance status, with elevated presence of splenic macronodular lesions and more germinal center B cell (GCB) sub-group cases than HCV-negative p-spDLBCL patients. However, HCV-positive ordinary DLBCL patients were found to have more non-GCB sub-group cases than HCV-negative ordinary DLBCL patients. HCV-positive DLBCL patients showed 20.6% (7/34) NS3 positivity, 16.7% (1/6) HCV-RNA in situ positivity, and 22.2% (2/9) detection of HCV-RNA in tumor tissue by RT-PCR. Splenic samples were found to have a higher frequency of HCV detection than lymph node samples, thus suggesting that HCV may be closely related to lymphomagenesis, especially in splenic lymphoma.
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Affiliation(s)
- Joji Shimono
- Department of Pathology, Kurume University, School of Medicine, Asahimachi 67, Kurume, Fukuoka, 830-0011, Japan
- Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Hiroaki Miyoshi
- Department of Pathology, Kurume University, School of Medicine, Asahimachi 67, Kurume, Fukuoka, 830-0011, Japan.
| | - Fumiko Arakawa
- Department of Pathology, Kurume University, School of Medicine, Asahimachi 67, Kurume, Fukuoka, 830-0011, Japan
| | - Kyohei Yamada
- Department of Pathology, Kurume University, School of Medicine, Asahimachi 67, Kurume, Fukuoka, 830-0011, Japan
| | - Takeshi Sugio
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Kohta Miyawaki
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Tetsuya Eto
- Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
| | | | - Koji Kato
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Koji Nagafuji
- Department of Hematology, Kurume University, School of Medicine, Kurume, Japan
| | - Koichi Akashi
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Takanori Teshima
- Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Koichi Ohshima
- Department of Pathology, Kurume University, School of Medicine, Asahimachi 67, Kurume, Fukuoka, 830-0011, Japan
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Sghaier I, Zidi S, Mouelhi L, Ghazoueni E, Brochot E, Almawi WY, Loueslati BY. TLR3 and TLR4 SNP variants in the liver disease resulting from hepatitis B virus and hepatitis C virus infection. Br J Biomed Sci 2018; 76:35-41. [PMID: 30421643 DOI: 10.1080/09674845.2018.1547179] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Chronic infection with hepatitis B (HBV) and C virus (HCV) is linked with a pro-inflammatory state, predisposing to cirrhosis and liver cancer, particularly hepatocellular carcinoma (HCC). A role for Toll-like receptor (TLR) signalling in hepatocarcinogenesis was recently documented. We hypothesised a link TLR3 and TLR4 polymorphisms and HCC, as surrogates for the significance of TLR signalling in the promotion and initiation of HCC. MATERIALS AND METHODS We recruited 174 HCV-infected patients, 100 HBV-infected patients and 360 healthy control subjects. TLR3 (rs3775290) and TLR4 (rs4986790) genotyping was done by PCR-restriction fragment length polymorphisms (PCR-RFLP), LFTs and AFP by standard routine techniques. Liver fibrosis was assessed clinically by the Fibrotest and Actitest. RESULT The TLR3 rs3775290 minor T genotype was linked with increased risk of chronic HBV (P = 0.05) and HCV (P = 0.031) infection. The TLR4 rs4986790 minor G genotype was linked with significantly increased risk for HBV/HCV chronic infection (P < 0.001). Subgroups analyses indicated decreased risk of HBV-related HCC in relation to TLR3 rs3775290 CC/CT genotype (P = 0.022), with increased risk ascribed to the minor (T) allele (P = 0.04). Likewise, TLR4 rs4985790 minor (GG) genotype was positively associated with HBV-linked HCC (P < 0.001). Furthermore, a link between TLR3 TT (P < 0.001) andTLR4 GG (P = 0.04) minor genotypes was noted in relation to increased risk of HCV-related disease. CONCLUSION TLR3 and TLR4 polymorphisms are promising biomarkers of liver cirrhosis and cancer associated with HBV and HCV infection.
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Affiliation(s)
- I Sghaier
- a Faculty of Sciences of Tunis , University of Tunis El Manar , Tunis , Tunisia
| | - S Zidi
- a Faculty of Sciences of Tunis , University of Tunis El Manar , Tunis , Tunisia
| | - L Mouelhi
- b Hepato-Gastro-Enterology department , Charles Nicolle Hospital , Tunis , Tunisia
| | - E Ghazoueni
- c Laboratory of Immunology , Military Hospital of Tunis , Tunis , Tunisia
| | - E Brochot
- d Department of Virology , Amiens University Medical Centre , Amiens , France.,e Virology Research Unit, EA 4294 , Jules Verne University of Picardie , Amiens , France
| | - W Y Almawi
- f Faculty of Sciences of Tunis, Laboratory of Mycology , University of Tunis El Manar , Tunis , Tunisia
| | - B Y Loueslati
- f Faculty of Sciences of Tunis, Laboratory of Mycology , University of Tunis El Manar , Tunis , Tunisia
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8
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HCV load as a possible prognostic factor in patients with HCV-related DLBCL. Ann Hematol 2017; 97:351-354. [DOI: 10.1007/s00277-017-3124-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 08/26/2017] [Indexed: 01/09/2023]
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Shimono J, Miyoshi H, Kato T, Sugio T, Miyawaki K, Kamimura T, Miyagishima T, Eto T, Imaizumi Y, Kato K, Nagafuji K, Akashi K, Seto M, Teshima T, Ohshima K. Hepatitis C virus infection is an independent prognostic factor in follicular lymphoma. Oncotarget 2017; 9:1717-1725. [PMID: 29416725 PMCID: PMC5788593 DOI: 10.18632/oncotarget.23138] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Accepted: 11/13/2017] [Indexed: 01/08/2023] Open
Abstract
Hepatitis C virus (HCV) is a single-stranded RNA virus that not only affects hepatocytes, by B cells as well. It is thought that HCV is involved in the onset of B-cell lymphoma. The clinicopathological characteristics of HCV-positive diffuse large B-cell lymphoma (DLBCL) and HCV-positive splenic marginal zone lymphoma (SMZL) are known, but there has been no report on HCV-positive follicular lymphoma (FL). In this study, the clinicopathological characteristics of HCV-positive FL were examined in 263 patients with FL who were classified into a HCV-positive group with HCV antibody and negative groups without one. The number of patients with HCV-positive FL and HCV-negative FL was 10 (3.8%) and 253 (96.2%), respectively. The patients with HCV-positive FL commonly had more than one region of lymphadenopathy, Ann Arbor stage III/IV, hemoglobin <120 g/l, elevated lactate dehydrogenase level, and high-risk categorization of Follicular Lymphoma International Prognostic Index (FLIPI) than in patients with HCV-negative FL. Overall survival and progression-free survival were poorer in patients with HCV-positive FL than in those with HCV-negative FL (p < 0.0001 and 0.006, respectively). Also, multivariate analysis revealed that positive HCV antibody was a poor prognostic factor of OS. In conclusion, HCV-positive FL has unique clinical features and may have a great impact on the overall survival of affected patients.
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Affiliation(s)
- Joji Shimono
- Department of Pathology, Kurume University, School of Medicine, Kurume, Japan.,Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Hiroaki Miyoshi
- Department of Pathology, Kurume University, School of Medicine, Kurume, Japan
| | - Takeharu Kato
- Department of Hematology, Sasebo City General Hospital, Sasebo, Japan.,Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan
| | - Takeshi Sugio
- Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan
| | - Kohta Miyawaki
- Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan
| | | | | | - Tetsuya Eto
- Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
| | - Yoshitaka Imaizumi
- Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan
| | - Koji Kato
- Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan
| | - Koji Nagafuji
- Department of Hematology, Kurume University, School of Medicine, Kurume, Japan
| | - Koichi Akashi
- Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan
| | - Masao Seto
- Department of Pathology, Kurume University, School of Medicine, Kurume, Japan
| | - Takanori Teshima
- Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Koichi Ohshima
- Department of Pathology, Kurume University, School of Medicine, Kurume, Japan
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10
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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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11
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Chen YY, Huang CE, Liang FW, Lu CH, Chen PT, Lee KD, Chen CC. Prognostic impact of hepatitis C virus infection in patients with diffuse large B-cell lymphoma treated with immunochemotherapy in the context of a novel prognostic index. Cancer Epidemiol 2015; 39:382-7. [PMID: 25899771 DOI: 10.1016/j.canep.2015.04.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2014] [Revised: 03/27/2015] [Accepted: 04/05/2015] [Indexed: 01/08/2023]
Abstract
OBJECTIVE Patients with hepatitis C virus (HCV) infection have been associated with development of diffuse large B-cell lymphoma (DLBCL), yet its impact on several clinical aspects, including phenotypic characteristics and treatment-related toxicities as well as survival outcome after rituximab-based immunochemotherapy, remains controversial. METHODS To elucidate the characteristics of HCV-positive DLBCL in the context of a new prognostic model, the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), we retrospectively analyzed DLBCL patients diagnosed and treated with immunochemotherapy at our institute during the last decade. RESULTS In all, HCV infection was identified in 22 (17.7%) of 124 DLBCL patients. Except for being more likely to present with an advanced stage of disease, patients with HCV infection were phenotypically indistinguishable from HCV-negative cases. Multivariate analysis showed 3 factors independently predicted a dismal overall survival (OS) outcome: lower albumin level (<3 g/dL vs. ≥3 g/dL, p<0.001; HR=13.21, 95% CI=2.69-64.98, p=0.001), presence of HCV infection (vs. HCV-negative; HR=9.75, 95% CI=1.97-48.34, p=0.005), and poor NCCN-IPI risk (high-intermediate or high vs. low-intermediate or low; HR=5.56, 95% CI=1.17-26.55, p=0.031). CONCLUSIONS Our study has demonstrated that HCV infection status and low serum albumin level add important prognostic values to the newly proposed NCCN-IPI model for patients with DLBCL.
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Affiliation(s)
- Yi-Yang Chen
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Cih-En Huang
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Fu-Wen Liang
- Department of Public Health, College of Medicine National Cheng Kung University, Tainan, Taiwan
| | - Chang-Hsien Lu
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan
| | - Pin-Tsung Chen
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan
| | - Kuan-Der Lee
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan; College of Medicine, Chang Gung University, Tao-Yuan, Taiwan
| | - Chih-Cheng Chen
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
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12
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Michot JM, Canioni D, Driss H, Alric L, Cacoub P, Suarez F, Sibon D, Thieblemont C, Dupuis J, Terrier B, Feray C, Tilly H, Pol S, Leblond V, Settegrana C, Rabiega P, Barthe Y, Hendel-Chavez H, Nguyen-Khac F, Merle-Béral H, Berger F, Molina T, Charlotte F, Carrat F, Davi F, Hermine O, Besson C. Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B-cell non-Hodgkin lymphomas, ANRS HC-13 lympho-C study. Am J Hematol 2015; 90:197-203. [PMID: 25417909 DOI: 10.1002/ajh.23889] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2014] [Revised: 10/28/2014] [Accepted: 10/30/2014] [Indexed: 12/16/2022]
Abstract
Hepatitis C virus (HCV) infection increases the risk of B-cell non-Hodgkin lymphomas (B-NHL). Antiviral treatment (AT) can induce hematological responses in patients with marginal zone lymphomas (MZL). The ANRS HC-13 Lympho-C study aimed at a better understanding of the impact of AT on HCV associated B-NHL. This multicentric study enrolled 116 HCV-positive patients with B-NHL between 2006 and 2012. Cytological and histological samples were collected for centralized review. At lymphoma diagnosis, median age was 61 years and gender ratio M/F was 1. Cytohistological distribution was marginal zone lymphoma (MZL) n = 45 (39%), diffuse large B-cell lymphoma (DLBCL) n = 45 (39%), and other types n = 26 (22%). MZL patients had more frequent detection of rheumatoid factor (68% vs. 35%; P = 0.001) and more frequently mixed cryoglobulinemia (74% vs. 44%; P = 0.021) than patients with DLBCL. Among patients receiving AT, a sustained virologic response was achieved in 23 of 38 (61%) patients with MZL and in 9 of 17 (53%) with DLBCL (P = 0.42). Three-year overall survival (OS) and progression-free survival were 78% 95%CI [63-88] and 64% [48-76], respectively, without difference between cytohistological groups. Outcome analysis showed a favorable association between OS and AT in all patients (P = 0.05) and in the subgroup of MZL patients only (P = 0.04). Our data support that AT improves the outcomes of HCV-associated NHLs. The impact of new AT regimen with protease inhibitor needs to be investigated in this setting. [clinicalTrials.gov Identification number NCT01545544]
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Affiliation(s)
- Jean-Marie Michot
- Department of Internal Medicine and Clinical Immunology; Paris Sud University; AP-HP, Hôpital Bicêtre Le Kremlin-Bicêtre France
| | - Danielle Canioni
- Department of Pathology; Paris 5 Descartes University; AP-HP, Hôpital Necker Paris France
| | - Henda Driss
- Epidemiology of Infectious Diseases INSERM Unité 707; Paris 6 Pierre et Marie Curie University; Paris France
| | - Laurent Alric
- Department of Internal Medicine and Digestive Diseases; Toulouse 3 University; UMR 152 IRD, Hôpital Purpan Toulouse France
| | - Patrice Cacoub
- Department of Internal Medicine; APHP; Hôpital Pitié-Salpétrière; Paris 6 Pierre et Marie Curie University; UMR 7211, INSERM, UMR S 959, CNRS Paris France
| | - Felipe Suarez
- Department of Adult Hematology; Paris 5 Descartes University; AP-HP, Hôpital Necker Paris France
- Imagine Institute; Université Sorbonne Paris Cité; INSERM U 1163, CNRS ERL 8254 Paris France
| | - David Sibon
- Department of Adult Hematology; Paris 5 Descartes University; AP-HP, Hôpital Necker Paris France
- Imagine Institute; Université Sorbonne Paris Cité; INSERM U 1163, CNRS ERL 8254 Paris France
| | - Catherine Thieblemont
- Service d'hémato-oncologie; Université Paris Sorbonne P7; INSERM U728, AP-HP, Hôpital Saint-Louis Paris France
| | - Jehan Dupuis
- Department of Lymphoid Malignancies and Clinical Hematology; Paris 12 Est Créteil University; AP-HP, Hôpital Henri-Mondor Créteil France
| | - Benjamin Terrier
- Department of Internal Medicine; APHP; Hôpital Pitié-Salpétrière; Paris 6 Pierre et Marie Curie University; UMR 7211, INSERM, UMR S 959, CNRS Paris France
| | - Cyrille Feray
- Department of Hepatology; Nantes University; Hôpital de Nantes Nantes France
| | - Hervé Tilly
- Department of Hematology; Rouen University; Centre Henri Becquerel Rouen France
| | - Stanislas Pol
- Department of Hepatology; Paris 5 Descartes University; INSERM U-1016, AP-HP, Hôpital Cochin Paris France
| | - Véronique Leblond
- Department of Clinical Hematology; Paris 6 Pierre et Marie Curie University; AP-HP, Hôpital Pitié-Salpêtrière Paris France
| | - Catherine Settegrana
- Department of Biological Hematology and Cytogenetic; Paris 6 Pierre et Marie Curie University; AP-HP, Hôpital Pitié-Salpêtrière Paris France
| | - Pascaline Rabiega
- Epidemiology of Infectious Diseases INSERM Unité 707; Paris 6 Pierre et Marie Curie University; Paris France
| | - Yoann Barthe
- Epidemiology of Infectious Diseases INSERM Unité 707; Paris 6 Pierre et Marie Curie University; Paris France
| | - Houria Hendel-Chavez
- Department of Biological Immunology and Hematology; Paris 11 Sud University; AP-HP, Hôpital Bicêtre Le Kremlin-Bicêtre France
| | - Florence Nguyen-Khac
- Department of Biological Hematology and Cytogenetic; Paris 6 Pierre et Marie Curie University; AP-HP, Hôpital Pitié-Salpêtrière Paris France
| | - Hélène Merle-Béral
- Department of Biological Hematology and Cytogenetic; Paris 6 Pierre et Marie Curie University; AP-HP, Hôpital Pitié-Salpêtrière Paris France
| | - Françoise Berger
- Department of Pathology; Lyon Sud University, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud; Lyon France
| | - Thierry Molina
- Department of Pathology; Paris 5 Descartes University; AP-HP, Hôpital Necker Paris France
| | - Frédéric Charlotte
- Department of Pathology; Paris 6 Pierre et Marie Curie University; AP-HP, Hôpital Pitié-Salpêtrière Paris France
| | - Fabrice Carrat
- Epidemiology of Infectious Diseases INSERM Unité 707; Paris 6 Pierre et Marie Curie University; Paris France
| | - Frédéric Davi
- Department of Biological Hematology and Cytogenetic; Paris 6 Pierre et Marie Curie University; AP-HP, Hôpital Pitié-Salpêtrière Paris France
| | - Olivier Hermine
- Department of Adult Hematology; Paris 5 Descartes University; AP-HP, Hôpital Necker Paris France
- Imagine Institute; Université Sorbonne Paris Cité; INSERM U 1163, CNRS ERL 8254 Paris France
| | - Caroline Besson
- Department of Internal Medicine and Clinical Immunology; Paris Sud University; AP-HP, Hôpital Bicêtre Le Kremlin-Bicêtre France
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13
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Hepatitis C virus and lymphoma. Crit Rev Oncol Hematol 2014; 93:246-56. [PMID: 25457774 DOI: 10.1016/j.critrevonc.2014.10.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 08/19/2014] [Accepted: 10/14/2014] [Indexed: 12/16/2022] Open
Abstract
Hepatitis C virus (HCV) is a hepatotrophic and lymphotrophic virus and is a global health problem. Cirrhosis and hepatocellular cancer are the most common complications of HCV. Association between HCV and B cell non-Hodgkin lymphomas (B-NHL) has been shown in epidemiological studies in the last 20 years. High prevalence of HCV infection among patients with NHL has been reported in the early 1990s by Ferri in Italy and this association has been confirmed in later studies. Geographically, HCV related NHL is highly variable and chronic rather than cleared HCV infection is required for lymphomagenesis. Although anti-HCV antibody test is the most commonly used technique in epidemiological studies, HCV-RNA is more useful test to detect the association between HCV and NHL. The optimal management of HCV related NHL is not clear. However, anti-viral treatment may be sufficient for cases with low grade and/or asymptomatic lymphomas, while immuno-chemotherapy is necessary, in spite of probable hepatic toxicity, in cases with high grade lymphomas.
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14
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Visco C, Finotto S. Hepatitis C virus and diffuse large B-cell lymphoma: Pathogenesis, behavior and treatment. World J Gastroenterol 2014; 20:11054-11061. [PMID: 25170194 PMCID: PMC4145748 DOI: 10.3748/wjg.v20.i32.11054] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2013] [Revised: 02/25/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
A significant association between hepatitis C virus (HCV) infection and B-cell lymphoma has been reported by epidemiological studies, most of them describing a strong relationship between indolent lymphomas and HCV. Furthermore, the curative potential of antiviral therapy on HCV related indolent lymphomas supports a specific role for the virus in lymphomagenesis. These observations are reinforced by numerous laboratory experiments that led to several hypothetical models of B-cell transformation by HCV. Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype in the western countries, has been associated to HCV infection despite its aggressive nature. This association seems particularly prominent in some geographical areas. Clinical presentation of HCV-associated DLBCL has consistently been reported to differ from the HCV-negative counterpart. Nevertheless, histopathology, tolerance to standard-of-care chemo-immunotherapy (R-CHOP or CHOP-like regimens) and final outcome of HCV-positive DLBCL patients is still matter of debate. Addition of rituximab has been described to enhance viral replication but the probability of severe hepatic complications remains low, with some exceptions (i.e., hepatitis B virus or immune immunodeficiency virus co-infected patients, presence of grade > 2 transaminases elevation, cirrhosis or hepatocarcinoma). HCV viral load in this setting is not necessarily directly associated with liver damage. Overall, treatment of HCV associated DLBCL should be performed in an interdisciplinary approach with hepatologists and hematologists with close monitoring of liver function. Available reports reveal that the final outcome of HCV-positive DLBCL that receive standard immunochemotherapy is not inferior to their HCV-negative counterpart. This review summarizes data on epidemiology, pathogenesis and therapeutic approach on HCV-associated DLBCL. Several issues that are matter of debate like clinical management of patients with transaminase elevation, criteria for discontinuing or starting immuno-chemotherapy, as well as the exact role of monoclonal antibodies will be analyzed.
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MESH Headings
- Animals
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Antiviral Agents/therapeutic use
- Cell Transformation, Viral
- Drug Resistance, Neoplasm
- Hepacivirus/drug effects
- Hepacivirus/pathogenicity
- Hepatitis C/diagnosis
- Hepatitis C/drug therapy
- Hepatitis C/epidemiology
- Hepatitis C/virology
- Humans
- Lymphoma, Large B-Cell, Diffuse/diagnosis
- Lymphoma, Large B-Cell, Diffuse/drug therapy
- Lymphoma, Large B-Cell, Diffuse/epidemiology
- Lymphoma, Large B-Cell, Diffuse/virology
- Treatment Outcome
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15
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Rojas-Hernandez CM, Coleman JF, Czuchlewski DR, Fekrazad MH. Spontaneous regression of high grade primary gastric Lymphoma in an untreated viral hepatitis infection. Leuk Lymphoma 2014; 55:2643-5. [DOI: 10.3109/10428194.2014.887710] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- Cristhiam M. Rojas-Hernandez
- Internal Medicine/Hematology and Oncology, The University of New Mexico Health Sciences Center,
Albuquerque, NM, USA
| | | | | | - M. Houman Fekrazad
- Internal Medicine/Hematology and Oncology, The University of New Mexico Health Sciences Center,
Albuquerque, NM, USA
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16
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Barcelos MM, Santos-Silva MC. Molecular approach to diagnose BCR/ABL negative chronic myeloproliferative neoplasms. Rev Bras Hematol Hemoter 2012; 33:290-6. [PMID: 23049320 PMCID: PMC3415756 DOI: 10.5581/1516-8484.20110079] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2010] [Accepted: 04/01/2011] [Indexed: 01/01/2023] Open
Abstract
Chronic myeloproliferative neoplasms arise from clonal proliferation of hematopoietic stem cells. According to the World Health Organization myeloproliferative neoplasms are classified as: chronic myelogenous leukemia, polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic neutrophilic leukemia, chronic eosinophilic leukemia, hypereosinophilic syndrome, mast cell disease, and unclassifiable myeloproliferative neoplasms. In the revised 2008 WHO diagnostic criteria for myeloproliferative neoplasms, mutation screening for JAK2V617F is considered a major criterion for polycythemia vera diagnosis and also for essential thrombocythemia and primary myelofibrosis, the presence of this mutation represents a clonal marker. There are currently two hypotheses explaining the role of the JAK2V617F mutation in chronic myeloproliferative neoplasms. According to these theories, the mutation plays either a primary or secondary role in disease development. The discovery of the JAK2V617F mutation has been essential in understanding the genetic basis of chronic myeloproliferative neoplasms, providing some idea on how a single mutation can result in three different chronic myeloproliferative neoplasm phenotypes. But there are still some issues to be clarified. Thus, studies are still needed to determine specific molecular markers for each subtype of chronic myeloproliferative neoplasm.
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17
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Huh J. Epidemiologic overview of malignant lymphoma. THE KOREAN JOURNAL OF HEMATOLOGY 2012; 47:92-104. [PMID: 22783355 PMCID: PMC3389073 DOI: 10.5045/kjh.2012.47.2.92] [Citation(s) in RCA: 85] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2012] [Revised: 06/08/2012] [Accepted: 06/13/2012] [Indexed: 12/19/2022]
Abstract
Malignant lymphoma encompasses a wide variety of distinct disease entities. It is generally more common in developed countries and less common in developing countries. The East Asia region has one of the lowest incidence rates of malignant lymphoma. The incidence of malignant lymphoma around the world has been increasing at a rate of 3-4% over the last 4 decades, while some stabilization has been observed in developed countries in recent years. The reasons behind this lymphoma epidemic are poorly understood, although improving diagnostic accuracy, the recent AIDS epidemic, an aging world population and the increasing adoption of cancer-causing behaviors are suggested as contributing factors. Etiologies of malignant lymphoma include infectious agents, immunodeficiency, autoimmune disease, exposure to certain organic chemicals, and pharmaceuticals. The distribution of many subtypes exhibit marked geographic variations. Compared to the West, T/natural killer (NK) cell lymphomas (T/NK-cell lymphoma) and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are relatively more common, whereas other B-cell lymphomas, particularly follicular lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, are less common in Asia. Some subtypes of T/NK-cell lymphomas defined by Epstein-Barr virus association are predominantly Asian diseases, if not exclusively so. Both ethnic and environmental factors play roles in such diversity. In this review, we discuss the geographic distribution and etiology of malignant lymphoma, as well as the trend.
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Affiliation(s)
- Jooryung Huh
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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18
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Nooka A, Shenoy PJ, Sinha R, Lonial S, Flowers CR. Hepatitis C reactivation in patients who have diffuse large B-cell lymphoma treated with rituximab: a case report and review of literature. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2011; 11:379-84. [PMID: 21729690 DOI: 10.1016/j.clml.2011.04.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2011] [Revised: 03/17/2011] [Accepted: 04/08/2011] [Indexed: 01/27/2023]
Abstract
BACKGROUND Whether to interrupt or to continue induction therapy for lymphoma when hepatitis C virus (HCV) reactivation occurs during therapy with rituximab and chemotherapy remains a controversial question. There is limited evidence-based literature to help guide the management of patients with lymphoma in the setting of HCV reactivation. To address this issue we report an illustrative case and review the prevalence of non-Hodgkin lymphoma (NHL) in HCV-infected patients; the role of HCV in lymphomagenesis; the role of antiviral therapy in the management of HCV-associated lymphomas; as well as comparing the outcomes for NHL patients with and without HCV infection. CASE REPORT A patient diagnosed with diffuse large B-cell lymphoma was treated with rituximab and chemotherapy with the patient achieving a complete remission, but treatment was complicated by asymptomatic HCV reactivation. Because conflicting data exist regarding management of such cases, the criteria for discontinuing chemotherapy, in the event of escalation in HCV replication in an asymptomatic patient, remain unclear. CONCLUSION Patients with HCV have increased prevalence of marginal zone lymphoma, diffuse large B-cell lymphoma, and lymphoplasmacytic lymphoma. Whether HCV has a role in the lymphomagenesis is still uncertain, and limited to conjecture. The question whether to treat HCV-related lymphomas with antiviral therapy is debatable and not well-supported. Without initial liver dysfunction, HCV-infected patients can experience a similar outcome compared to their HCV-negative counterparts when treated with standard chemotherapy/immunotherapy despite differences in the presentation of the disease.
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Affiliation(s)
- Ajay Nooka
- Winship Cancer Institute-Hematology and Medical Oncology, Emory University-School of Medicine, Atlanta, GA, USA
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19
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Fazi C, Dagklis A, Cottini F, Scarfò L, Bertilaccio MTS, Finazzi R, Memoli M, Ghia P. Monoclonal B cell lymphocytosis in hepatitis C virus infected individuals. CYTOMETRY PART B-CLINICAL CYTOMETRY 2010; 78 Suppl 1:S61-8. [DOI: 10.1002/cyto.b.20545] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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20
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Diffuse Large B-Cell Lymphoma in a Hepatitis C Virus-Infected Patient Presenting With Lactic Acidosis and Hypoglycemia. Am J Med Sci 2010; 339:202-4. [DOI: 10.1097/maj.0b013e3181c3fdeb] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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