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Clinical Sciences |

Hepatitis C Virus Infection in Ocular Adnexal Lymphomas FREE

Diego Strianese, MD, PhD; Fausto Tranfa, MD; Marialuisa Finelli, MD, PhD; Amalia De Renzo, MD; Stefania Staibano, MD; Roberta Schiemer, MD; Domenico Cardone, MD; Roberto Pacelli, MD; Fabiana Perna, MD; Massimo Mascolo, MD; Gaetano De Rosa, MD; Giulio Bonavolontà, MD
[+] Author Affiliations

Author Affiliations: Department of Ophthalmological Sciences (Drs Strianese, Tranfa, Finelli, Schiemer, Cardone, and Bonavolontà), Pathology Section, Department of Biomorphological and Functional Sciences (Drs Staibano, Mascolo, and De Rosa), and Departments of Diagnostic Imaging and Radiation Oncology (Dr Pacelli) and Haematology (Drs De Renzo and Perna), University of Naples Federico II, Naples, Italy.


Arch Ophthalmol. 2010;128(10):1295-1299. doi:10.1001/archophthalmol.2010.233.
Text Size: A A A
Published online

Objective  To assess the influence of hepatitis C virus (HCV) infection on disease appearance and outcome of ocular adnexal non-Hodgkin lymphoma (ONHL).

Design  Retrospective comparative study (from January 1, 1992, through December 31, 2006).

Methods  The medical records of 129 patients with ONHL were retrospectively reviewed. All the patients were tested serologically for the presence of HCV infection. Patients were divided into 2 groups according to the presence or absence of HCV infection.

Main Outcome Measures  Prevalence of HCV infection, staging to evaluate the extent of disease at the onset, and clinical outcome data on overall and disease-free survival.

Results  The prevalence of HCV infection among the patients with ONHL was 17.8%. Seropositivity for HCV infection was significantly associated with extraorbital lymphoma at the onset (P = .006). High prevalence of mucosa-associated lymphoid tissue disease (79.8%) was registered. Protocol therapy included radiotherapy and chemotherapy, depending on the stage of the disease. Complete remission was achieved in 99 patients (76.7%). A total of 23.6% of patients with HCV-seronegative status and 21.7% of those with HCV-seropositive status experienced relapse of the lymphomatous disease. No significant differences in the 5-year overall survival and disease-free survival between the 2 groups were observed.

Conclusions  Prevalence of HCV infection in patients with ONHL is a relevant issue, accounting for 17.8% of the examined patients. Infection with HCV may influence the initial appearance of ONHL because it is associated with more widespread disease at the onset. However, the overall and disease-free survival of the infected patients are not statistically different than that of patients who are not infected.

Figures in this Article

Hepatitis C virus (HCV) represents a viral pandemic and is well known as the causative agent of chronic viral hepatitis, which has been linked to the development of hepatocellular carcinoma.1 Hepatitis C virus is a hepatotropic virus that can also replicate in lymphoid cells. The virus has been shown to sustain clonal expansion of B lymphocytes in patients with HCV infection.2 This observation raised the question of whether HCV is a lymphomagenic virus and has led to evaluation of the potential role of HCV infection within B-cell non-Hodgkin lymphoma, as well as other hematologic malignant neoplasms.36 A pathogenic link between HCV and non-Hodgkin lymphoma (NHL), mostly marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT), has been suggested.310 In contrast, other authors1113 have not confirmed such an association.

Ocular adnexal non-Hodgkin lymphoma (ONHL) (eg, conjunctiva, lachrymal gland, and orbital soft tissue) is one of the most common forms of extranodal lymphomas and usually displays limited stages of disease, an indolent clinical course, and a tendency to remain localized for several years.14 Only 1 study10 shows a positive association between HCV infection and the development of ONHL. The authors of this previous article state that HCV infection concomitant to ONHL is associated with more disseminated disease at the diagnosis and with poor prognosis. The current study aims to assess whether HCV infection plays a role in determining the clinical features of HCV-seropositive orbital lymphomas, especially regarding the prognosis.

STUDY GROUP

A retrospective study of a series of 129 patients with orbital ONHL, who had been referred from January 1, 1992, through December 31, 2006, to the Orbital Unit of the University of Naples Federico II, was performed. The patients included in this study had the onset symptom of orbital localization of ONHL. Data concerning age, sex, mass localization, and follow-up were available for all the examined patients. All the patients had a diagnosis of orbital lymphoma based on pathologic examination of an incisional biopsy specimen. The patients with ONHL diagnosed according to the previous classification for NHL (Working Formulation classification) were reclassified according to the latest criteria of the World Health Organization classification15 by pathologic reevaluation with additional immunochemical examinations.

The staging workup consisted of physical examination, biochemical blood profile, total-body computed tomography, and bone marrow biopsy. In patients with conditions diagnosed after 2002, positron emission tomography was also performed.

Each patient underwent tests for antibodies to HCV assayed by a second-generation enzyme-linked immunoassay (HCV RNA qualitative reverse-transcriptase polymerase chain reaction standardized method) and determination of HCV genotype. Furthermore, we analyzed the presence of chronic hepatic disease. The patients who had HCV-seropositive status underwent liver biopsy with the aim of evaluating the hepatic disease associated with the viral infection. The chronic liver disease was classified according to criteria developed by Ishak et al.16

First-line treatment consisted of radiotherapy, in proportions of 1.8 or 2.0 Gy, 5 times per week, with total doses ranging from 34.2 to 50.0 Gy, when the disease was localized at the only orbit. When the lymphomatous disease appeared to be disseminated, according to the staging, a conventional protocol therapy based on cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP) chemotherapy or a CHOP-like scheme was administrated. In selected patients whose conditions were diagnosed after 2002, rituximab was added.

After antineoplastic treatment, 6 patients with HCV-seropositive status who had ONHL were treated with interferon alfa (3 000 000 units 3 times a week for 12 months) subcutaneously. They were also given ribavirin, 1000 mg/d, orally.

All patients were followed up every 3 months with clinical evaluation and laboratory tests. They were also followed up every 6 months with ultrasonography and computed tomography (with positron emission tomography and computed tomography after 2002).

STATISTICAL ANALYSIS

Clinical characteristics and disease extent at onset of the HCV-seropositive and HCV-seronegative groups were verified with the χ2 test and t test for nominal and continuous clinical variables, respectively. Cumulative risk for relapse of ONHL (ie, disease-free survival) or death (ie, overall survival) during the follow-up was assessed by Kaplan-Meier curves, and a comparison between HCV-seropositive and HCV-seronegative patients with NHL was performed with the log-rank test.

Overall survival was calculated starting from the date of pathologic diagnosis to death or to the latest date of follow-up visit, whereas time to progression and disease-free survival were calculated from first day of treatment to relapse, time to progression and time of death, or the latest date of follow-up visit.

The follow-up varied from a minimum of 12 months to a maximum of 185 months, with an average of 75 months. The frequency of the different histologic types of ONHL is shown in Figure 1. The clinical characteristics of the 129 patients included in this study are summarized in Table 1. The median age of the patients was 62.88 years (range, 26-93 years), and the male to female ratio was 0.61.

Place holder to copy figure label and caption
Figure 1.

Comparison of the overall survival between the 2 groups of patients (hepatitis C virus [HCV] seropositive and seronegative) assessed by Kaplan-Meier curves (P = .79).

Graphic Jump Location
Table Graphic Jump LocationTable 1. Clinical Characteristics at Disease Onset

Twenty-three patients (17.8%) were infected with HCV. In all patients, the diagnosis of HCV infection preceded the diagnosis of lymphoma. All patients had HCV RNA detectable by polymerase chain reaction.

Mucosa-associated lymphoid tissue is the most frequent type of lymphoma, resulting in 79.8% of cases. A similar percentage was found among patients with HCV-seropositive status. No significant differences were found between the 2 groups in terms of distribution of the different histopathologic subtypes (Table 2). The histologic analysis of the hepatic tissue in the HCV-seropositive patients showed chronic active hepatitis in 6 patients (26.1%) and no signs of liver disease in the remaining 17 patients (73.9%). The apparent disease duration was calculated as the time passed by the first known risk of infection (eg, major or minor surgery, transfusion, tattooing, or intravenous drug abuse) to the time of the diagnosis of the orbital lymphoma. The average time was 22.6 years (SD, 13.9 years).

Table Graphic Jump LocationTable 2. Distribution of Different Disease Subtypes Between the 2 Groups of Patients

As reported in Table 1, the extent of the disease was significantly different between the 2 groups: 8 (34.8%) patients with HCV-seropositive status had stage IV disease at the diagnosis vs 11 (10.4%) patients with HCV-seronegative status. Infection with HCV was significantly associated with extraorbital disease at the onset (P = .006).

Radiotherapy treatment was administered in 108 patients (83.7%) as single-line therapy, whereas 21 patients (16.3%) were treated with a combination of radiotherapy and chemotherapy. The therapeutic outcome is summarized in Table 3. Ninety-nine patients (76.7%) achieved complete remission of the NHL. Thirty patients experienced relapse of the disease with extranodal localization: 25 (23.6%) of these patients had HCV-seronegative status and 5 patients (21.7%) had HCV-seropositive status (P = .99). The median time to disease progression was 57.6 and 55.0 months for the HCV-seronegative and HCV-seropositive groups, respectively. The 5-year overall survival and disease-free survival were not significantly different in the 2 groups (P = NS) (Figure 1 and Figure 2).

Place holder to copy figure label and caption
Figure 2.

Comparison of the progression-free survival between the 2 groups of patients (hepatitis C virus [HCV] seropositive and seronegative) assessed by Kaplan-Meier curves (P = .53).

Graphic Jump Location

The association between HCV infection and NHL has been postulated in several studies.110 This correlation has been mostly observed in countries such as Italy, the United States, and Japan.6,810 However, this issue remains controversial based on additional studies.12,17 In Italy a prevalence of HCV infection in NHL ranging from 15% to 30% has been reported.4,6

In the literature there are few studies10,12,13,18 that explore the association of HCV infection and ocular adnexal lymphomas (eg, conjunctiva, lachrymal gland, and orbital soft tissue), even though the ocular region is one of the most common sites of extranodal lymphomas. Ferreri and coworkers10 have shown clinical implications of HCV infection in MALT-type lymphoma of the ocular adnexa. Of 55 patients, 13% tested seropositive for HCV. The concomitant HCV infection was associated with more disseminated disease and aggressive behavior in ocular adnexal lymphoma. By contrast, in an Austrian study,12 only 2 of 45 patients (4%) had a concomitant HCV infection, and neither influence of HCV on clinical course nor risk of relapse was found. In a short report,13 performed in France, of 40 analyzed patients with ONHL, only 1 patient had HCV-seropositive status.

In the present study, the prevalence of HCV infection in the examined population with ONHL was 17.8%, similar to what has been reported in other Italian studies on patients from other districts with NHL localized in different sites.3,12 The variable worldwide prevalence of HCV together with different environmental and genetic factors could explain these contrasting results. In fact, the prevalence of HCV infection in Italy is high (3%-5%).5 For comparison, the role of Chlamydia psittaci in ocular adnexal lymphoma appears to be especially pronounced in Italy,19 whereas widely varying rates of infection could be found in different geographic regions.20

Recently, an increasing amount of biologic data have been found that support the role of HCV in lymphomagenesis.2123 It seems that the long-term antigenic stimulation provided by these agents may elicit host immune responses able to promote and sustain clonal B-cell expansion.3 A significant increase of NHL in patients with more than 15 years of HCV infection has been reported.6 In our study the median duration of HCV infection was 22 years, with 34.8% of patients with HCV-seropositive status having disseminated disease at onset and only 9.4% of patients with seronegative status having widespread disease at onset (P = .004) (Table 1). This finding supports the hypothesis that HCV infection allows spreading of the lymphoma, sustaining its clonal expansion. Although the HCV genome and its replicative intermediates have been detected in peripheral blood mononuclear cells and in lymphoid tissues of chronically infected patients,21 its role as a trigger agent of a frank B-cell neoplastic disorder is not clear yet.2123 In fact, because the virus lacks reverse transcriptase, it is unable to integrate into the host genome and to encode for any known oncogenesis. Considering this possible pathogenic mechanism, the need for analysis of the biopsied tissue for the presence of HCV is uneventful, as advocated by some authors.18

A history of liver disease may be considered a possible pathogenic factor on the progression of lymphoma staging in patients with HCV-seropositive status.4 However, only 6 of 23 patients in our cohort had an active viral liver disease. Considering these data, we were not able to state that liver disease gravity may have conditioned lymphoma staging in our group of patients.

Patients included in this study received radiotherapy alone or with adjuvant chemotherapy, depending on the stage of the disease. As we previously reported in primary NHL with different site distribution, the use of an appropriate therapeutic option also resulted in a favorable outcome for this subset of patients with extranodal lymphomas.5 The overall outcome resulted in a complete remission of NHL in 99 patients (76.7%). A total of 25 (23.6%) of the patients with HCV-seronegative status and 5 (21.7%) of those with HCV-seropositive status experienced relapse of the disease; however, we did not observe a statistically significant difference in the 5-year overall survival and disease free survival between the 2 groups (Tables 1 and 3 and Figures 1 and 2). It can be argued that the appropriate use of the protocol therapy based on a careful evaluation of the stage or extent of the disease can minimize the negative effect of HCV infection.

The results of this study were compared with those of the only previously published large Italian study10 in the PubMed database, to our knowledge, which concerned the positive link between HCV infection and ocular adnexal lymphoma. The authors of the other study similarly found that HCV infection is associated with a more aggressive clinical stage at the onset, but they conversely reported that patients with HCV-seropositive status had a poor prognosis over time compared with those with HCV-seronegative status. Possible explanations of the difference regarding the outcome between these reported data and our own data may be ascribed to differences in the first-line therapy choices.

In a study24 performed with a French population that demonstrated the link between HCV infection and the diffuse large cell lymphoma, the authors suggested that specific protocols, including antiviral therapy, should be designed for patients affected by lymphoma. Recent reports, attesting to the efficacy of antiviral treatment on the course of HCV-related B-cell NHL, strengthen the hypothesis of a link between HCV infection and B-cell lymphoma.25,26 The value of the antiviral therapy was ruled out by the statistical analysis of this study because of the paucity of patients with HCV-seropositive status treated. Nevertheless, the use of antiviral therapy may improve the outcome of patients infected with NHL, as we reported in a previous study.25

To summarize, HCV infection has a potential negative effect on patients infected with ocular lymphoma because it is associated with a more diffuse dissemination at the onset. Discrepancy with previous studies in terms of the incidence of HCV-seropositive cases among patients infected with ONHL may be explained by the geographic variations of this infection. Therefore, although an influence of HCV infection on lymphoma exists, the different prevalence can modify its role as a prognostic factor. Outcome seems to be slightly modified by the presence of this infection, probably because the effectiveness of the recent first-line treatment could minimize the influence of this risk factor. However, future studies will be necessary to better assess the influence of infectious agents and malignant neoplasms and the possible role of antiviral therapy. It must be considered that the data reported herein were collected in a single referral center.

Correspondence: Diego Strianese, MD, PhD, Department of Ophthalmological Sciences, University of Naples Federico II, Via Pansini 5, Naples 80131, Italy (strianes@unina.it).

Submitted for Publication: April 25, 2009; final revision received November 20, 2009; accepted November 28, 2009.

Financial Disclosure: None reported.

Saito  IMiyamura  TOhbayashi  A  et al.  Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc Natl Acad Sci U S A 1990;87 (17) 6547- 6549
PubMed
King  PDWilkes  JDDiaz-Arias  AA Hepatitis C virus infection in non-Hodgkin's lymphoma. Clin Lab Haematol 1998;20 (2) 107- 110
PubMed
Luppi  MGrazia Ferrari  MBonaccorsi  G  et al.  Hepatitis C virus infection in subsets of neoplastic lymphoproliferations not associated with cryoglobulinemia. Leukemia 1996;10 (2) 351- 355
PubMed
Gisbert  JPGarcía-Buey  LPajares  JMMoreno-Otero  R Prevalence of hepatitis C virus infection in B-cell non-Hodgkin's lymphoma: systematic review and meta-analysis. Gastroenterology 2003;125 (6) 1723- 1732
PubMed
De Renzo  APerna  FPersico  M  et al.  Excellent prognosis and prevalence of HCV infection of primary hepatic and splenic non-Hodgkin's lymphoma. Eur J Haematol 2008;81 (1) 51- 57
PubMed
Mele  APulsoni  ABianco  E  et al.  Hepatitis C virus and B-cell non-Hodgkin lymphomas: an Italian multicenter case-control study. Blood 2003;102 (3) 996- 999
PubMed
Duberg  A-SNordström  MTörner  A  et al.  Non-Hodgkin's lymphoma and other nonhepatic malignancies in Swedish patients with hepatitis C virus infection. Hepatology 2005;41 (3) 652- 659
PubMed
Takeshita  MSakai  HOkamura  S  et al.  Prevalence of hepatitis C virus infection in cases of B-cell lymphoma in Japan. Histopathology 2006;48 (2) 189- 198
PubMed
Morgensztern  DRosado  MSilva  O  et al.  Prevalence of hepatitis C infection in patients with non-Hodgkin's lymphoma in South Florida and review of the literature. Leuk Lymphoma 2004;45 (12) 2459- 2464
PubMed
Ferreri  AJMViale  EGuidoboni  M  et al.  Clinical implications of hepatitis C virus infection in MALT-type lymphoma of the ocular adnexa. Ann Oncol 2006;17 (5) 769- 772
PubMed
Grünberger  BWöhrer  SStreubel  B  et al.  Antibiotic treatment is not effective in patients infected with Helicobacter pylori suffering from extragastric MALT lymphoma. J Clin Oncol 2006;24 (9) 1370- 1375
PubMed
Gruenberger  BWoehrer  STroch  M  et al.  Assessment of the role of hepatitis C, Helicobacter pylori and autoimmunity in MALT lymphoma of the ocular adnexa in 45 Austrian patients. Acta Oncol 2008;47 (3) 355- 359
PubMed
Arnaud  PEscande  M-CLecuit  M  et al.  Hepatitis C virus infection and MALT-type ocular adnexal lymphoma. Ann Oncol 2007;18 (2) 400- 403
PubMed
Svoboda  JAndreadis  CDowns  LHMiller  WT  JrTsai  DESchuster  SJ Regression of advanced non-splenic marginal zone lymphoma after treatment of hepatitis C virus infection. Leuk Lymphoma 2005;46 (9) 1365- 1368
PubMed
Harris  NLJaffe  ESDiebold  J  et al.  World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 1999;17 (12) 3835- 3849
PubMed
Ishak  KBaptista  ABianchi  L  et al.  Histological grading and staging of chronic hepatitis. J Hepatol 1995;22 (6) 696- 699
PubMed
Besson  CCanioni  DLepage  E  et al. Groupe d’Etude des Lymphomes de l’Adulte Programs, Characteristics and outcome of diffuse large B-cell lymphoma in hepatitis C virus-positive patients in LNH 93 and LNH 98 Groupe d’Etude des Lymphomes de l’Adulte programs. J Clin Oncol 2006;24 (6) 953- 960
PubMed
Verma  VShen  DSieving  PCChan  CC The role of infectious agents in the etiology of ocular adnexal neoplasia. Surv Ophthalmol 2008;53 (4) 312- 331
PubMed
Ferreri  AJMGuidoboni  MPonzoni  M  et al.  Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst 2004;96 (8) 586- 594
PubMed
Chanudet  EZhou  YBacon  CM  et al.  Chlamydia psittaci is variably associated with ocular adnexal MALT lymphoma in different geographical regions. J Pathol 2006;209 (3) 344- 351
PubMed
Machida  KCheng  KT-NSung  VM-H  et al.  Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes. Proc Natl Acad Sci U S A 2004;101 (12) 4262- 4267
PubMed
Chan  CHHadlock  KGFoung  SKHLevy  S V(H)1-69 gene is preferentially used by hepatitis C virus-associated B cell lymphomas and by normal B cells responding to the E2 viral antigen. Blood 2001;97 (4) 1023- 1026
PubMed
Marasca  RVaccari  PLuppi  M  et al.  Immunoglobulin gene mutations and frequent use of VH1-69 and VH4-34 segments in hepatitis C virus-positive and hepatitis C virus-negative nodal marginal zone B-cell lymphoma. Am J Pathol 2001;159 (1) 253- 261
PubMed
Hermine  OLefrère  FBronowicki  JP  et al.  Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 2002;347 (2) 89- 94
PubMed
La Mura  VDe Renzo  APerna  F  et al.  Antiviral therapy after complete response to chemotherapy could be efficacious in HCV-positive non-Hodgkin's lymphoma. J Hepatol 2008;49 (4) 557- 563
PubMed
Vallisa  DBernuzzi  PArcaini  L  et al.  Role of anti-hepatitis C virus (HCV) treatment in HCV-related, low-grade, B-cell, non-Hodgkin's lymphoma: a multicenter Italian experience. J Clin Oncol 2005;23 (3) 468- 473
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Comparison of the overall survival between the 2 groups of patients (hepatitis C virus [HCV] seropositive and seronegative) assessed by Kaplan-Meier curves (P = .79).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Comparison of the progression-free survival between the 2 groups of patients (hepatitis C virus [HCV] seropositive and seronegative) assessed by Kaplan-Meier curves (P = .53).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Clinical Characteristics at Disease Onset
Table Graphic Jump LocationTable 2. Distribution of Different Disease Subtypes Between the 2 Groups of Patients

References

Saito  IMiyamura  TOhbayashi  A  et al.  Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc Natl Acad Sci U S A 1990;87 (17) 6547- 6549
PubMed
King  PDWilkes  JDDiaz-Arias  AA Hepatitis C virus infection in non-Hodgkin's lymphoma. Clin Lab Haematol 1998;20 (2) 107- 110
PubMed
Luppi  MGrazia Ferrari  MBonaccorsi  G  et al.  Hepatitis C virus infection in subsets of neoplastic lymphoproliferations not associated with cryoglobulinemia. Leukemia 1996;10 (2) 351- 355
PubMed
Gisbert  JPGarcía-Buey  LPajares  JMMoreno-Otero  R Prevalence of hepatitis C virus infection in B-cell non-Hodgkin's lymphoma: systematic review and meta-analysis. Gastroenterology 2003;125 (6) 1723- 1732
PubMed
De Renzo  APerna  FPersico  M  et al.  Excellent prognosis and prevalence of HCV infection of primary hepatic and splenic non-Hodgkin's lymphoma. Eur J Haematol 2008;81 (1) 51- 57
PubMed
Mele  APulsoni  ABianco  E  et al.  Hepatitis C virus and B-cell non-Hodgkin lymphomas: an Italian multicenter case-control study. Blood 2003;102 (3) 996- 999
PubMed
Duberg  A-SNordström  MTörner  A  et al.  Non-Hodgkin's lymphoma and other nonhepatic malignancies in Swedish patients with hepatitis C virus infection. Hepatology 2005;41 (3) 652- 659
PubMed
Takeshita  MSakai  HOkamura  S  et al.  Prevalence of hepatitis C virus infection in cases of B-cell lymphoma in Japan. Histopathology 2006;48 (2) 189- 198
PubMed
Morgensztern  DRosado  MSilva  O  et al.  Prevalence of hepatitis C infection in patients with non-Hodgkin's lymphoma in South Florida and review of the literature. Leuk Lymphoma 2004;45 (12) 2459- 2464
PubMed
Ferreri  AJMViale  EGuidoboni  M  et al.  Clinical implications of hepatitis C virus infection in MALT-type lymphoma of the ocular adnexa. Ann Oncol 2006;17 (5) 769- 772
PubMed
Grünberger  BWöhrer  SStreubel  B  et al.  Antibiotic treatment is not effective in patients infected with Helicobacter pylori suffering from extragastric MALT lymphoma. J Clin Oncol 2006;24 (9) 1370- 1375
PubMed
Gruenberger  BWoehrer  STroch  M  et al.  Assessment of the role of hepatitis C, Helicobacter pylori and autoimmunity in MALT lymphoma of the ocular adnexa in 45 Austrian patients. Acta Oncol 2008;47 (3) 355- 359
PubMed
Arnaud  PEscande  M-CLecuit  M  et al.  Hepatitis C virus infection and MALT-type ocular adnexal lymphoma. Ann Oncol 2007;18 (2) 400- 403
PubMed
Svoboda  JAndreadis  CDowns  LHMiller  WT  JrTsai  DESchuster  SJ Regression of advanced non-splenic marginal zone lymphoma after treatment of hepatitis C virus infection. Leuk Lymphoma 2005;46 (9) 1365- 1368
PubMed
Harris  NLJaffe  ESDiebold  J  et al.  World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 1999;17 (12) 3835- 3849
PubMed
Ishak  KBaptista  ABianchi  L  et al.  Histological grading and staging of chronic hepatitis. J Hepatol 1995;22 (6) 696- 699
PubMed
Besson  CCanioni  DLepage  E  et al. Groupe d’Etude des Lymphomes de l’Adulte Programs, Characteristics and outcome of diffuse large B-cell lymphoma in hepatitis C virus-positive patients in LNH 93 and LNH 98 Groupe d’Etude des Lymphomes de l’Adulte programs. J Clin Oncol 2006;24 (6) 953- 960
PubMed
Verma  VShen  DSieving  PCChan  CC The role of infectious agents in the etiology of ocular adnexal neoplasia. Surv Ophthalmol 2008;53 (4) 312- 331
PubMed
Ferreri  AJMGuidoboni  MPonzoni  M  et al.  Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst 2004;96 (8) 586- 594
PubMed
Chanudet  EZhou  YBacon  CM  et al.  Chlamydia psittaci is variably associated with ocular adnexal MALT lymphoma in different geographical regions. J Pathol 2006;209 (3) 344- 351
PubMed
Machida  KCheng  KT-NSung  VM-H  et al.  Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes. Proc Natl Acad Sci U S A 2004;101 (12) 4262- 4267
PubMed
Chan  CHHadlock  KGFoung  SKHLevy  S V(H)1-69 gene is preferentially used by hepatitis C virus-associated B cell lymphomas and by normal B cells responding to the E2 viral antigen. Blood 2001;97 (4) 1023- 1026
PubMed
Marasca  RVaccari  PLuppi  M  et al.  Immunoglobulin gene mutations and frequent use of VH1-69 and VH4-34 segments in hepatitis C virus-positive and hepatitis C virus-negative nodal marginal zone B-cell lymphoma. Am J Pathol 2001;159 (1) 253- 261
PubMed
Hermine  OLefrère  FBronowicki  JP  et al.  Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 2002;347 (2) 89- 94
PubMed
La Mura  VDe Renzo  APerna  F  et al.  Antiviral therapy after complete response to chemotherapy could be efficacious in HCV-positive non-Hodgkin's lymphoma. J Hepatol 2008;49 (4) 557- 563
PubMed
Vallisa  DBernuzzi  PArcaini  L  et al.  Role of anti-hepatitis C virus (HCV) treatment in HCV-related, low-grade, B-cell, non-Hodgkin's lymphoma: a multicenter Italian experience. J Clin Oncol 2005;23 (3) 468- 473
PubMed

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For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
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