Gastroenterology

Gastroenterology

Volume 125, Issue 6, December 2003, Pages 1723-1732
Gastroenterology

Clinical-liver, pancreas, and biliary tract
Prevalence of hepatitis C virus infection in B-cell non-Hodgkin’s lymphoma: systematic review and meta-analysis

https://doi.org/10.1053/j.gastro.2003.09.025Get rights and content

Abstract

Background & Aims: The aim of our study was to conduct a systematic review of studies evaluating prevalence of hepatitis C virus (HCV) infection in B-cell non-Hodgkin’s lymphoma (B-NHL) and to perform a meta-analysis of case-control studies comparing this prevalence with that of a reference group.Methods: Data sources: Electronic databases and the Cochrane Controlled Trials Register. Study selection: Studies evaluating prevalence of HCV infection in patients with B-NHL. Studies comparing HCV prevalence in B-NHL (cases) and in a reference group (controls) were included in the meta-analysis. Data extraction: Author/country, diagnostic method (serology/PCR), control type, matching/design, and VHC prevalence. Data synthesis: Prevalence of HCV infection and meta-analysis combining the odds ratios (OR).Results: Forty-eight studies (5542 patients) were identified. Mean HCV infection prevalence was 13% (95% CI: 12%–14%), which was higher in Italy (20%) and Japan (14%). Ten studies compared HCV prevalence in B-NHL (17%) and healthy controls (1.5%) (OR: 10.8; 95% CI: 7.4–16), results being homogeneous; OR increased up to 14.1 when only Italian studies were considered. Sixteen studies compared HCV prevalence in B-NHL (13%) and in other hematologic malignancies (2.9%) (OR: 4.2; 95% CI: 2.5–7), also with homogeneous results; OR increased up to 7.8 when subanalysis included only Italian studies.Conclusions: HCV prevalence in patients with B-NHL is approximately 15%, higher than that reported not only in general population (1.5%) but also in patients with other hematologic malignancies (2.9%), suggesting a role of HCV in the etiology of B-NHL. The striking geographic variation in this association suggests that genetic and/or environmental factors are also involved in the pathogenesis of this disorder.

Section snippets

Types of studies and participants

Studies evaluating the prevalence of HCV infection in patients with B-cell NHL were considered. Only case-control studies comparing the prevalence of HCV infection in patients with B-cell NHL and in respective controls were eligible for inclusion in the meta-analysis.

Types of outcome measures

The outcome considered in this review was “prevalence of HCV infection.”

Search strategy for identification of studies

Bibliographic searches were performed in MEDLINE (January 1966 to October 2002), EMBASE (January 1988 to October 2002), and CINAHL (January 1982 to October

Results

Eight studies identified with the search strategy were excluded from the calculations of this systematic review because they did not clearly separate the prevalence of HCV infection in patients with B-cell NHL and in other types of lymphomas, or they did not specify that B-cell was the only type of NHL included in the study.8, 9, 10, 11, 12, 13, 14, 15 One study with all patients having B-cell NHL complicating essential mixed cryoglobulinemia16 was excluded, and 7 studies with all patients

Discussion

HCV is a positive, single-strand RNA virus without a DNA intermediate in its replicative cycle so that integration of HCV nucleic-acid sequences into the host genome seems unlikely. Therefore, it cannot be considered a typical oncogenic virus, but it can exert its oncogenetic potential indirectly by contributing to the modulator effects of the host immune system.5, 6 It has been suggested that HCV could exert a chronic stimulus on the immune system, which facilitates the development and

Acknowledgements

The authors thank Brenda Ashley for assistance with the English.

References (85)

  • M.J Alter et al.

    The prevalence of hepatitis C virus infection in the United States, 1988 through 1994

    N Engl J Med

    (1999)
  • J.B Wong et al.

    Estimating future hepatitis C morbidity, mortality, and costs in the United States

    Am J Public Health

    (2000)
  • S.C Gumber et al.

    Hepatitis C: a multifaceted disease. Review of extrahepatic manifestations

    Ann Intern Med

    (1995)
  • L.R Pena et al.

    Hepatitis C virus infection and lymphoproliferative disorders

    Dig Dis Sci

    (2000)
  • C Ferri et al.

    Viruses and cancerspossible role of hepatitis C virus

    Eur J Clin Invest

    (1997)
  • F Silvestri et al.

    Hepatitis C virus-related lymphomas

    Br J Haematol

    (1997)
  • D Gasparotto et al.

    Hepatitis C virus, B-cell proliferation and lymphomas

    Leuk Lymphoma

    (2002)
  • L Cavanna et al.

    High prevalence of antibodies to hepatitis C virus in patients with lymphoproliferative disorders

    Haematologica

    (1995)
  • P Pioltelli et al.

    HCV and non-Hodgkin lymphoma

    Lancet

    (1996)
  • E Kocabas et al.

    Hepatitis B and C virus infections in Turkish children with cancer

    Eur J Epidemiol

    (1997)
  • A Timuraglu et al.

    Hepatitis C virus association with non-Hodgkin’s lymphoma

    Haematologia (Budap)

    (1999)
  • S Paydas et al.

    Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders in Southern Turkey

    Br J Cancer

    (1999)
  • C Udomsakdi-Auewarakul et al.

    Hepatitis C virus infection in patients with non-Hodgkin lymphoma in Thailand

    Blood

    (2000)
  • M Kuniyoshi et al.

    Prevalence of hepatitis B or C virus infections in patients with non-Hodgkin’s lymphoma

    J Gastroenterol Hepatol

    (2001)
  • K Visona et al.

    Impact of hepatitis B and hepatitis C virus infections in a hematology-oncology unit at a children’s hospital in Nicaragua, 1997 to 1999

    Clin Diagn Lab Immunol

    (2002)
  • C Ferri et al.

    Can type C hepatitis infection be complicated by malignant lymphoma?

    Lancet

    (1995)
  • M Luppi et al.

    Additional neoplasms and HCV infection in low-grade lymphoma of MALT type

    Br J Haematol

    (1996)
  • F Silvestri et al.

    Hepatitis C virus infection (and additional neoplasms) among marginal zone lymphomas

    Br J Haematol

    (1997)
  • V Ascoli et al.

    Extranodal lymphomas associated with hepatitis C virus infection

    Am J Clin Pathol

    (1998)
  • E.M Tkoub et al.

    Chronic hepatitis C virus and gastric MALT lymphoma

    Blood

    (1998)
  • D Vallisa et al.

    Association between hepatitis C virus and non-Hodgkin’s lymphoma, and effects of viral infection on histologic subtype and clinical course

    Am J Med

    (1999)
  • T Hiyama et al.

    Clinicopathological features of gastric mucosa-associated lymphoid tissue lymphomaa comparison with diffuse large B-cell lymphoma without a mucosa-associated lymphoid tissue lymphoma component

    J Gastroenterol Hepatol

    (2001)
  • C Ferri et al.

    Hepatitis C virus infection in patients with non-Hodgkin’s lymphoma

    Br J Haematol

    (1994)
  • C Mussini et al.

    Monoclonal gammopathies and hepatitis C virus infection

    Blood

    (1995)
  • M Luppi et al.

    Hepatitis C virus infection in subsets of neoplastic lymphoproliferations not associated with cryoglobulinemia

    Leukemia

    (1996)
  • F Silvestri et al.

    Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders

    Blood

    (1996)
  • P Musto et al.

    Hepatitis C virus infectiona new bridge between hematologists and gastroenterologists?

    Blood

    (1996)
  • C Mazzaro et al.

    Hepatitis C virus and non-Hodgkin’s lymphomas

    Br J Haematol

    (1996)
  • C Musolino et al.

    Evaluation of hepatitis B and C virus infections in patients with non-Hodgkin’s lymphoma and without liver disease

    Haematologica

    (1996)
  • F Silvestri et al.

    Hepatitis C virus infection among cryoglobulinemic and non-cryoglobulinemic B-cell non-Hodgkin’s lymphomas

    Haematologica

    (1997)
  • F Silvestri et al.

    The genotype of the hepatitis C virus in patients with HCV-related B cell non-Hodgkin’s lymphoma

    Leukemia

    (1997)
  • S De Vita et al.

    Characterization of overt B-cell lymphomas in patients with hepatitis C virus infection

    Blood

    (1997)
  • G De Rosa et al.

    High prevalence of hepatitis C virus infection in patients with B-cell lymphoproliferative disorders in Italy

    Am J Hematol

    (1997)
  • M Luppi et al.

    Clinico-pathological characterization of hepatitis C virus-related B-cell non-Hodgkin’s lymphomas without symptomatic cryoglobulinemia

    Ann Oncol

    (1998)
  • C Catassi et al.

    High prevalence of hepatitis C virus infection in patients with non-Hodgkin’s lymphoma at the onset. Preliminary results of an Italian multicenter study

    Recenti Prog Med

    (1998)
  • P Pioltelli et al.

    Hepatitis C virus in non-Hodgkin’s lymphoma. A reappraisal after a prospective case-control study of 300 patients. Lombart Study Group of HCV-Lymphoma

    Am J Hematol

    (2000)
  • M Montella et al.

    HCV and cancera case-control study in a high-endemic area

    Liver

    (2001)
  • M Montella et al.

    HCV and tumors correlated with immune systema case-control study in an area of hyperendemicity

    Leuk Res

    (2001)
  • T Izumi et al.

    B cell malignancy and hepatitis C virus infection

    Leukemia

    (1997)
  • M Yoshikawa et al.

    Prevalence of hepatitis C virus infection in patients with non-Hodgkin’s lymphoma and multiple myeloma. A report from Japan

    J Clin Gastroenterol

    (1997)
  • F Mizorogi et al.

    Hepatitis C virus infection in patients with B-cell non-Hodgkin’s lymphoma

    Intern Med

    (2000)
  • Y Imai et al.

    High prevalence of HCV infection in patients with B-cell non-Hodgkin’s lymphomacomparison with birth cohort- and sex-matched blood donors in a Japanese population

    Hepatology

    (2002)
  • Cited by (0)

    Supported in part by a Grant from the Instituto de Salud Carlos III (C03/02).

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