Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma: A systematic review

Table 9 Characteristics of available systematic review and/or meta-analyses, reported in English, assessing the association between hepatitis C virus infection and lymphomas

First author/Country	Title	Number of studies considered	Main conclusion	Matching factors considered
Gisbert JP, 2003	Prevalence of hepatitis C virus infection in B-cell non-Hodgkin's lymphoma: systematic review and meta-analysis	23	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	Age, sex, smoking, race, when available
Matsuo K, 2004	Effect of hepatitis C virus infection on the risk of non-Hodgkin’s lymphoma: a meta-analysis of epidemiological studies	23	Strongly positive association between anti-HCV seropositive test subjects and risk of NHL. Individualists with anti-HCV positive test have approximately five times higher risk of NHL. This association is consistent regardless of the endemic status of HCV, as well as subgroup analysis for B-/T-NHL	Age and sex, when available
Negri E, 2004	B-cell non-Hodgkin’s lymphoma and hepatitis C virus infection: a systematic review	15	A high HCV prevalence in B-NHL was found in southern and eastern Europe, Japan and the southern United States, but not in central and northern Europe, Canada, northern United States, or a few Asian countries. The odds ratio of B-NHL for HCV infection was relatively weak, ranging from 2 to 4 in most studies. Thus, even if the observed association were causal, the percentage of cases of B-NHL attributable to HCV infection would be relatively low (10%) also in countries with a high prevalence of HCV infection in the general population, and extremely low in other countries	Age and sex, whether available
Dal Maso L, 2006	Hepatitis C Virus and Risk of Lymphoma and Other Lymphoid Neoplasms: A Meta-analysis of Epidemiologic Studies	18	The pooled relative risks (RR) were consistently increased for all major B-NHL subtypes, T-NHL, and primary sites of NHL presentation. The etiologic fraction of NHL attributable to HCV varies greatly by country, and may be upward of 10% in areas,where HCV prevalence is high .Associations weaker than with NHL were found between HCV infection and Hodgkin’s lymphoma	Age and sex, when available
de Sanjose S, 2008	Hepatitis C and non-Hodgkin lymphoma among 4784 cases and 6269 controls from the International Lymphoma Epidemiology Consortium	7	The results of the present study confirm the association between HCV infection and NHL and specific B-NHL subtypes (diffuse large B-cell lymphoma, marginal zone lymphoma and lymphoplasmacytic lymphoma). This research has sufficient statistical power to confirm these associations in populations with low HCV prevalence	Age, sex, county of residence, study site, geographic area, when available
Libra M, 2010	Extrahepatic disorders of HCV infection: A distinct entity of B-cell neoplasia?	18 Review of Italian studies	The results of the study confirm the association between HCV infection and NHL and specific B-NHL subtypes. The higher prevalence of anti-HCV Abs was observed among lymphoplasmacytoid/lymphoplasmacytic/immunocytoma histotype whereas the lowest was among small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). Overall, these studies strongly support the notion that HCV-associated lymphomas may be a distinct entity and further characterization of the mechanisms by which HCV infection contributes to B-cell NHL development may improve its diagnosis, classification and treatment	NR

HCV: Hepatitis C virus; NHL: Non-hodgkin-lymphoma.