Effect of hepatitis C virus infection on the risk of non‐Hodgkin's lymphoma: A meta‐analysis of epidemiological studies

Abstract

Although a high prevalence of hepatitis C virus (HCV) infection among non-Hodgkin's lymphoma (NHL) patients had been reported, subsequent epidemiological studies conducted to examine a causal association between HCV and NHL have provided inconsistent results across studies. A strikingly positive association has been reported primarily from Italy and Japan, while no association was found in other regions of the world. To clarify the association between HCV and NHL, we conducted a systematic literature review. Eligible study designs were nested casecontrol studies, population-based case-control studies, and hospital-based case-control studies using non-cancer subjects as controls. The studies published through January 1991 to August 2003 were searched through Medline. Ultimately, 23 studies with 4049 NHL patients and 1,813,480 controls were identified. Summary statistics were crude odds ratios (ORs) comparing the anti-HCV seropositive and seronegative subjects. As we identified heterogeneity between studies, summary statistics were calculated based on a random-effect model. We did not find any evidence of publication bias. The major sources of variation were the use of blood donor controls and year of publication. The summary OR for NHL was 5.70 (95% confidence interval (CI), 4.09-7.96, P < < < <0.001). The subgroup analysis by phenotype showed a similar trend for B-cell on-Hodgkin's lymphoma (NHL) is a set of malignant diseases arising from lymphoid tissues. As it is heterogeneous in terms of classification and has relatively low incidence, epidemiological studies regarding causative factors for NHL have not been satisfactorily conducted compared with other malignant diseases. However, several possible causative factors have been identified, including pesticides, blood transfusion, immunodeficiency, radiation, smoking and several types of diet, as summarized elsewhere.1) Among them, infectious agents, such as Helicobacter pylori, human T-cell leukemia virus (HTLV-I), and human immunodeficiency virus (HIV), are promising factors from the viewpoint of prevention.Hepatitis C virus (HCV) is a hepatotrophic virus contributing to the development of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Extrahepatic manifestations resulting from HCV, including lymphoproliferative syndromes such as type II mixed cryoglobulinemia (MC),2) have received increased attention. High prevalence of HCV infection among NHL patients was reported in the early 1990s, 3) suggesting a causal association between HCV and NHL. Subsequent epidemiological studies examined this potential association, but yielded inconsistent results across studies. The studies reporting a significantly positive association are from HCV endemic areas such as Italy and Japan, while other studies reporting no association come from non-endemic countries. 4)The aim of this study is to clarify the association between HCV infection and risk of NHL by means of a systematic review of the literature. Materials and MethodsSelection of studies. We used Medline to i...

The non-Hodgkin lymphomas: A review of the epidemiologic literature

“…The mean weighted prevalence of HCV in NHL cases from 48 studies that included a total of 5,542 patients was 13% (95% CI, 12-14%), with the highest proportions observed in Italy (20%) and Japan (14%). In a subsequent meta-analysis, Matsuo et al 581 identified 23 case-control studies that yielded a meta-OR of 5.70 (95% CI, 4.09-7.96) for HCV-seropositive patients compared to seronegative patients. Endemic country status (with HCV seroprevalence 2.5%) was not a major effect modifier of the overall association (meta-OR in endemic countries [Brazil, Japan, and Italy] 5 5.69, 95% CI, 3.85-8.42; meta-OR in nonendemic countries [Canada, France, Mexico, Saudi Arabia, Switzerland, Turkey and the US] 5 7.14, 95% CI, 4.…”

Hepatitis C virus and autoimmunity

“…Genetic susceptibility, toxicity and other environmental factors may play a role in the induction of autoimmunity by HCV (for example, concerning the prevalence of lymphomas, it is evident that a clear south-north gradient exists in part reflecting different HCV infection prevalence in the general population, therefore suggesting the contribution of environmental and/or genetic factors [6,7]). These factors influence the ability of the host to clear the virus or sustain humoral or cell-mediated immune responses and trigger autoimmunity [8].…”

“…The association between NHL and HCV infection has been examined in many retrospective case-control studies [7,65,66]. According to Monti et al [67] patients with MC have a 35 times higher risk of NHL than the general population.…”

Mixed cryoglobulinemia

“…Of interest, HCV-driven lymphoproliferation may explain the pathogenetic role of HCV infection also in 'idiopathic' B-cell lymphomas [11,59,64,65,80]. This association was firstly described in unselected Italian patients with 'idiopathic' B-cell lymphomas [64] and successively confirmed by different epidemiological and laboratory studies, mainly in the same geographical areas where HCV-associated MC is commonly found [65].…”

“…B-cell lymphoma is the most frequent neoplastic manifestation complicating MC, often as late manifestation of the MC syndrome [58][59][60][61][62][63][64][65]. This complication may be related to peripheral B-lymphocyte expansion and to lymphoid infiltrates observed in the liver and bone marrow of MC patients [19,39,58,59].…”