Hepatitis C infection is not associated with systemic HIV‐associated non‐hodgkin's lymphoma: A cohort study

Abstract

Immunosuppression induced by the human immunodeficiency virus (HIV) increases the risk of developing non-Hodgkin's lymphoma (NHL). As the hepatitis C virus (HCV) has been implicated in the development of B cell lymphomas, we compared the incidence of systemic NHL during HIV infection compared to HIV and HCV co-infection. Of 5,832 individuals studied during the era of highly active anti-retroviral therapy (HAART), 102 patients were diagnosed with systemic NHL. The incidence of systemic NHL was 6.9 of 10 4 patient years during HIV infection compared to 7.1 of 10 4 patient years during HIV alone (p ¼ 0.9). In this immunocompromised patient population, there was no association between HCV infection and an increased risk of lymphoma. ' 2005 Wiley-Liss, Inc.Key words: hepatitis C; HIV; non-Hodgkin's lymphomaThe use of HAART has resulted in marked declines in HIVrelated morbidity and mortality, by mainly reducing the incidence of opportunistic infections 1 High grade B-cell non-Hodgkin's lymphoma (NHL) is an AIDS defining illness, having first been described in association with HIV in the early 1980s. 2 NHL occurs at a greatly increased frequency in HIV-infected populations and despite a reduction in its incidence during the HAART era, it remains the second commonest AIDS defining malignancy after Kaposi's sarcoma. [3][4][5][6][7] Many of the 200 million individuals infected with HCV and the 50 million individuals infected with HIV are co-infected with both viruses. [8][9][10] As well as shared routes of transmission, there are many interactions between these small RNA viruses in which infection is often characterised by parenteral transmission followed by a seroconversion illness and then a long latent period lasting many years. 11 Once established, HIV-1 infection seems to increase the persistence of the hepatitis C virus, the level of HCV RNA and progression of HCV-related disease. [12][13][14][15][16] There are conflicting reports concerning whether HCV infection alters the course of HIV. 17 Some studies before the advent of highly active anti-retroviral therapy (HAART) suggested that survival and progression to AIDS were the same in patients with HCV/HIV co-infection as in those with HIV alone 18,19 whereas others suggested an adverse effect. 13,20 In the pre-HAART era, HCV infection was deemed an irrelevance as it was HIV that affected morbidity and mortality. With the increased life expectancy of individuals with HIV, however, HCV has emerged as a problem that adversely affects survival of individuals with HIV. 8,16,21 HCV is a well-established risk factor in the etiology of hepatocellular carcinomas and of mixed cryoglobulinemia Type II, a condition that can evolve to malignant lymphoma in 8-10% of affected cases. 22 In the non-HIV setting, data from case-case comparisons and case-control studies indicate several-fold higher prevalence of HCV infection (as indicated by the presence of antibodies or HCV RNA) among B cell lymphoma patients compared to control populations. 23 Attempts have been made to evaluate an...

Hepatitis C virus infection and risk of posttransplantation lymphoproliferative disorder among solid organ transplant recipients

“…Successful antiviral therapy to treat HCV has been shown to lead to regression of marginal zone lymphoma 29,30 and to eliminate t(14;18) translocation-positive B cells (the defining event of follicular lymphoma). 31 Although our finding that HCV is not an important risk factor for PTLD may seem surprising, it is consistent with the lack of association between HCV and lymphoma observed in persons with HIV/AIDS, [32][33][34][35][36][37] another immunosuppressed population. In the setting of solid organ transplantation, immunosuppression medications prevent graft rejection by suppressing T-cell function, 38 which can also result in uncontrolled proliferation of B-lymphocytes and development of PTLD.…”

Hepatitis C virus and non-Hodgkin's lymphoma: findings from the Swiss HIV Cohort Study

“…Our findings on HCV, the most studied hepatitis virus in respect to NHL risk (Dal Maso and Franceschi, in press), are consistent with previous studies of PHIV that also did not show an association (Besson et al, 1999;Levine et al, 1999;Waters et al, 2005). Compared to earlier reports on the topic, our study was, however, much larger, allowing stratification by, and more accurate allowance for, other correlates of NHL risk.…”

“…Some investigators also attempted to evaluate whether coinfection with HCV increased the risk of NHL among PHIV, but did not find any association (Besson et al, 1999;Levine et al, 1999;Engels et al, 2002;de Sanjosé et al, 2004;Waters et al, 2005). None of these studies, however, included more than 12 cases of NHL positive for both HIV and HCV (Besson et al, 1999;Levine et al, 1999;de Sanjosé et al, 2004;Waters et al, 2005).…”

Hepatitis C virus infection and non‐Hodgkin lymphoma: Interesting association or causal relationship?

“…The HCV-NHL association is generally coherent with what is known about the development of NHL. However, we note a striking absence of association between HCV and NHL among people infected with human immunodeficiency virus [25][26][27] and transplant patients, 28 two groups with very high NHL risk. If HCV causes NHL, the absence of an association in these immunosuppressed populations is somewhat surprising.…”