Low prevalence of chronic hepatitis C virus infection in B-cell non-Hodgkin's lymphoma patients from a population with a high prevalence of healthy Hepatitis c virus carriers

The hepatitis C virus (HCV) has recently been implicated in the pathogenesis of several B-cell lymphoproliferative disorders. In particular, anti-HCV antibodies and/or HCV RNA have been detected in most patients with type II mixed cryoglobulinaemia and in a large proportion of Italian patients with B-cell non-Hodgkin's lymphoma (NHL) (reviewed by Silvestri et al, 1996; Agnello, 1997; Ivanovski et al, 1998 ). Moreover, an asymptomatic monoclonal B-cell expansion has been demonstrated by molecular methods in ≈ 20% of Italian patients with HCV-associated chronic liver disease ( Franzin et al, 1995 ).

The high prevalence of chronic HCV infection among patients with B-cell NHL has been observed primarily in Mediterranean countries, particularly in Italy (9–32%), where the prevalence of HCV carriers in the general population is quite high and ranges from 1% to 5·4%. A recent US study investigating predominantly Hispanic patients also showed a significantly higher prevalence of HCV infection in NHL patients (22%) than in age-matched controls ( Zuckerman et al, 1997 ). However, other studies from the USA, Canada, Germany, the UK and France have not confirmed this association (reviewed by Germanidis et al, 1999 ). A possible explanation for this difference is the significantly lower prevalence of HCV infection in the general population of the latter countries.

To test this last possibility, we investigated the prevalence of HCV infection in B-cell NHL patients from the Republic of Macedonia, which is characterized by a relatively high prevalence of HCV carriers within the general population (2·0%). We tested 112 consecutive patients with NHL (93 Macedonian and 19 Albanian) and a control group of 137 patients with other B-cell malignancies (38 with Hodgkin's disease, 43 with chronic lymphocytic leukaemia, nine with acute lymphoblastic leukaemia, 26 with multiple myeloma and one with Waldenström's macroglobulinaemia). The diagnosis was based on histological and immunohistochemical analysis of a lymph node and/or bone marrow biopsy according to the Revised European–American Classification (REAL) of lymphoid neoplasms. The serum samples were tested for antibodies to HCV by third-generation enzyme-linked immunosorbent assay (ELISA) using commercially available kits and for HCV RNA by reverse transcriptase–polymerase chain reaction (RT–PCR) amplification of the 5′ untranslated region of HCV.

Table I summarizes the results for the different NHL subtypes and the controls. HCV infection was detected in only one patient with NHL (0·89%) and in one of the 137 patients with other B-cell malignancies (0·72%).

Thus, our study demonstrates a low prevalence of HCV infection in patients with B-cell NHL from Macedonia and a lack of association between the two disorders. The comparable prevalence of HCV infection in the general population of Macedonia with that in Italy indicates that HCV infection requires additional environmental factors and/or a distinct genetic background to induce a malignant B-cell disorder. The same appears to be true for the benign HCV-associated B-cell lymphoproliferations, such as type II mixed cryoglobulinaemia, and the asymptomatic monoclonal B-cell expansions; both disorders were recently found to be significantly less prevalent in Japanese than in Italian patients with HCV-positive chronic liver disease ( Pozzato et al, 1999 ). Therefore, it seems likely that HCV-associated lymphoproliferative disorders have a multifactorial aetiology, which includes additional, presently undetermined, genetic and environmental factors that may vary widely with geography.