Hepatitis C virus and hepatitis B virus in indolent lymphomas: Prospective data from the international observational NF10 study

To the Editor, Hepatitis C virus (HCV) chronic infection has been unequivocally associated with a wide spectrum of B-cell lymphoproliferative disorders,1 ranging from mixed cryoglobulinaemia to overt B-cell non-Hodgkin lymphomas (B-NHL), including both indolent, especially marginal zone lymphomas (MZL), and aggressive subtypes, mainly diffuse large B-cell lymphomas (DLBCL).2, 3 HCV has been estimated as associated with up to 20% of B-NHL cases in Italy, 14% in Japan and 11% in the United States, while rates in the remaining European countries are lower (6%).4 Among indolent lymphomas, MZL are a group of indolent B-cell non-Hodgkin lymphomas characterized by their diverse clinical presentations and HCV-associated MZL represents an antigen-driven model of lymphomagenesis.5 However, HCV infection has also been associated with other indolent lymphomas6 and the prevalence of HCV infection cases varies widely across different geographical areas due to the specific epidemiology of the infection. In the last two decades, retrospective observations reported that antiviral therapy with either interferon-based or, more recently, interferon-free combinations is able to induce a significant rate of lymphoma regression in HCV-positive MZLs.7 A recent study from Fondazione Italiana Linfomi (FIL_BArT) prospectively investigated the use of direct-acting antivirals (DAAs) as primary treatment in patients with HCV-positive indolent lymphomas not requiring immediate conventional therapy.8 Hepatitis B virus (HBV) infection has been increasingly linked to various types of malignancies, including lymphomas.9 The association between HBV infection and NHL has been demonstrated for (Hepatitis B surface Antigen) HbsAg-positive patients, although patients with occult HBV infection have been shown to also be at high risk of NHL.10 Meta-analyses confirmed this association, regardless of the region and endemicity of HBV,11 even if only a few studies have analysed the characteristics of HBV-associated NHL in low-endemicity regions.12 The relationship between HBV and lymphoma is further complicated by the impact of immunosuppressive treatments, which are commonly used in the management of lymphoma. Immunosuppressive therapies, such as chemotherapy and monoclonal antibodies, can lead to viral reactivation in HBV carriers, resulting in acute liver failure and other serious complications.13 In patients with lymphoma and active HBV, antiviral treatment has been shown to reduce the risk of reactivation and improve outcomes. While previous studies have identified various prognostic factors, the influence of chronic infections such as HCV and HBV on disease progression remains poorly understood. This study aimed to evaluate the prevalence of HCV and HBV in MZL patients enrolled in the NF10 study (NCT02904577) and determine their impact on outcome (additional information reported in Material S1). Of 1340 patients enrolled, HCV serology was available for 1267 of which 768 MZLs (61%), divided into 327 extra-nodal MZL (43%), 255 splenic MZL (33%), 81 nodal MZL (11%) and 105 disseminated MZL (14%), and was positive in 6.6% ranging from 2.3% in small lymphocytic lymphoma (SLL) to 12.4% in nodal marginal zone lymphoma (NMZL) and in disseminated MZL. Forty-three per cent of patients in the cohort had age ≥70 years, 46% were females and 82% presented with stage III–IV. Age ≥ 70 years, female sex, absolute lymphocyte count (ALC)