Diffuse Large B-Cell Lymphomas (DLBCL) with Hepatitis-C Virus (HCV) Infection: Incidence, Clinical Outcome and Preliminary Results of Antiviral Treatments (AVT) after Chemotherapy.
Authors: Musto Pellegrino , Luminari Stefano , De Renzo Amalia , Persico Marcello , Iannitto Emilio , Dell’Olio Matteo , Vallisa Daniele , Pozzi Samantha , Ferreri Andres , Angrilli Francesco , Mazza Patrizio , Quarta Giovanni , Guariglia Roberto , Barone Marialucia , Pietrantuono Giuseppe , D’Auria Fiorella , Perna Fabiana , Lamura Vincenzo , Pulsoni Alessandro , Marcucci Fabrizio , Mele Alfonso , Sacchi Stefano , Rotoli Bruno 
Published: October 2019

Abstract
A possible relationship between HCV and some sub-types of low-grade lymphomas (in particular, immunocytomas and nodal/extranodal marginal lymphomas) has been suggested. In these patients, AVT has shown to be effective in inducing neoplastic regression without chemotherapy (CT). In the present study we aimed to define epidemiological, clinical and therapeutic issues in DLBCL with concomitant HCV infection.
We evaluated the incidence of HCV infection in 881 consecutive Italian patients with DLBCL (676 of whom collected by GISL - Gruppo Italiano Studio Linfomi, and 205 by ISS - Istituto Superiore di Sanità), in whom HCV determination was available. We found that 105 out of them (11.9%) were HCV+ve.
We also looked at the clinical outcome of 61 patients, who had complete clinical and laboratory work-up and long term follow-up. With respect to a cohort of comparable historical controls without HCV infection, HCV+ve DLBCL showed older age (62 vs 48 years, p < 0.03), more frequently signs of liver damage (59% vs 8%, p < 0.001) and presence of monoclonal gammopathy (17% vs 3%, p < 0.05), increased rate of autoimmune disorders (19% vs 3 %, p < 0.02) and extranodal localizations (65.3% vs 35%, p < 0.04), including, in particular, liver, spleen, and other unusual sites (esophagous, vagina), often as primitive disease.
First line CT for HCV+ve DLBCL. mainly consisted of classic/modified CHOP+/−rituximab or PROMACE-CytaBOM regimens. Response rate (complete + partial remission) was not different, approaching 60% in both groups. Six-year overall survival (OS) was also similar (62% for HCV+ve and 65% for HCV−ve DLBCL, p 0.67). However, during the first two years, there was a worse trend for HCV+ve patients with increased ALT levels, high viral load (> 800.000 IU RNA viral copies) and evidence of active hepatitis or cirrhosis at liver biopsy.
Finally, we evaluated the possible role of AVT given after standard CT in HCV+ve DLBCL. Preliminary data available from 37 patients who have received at least three months of interferon (alpha or pegylated) +/− ribavirin in remission phase, indicate that such a sequential treatment is feasible, may induce complete virus clearance and may be associated with prolonged remission duration, without affecting, however, OS.
In conclusion, about 12% of Italian patients with DBLCL have concomitant HCV infection and show some distinctive clinical and biological characteristics. In absence of liver dysfunction, these subjects should receive standard treatments as their HCV−ve counterparts. Monitoring of viral load and liver biopsy appears also to be useful for an appropriate management. A sequence of standard CT followed by AVT is a feasible approach which warrants to be further investigated.