Background: Mixed cryoglobulinemia (MC) is an HCV-related lymphoproliferative disorder (LPD) that may evolve to lymphoma and be associated with invalidating symptoms. Antiviral therapy is the first therapeutic option, but limited data exist about the long-term outcome of patients achieving HCV eradication. This study was aimed at evaluating the long-term behavior of MC syndrome (MCS) in a large population of patients experiencing SVR after IFN-based treatment. Patients and Methods: The prospective study included 28 HCV+MCS resulting SVR (Group A); 13 HCV+ MCS resulting NR (Group B, differently treated during follow-up (f-u)) and 89 HCV+ patients without MC (Group C) resulting SVR, consecutively recruited from July, 2003 to November, 2008. The mean post-treatment f-u period was 31 months, ranging from 12 to 64 months. According to treatment exclusion criteria (see Dig Liver Dis. 2007; 39:2−17), none of the patients had very severe/life treating MCS before antiviral therapy. Patients clinical and biohumoral data were analyzed twice yearly. HCV occult infection (OI) in serum, liver and in both uncultured and mitogen-stimulated PBMC samples, was evaluated in SVR patients by PCR, TMA test and Real-time-PCR. The persistence of t(14;18)+B-cells was also evaluated by PCR. Results: Complete disappearance of any MC symptoms was observed in the majority (58%) of Group A patients and in none of Group B. In the remaining Group A patients, some milder MC symptoms persisted. In SVR patients OI was repeatedly shown in PBMC (mainly lymphocytes) from the 11% of SVR cases and was significantly associated with persisting MC symptoms and expansion of t(14;18)+B-cell clones. In only one clinically advanced case, previously unresponsive to other treatments, a complete – although clinically milder – MCS persisted in spite of no evidence of OI. Conclusions: These data show that viral eradication may lead to persisting resolution of MCS, being the only treatment able to induce MCS resolution. Furthermore, it could be hypothesized that, analogously with different LPDs, MC may evolve to progressive independence from the etiologic agent, thus suggesting the opportunity of early viral eradication. The key role played by lymphatic infection in the pathogenesis of MC is also hypothesized.
Long-term outcome of HCV-related mixed cryoglobulinemia in patients achieving sustained viral sustained viral response (SVR) after antiviral therapy
GRAGNANI, LAURA;
2010-01-01
Abstract
Background: Mixed cryoglobulinemia (MC) is an HCV-related lymphoproliferative disorder (LPD) that may evolve to lymphoma and be associated with invalidating symptoms. Antiviral therapy is the first therapeutic option, but limited data exist about the long-term outcome of patients achieving HCV eradication. This study was aimed at evaluating the long-term behavior of MC syndrome (MCS) in a large population of patients experiencing SVR after IFN-based treatment. Patients and Methods: The prospective study included 28 HCV+MCS resulting SVR (Group A); 13 HCV+ MCS resulting NR (Group B, differently treated during follow-up (f-u)) and 89 HCV+ patients without MC (Group C) resulting SVR, consecutively recruited from July, 2003 to November, 2008. The mean post-treatment f-u period was 31 months, ranging from 12 to 64 months. According to treatment exclusion criteria (see Dig Liver Dis. 2007; 39:2−17), none of the patients had very severe/life treating MCS before antiviral therapy. Patients clinical and biohumoral data were analyzed twice yearly. HCV occult infection (OI) in serum, liver and in both uncultured and mitogen-stimulated PBMC samples, was evaluated in SVR patients by PCR, TMA test and Real-time-PCR. The persistence of t(14;18)+B-cells was also evaluated by PCR. Results: Complete disappearance of any MC symptoms was observed in the majority (58%) of Group A patients and in none of Group B. In the remaining Group A patients, some milder MC symptoms persisted. In SVR patients OI was repeatedly shown in PBMC (mainly lymphocytes) from the 11% of SVR cases and was significantly associated with persisting MC symptoms and expansion of t(14;18)+B-cell clones. In only one clinically advanced case, previously unresponsive to other treatments, a complete – although clinically milder – MCS persisted in spite of no evidence of OI. Conclusions: These data show that viral eradication may lead to persisting resolution of MCS, being the only treatment able to induce MCS resolution. Furthermore, it could be hypothesized that, analogously with different LPDs, MC may evolve to progressive independence from the etiologic agent, thus suggesting the opportunity of early viral eradication. The key role played by lymphatic infection in the pathogenesis of MC is also hypothesized.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
