Effects of depletion of B cell by anti-CD20 monoclonal antibody in HCV+ mixed cryoglobulinemia (MC) and liver cirrhosis

Background. Antiviral therapy is the first therapeutic option in HCV-related MC; however, patients are frequently excluded due to contraindications. The effectiveness of B-cell depletion by anti-CD20mAb (Rituximab) was described, but the possibility of an immunodepression-related increase in viral replication and ALT limits its use in cirrhosis. MC patients frequently have cirrhosis. Patients. 14 HCV+ patients (3males, mean age: 59yrs.) with invalidating MC and liver cirrhosis, who were excluded from antiviral therapy, were treated with Rituximab (4weekly infusions of 375 mg/m2) and followed-up for 6months. Results. Pre-treatment MC included, in addition to purpura, arthropathy, and weakness, sensory-motor polyneuropaty in 12, nephropathy in 2, and leg ulcers in 2 cases. Cirrhosis was class A in 10, class B in 3, and class C in 1 patient (Child-Pugh classification). Four patients showed ascitic decompensation. A consistent improvement of MC symptoms and biohumoral data was evident at the end-of-treatment (EOT) and end-of-follow-up (EOFU), with disappearance of purpura and leg ulcers and improvement/disappearance of weakness, arthralgias, polyneuropaty and nephropathy. Some modification in mean viral titres (2.6x106, 4.2x106 and 2.5x106 IU/mL at admission, EOT and EOFU, respectively) and in mean ALT values (54.9, 45,8 and 66.3IU/L) were observed. Improvement of liver protidosyntetic activity, protrombin time, ascites, portal hypertension, and encephalopathy was observed at EOT and EOFU, especially in advanced cases. The Child-Pugh score improved from C11 to B7, B8 to A6, B7 to A5 and B9 to B7 respectively in patients with Child-Pugh >A. In 2 patients, pre- and post-treatment transjugular liver biopsies showed disappearance of lymphocytic infiltration. Conclusions. This study confirms the effectiveness and safety of Rituximab in MC and, for the first time, shows its safety also in patients with advanced cirrhosis. Moreover, the Rituximab-related depletion of CD20+B-cells was followed by cirrhosis improvement in spite of a moderate and inconstant increase of both viraemia and ALT values. The mechanisms involved are unknown. Interesting working hypotheses may implicate a role played by direct B-cell hepatotoxicity with the contribution of B-cell infiltrates in conditioning liver damage. The improvement of Kuppfer cell function due to the cryocrit value reduction might also play a role.