Direct-acting antiviral agents for hepatitis C virus-mixed cryoglobulinaemia: dissociated virological and haematological responses.

The hepatitis C virus-positive (HCV+) mixed cryoglobulinaemia (MC) is associated with haematological alterations such as monoclonal B-cell lymphocytosis or non-Hodgkin lymphomas (NHLs). Antiviral therapy for MC, based on interferon and ribavirin, has been shown to be able to eliminate the viral replication as well as the B-cell monoclonal alterations. Many studies have reported the efficacy of direct-acting antivirals (DAAs) in the treatment of HCV+ MC. However, some authors noticed the persistence of haematological diseases despite HCV eradication. To verify the effects of DAAs on B-cell proliferation, we evaluated 67 patients with HCV+ MC. Six patients had an overt NHL and 30% had monoclonal B-lymphocytosis. In 20% of the patients, the mutation L265P of the myeloid differentiation factor 88 (MYD88) gene was detected in peripheral blood. All patients had negative HCV viraemia at week 12; one had a breakthrough, while two cases relapsed. A complete clinical response of vasculitis was seen in 60% of the patients. Among the six patients with NHL, one showed a complete response, whereas in the others there were no changes in the number and size of the nodes. Among the patients carrying a clonal population in peripheral blood, only 22% became negative. These data indicate that DAAs are not able to eliminate the clonal alterations induced by HCV in a large proportion of cases.

Long-term effects of the new direct antiviral agents (DAAs) therapy for HCV-related mixed cryoglobulinaemia without renal involvement: a multicentre open-label study.

OBJECTIVES: To investigate the long-term effects and safety of new direct anti-viral agents (DAAs) in patients with hepatitis C virus (HCV)-related mixed cryoglobulinaemia (MC) without renal involvement. METHODS: The study enrolled 22 consecutive patients, 19 received sofosbuvir-based regimen and three patients received other DAAs, individually tailored according to latest guidelines. As of December 2016, the median length of follow-up was 17 months (range 13-21). RESULTS: Extra-hepatic manifestations at enrollment were: purpura and arthralgia (12 cases), peripheral neuropathy (10 cases) and marginal zone B- lymphomas (2 cases). After a four-week DAA therapy, all patients became HCV- negative. Moreover, after 48 weeks since the beginning of DAA treatment, sustained regression of purpura and arthralgias was observed respectively in eight and in nine cases; peripheral neuropathy improved in seven cases, and cryocrit median values decreased from three (1-20) at baseline to two (1-12) after 48 weeks. Two cases with indolent marginal zone lymphomas did not show any haematological response: size and number of the involved nodes remained unchanged. In addition, the monoclonal B-cell population found in the peripheral blood in four cases did not disappear after recovery from HCV- RNA. Mild side effects occurred in nine patients, but six patients developed ribavirin-related anaemia requiring reduction of ribavirin dose. CONCLUSIONS: DAA therapy is safe and effective to eradicate HCV in MC, but seems associated with satisfactory clinical response in mild or moderate cryoglobulinaemic vasculitis and no response in B-NHL.