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

Br J Haematol. 2020 Dec;191(5):775-783. doi: 10.1111/bjh.17036. Epub 2020 Aug 13.

Abstract

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.

Keywords: direct antiviral agents; hepatitis C virus; interferon; mixed cryoglobulinaemia; non-Hodgkin lymphoma; ribavirin.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Amino Acid Substitution
  • Antiviral Agents* / administration & dosage
  • Antiviral Agents* / adverse effects
  • Cryoglobulinemia* / blood
  • Cryoglobulinemia* / chemically induced
  • Cryoglobulinemia* / genetics
  • Female
  • Hepacivirus / genetics
  • Hepacivirus / metabolism*
  • Hepatitis C* / blood
  • Hepatitis C* / drug therapy
  • Hepatitis C* / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Myeloid Differentiation Factor 88* / blood
  • Myeloid Differentiation Factor 88* / genetics
  • Viremia / blood
  • Viremia / genetics

Substances

  • Antiviral Agents
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88