Hepatitis B Virus-Related Cryoglobulinemic Vasculitis: Review of the Literature and Long-Term Follow-Up Analysis of 18 Patients Treated with Nucleos(t)ide Analogues from the Italian Study Group of Cryoglobulinemia (GISC)

Viruses. 2021 May 30;13(6):1032. doi: 10.3390/v13061032.


Hepatitis B virus (HBV) chronic infection causes progressive liver damage, although about 20% of patients develop extrahepatic manifestations such as cryoglobulinemic vasculitis (CV). Clinical manifestations range from mild to moderate (purpura, asthenia, arthralgia) to severe (leg ulcers, peripheral neuropathy, glomerulonephritis, non-Hodgkin lymphoma). A comprehensive review of therapeutic options for HBV-related CV is lacking. Nucleos(t)ide analogues (NA) suppress HBV replication in 90-100% of cases and induce clinical response in most patients with mild-to-moderate CV. Plasma exchange can be performed in patients with severe CV and should be considered in severe or life-threatening cases combined with high doses of corticosteroids and antiviral treatment. A cautious use of rituximab can be considered only in association with NA treatment in refractory cases. A review of the literature and an analysis of data collected by six centers of the Italian Group for the Study of Cryoglobulinemia on 18 HBV-CV nucleotide/nucleoside analogues (NAs)-treated patients were carried out.

Keywords: cryoglobulinemia; entecavir; hepatitis B virus; tenofovir; vasculitis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Combined Modality Therapy
  • Cryoglobulinemia / diagnosis
  • Cryoglobulinemia / etiology*
  • Cryoglobulinemia / therapy*
  • Disease Management
  • Disease Susceptibility
  • Female
  • Follow-Up Studies
  • Hepatitis B / complications*
  • Hepatitis B / virology
  • Hepatitis B virus*
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Nucleosides / analogs & derivatives
  • Nucleosides / therapeutic use
  • Phenotype
  • Treatment Outcome
  • Vasculitis / diagnosis
  • Vasculitis / etiology*
  • Vasculitis / therapy*


  • Nucleosides