Hepatitis E virus-associated cryoglobulinemia in solid-organ-transplant recipients

Liver Int. 2018 Dec;38(12):2178-2189. doi: 10.1111/liv.13894. Epub 2018 Jun 14.


Background & aims: An association between hepatitis E virus (HEV) infection and cryoglobulinemia has been suggested. The aims of this study were to assess the prevalence of cryoglobulinemia during HEV infection in solid-organ-transplant (SOT) recipients, to describe its outcomes under ribavirin therapy and to evaluate its effects on kidney function and histology.

Methods: Between November 2005 and June 2016, 128 cases of HEV infection were diagnosed among SOT recipients followed in our institution. Cryoglobulinemia data obtained from 66 patients during acute-phase HEV and 51 patients during chronic-phase HEV were compared to a historical control group of 89 SOT recipients without HEV markers. Cryoglobulins were also monitored in a group of 43 patients treated by ribavirin.

Results: The prevalence of cryoglobulinemia was increased in HEV-infected SOT patients during a chronic phase (52.9%) compared to HEV-infected SOT patients at acute phase (36.4%) (P = .1) and to HEV-negative SOT patients (23.6%) (P < .001). HEV infection was identified as an independent predictive factor for cryoglobulinemia (OR 2.3, CI 95%: 1.17-4.55, P = .02). After ribavirin therapy and HEV clearance, the prevalence of cryoglobulin was significantly decreased from 53.5% to 20.9% (P = .003). Kidney function was significantly worse and proteinuria tended to be higher in chronically HEV-infected patients with cryoglobulinemia compared to those without cryoglobulinemia. Membranoproliferative glomerulonephritis was diagnosed in 2 patients, of which 1 had detectable cryoglobulinemia.

Conclusions: In conclusion, a relationship between HEV and cryoglobulin formation seems to exist. However, the clinical impact of cryoglobulinemia in SOT patients infected with HEV has to be confirmed.

Keywords: cryoglobulinemia; hepatitis E virus; ribavirin therapy; transplantation.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Cryoglobulinemia / virology*
  • Female
  • France
  • Hepatitis E / complications*
  • Hepatitis E / diagnosis
  • Hepatitis E / drug therapy
  • Humans
  • Immunocompromised Host
  • Kidney / physiopathology
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Ribavirin / therapeutic use
  • Transplant Recipients*


  • Antiviral Agents
  • Ribavirin