Hepatitis E virus (HEV)
infections are responsible for
chronic hepatitis in immunocompromised patients, and this can evolve to
cirrhosis. Like all RNA viruses, HEV exists as a mixture of heterogeneous viruses defining quasispecies. The relationship between the genetic heterogeneity described as a quasispecies,
cytokine secretion, and the outcome of acute
hepatitis in immunocompromised patients remains to be elucidated. We cloned and sequenced the region encoding the M and P capsid domains of HEV from eight solid-organ transplant (SOT) patients with acute HEV
infection who subsequently cleared the virus and from eight SOT patients whose
infection became chronic. We analyzed the
cytokines and
chemokines in the sera of these SOT patients by multianalyte profiling. The nucleotide sequence entropy and genetic distances were greater in patients whose
infections became chronic. A lower K(a)/K(s) ratio was associated with the persistence of HEV. The patients who developed
chronic infection had lower serum concentrations of
interleukin-1 (IL-1) receptor antagonist and soluble
IL-2 receptor. Increased concentrations of the
chemokines implicated in leukocyte recruitment to the liver were associated with
persistent infection. Those patients with chronic HEV
infection and progressing
liver fibrosis had less quasispecies diversification during the first year than patients without
liver fibrosis progression. Great quasispecies heterogeneity, a weak inflammatory response, and high serum concentrations of the
chemokines involved in leukocyte recruitment to the liver in the acute phase were associated with persistent HEV
infection. Slow quasispecies diversification during the first year was associated with rapidly developing
liver fibrosis.