Identification, diagnosis and management of persistent Hepatitis E virus infection

Abstract

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the UK and leads to persistent HEV infection in immunosuppressed individuals. The prevalence and clinical outcomes of persistent HEV are unknown in the UK. It is hypothesized that persistent HEV is an under-recognised disease in the UK, that screening of high-risk immunocompromised patients will be cost-effective and enhanced surveillance of persistent HEV cases will identify pragmatic parameters for clinical monitoring. Within this study, the prevalence of HEV infection was investigated in three distinct immunocompromised cohorts. A commercial assay for detecting HEV antigen (HEV-Ag) was explored for use as a screening assay and monitoring tool. A cost-effectiveness analysis modelled the impact of annual HEV screening in solid organ transplant (SOT) recipients. The diagnostic findings and clinical outcomes were reported on a case series of persistent HEV infections across England and Wales and whole genome sequencing (WGS) was utilized to explore viral mutations with and without antiviral pressure. This work demonstrates that persistent HEV infections are under-recognised in transplant recipients, with biochemical abnormalities often attributed to other causes by clinicians. Viraemia rates were similar to other European studies among SOT recipients. HEV-Ag had both high sensitivity and specificity as a screening assay for persistent HEV infections. The annual screening of SOT recipients either by RNA or HEV-Ag testing is projected to be cost-effective for the NHS. The case series showed that a broad range of immunosuppressed patients are at risk of persistent infection, however the magnitude of risk in antibody-deficient patients and those with a haematological malignancy were lower than in SOT. Finally, WGS revealed the emergence of mutations in the RNA-dependent RNA polymerase region associated with clinical phenotypic resistance to ribavirin. However, further optimization of HEV sequencing is required to investigate samples with lower HEV viral loads.