Hepatitis E virus infection in the liver transplant recipients:Clinical presentation and management

Hepatitis E virus(HEV) is an emerging pathogen and an increasingly recognized cause of graft hepatitis, especially in the post-orthotopic liver transplantation immunocompromised population. The exact incidence and prevalence of HEV infection in this population remains unclear but is certainly greater than historical estimates. Identifying acute HEV infection in this population is imperative for choosing the right course of management as it is very difficult to distinguish histologically from acute rejection on liver biopsy. Current suggested approach to manage acute HEV involves modifying immunosuppression, especially discontinuing calcineurin inhibitors which are the preferred immunosuppressive agents post-orthotopic liver transplantation. The addition of ribavirin monotherapy has shown promising success rates in clearing HEV infection and is used commonly in reported cases.

An Analysis of Epidemiological Characteristics and the Clinical Features of 394 Cases of Sporadic Acute Hepatitis E in Southwest China from 2008 to 2010

Background and Aims Recently, epidemiology studies of hepatitis E in different areas are attracted more attention. Extensive studies of prevalent status and clinical manifestations could help us to broaden our knowledge, so as to excellently prevent and treat hepatitis E. The study analyzed the epidemiological characteristics and clinical features of 394 cases of sporadic acute hepatitis E(AHE) in Southwest of China from 2008 to 2010. Methods The clinical data of 394 cases with sporadic AHE in Southwest of China from 2008 to 2010 were reviewed.Results In the 394 cases with sporadic AHE, the ratio of male/female was 1.432∶1, and the mean age was(31.53 ± 18.12) years. Totally, 94(23.86%) patients aged under 18, 271(68.78%) patients aged between 18 and 60, and 29(7.36%) patients aged above 60. The incidence rate was significantly increased in summer(P = 0.000), especially in May(14.72%) and July(13.71%). In addition, the characteristics of occupation and ethnic group distribution were migrant laborers(106/394, 26.90%) and Han people(365/394, 92.64%). The length of stay, incidence of jaundice, the peak value of total bilirubin and alanine aminotransferase in male patients were all higher than those in female patients significantly(P < 0.05). The prolonged length of stay, decreased levels of ALT/ALB/CHE, increased levels of TBil, and increased incidence of jaundice and fatigue were associated with older age significantly(P < 0.05). The differences in peak values of total bilirubin(TBil), total bile acid(TBA), glutamyltransferase(GGT), cholinesterase(CHE) between AHE group and the groups of AHE accompanied respectively by chronic hepatitis B(CHB), acute alcoholic fatty liver(AFL), nonalcoholic fatty liver disease(NAFLD) were significant(P < 0.05). In addition, no significant difference was found in length of stay and biochemical indexes among anti-HEV-Ig G positive group, anti-HEV-Ig M positive group and antiHEV-Ig M/Ig G both positive group(P > 0.05).Conclusions Four epidemiological characteristics, including aged between 18 and 60, male, summer and migrant laborers, are found to be associated with acute hepatitis E. The prognosis of AHE in the majority of patients was favorable, but aged above 60 years and coexistence with CHB, AFL and NAFLD could be considerede as the factors inducing the infaust prognosis.

Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions

Hepatitis E virus(HEV)infection can cause severe complications and high mortality,particularly in pregnant women,organ transplant recipients,individuals with pre-existing liver disease and immunosuppressed patients.However,there are still unmet needs for treating chronic HEV infections.Herein,we screened a best-in-class drug repurposing library consisting of 262 drugs/compounds.Upon screening,we identified vidofludimus calcium and pyrazofurin as novel anti-HEV entities.Vidofludimus calcium is the next-generation dihydroorotate dehydrogenase(DHODH)inhibitor in the phase 3 pipeline to treat autoimmune diseases or SARS-CoV-2 infection.Pyrazofurin selectively targets uridine monophosphate synthetase(UMPS).Their anti-HEV effects were further investigated in a range of cell culture models and human liver organoids models with wild type HEV strains and ribavirin treatment failure-associated HEV strains.Encouragingly,both drugs exhibited a sizeable therapeutic window against HEV.For instance,the IC50 value of vidofludimus calcium is 4.6–7.6-fold lower than the current therapeutic doses in patients.Mechanistically,their anti-HEV mode of action depends on the blockage of pyrimidine synthesis.Notably,two drugs robustly inhibited ribavirin treatment failure-associated HEV mutants(Y1320H,G1634R).Their combination with IFN-αresulted in synergistic antiviral activity.In conclusion,we identified vidofludimus calcium and pyrazofurin as potent candidates for the treatment of HEV infections.Based on their antiviral potency,and also the favorable safety profile identified in clinical studies,our study supports the initiation of clinical studies to repurpose these drugs for treating chronic hepatitis E.