Monitoring hepatitis E virus fecal shedding to optimize ribavirin treatment duration in chronically infected transplant patients

Marion, Olivier; Lhomme, Sébastien; Bello, Arnaud Del; Abravanel, Florence; Esposito, Laure; Hébral, Anne Laure; Lavayssière, Laurence; Cointault, Olivier; Ribes, David; Izopet, Jacques; Kamar, Nassim

doi:10.1016/j.jhep.2018.09.011

Cited by 31 publications

(33 citation statements)

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“…While some patients experience relapses or become unresponsive to ribavirin, approximately 80% of patients have a sustained virological response after a first course of ribavirin 8. We have shown that the persistence of HEV RNA only in the faeces of chronically infected patients at the end of ribavirin therapy is associated with a greater risk of HEV infection relapse 9 10. Our new data suggest that ribavirin does not completely inhibit HEV replication in polarised human enterocytes; it blocks the basal release of HEV virions but not their apical release.…”

Section: Discussionmentioning

confidence: 75%

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Hepatitis E virus replication in human intestinal cells

Marion

Lhomme

Nayrac

et al. 2019

Gut

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ObjectiveHepatitis E virus (HEV), one of the most common agent of acute hepatitis worldwide, is mainly transmitted enterically, via contaminated water for HEV genotypes 1 (HEV1) and HEV2, or by eating raw or undercooked infected meat for HEV genotype 3 (HEV3) and HEV4. However, little is known about how the ingested HEV reaches the liver or its ability to replicate in intestinal cells.DesignWe developed human primary cultures of small intestine epithelial cells and intestinal explants obtained from small bowel resections. The epithelial cells were also polarised on transwells. Cells were infected with Kernow-p6 strain or clinically derived virions.ResultsPrimary intestinal cells supported the growth of Kernow-p6 strain and HEV1 and HEV3 clinically derived virions. Polarised enterocytes infected with HEV1 and HEV3 strains released HEV particles vectorially: mostly into the apical compartment with a little basally. Iodixanol density gradient centrifugation of enterocyte-derived HEV virions gave bands at a density of 1.06–1.08 g/cm3, corresponding to that of quasi-enveloped HEV particles. Ribavirin therapy inhibited HEV excretion from the basal surface but not from the apical side of infected human enterocytes. HEV virions also infected intestinal tissue explants. Lastly, HEV RNA and antigen were detected in the intestinal crypts of a chronically infected patient.ConclusionHEV can replicate in intestinal cells and reaches the liver as quasi-enveloped virions.

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Section: Discussionmentioning

confidence: 75%

“…A 3-month course of ribavirin monotherapy is the treatment of choice if HEV replication persists 8. Protracted faecal shedding of HEV after ribavirin therapy is stopped is associated with infection relapse, suggesting that the GI tract is an HEV reservoir 9 10…”

Section: Introductionmentioning

confidence: 99%

Hepatitis E virus replication in human intestinal cells

Marion

Lhomme

Nayrac

et al. 2019

Gut

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“…They cite the 2019 publication on the importance of fecal hepatitis E PCR in determining clearance of chronic infection. (1) However, our patient initially received ribavirin in 2013, with his second course in 2015, and his final treatment with ribavirin and sofosbuvir occurring in 2017. It must be noted that it was only in 2017 that a PCR test for hepatitis E became commercially available in the United States, where our patient was treated.…”

Section: Replymentioning

confidence: 82%

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Drinane

2019

Hepatology

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“…The optimal duration of treatment has still to be determined. Treatment should be continued for a further three months if HEV RNA is detected in the stool at the end of the scheduled duration [184]. Thus, HEV RNA in the stools should be monitored before stopping therapy.…”

Section: Treatmentmentioning

confidence: 99%

Clinical Manifestations, Pathogenesis and Treatment of Hepatitis E Virus Infections

Lhomme

Marion

Abravanel

et al. 2020

JCM

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Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis throughout the world. Most infections are acute but they can become chronic in immunocompromised patients, such as solid organ transplant patients, patients with hematologic malignancy undergoing chemotherapy and those with a human immunodeficiency virus (HIV) infection. Extra-hepatic manifestations, especially neurological and renal diseases, have also been described. To date, four main genotypes of HEV (HEV1-4) were described. HEV1 and HEV2 only infect humans, while HEV3 and HEV4 can infect both humans and animals, like pigs, wild boar, deer and rabbits. The real epidemiology of HEV has been underestimated because most infections are asymptomatic. This review focuses on the recent advances in our understanding of the pathophysiology of acute HEV infections, including severe hepatitis in patients with pre-existing liver disease and pregnant women. It also examines the mechanisms leading to chronic infection in immunocompromised patients and extra-hepatic manifestations. Acute infections are usually self-limiting and do not require antiviral treatment. Conversely, a chronic HEV infection can be cleared by decreasing the dose of immunosuppressive drugs or by treating with ribavirin for 3 months. Nevertheless, new drugs are needed for those cases in which ribavirin treatment fails.

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Monitoring hepatitis E virus fecal shedding to optimize ribavirin treatment duration in chronically infected transplant patients

Cited by 31 publications

References 11 publications

Hepatitis E virus replication in human intestinal cells

Hepatitis E virus replication in human intestinal cells

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Clinical Manifestations, Pathogenesis and Treatment of Hepatitis E Virus Infections

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