Loss of Anti-Hepatitis E Virus Antibodies in Organ Transplant Patients with Hepatitis E

Hepatitis E virus is an important emerging pathogen producing a lethal impact on the pregnant population and immunocompromised patients. Starting in 1983, it has been described as the cause for acute hepatitis transmitted via the fecal–oral route. However, zoonotic and blood transfusion transmission of HEV have been reported in the past few decades, leading to the detailed research of HEV pathogenesis. The reason behind HEV being highly virulent to the pregnant population particularly during the third trimester, leading to maternal and fetal death, remains unknown. Various host factors (immunological, nutritional, hormonal) and viral factors have been studied to define the key determinants assisting HEV to be virulent in pregnant and immunocompromised patients. Similarly, chronic hepatitis is seen particularly in solid organ transplant patients, resulting in fatal conditions. This review describes recent advances in the immunopathophysiology of HEV infections in general, pregnant, and immunocompromised populations, and further elucidates the in vitro and in vivo models utilized to understand HEV pathogenesis.

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An Early Viral Response Predicts the Virological Response to Ribavirin in Hepatitis E Virus Organ Transplant Patients

Transplantation Journal ◽

10.1097/tp.0000000000000850 ◽

2015 ◽

Vol 99 (10) ◽

pp. 2124-2131 ◽

Cited By ~ 48

Author(s):

Nassim Kamar ◽

Sebastien Lhomme ◽

Florence Abravanel ◽

Olivier Cointault ◽

Laure Esposito ◽

...

Keyword(s):

Virological Response ◽

Hepatitis E Virus ◽

Organ Transplant ◽

Hepatitis E ◽

Viral Response ◽

Transplant Patients ◽

Early Viral Response

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Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02496-15 ◽

2015 ◽

Vol 60 (3) ◽

pp. 1608-1614 ◽

Cited By ~ 40

Author(s):

Sebastien Lhomme ◽

Nassim Kamar ◽

Florence Nicot ◽

Jacques Ducos ◽

Michael Bismuth ◽

...

Keyword(s):

Deep Sequencing ◽

Hepatitis E Virus ◽

Organ Transplant ◽

Hepatitis E ◽

Virologic Response ◽

Solid Organ Transplant ◽

Solid Organ ◽

Viral Response ◽

Transplant Patients ◽

Initial Decrease

Hepatitis E virus (HEV) can lead to chronic infection in solid-organ transplant patients. Ribavirin is efficient for treatment of chronically infected patients. Recently, the1634R mutation in the HEV polymerase has been associated with treatment failure. However, it is unclear if this mutation can be used as a prognostic marker of treatment outcome. We studied the prevalence of the 1634R mutation in the HEV polymerase of patients starting ribavirin therapy, the influence of the 1634R variants on the viral response, the frequency of the 1634R mutation in patients whose treatment failed, and its impact on ribavirin retreatment. We analyzed pretreatment samples from 63 solid-organ transplant patients with chronic hepatitis E using deep sequencing; 42 patients had a sustained virologic response (SVR), and 21 were non-SVR patients. We detected the 1634R variant by deep sequencing in 36.5% (23/63) of the patients (proportions, 1.3 to 100%). The 1634R variant was detected in 31.0% (13/42) of baseline plasma samples from patients with SVR and in 47.6% (10/21) in the other patients (P= 0.2). The presence of this mutation did not influence the initial decrease in viral RNA. Lastly, a second prolonged ribavirin treatment led to SVR in 70% of the patients who initially did not have SVR, despite the presence of the 1634R variant. We conclude that the presence of the 1634R variant at ribavirin initiation does not lead to absolute ribavirin resistance. Although its proportion increased in patients whose treatment failed, the presence of the 1634R variant did not compromise the response to a second ribavirin treatment.

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Plasma Hepatitis E Virus Kinetics in Solid Organ Transplant Patients Receiving Ribavirin

Viruses ◽

10.3390/v11070630 ◽

2019 ◽

Vol 11 (7) ◽

pp. 630 ◽

Cited By ~ 4

Author(s):

Sebastien Lhomme ◽

Swati DebRoy ◽

Nassim Kamar ◽

Florence Abravanel ◽

David Metsu ◽

...

Keyword(s):

Partial Response ◽

Half Life ◽

Hepatitis E Virus ◽

Organ Transplant ◽

Hepatitis E ◽

Solid Organ Transplant ◽

Response To Therapy ◽

Solid Organ ◽

Transplant Patients ◽

Viral Kinetic

Hepatitis E virus (HEV) infection causes chronic hepatitis in solid organ transplant (SOT) recipients. Antiviral therapy consists of three months of ribavirin, although response rates are not optimal. We characterized plasma HEV kinetic patterns in 41 SOT patients during ribavirin therapy. After a median pharmacological delay of three (range: 0–21) days, plasma HEV declined from a median baseline level of 6.12 (3.53–7.45) log copies/mL in four viral kinetic patterns: (i) monophasic (n = 18), (ii) biphasic (n = 13), (iii) triphasic (n = 8), and (iv) flat-partial response (n = 2). The mean plasma HEV half-life was estimated to be 2.0 ± 0.96 days. Twenty-five patients (61%) had a sustained virological response (SVR) 24 weeks after completion of therapy. Viral kinetic patterns (i)–(iii) were not associated with baseline characteristics or outcome of therapy. A flat-partial response was associated with treatment failure. All patients with a log concentration decrease of plasma HEV at day seven of >15% from baseline achieved SVR. In conclusion, viral kinetic modeling of plasma HEV under ribavirin therapy showed, for the first time, four distinct kinetic profiles, a median pharmacologic delay of three days, and an estimated HEV half-life of two days. Viral kinetic patterns were not associated with response to therapy, with the exception of a flat-partial response.

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Ribavirin as a First Treatment Approach for Hepatitis E Virus Infection in Transplant Recipient Patients

Microorganisms ◽

10.3390/microorganisms8010051 ◽

2019 ◽

Vol 8 (1) ◽

pp. 51 ◽

Cited By ~ 1

Author(s):

Antonio Rivero-Juarez ◽

Nicolau Vallejo ◽

Pedro Lopez-Lopez ◽

Ana Isabel Díaz-Mareque ◽

Mario Frias ◽

...

Keyword(s):

Hepatitis E Virus ◽

Treatment Approach ◽

Organ Transplant ◽

Hepatitis E ◽

Drug Dosage ◽

Viral Origin ◽

Off Label ◽

Transplant Patients ◽

Drug Of Choice ◽

Susceptible Populations

The hepatitis E virus (HEV) is the major cause of acute hepatitis of viral origin worldwide. Despite its usual course as an asymptomatic self-limited hepatitis, there are highly susceptible populations, such as those with underlying immunosuppression, which could develop chronic hepatitis. In this situation, implementation of therapy is mandatory in the sense to facilitate viral clearance. Currently, there are no specific drugs approved for HEV infection, but ribavirin (RBV), the drug of choice, is used for off-label treatment. Here, we present two cases of chronic HEV infection in transplant patients, reviewing and discussing the therapeutic approach available in the literature. The use of RBV for the treatment of an HEV infection in organ transplant patients seems to be effective. The recommendation of 12 weeks of therapy is adequate in terms of efficacy. Nevertheless, there are important issues that urgently need to be assessed, such as optimal duration of therapy and drug dosage.

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