Combination therapy of sofosbuvir and ribavirin fails to clear chronic hepatitis E infection in a multivisceral transplanted patient

Schulz, Marten; Papp, C. Patrick; Bock, C.‐Thomas; Hofmann, Jörg; Gerlach, Undine; Maurer, Maik; Eurich, Dennis; Müller, Tobias

doi:10.1016/j.jhep.2019.03.029

Cited by 22 publications

(16 citation statements)

References 17 publications

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“…Nevertheless, its application in a clinical setting is inconclusive. While several studies have reported a successful treatment outcome of the combination of SOF + RBV in transplant recipients with chronic HEV infection, including one case of kidney and other of alloHSCT [61][62][63], others have not demonstrated its efficacy in this population [45,64,65]. Due to that, SOF seems to not add antiviral activity to RBV in vivo.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…However, no antiviral activity was observed in HEK293, U‐87MG and Huh7 cell lines 117 . Furthermore, clinical case studies with SOF in combination with RBV showed mixed results; some patients cleared HEV and some not 118‐120 . Recently, a multicenter HepNet pilot study was conducted in Europe to treat chronic hepatitis E with SOF only in those patients who did not respond to RBV treatment (Clinical trial.…”

Section: Treatment Optionsmentioning

confidence: 99%

Hepatitis E: An update on One Health and clinical medicine

Velavan

Pallerla

Johne

et al. 2021

Liver International

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The hepatitis E virus (HEV) is one of the main causes of acute hepatitis and the de facto global burden is underestimated. HEV‐related clinical complications are often undetected and are not considered in the differential diagnosis. Convincing findings from studies suggest that HEV is clinically relevant not only in developing countries but also in industrialized countries. Eight HEV genotypes (HEV‐1 to HEV‐8) with different human and animal hosts and other HEV‐related viruses are in circulation. Transmission routes vary by genotype and location, with large waterborne outbreaks in developing countries and zoonotic food‐borne infections in developed countries. An acute infection can be aggravated in pregnant women, organ transplant recipients, patients with pre‐existing liver disease and immunosuppressed patients. HEV during pregnancy affects the fetus and newborn with an increased risk of vertical transmission, preterm and stillbirth, neonatal jaundice and miscarriage. Hepatitis E is associated with extrahepatic manifestations that include neurological disorders such as neuralgic amyotrophy, Guillain‐Barré syndrome and encephalitis, renal injury and haematological disorders. The risk of transfusion‐transmitted HEV is increasingly recognized in Western countries where the risk may be because of a zoonosis. RNA testing of blood components is essential to determine the risk of transfusion‐transmitted HEV. There are currently no approved drugs or vaccines for HEV infections. This review focuses on updating the latest developments in zoonoses, screening and diagnostics, drugs in use and under development, and vaccines.

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“…In contrast, other studies demonstrated that sofosbuvir/ribavirin combination therapy was not able to provide sustained virologic response in chronic HEV infections observed in solid-organ transplant recipients and patients infected by the HIV[ 139 - 141 ]. Similarly, Schulz et al[ 142 ] reported that sustained virologic response could not be achieved with ribavirin and sofosbuvir combination in a multi-organ transplanted patient with chronic HEV3 infection. In the deep sequence analysis undertaken at three separate time points, a stepwise accumulation of four well-characterized ribavirin-associated resistance mutations ( K1383N , D1384N, V1479I , and G1634R ) was identified.…”

Section: Promising Treatment Options For Ribavirin-resistant Hev Infementioning

confidence: 99%

Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment

Aslan

Balaban

2020

WJG

119

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The hepatitis E virus (HEV) is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s. Globally, it is one of the most frequent causes of acute viral hepatitis. The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus. Among the eight different genotypes identified to date, HEV genotype 1 (HEV1), HEV2, HEV3, and HEV4 are the most frequent genotypes causing infections in humans. HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies. They are also responsible for severe hepatitis in pregnant patients and infants. In contrast, HEV3 and HEV4 are zoonotic, and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals. Their main reservoir is the pig, and they are mostly encountered in developed countries. The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women, infants, older people, immunocompromised individuals, patients with underlying chronic liver diseases, and workers that come into close contact with HEV-infected animals. In the clinical perspective, HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis, acute-on-chronic liver disease, chronic hepatitis, cirrhosis, and liver failure. Although HEV mainly results in acute self-limiting infection, chronic HEV infection may occur among immunocompromised patients ( e.g ., solid-organ transplant recipients). Additionally, HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade, although the causal link for many of them still needs to be proven. Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success. However, ribavirin is contraindicated in pregnant patients, and interferon-alpha cannot be used in most transplant recipients. Therefore, there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirin-resistant HEV. In this review article, a literature search using PubMed and MEDLINE databases was performed, up to March 2020. Only the articles published in English were reviewed.

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Combination therapy of sofosbuvir and ribavirin fails to clear chronic hepatitis E infection in a multivisceral transplanted patient

Cited by 22 publications

References 17 publications

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

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

Hepatitis E: An update on One Health and clinical medicine

Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment

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