Ribavirin Treatment Failure-Associated Mutation, Y1320H, in the RNA-Dependent RNA Polymerase of Genotype 3 Hepatitis E Virus (HEV) Enhances Virus Replication in a Rabbit HEV Infection Model

Wang, Bo; Mahsoub, Hassan M.; Li, Wen; Heffron, C. Lynn; Tian, Debin; Hassebroek, Anna; LeRoith, Tanya; Meng, Xiang‐Jin

doi:10.1128/mbio.03372-22

Cited by 7 publications

(7 citation statements)

References 68 publications

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“…S6C ). Consistent with previous studies ( Debing et al., 2014 , 2016 ; Wang et al., 2023 ), two single mutants exhibit significantly higher ratios of HEV-positive cells compared with wild type (WT). In contrast, the double mutant strain does not exhibit enhanced levels of HEV, probably due to the incompatibility of these two mutations.…”

Section: Resultssupporting

confidence: 91%

“…However, a proportion of patients either does not respond to treatment or remain viremic despite long-term ribavirin treatment ( Kamar et al., 2014 ). Moreover, ribavirin-associated mutations in HEV RNA polymerase may increase the replication capacity of HEV, thereby complicating the disease outcomes ( Debing et al., 2014 , 2016 ; Wang et al., 2023 ). Lastly, both PegIFN-α and ribavirin are contraindicated for use in pregnant women ( Kinast et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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

Guo,

Liu,

Liu

et al. 2024

Virologica Sinica

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Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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

Guo,

Liu,

Liu

et al. 2024

Virologica Sinica

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“… 37 Ribavirin treatment failure-associated mutation Y1320H in the RNA-dependent RNA polymerase of HEV gt 3 has been found to enhance virus replication in a rabbit HEV infection model. 38 The ability of ribavirin to induce HEV mutagenesis in treated patients has been reported. 37 The analysis of plasma HEV kinetic patterns in 41 SOT patients during ribavirin therapy demonstrated no association with response to therapy, with the exception of a flat-partial response.…”

Section: Hev In Solid Organ Transplant (Sot) Recipientsmentioning

confidence: 99%

Hepatitis E Virus (HEV) Infection Among Immunocompromised Individuals: A Brief Narrative Review

Alexandrova,

Tsachev,

Kirov

et al. 2024

IDR

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Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus that belongs to Hepeviridae family. HEV is the most common cause of acute viral hepatitis worldwide. According to the World Health Organization (WHO), there are estimated 20 million HEV infections worldwide every year, leading to estimated 3.3 million symptomatic cases of HEV infection. The WHO estimates that HEV infection caused approximately 44,000 deaths in 2015, which represents 3.3% of mortality rates due to viral hepatitis. In low-income (LI) countries and lower-middle-income (LMI) countries, HEV is a waterborne infection induced by HEV genotype (gt) 1 and HEV gt 2 that cause large outbreaks and affect young individuals with a high mortality rate in pregnant women from South Asian countries and patients with liver diseases. HEV gt 3, HEV gt 4, and HEV gt 7 are responsible for sporadic infections with zoonotic transmission mainly through the consumption of raw or undercooked meat from different animals. Acute HEV infection is relatively asymptomatic or mild clinical form, in rare cases the disease can be moderate/severe clinical forms and result in fulminant hepatitis or acute liver failure (ALF). Furthermore, HEV infection is associated with extrahepatic manifestations, including renal and neurological clinical signs and symptoms. Pregnant women, infants, older people, immunocompromised individuals, patients with comorbidities, and workers who come into close contact with HEV-infected animals are recognized as major risk groups for severe clinical form of HEV infection and fatal outcome. Chronic HEV infection can occur in immunocompromised individuals with the possibility of progression to cirrhosis.

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“…It was also recently shown that although RBV increases viral heterogeneity, RBV-induced metagenesis seems to be reversible after therapy is stopped [ 82 ]. Another study showed that an RBV-failure-associated mutation (Y1320H) in the RNA-dependent RNA polymerase of HEV genotype 3 enhanced viral replication in a rabbit HEV infection model [ 83 ]. A more precise investigation is needed to clarify the effect and the reason for failure of the RBV treatment.…”

Section: Chronic Hepatitis E (Che)mentioning

confidence: 99%

The Diagnosis, Pathophysiology, and Treatment of Chronic Hepatitis E Virus Infection—A Condition Affecting Immunocompromised Patients

Takakusagi¹,

Kakizaki

Takagi³

2023

Microorganisms

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Hepatitis E is a zoonosis caused by hepatitis E virus (HEV), which was first discovered 40 years ago. Twenty million HEV infections worldwide are estimated each year. Most hepatitis E cases are self-limiting acute hepatitis, but the virus has been recognized to cause chronic hepatitis. Following the first case report of chronic hepatitis E (CHE) in a transplant recipient, CHE has recently been identified as associated with chronic liver damage induced by HEV genotypes 3, 4, and 7—usually in immunocompromised patients such as transplant recipients. In addition, patients infected with HIV and those receiving chemotherapy for malignancy, along with patients with rheumatic disease and COVID-19, have recently been reported as having CHE. CHE can be easily misdiagnosed by usual diagnostic methods of antibody response, such as anti-HEV IgM or IgA, because of the low antibody response in the immunosuppressive condition. HEV RNA should be evaluated in these patients, and appropriate treatments—such as ribavirin—should be given to prevent progression to liver cirrhosis or liver failure. While still rare, cases of CHE in immunocompetent patients have been reported, and care must be taken not to overlook these instances. Herein, we conduct an overview of hepatitis E, including recent research developments and management of CHE, in order to improve our understanding of such cases. The early diagnosis and treatment of CHE should be performed to decrease instances of hepatitis-virus-related deaths around the world.

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Ribavirin Treatment Failure-Associated Mutation, Y1320H, in the RNA-Dependent RNA Polymerase of Genotype 3 Hepatitis E Virus (HEV) Enhances Virus Replication in a Rabbit HEV Infection Model

Abstract: HEV-3 causes chronic hepatitis E that requires antiviral therapy in immunosuppressed individuals. RBV is the main therapeutic option for chronic hepatitis E as an off-label use.

Cited by 7 publications

References 68 publications

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

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

Hepatitis E Virus (HEV) Infection Among Immunocompromised Individuals: A Brief Narrative Review

The Diagnosis, Pathophysiology, and Treatment of Chronic Hepatitis E Virus Infection—A Condition Affecting Immunocompromised Patients

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