A Decade of Chronic #Hepatitis E #Treatment: #Ribavirin Effectiveness, Safety, and the Association of Torque Teno Virus Load With Treatment Outcomes

 

Highlights

    • Ribavirin achieved 81% SVR in immunocompromised patients with chronic HEV.

    • Adverse events occurred in 56% and led to discontinuation in 17%.

    • Ribavirin dose reduction was associated with failure to achieve SVR.

    • Higher baseline HEV RNA levels were associated with non-SVR.

    • Baseline TTV load showed a nonsignificant trend toward higher levels in non-SVR patients.

Abstract

Background

Hepatitis E virus (HEV) affects immunocompromised individuals. Unlike immunocompetent hosts, who rarely develop chronic infection, up to two-thirds of immunocompromised patients progress to chronicity. Ribavirin is the recommended antiviral therapy, yet predictors of sustained virological response (SVR) remain unclear. Torque Teno Virus (TTV), a marker of immunosuppression, has been proposed as a potential predictor of viral clearance.

Objectives

We evaluated ribavirin treatment outcomes and adverse effects in immunocompromised patients with HEV infection, and assessed whether TTV load predicts SVR.

Study Design

A retrospective cohort study was conducted at the University Medical Center Groningen including solid organ transplant recipients (SOTR) and haematology patients treated with ribavirin for HEV infection between 2010 and 2022. Clinical data and stored serum samples were analysed to determine infection duration and TTV load at treatment initiation and after three months. TTV loads in treated patients were compared with TTV loads of transplant recipients who spontaneously cleared HEV.

Results

Fifty-two patients received ribavirin; 27 had confirmed chronic infection. SVR was achieved in 81% of chronic cases. Adverse events occurred in 56%, leading to dose reduction in 25% and discontinuation in 17%. Non-SVR was associated with ribavirin dose reduction, lower mean daily dose, higher baseline HEV RNA, and lower ALT. Baseline TTV load showed a nonsignificant trend toward higher levels in non-SVR patients. TTV loads did not differ between treated patients and spontaneous clearers.

Conclusions

Ribavirin is effective for chronic HEV, but treatment-limiting toxicity is common. Adequate dosing appears critical for achieving SVR. TTV load did not reliably predict treatment outcome, underscoring the need for further research into immunological and virological predictors of response.

Source: 

Link: https://doi.org/10.1016/j.jcv.2026.106003

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Synergistic #antiviral effect of #Asunaprevir and #Ribavirin in combination against Murray Valley #Encephalitis Virus replication

 

Highlights

    • Renilla luciferase-based MVEV sub-genomic replicon was constructed and applied in antiviral drug evaluation.

    • Removal of Stem Loop I from 3’UTR impairs viral genome replication.

    • Asunaprevir and ribavirin exhibit synergistic antiviral activity against MVEV.

    • A single-round MVEV infectious particle platform was developed.

Abstract

Murray Valley encephalitis virus (MVEV) is a mosquito-borne flavivirus known for causing severe neurological diseases in humans. Despite the rising number of reported infections and high mortality rate among hospitalized patients, no antiviral therapies or licensed vaccines are available. To strengthen preparedness against this reemerging virus, we establish a subgenomic replicon (SGR) platform and a complementary single-round infectious particles (SRIPs) production system, using widely circulating genotype 1 (G1) MVEV as backbone. Stem-loop I(SLI) from 3’UTR stands for the major difference among 4 MVEV genotypes and removal of SLI resulted in mild decrease of genome replication. Through screening a mini anti-flavivirus drug library, we identified that asunaprevir (ASV) and ribavirin (RBV) inhibit MVEV infection independently. Combination of ASV and RBV also showed synergistic activity against MVEV. These results underscore the value of the MVEV replicon system as a versatile tool for evaluating antiviral compounds, supporting the potential of ASV and RBV as a combinatorial therapeutic approach.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0166354226001567?via%3Dihub

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#Ribavirin post-exposure #prophylaxis for #Andes virus #exposure: a viewpoint

 

Summary

Andes virus (ANDV) is unique among hantaviruses because person-to-person transmission is possible. This raises questions on the relevance of post-exposure prophylaxis (PEP), particularly following high-risk household, healthcare-associated, or laboratory exposures, considering its high case fatality rate. Ribavirin has demonstrated antiviral activity against hantaviruses in vitro and in animal models, although clinical evidence supporting its use for ANDV remains extremely limited. This viewpoint summarises the currently available evidence regarding ribavirin as PEP after potential ANDV exposure. We discuss the knowledge gaps that may limit the applicability of ribavirin PEP, to make informed decisions on the use of ribavirin in the setting of PEP. Potential dosing strategies are visualised by modelling and simulation, and potential dose and duration are discussed. Although the biological rationale for ribavirin PEP appears compelling, absence of controlled human studies and potential toxicity currently limit its role to highly selected exposure scenarios and use shortly after exposure.

Source: 

Link: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(26)00270-7/fulltext

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First reported case of #Andes #hantavirus cardiopulmonary syndrome treated with a combination of #favipiravir, #ribavirin, icatibant and baricitinib

 

ABSTRACT

Objectives

To describe the first documented case of Andes virus (ANDV) hantavirus cardiopulmonary syndrome (HCPS) in Spain and the first worldwide use of a therapeutic regime including two antivirals (favipiravir and ribavirin) and two host-directed drugs (baricitinib and icatibant).

Methods

A 69-year-old Spanish man, repatriated following a multinational ANDV outbreak aboard a cruise ship, was managed in a high-level isolation unit. Diagnosis was established by RT-PCR and serology while he was still asymptomatic as part of protocol-driven screening. Under compassionate-use authorisation and written informed consent, the patient received ribavirin (initially intravenous, then switched to oral on day +4), oral favipiravir, subcutaneous icatibant, and oral baricitinib, with serial clinical, laboratory, and radiological monitoring.

Results

Hypoxaemia, bilateral B-lines, thrombocytopenia, lymphopenia, and hyponatraemia developed within 24 hours after diagnosis. The combination regimen was initiated on day 0, and baricitinib was added on day +1, coinciding with the need for high-flow nasal oxygen. Sustained clinical, laboratory, and radiological recovery occurred from day +2 onwards, without progression to invasive ventilation or vasopressors. Mild diarrhoea attributed to ribavirin led to its discontinuation on day +5, shortly after the IV-to-oral switch. Severe recurrent diarrhoea on day +8, attributed to favipiravir, prompted its withdrawal before completion of the planned 10-day course; baricitinib was completed on day +10.

Conclusions

This sentinel case of imported HCPS in non-endemic Europe was managed with, to our knowledge, the first reported combined antiviral and host-directed regimen for this syndrome and the first reported use of favipiravir in a patient with hantavirus infection. The favourable outcome supports prospective evaluation of antiviral combinations and adjunctive immunomodulation within international preparedness protocols.

Source: 

Link: https://www.clinicalmicrobiologyandinfection.org/article/S1198-743X(26)00310-1/fulltext

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Antiviral activities of multiple #antivirals against highly pathogenic avian #influenza A #H5N1 in vitro and in mice

 

ABSTRACT

In 2024, a bovine H5N1 strain was first isolated from dairy cows in Texas and confirmed to transmit cross-species to humans. Therefore, research on treatments for human infection should be accelerated. In our study, the antiviral effects of baloxavir acid (BXA), oseltamivir carboxylate (OSC), EIDD-1931 (NHC), and ribavirin (RBV) against five H5N1 strains were evaluated in vitro. Cell viability and viral replication were measured to assess the antiviral effects. The results showed that the EC50 of BXA treatment was the lowest. The BXA/NHC and BXA/OSC combination treatments showed more potent inhibitory effects than each monotherapy. The 15 mg/kg baloxavir marboxil (BXM) / 125 mg/kg molnupiravir (MNP) and the 15 mg/kg BXM / 10 mg/kg oseltamivir phosphate (OSP) were tested in BALB/c mice. The mice were inoculated with 10 times the 50% mouse lethal dose (10 MLD50) of bovine H5N1 virus. Treatments began 1-day post-infection (1 dpi) and were administered orally twice daily for 5 or 7 days. Changes in body weight, clinical signs, and survival were monitored; lung and brain tissues were collected for virological, immunological, and histological analyses. Most mice died from severe neurological symptoms. Compared with the 5-day treatment, the 7-day treatment effectively inhibited viral replication and increased survival rates to 50% in BXM, BXM/MNP, and BXM/OSP treatments. Mice treated with BXM/MNP or BXM/OSP combination therapy showed lower viral yields in the lungs than those treated with BXM alone. The results provide a reference for human treatment, and extending the 7-day combination treatment should be considered.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/journals/temi20

Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2645843

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Coadministration of #ribavirin and #arenaviral entry #inhibitor LHF-535 enhances antiviral benefit against authentic #Lassa virus

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Highlights

• A new strain of Lassa virus (LASV) was successfully isolated and characterized.

• The combination of ribavirin and LHF-535 has been demonstrated to exhibit synergistic effects in inhibiting LASV.

• The findings provide new directions for the development of antiviral drugs and vaccines for Lassa fever.

Dear Editor,

Lassa virus (LASV) is the causative agent of the acute viral hemorrhagic Lassa fever (LF), which is classified into Mammarenavirus within the Arenaviridae family, with a single-stranded, negative-sense, bi-segmented RNA genome. Due to its high pathogenicity and lethality, LASV is considered as a priority threat to public health, with an estimated cases of 300,000 infections and 5,000 deaths annually. LASV was first isolated and described as a clinical entity in 1969 in Lassa, Nigeria (Garry, 2023). LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up to seven lineages, with each lineage predominately localized in specific countries. Although the research on LF has been carried out for decades since the pathogen first characterized, there is no approved antiviral drugs or vaccines for clinical use against LASV to date (Grant et al., 2023). One possible reason that hindered the development of countermeasures is that the preclinical studies on authentic LASV are restricted in high bio-containment biosafety level 4 (BSL-4) facilities. In this letter, we describe isolation, and characterization of the LASV from the clinical samples. And we applied a coadministration assay of antiviral drugs for LASV by using a clinically isolated Mammarenavirus lassaense strain in the BSL-4 facility, aiming to investigate new therapeutic strategies for LASV infection.

(...)

Source: Virologica Sinica, https://www.sciencedirect.com/science/article/pii/S1995820X25000380?via%3Dihub

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Improving #clinical #care of patients in #Nipah #outbreaks: moving beyond ‘compassionate use’

Summary

The 2024 Nipah outbreak in Kerala, India—its fifth in six years—and the recurring annual outbreaks in Bangladesh underscore the persistent threat posed by the Nipah virus (NiV) in the region. With a high mortality rate, human-to-human transmission potential, and the widespread presence of Pteropus bats, the natural reservoir, NiV remains a significant epidemic threat. Despite being a WHO priority pathogen, there has been no systematic effort to improve patient care for NiVD, leading to consistently poor outcomes. Current care relies on supportive measures and the ‘compassionate use’ of unapproved drugs like ribavirin and remdesivir. Drugs used ‘off-label’ during outbreaks can become the ‘standard of care’ without robust evidence of their safety or efficacy, complicating the testing of new therapies and perpetuating uncertainty about their true effectiveness. To improve NiVD care, we propose four key strategies: 1) Enhance early case detection, 2) optimize supportive care to improve outcomes and create a standard for future trials, 3) adopt a syndromic approach centered on encephalitis, and 4) explore innovative trial designs tailored to low case numbers as an alternative to ‘compassionate use’. By integrating these strategies, healthcare systems in NiV-endemic regions will be better equipped to manage both current and future outbreaks.

Source: Lancet Regional Health South-East Asia, https://www.thelancet.com/journals/lansea/article/PIIS2772-3682(24)00177-X/fulltext

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