Ledipasvir/sofosbuvir and ribavirin for the treatment of ribavirin-refractory persistent hepatitis E virus infection

Persistent Hepatitis E Virus infection (HEV) is a rare but increasingly recognised condition in immunocompromised individuals. Untreated, this infection can rapidly progress to cirrhosis. Ribavirin is recommended as the first line treatment and the majority achieve sustained viral clearance. However...

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Main Authors: Jennifer Gallacher, Yusri Taha, Ana da Silva Filipe, Samreen Ijaz, Stuart McPherson
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:IDCases
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2214250923000653
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author Jennifer Gallacher
Yusri Taha
Ana da Silva Filipe
Samreen Ijaz
Stuart McPherson
author_facet Jennifer Gallacher
Yusri Taha
Ana da Silva Filipe
Samreen Ijaz
Stuart McPherson
author_sort Jennifer Gallacher
collection DOAJ
description Persistent Hepatitis E Virus infection (HEV) is a rare but increasingly recognised condition in immunocompromised individuals. Untreated, this infection can rapidly progress to cirrhosis. Ribavirin is recommended as the first line treatment and the majority achieve sustained viral clearance. However, treatment options are limited for those who fail ribavirin. We report a case of a patients with ribavirin-refractory persistent HEV who responded to ledipasvir/sofosbuvir and ribavirin treatment. This patients had failed 2 course of ribavirin and 1 course of PEG-Interferon and ribavirin and he was known to harbour ribavirin-associated mutations (G1634R, D1384G and K1383N) in the RNA dependent RNA polymerase. He was treated with ledipasvir/sofosbuvir (LDV/SOF; Harvoni 90/400 mg) and ribavirin (R) 400 mg twice daily for 32 weeks. At treatment initiation his HEV RNA was 1.1 × 106 IU/ML and reduced to 1.8 × 104 IU/ML and 43 IU/ML at one and four weeks of treatment, respectively, becoming not detected in blood and stool by week eight. His blood HEV RNA remained undetectable for seven months after treatment completion. Unfortunately, at eight months post-treatment, his blood HEV RNA became detectable at a low level (35 IU/ML). His stool HEV RNA was also detectable at 620 IU/ML consistent with a late relapse. He restarted LDV/SOF+R and by week four of treatment HEV RNA was not detected in blood and stool. He remains on treatment. In conclusion, this is the first report demonstrating the antiviral activity of LDV/SOF+R in the treatment of persistent HEV infection.
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spelling doaj.art-ae83074acae541bba1e646dd2ca1ea962023-06-07T04:48:06ZengElsevierIDCases2214-25092023-01-0132e01741Ledipasvir/sofosbuvir and ribavirin for the treatment of ribavirin-refractory persistent hepatitis E virus infectionJennifer Gallacher0Yusri Taha1Ana da Silva Filipe2Samreen Ijaz3Stuart McPherson4Viral Hepatitis Service, The Newcastle upon Tyne Hospitals NHS Foundation Trust, United Kingdom; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United KingdomViral Hepatitis Service, The Newcastle upon Tyne Hospitals NHS Foundation Trust, United KingdomMRC-University of Glasgow Centre for Virus Research, Glasgow, United KingdomBlood Borne Virus Unit, UK Health Security Agency, London, United KingdomViral Hepatitis Service, The Newcastle upon Tyne Hospitals NHS Foundation Trust, United Kingdom; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; Correspondence to: The Newcastle upon Tyne Hospitals NHS Foundation Trust, Liver Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN, United Kingdom.Persistent Hepatitis E Virus infection (HEV) is a rare but increasingly recognised condition in immunocompromised individuals. Untreated, this infection can rapidly progress to cirrhosis. Ribavirin is recommended as the first line treatment and the majority achieve sustained viral clearance. However, treatment options are limited for those who fail ribavirin. We report a case of a patients with ribavirin-refractory persistent HEV who responded to ledipasvir/sofosbuvir and ribavirin treatment. This patients had failed 2 course of ribavirin and 1 course of PEG-Interferon and ribavirin and he was known to harbour ribavirin-associated mutations (G1634R, D1384G and K1383N) in the RNA dependent RNA polymerase. He was treated with ledipasvir/sofosbuvir (LDV/SOF; Harvoni 90/400 mg) and ribavirin (R) 400 mg twice daily for 32 weeks. At treatment initiation his HEV RNA was 1.1 × 106 IU/ML and reduced to 1.8 × 104 IU/ML and 43 IU/ML at one and four weeks of treatment, respectively, becoming not detected in blood and stool by week eight. His blood HEV RNA remained undetectable for seven months after treatment completion. Unfortunately, at eight months post-treatment, his blood HEV RNA became detectable at a low level (35 IU/ML). His stool HEV RNA was also detectable at 620 IU/ML consistent with a late relapse. He restarted LDV/SOF+R and by week four of treatment HEV RNA was not detected in blood and stool. He remains on treatment. In conclusion, this is the first report demonstrating the antiviral activity of LDV/SOF+R in the treatment of persistent HEV infection.http://www.sciencedirect.com/science/article/pii/S2214250923000653Hepatitis E virusTreatmentAntiviral resistanceChronic infectionImmunosuppressed
spellingShingle Jennifer Gallacher
Yusri Taha
Ana da Silva Filipe
Samreen Ijaz
Stuart McPherson
Ledipasvir/sofosbuvir and ribavirin for the treatment of ribavirin-refractory persistent hepatitis E virus infection
IDCases
Hepatitis E virus
Treatment
Antiviral resistance
Chronic infection
Immunosuppressed
title Ledipasvir/sofosbuvir and ribavirin for the treatment of ribavirin-refractory persistent hepatitis E virus infection
title_full Ledipasvir/sofosbuvir and ribavirin for the treatment of ribavirin-refractory persistent hepatitis E virus infection
title_fullStr Ledipasvir/sofosbuvir and ribavirin for the treatment of ribavirin-refractory persistent hepatitis E virus infection
title_full_unstemmed Ledipasvir/sofosbuvir and ribavirin for the treatment of ribavirin-refractory persistent hepatitis E virus infection
title_short Ledipasvir/sofosbuvir and ribavirin for the treatment of ribavirin-refractory persistent hepatitis E virus infection
title_sort ledipasvir sofosbuvir and ribavirin for the treatment of ribavirin refractory persistent hepatitis e virus infection
topic Hepatitis E virus
Treatment
Antiviral resistance
Chronic infection
Immunosuppressed
url http://www.sciencedirect.com/science/article/pii/S2214250923000653
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