Sofosbuvir and Daclatasvir Anti–Viral Therapy Fails to Clear HEV Viremia and Restore Reactive T Cells in a HEV/HCV Co-Infected Liver Transplant Recipient

No Clear Evidence for an Effect of Sofosbuvir Against Hepatitis E Virus in Organ Transplant Patients

“…As mentioned, there is hyperdynamic state and increased sympathetic discharge, so adding norepinephrine is likely to make little difference. (3) Terlipressin compared with noradrenaline causes greater constriction of efferent arterioles and greater increase in fractional excretion of sodium and urine output. (3) Despite some negative effect on cardiac output, it promotes renal blood flow to a greater extent compared with noradrenaline.…”

Reply

“…This case report was meant to provide contrast to the report by Donnelly et al, where sofosbuvir was used in combination with daclatasvir, but not ribavirin (3) and foster further investigation of the role of sofosbuvir with ribavirin in management of hepatitis E. To clarify some points from the original case report, the patient was confirmed to be genotype 3. His second course of ribavirin in 2015 was discontinued when his hepatitis E levels were increasing despite being on 600 mg daily of ribavirin (recommended dosing at that time) because of concerns of lack of efficacy.…”

“…Previous reports have failed to find a beneficial effect of sofosbuvir against HEV. (3,4) Finally, the HEV genome, levels of immunosuppressants, and immunological parameters during follow-up are unknown. Hence, there is still no evidence for an antiviral effect of sofosbuvir against HEV.…”

Recent Advances Towards the Development of a Potent Antiviral Against the Hepatitis E Virus

“…However, those data were not fully reproducible by Wang et al 55 and, moreover, sofosbuvir treatment failed to clear HEV viremia in an immunosuppressed patient with chronic HCV and HEV without ribavirin. 56 Therefore, usage of sofosbuvir as an anti-HEV therapeutic needs further validation (discussed further in the RNA-dependent RNA polymerase section of this manuscript).…”

“…76 Dao Thi et al indicated the effectiveness of sofosbuvir in inhibiting HEV replication; however, subsequent studies failed to observe its potent inhibitory effect. [54][55][56] Nevertheless, optimization of the sofosbuvir structure that improves its inhibitory effect on HEV RNA-dependent RNA polymerase is an attractive area of investigation. Knowledge of HEV RNA-dependent RNA polymerase structure might expedite the above study.…”