HCV: FDA warns of rare liver injury with certain DAAs

  • FDA

  • von Yael Waknine
  • Clinical Essentials
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  • The FDA has issued a warning regarding rare cases of severe liver injury with certain HCV direct-acting antivirals (DAAs).
  • Most patients had moderate-to-severe hepatic impairment, a contraindication to protease inhibitors.
  • The DAAs in question include glecaprevir/pibrentasvir (GLE/PIB, Mavyret), elbasvir/grazoprevir (EBR/GZR, Zepatier), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX, Vosevi).


  • The FDA has received 63 reports of worsening liver function with GLE/PIB (n=46), EBR/GZR (n=14), and SOF/VEL/VOX (n=3).
    • 10 cases reported isolated hyperbilirubinemia and jaundice without transaminase elevations or other decompensation events.
  • Most cases occurred in the first 4 weeks of treatment (median onset, 22 days; range, 2 days to 16 weeks).
    • Events included hyperbilirubinemia (n=42), jaundice (n=32), ascites (n=27), and hepatic encephalopathy (n=12).
  • 39/63 cases (61.9%) resolved or improved on discontinuation of therapy; 8 patients died.
  • Most patients had known moderate-to-severe liver impairment (Child-Pugh class B or C).
  • More than half the patients reported as having no/compensated cirrhosis had been incorrectly classified despite having low baseline platelets, portal hypertension, or risk factors such as prior decompensation, alcohol abuse, liver cancer, or other contributing illness.  


  • These DAAs are safe when used as indicated for HCV in patients with no or mild (Child-Pugh class A) liver impairment.
  • GLE/PIB and EBR/GZR should not be used in patients with prior hepatic decompensation.
  • Salvage SOF/VEL/VOX should only be used in patients with prior decompensation if benefits outweigh risks.
  • Patients should be advised to seek immediate care for symptoms of fatigue, weakness, loss of appetite, nausea/vomiting, yellow eyes/skin, or light-colored stools.
  • Health professionals and patients are encouraged to report adverse events to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.