Serious Liver Injury Tied to HCV Drugs in Rare Cases, FDA Warns

Rabiya S. Tuma, PhD


August 29, 2019

The US Food and Drug Agency (FDA) warned on Wednesday that three direct-acting antiviral drugs have been associated with rare cases of severe liver injury in patients being treated for chronic hepatitis C virus (HCV) infection.

The agency has identified 63 cases of liver decompensation, including liver failure and death, among patients treated with glecaprevir/​pibrentasvir (Mavyret, AbbVie; n = 46), elbasvir/​grazoprevir (Zepatier, Merck & Co; n = 14), and sofosbuvir/​velpatasvir/​voxilaprevir (Vosevi, Gilead; n = 3).

The cases were reported to the FDA Adverse Event Reporting System (FAERS) database or identified in the medical literature through January 8, 2019.

All three drugs are approved to treat chronic HCV infection in patients without liver impairment or mild liver impairment (Child-Pugh A). However, the cases were concentrated in patients who had evidence of more advanced liver disease at baseline.

"In many of the reported cases, liver failure occurred in patients who had signs and symptoms of moderate to severe liver impairment (Child-Pugh B or C) or other serious liver problems and should not have been treated with these medicines," according to an August 28 FDA drug safety communication

Some cases occurred in patients who were incorrectly classified as having no cirrhosis or compensated cirrhosis with mild liver impairment (Child-Pugh A) prior to treatment but had evidence of more severe liver disease, including decreased platelets, portal hypertension, alcohol abuse, or serious medical illnesses associated with serious liver problems. 

The drugs have been widely used and "are safe and effective in patients with no or mild liver impairment," the FDA said.

The agency said physicians should continue to prescribe the drugs in appropriate patients. "Assess severity of liver disease at baseline and closely monitor for signs and symptoms of worsening liver function such as increases in liver enzymes, jaundice, ascites, encephalopathy, and variceal hemorrhage," the FDA said.

The median time to onset of liver-related adverse events was 22 days after starting treatment, with a range of 2 days to 16 weeks. Hyperbilirubinemia was the most common liver-related event occurring in 42 patients, followed by jaundice (n = 32), ascites (n = 27), and hepatic encephalopathy (n = 12).

Symptoms resolved after discontinuing treatment in 39 patients; two patients had symptom recurrence when they restarted treatment.

The agency noted that approximately 72,000 US patients were treated with the three drugs in 2018.

The FDA encourages clinicians to report any potential adverse events related to the use of these drugs to the FDA's MedWatch program.

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