FDA warns direct-acting antivirals can cause serious liver injury in patients with advanced liver disease
The US Food and Drug Administration (FDA) has received reports of rare cases of worsening liver function or liver failure in patients with chronic hepatitis C who have moderate-to-severe hepatic impairment and are treated with certain direct-acting antivirals. In most cases, liver failure or hepatic decompensation occurred within 4 weeks of starting treatment. Some cases have led to death.
The drugs involved include:
It is important to note that these drugs are not indicated in patients with moderate-to-severe hepatic impairment (Child-Pugh B or C), and most of the reported cases were in patients who should not have been prescribed these drugs because they had signs and symptoms of advanced liver disease (or other serious liver problems) prior to starting treatment. Worsening liver function improved and symptoms resolved in most patients after stopping the drug.
When prescribing these drugs, assess the severity of liver disease at baseline and monitor the patient for clinical signs and symptoms of worsening liver function (e.g., increases in liver enzymes, ascites, jaundice, variceal hemorrhage, encephalopathy) during treatment. This is especially important in patients with pre-existing serious liver problems or risk factors that can contribute to clinical worsening of liver function during treatment (e.g., hepatocellular carcinoma, alcohol abuse). These drugs should not be prescribed in patients with a history of prior hepatic decompensation. Discontinue use of these drugs in patients who develop evidence of hepatic decompensation or as clinically indicated.
These drugs are considered to be safe and effective in patients with no hepatic impairment or mild hepatic impairment (Child-Pugh A) and can be prescribed as indicated.
The FDA has previously issued a similar warning about ombitasvir/paritaprevir/ritonavir ± dasabuvir.
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Transmission is through percutaneous exposure to infected blood, most commonly through injection of illicit drugs or transfusion of contaminated blood products in developed countries, or via contaminated medical or dental equipment in resource-poor countries.
Following acute exposure to hepatitis C virus, about 55% to 85% of patients develop chronic hepatitis C. Most infections are asymptomatic; however, hepatic inflammation is often present and can lead to progressive hepatic fibrosis.
The goal of treatment is to eradicate the virus, achieve a sustained virologic response, and prevent disease progression. Oral direct-acting antiviral therapies are standard treatment.
Long-term complications of chronic infection include cirrhosis or hepatocellular carcinoma.
Hepatitis C virus (HCV) is an infectious, hepatotropic virus belonging to the Flavivirus family. Infection may present as an acute illness (e.g., fatigue, arthralgia, jaundice) in approximately one third of patients; however, the majority of patients are asymptomatic. Chronic infection causes liver inflammation and fibrosis, and a significant number of these patients will develop cirrhosis and liver failure or liver cancer over a period of approximately 20 to 50 years. The infection rarely resolves spontaneously in patients with chronic infection.
History and exam
- unsafe medical practices
- intravenous or intranasal drug use
- blood transfusion or organ transplant
- birth between 1945 and 1965
- heavy alcohol use
- interleukin (IL)-28B gene polymorphism
- healthcare work
- multiple sex partners
- infected mother (for fetus)
- male sex
Professor of Medicine
Division of Liver Diseases
Mount Sinai Hospital
JA declares that he has no competing interests.
Dr Jawad Ahmad would like to gratefully acknowledge Dr Brian L. Pearlman, the previous contributor to this topic.
Digestive Disease and Liver Transplant
AL has participated in an advisory board meeting with Gilead and Janssen, and is a primary investigator for Merck’s C-Surfer trial.
Director of Hepatology and Medical Director of Liver Transplantation
Associate Professor of Medicine
Strong Memorial Hospital
University of Rochester
BM belongs to the paid speaker’s bureau for pharmaceutical companies Gilead (maker of ledipasvir/sofosbuvir), AbbVie (maker of Viekira Pak® - ombitasvir/paritaprevir/ritonavir and dasabuvir), Merck, and Salix.
Bradford Teaching Hospitals Foundation Trust
SM has received sponsorship and has sat on advisory boards for BMS, Gilead, AbbVie, and Merck.
Nottingham University Hospitals NHS Trust
SR is an advisory board (paid) member for AbbVie, Gilead, Janssen, and MSD.
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