Due to risk of serious liver injury, FDA restricts use of Ocaliva (obeticholic acid) in primary biliary cholangitis (PBC) patients with advanced cirrhosis

FDA identified 25 cases of serious liver injury leading to liver decompensation or liver failure associated with use of Ocaliva reported in the FDA Adverse Event Reporting System (FAERS) database and in the medical literature¹ from the drug’s approval in 2016 through January 18, 2021. All of these cases described PBC patients with cirrhosis (compensated or decompensated) taking Ocaliva at recommended dosages prior to the initial liver-related adverse event.

Eighteen of 25 cases occurred in PBC patients with compensated cirrhosis who experienced liver injury that led to decompensation. Ten of these 18 patients had evidence or suspicion of portal hypertension at baseline, as suggested by one or more of the following: thrombocytopenia, varices, low albumin, and elevated bilirubin. The remaining eight cases did not provide sufficient clinical detail regarding the presence of portal hypertension. Although the disease in these PBC patients was not expected to progress rapidly, they experienced accelerated deterioration in clinical status within months of starting Ocaliva. The median time to liver decompensation (e.g., new onset ascites) after initiating Ocaliva treatment was 4 months, ranging from 2 weeks to 10 months. Four PBC patients with compensated cirrhosis required a liver transplant within 1.3 years after starting Ocaliva, and one PBC patient with compensated cirrhosis died from liver failure.

The other seven cases occurred in PBC patients with decompensated cirrhosis, two of whom died. Although there was a temporal relationship between Ocaliva initiation and liver injury, it is difficult to distinguish a drug-induced effect from disease progression in the patients with advanced baseline liver disease. The median time to a new decompensation event (e.g., hepatic encephalopathy) after initiating Ocaliva was 2.5 months, ranging from 10 days to 8 months.

In addition to liver transplant, evidence for liver decompensation included events such as new-onset ascites, variceal bleeding, hepatorenal syndrome, and worsening synthetic function. The most common associated liver-related adverse event among the 25 cases was worsening total bilirubin.