Can Propylthiouracil Cause Liver Cirrhosis?
Propylthiouracil (PTU) does not typically cause cirrhosis, but it can cause severe acute liver injury ranging from asymptomatic transaminase elevation to fulminant hepatic failure requiring liver transplantation or resulting in death. 1
Spectrum of PTU-Induced Liver Injury
PTU causes hepatotoxicity with a spectrum that includes:
- Asymptomatic transaminase elevation (most common presentation) 2
- Acute hepatitis with jaundice and coagulopathy 3
- Subacute hepatitis that can progress to liver failure if PTU is not discontinued 4
- Fulminant hepatic failure requiring transplantation or causing death 1, 2
The pattern is acute or subacute hepatocellular injury, not the chronic progressive fibrosis that characterizes cirrhosis. 2, 3
FDA Black Box Warning
The FDA mandates a black box warning stating that PTU causes "severe liver injury and acute liver failure, in some cases fatal" requiring liver transplantation in both adult and pediatric patients. 1 This emphasizes the acute nature of the injury rather than chronic cirrhotic progression.
Clinical Evidence
- Incidence: PTU-related liver toxicity occurs in approximately 1% of treated patients 4
- Progression to failure: Among those who develop acute or subacute hepatitis, approximately one-third progress to liver failure 4
- Fatal outcomes: Multiple case reports document deaths from PTU-induced acute liver failure, particularly when the drug is not discontinued promptly 5, 6
Critical Monitoring Requirements
Monthly alanine aminotransferase (ALT) monitoring is recommended, at minimum during the first 6 months of therapy, given the high incidence, potential severity, and delayed occurrence of liver toxicity. 4
Immediate discontinuation is mandatory if any signs of hepatic injury appear:
- Fever, loss of appetite, nausea, vomiting 1
- Fatigue, itchiness 1
- Right upper quadrant pain or tenderness 1
- Dark (tea-colored) urine 1
- Pale stools 1
- Jaundice (yellowing of skin or eyes) 1
Management of PTU-Induced Liver Injury
Stop PTU immediately upon detection of any hepatic dysfunction. 1, 5 Delayed discontinuation significantly worsens outcomes and increases mortality risk. 5, 4
For severe cases with fulminant hepatic failure:
- Corticosteroid therapy may be beneficial, as the hepatotoxic process can have autoimmune features requiring immunosuppression 7, 6
- Artificial liver support systems (ALSS) can serve as a bridge when liver transplantation is not immediately available 3
- Liver transplantation remains the definitive treatment for irreversible acute liver failure 2
Important Clinical Distinction
PTU has no proven benefit in alcoholic liver disease or alcoholic cirrhosis and should never be used for that indication. 8, 7 Multiple randomized controlled trials showed no improvement in mortality or liver outcomes when PTU was used in alcoholic cirrhosis patients. 8
Key Pitfall to Avoid
The most dangerous error is continuing PTU after signs of liver injury appear. 5, 4 One pediatric case report documented a patient who continued receiving PTU for several days after developing symptoms—her illness progressed to fulminant hepatic failure with encephalopathy and death, while another patient who had PTU discontinued promptly recovered quickly. 5