What are the causes of markedly elevated Liver Function Tests (LFTs)?

From the Guidelines

Liver function tests (LFTs) in the thousands are typically caused by severe acute hepatitis, which can result from several conditions, including immune checkpoint inhibitor (ICI) colitis and hepatitis, as seen in patients with cancer 1. The most common causes of such elevated LFTs include viral hepatitis (particularly hepatitis A, B, and E), drug-induced liver injury (from medications like acetaminophen, antibiotics, or statins), alcoholic hepatitis from excessive alcohol consumption, and autoimmune hepatitis. Other potential causes include:

• Ischemic hepatitis due to decreased blood flow to the liver
• Acute biliary obstruction
• Metabolic disorders like Wilson's disease
• ICI-related liver toxicity, which can be graded based on the severity of AST/ALT elevation and bilirubin levels, as outlined in the AGA clinical practice update 1 In cases of extremely elevated LFTs, immediate medical attention is necessary as this indicates significant liver cell damage. Treatment depends on the underlying cause, such as:
• Discontinuing hepatotoxic medications
• Antiviral therapy for viral hepatitis
• Corticosteroids for autoimmune hepatitis
• Management of ICI-related liver toxicity, which may involve holding or discontinuing ICI therapy, as well as administering glucocorticoids or other immunosuppressive agents 1 Supportive care is essential, including monitoring for complications like coagulopathy or encephalopathy. The liver has remarkable regenerative capacity, and with proper treatment, LFTs can normalize over time, though complete recovery may take weeks to months depending on the extent of damage and the underlying cause. It is also important to note that patients with cancer are at elevated risk for liver injury from a variety of causes, including hepatic metastasis, thromboembolic disease, biliary compression, perfusion injury, opportunistic infections, and drug reactions, and therefore require thorough evaluation and management of their LFTs 1.

From the FDA Drug Label

elevation in serum liver enzyme levels (usually reversible upon discontinuation), The cause of elevated liver function tests (LFTs) in the thousands can be elevation in serum liver enzyme levels due to prednisone use, which is usually reversible upon discontinuation 2.

• Key points: + Elevation in serum liver enzyme levels is a reported adverse reaction. + This elevation is usually reversible upon discontinuation of prednisone. + The exact liver enzyme levels are not specified in the drug label.

From the Research

Causes of Elevated Liver Function Tests (LFTs)

Elevated LFTs can be caused by various factors, including:

• Hepatitis C treatment with sofosbuvir and ribavirin, which can trigger autoimmune hepatitis 3
• Other medications or drugs that can cause liver damage
• Underlying liver diseases, such as hepatitis B or C, or cirrhosis

Liver Function Test (LFT) Abnormalities

LFT abnormalities are a common problem faced by emergency physicians, and can be caused by various factors, including:

• Hepatocellular, cholestatic, or functioning liver diseases
• Pathologic alterations to liver enzymes, which can be algorithmically assessed by separating disease processes into different groupings 4

Treatment-Related Causes of Elevated LFTs

Certain treatments, such as sofosbuvir-based regimens for chronic hepatitis C, can cause elevated LFTs, including:

• Sofosbuvir and ribavirin, which can trigger autoimmune hepatitis 3
• Entecavir, which can cause elevated LFTs in patients with decompensated liver disease, although it is generally well tolerated 5

Patient Characteristics and Treatment Adherence

Patient characteristics, such as age, sex, and liver disease severity, can affect treatment adherence and outcomes, including:

• Adherence rates to sofosbuvir-based regimens, which can range from 80.5% to 91.4% depending on the regimen and patient characteristics 6
• Treatment outcomes, such as sustained virologic response (SVR12) rates, which can be affected by patient characteristics and treatment adherence 6

Sofosbuvir and Hepatitis C Treatment

Sofosbuvir is a highly potent inhibitor of HCV NS5B polymerase, and has been shown to be effective in treating chronic hepatitis C, including:

• Patients with advanced liver disease, psychiatric conditions, anemia, or autoimmune diseases, who may not be eligible for pegylated interferon-based therapy 7
• Patients with all genotypes of HCV, who can benefit from sofosbuvir's broad spectrum of activity 7