What are the causes of elevated bilirubin and Alanine Transaminase (ALT) levels?

From the Guidelines

Elevated bilirubin and ALT levels indicate liver dysfunction that requires prompt medical evaluation, and you should schedule an appointment with your healthcare provider within the next few days for proper assessment and blood work. These abnormalities can result from various conditions including viral hepatitis, medication side effects, alcohol use, fatty liver disease, or autoimmune disorders, as noted in the guidelines on the management of abnormal liver blood tests 1. While waiting for your appointment, it is essential to avoid alcohol completely, discontinue any non-essential medications or supplements after consulting your doctor, maintain hydration, and eat a balanced diet low in processed foods and sugar.

The severity of elevation matters, with mild increases potentially requiring monitoring and significant elevations necessitating urgent care. Liver enzymes, such as ALT, serve as important biomarkers of liver cell damage, and bilirubin elevation can indicate problems with bile flow or red blood cell breakdown 1. It is also crucial to consider the potential impact of COVID-19 on patients with underlying liver disease, as highlighted in the management of patients with liver derangement during the COVID-19 pandemic 1.

Key considerations in the evaluation of elevated bilirubin and ALT include:

• The distinction between unconjugated and conjugated hyperbilirubinaemia, with the former often due to haemolysis or impaired conjugation and the latter typically resulting from parenchymal liver disease or biliary obstruction 1
• The role of albumin as a marker of liver synthetic function, although its levels can be influenced by various factors beyond liver disease 1
• The assessment of prothrombin time (PT) and international normalized ratio (INR) as indicators of liver function and potential coagulopathy 1
• The presence of thrombocytopenia as an indicator of advanced liver disease, resulting from decreased production, splenic sequestration, or increased destruction of platelets 1

Given the complexity and potential severity of liver dysfunction, prompt medical evaluation is essential to determine the underlying cause and guide appropriate management, taking into account the patient's specific values, medical history, and potential risk factors for liver disease 1.

From the FDA Drug Label

Hepatic Hepatotoxicity including transient abnormalities in liver function tests (e.g., elevations in serum bilirubin, alkaline phosphatase, serum transaminases, gamma-glutamyl transferase), hepatitis, a shock-like syndrome with hepatic involvement and abnormal liver function tests, and cholestasis have been reported

Raised bilirubin and ALT are potential adverse effects of rifampicin, as the drug label mentions hepatotoxicity including elevations in serum bilirubin and serum transaminases.

• The drug label explicitly states that elevations in serum bilirubin and liver function tests have been reported.
• It is essential to monitor liver function tests in patients taking rifampicin, especially if they have pre-existing liver conditions. 2

From the Research

Raised Bilirubin and ALT

• Elevated levels of bilirubin and alanine transaminase (ALT) can indicate liver damage or disease, as seen in studies 3, 4, 5, 6, 7
• The evaluation of abnormal liver chemistries, including bilirubin and ALT, is crucial in assessing liver health, with guidelines provided by 7
• Hepatocellular injury is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels, while cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels 7
• The degree of elevation of ALT and/or AST in the clinical setting helps guide the evaluation, with testing for viral hepatitis, nonalcoholic fatty liver disease, and alcoholic liver disease, among others 7

Causes of Elevated Bilirubin and ALT

• Elevated bilirubin levels can be caused by hepatocellular disease or cholestasis, with an elevated serum conjugated bilirubin implying hepatocellular disease or biliary obstruction in most settings 3, 7
• Elevated ALT levels can be caused by hepatocellular injury, with the majority of bilirubin circulating as unconjugated bilirubin 5, 7
• Other causes of elevated ALT levels include muscle damage, as ALT can also be of extrahepatic origin 5

Treatment and Management

• Ursodeoxycholic acid (UDCA) therapy has been shown to reduce serum liver function tests, including ALT, AST, and bilirubin, in patients with liver disease 4, 6
• The evaluation of patients with jaundice, which can be caused by elevated bilirubin levels, starts with a careful history and physical examination, followed by directed imaging of the biliary tree and liver 3