From the Guidelines
The increase in total bilirubin (TBIL) from 2.74 to 6.28 mg/dL indicates worsening hyperbilirubinemia that requires prompt evaluation, as suggested by the most recent guidelines 1. This patient should be referred to a gastroenterologist or hepatologist for urgent assessment. Initial workup should include:
- Comprehensive liver function tests
- Complete blood count
- Imaging (ultrasound or CT scan) to determine if the hyperbilirubinemia is conjugated or unconjugated and whether there is biliary obstruction While awaiting specialist care, the patient should avoid alcohol, acetaminophen, and other potentially hepatotoxic medications. If symptoms like jaundice, dark urine, light-colored stools, abdominal pain, or fever are present, emergency evaluation may be necessary. This significant rise in bilirubin could indicate various conditions including viral hepatitis, medication toxicity, biliary obstruction, or progression of underlying liver disease, as outlined in the guidelines for detection, assessment, and management of suspected acute drug-induced liver injury 1 and immune-mediated liver injury 1. The rate of increase is concerning and suggests an active, potentially serious process that requires prompt medical attention rather than watchful waiting, in line with the recommendations for the management of abnormal liver blood tests 1.
Given the complexity of interpreting liver test changes, a full medical and causality assessment are critical to detecting likely drug-induced liver injury or an alternative diagnosis, as recommended in the review article on detection, assessment, and management of suspected drug-induced liver injury during clinical trials in oncology patients 1. A tiered approach towards investigating liver test abnormalities is recommended, evaluating the most likely alternative causes of liver injury first, before moving onto investigations for rarer causes of liver injury. Liver biopsy may be useful in patients where liver biochemical tests fail to resolve, or worsen, despite removal of study drug, and where other testing is unremarkable, as suggested in the guidelines for detection, assessment, and management of suspected drug-induced liver injury 1.
From the Research
Significance of Increased Total Bilirubin (TBIL)
- The increase in Total Bilirubin (TBIL) from 2.74 to 6.28 may be associated with various clinical conditions, including liver dysfunction, sepsis, and hyperbilirubinemia 2, 3.
- Elevated TBIL levels have been linked to increased mortality and poor outcomes in patients with severe sepsis and septic shock 2, 3.
- A study found that patients with sepsis and TBIL levels ≥ 5 mg/dL had a higher risk of 1-year mortality compared to those with TBIL levels < 5 mg/dL 2.
- Another study reported that elevated serum bilirubin levels within 72 hours of admission were associated with an increased risk of mortality in patients with severe sepsis and septic shock 3.
Potential Causes and Associations
- Hyperbilirubinemia can be caused by various factors, including liver injury, infection, and hemolysis 4, 5.
- The level of extreme hyperbilirubinemia has been shown to be an important prognostic factor in critically ill patients 5.
- Transient elevation of liver function tests and bilirubin levels can occur after laparoscopic cholecystectomy, even in the absence of intraoperative injury or other obvious etiology 6.
Clinical Implications
- The increase in TBIL from 2.74 to 6.28 may indicate a worsening of liver function or the development of hyperbilirubinemia, which can have significant clinical implications 4, 5.
- Clinicians should be aware of the potential risks associated with elevated TBIL levels and monitor patients closely for signs of liver dysfunction or other complications 2, 3.