13.17: Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess the degree of hepatic impairment. However, it's important to note that these scores, while useful, do not have a direct correlation with the pharmacokinetics of drugs in individuals with liver disease.

Chronic liver disease is known to compromise drug metabolism significantly. In contrast, acute hepatitis can lead to more nuanced changes in how drugs are metabolized, underlining the necessity for a case-by-case approach to patient care and medication management. Despite ongoing efforts, establishing dosing guidelines for patients with hepatic impairment remains a complex and evolving area of study.

Critical to assessing liver function and managing medications in hepatic-impaired patients are specific markers, including aminotransferases, alkaline phosphatase, bilirubin, and prothrombin time. Each marker provides valuable insights into the liver's ability to clear drugs and maintain its functional capacity. For example, an elevated AST/ALT ratio might indicate acute liver damage or be a sign of alcoholic hepatitis. In contrast, a significant increase in alkaline phosphatase levels could point towards hepatic tumors or biliary obstruction.

Additionally, variations in urinary bilirubin levels are instrumental in diagnosing hepatobiliary diseases. At the same time, deviations in prothrombin time can signal liver failure or biliary obstruction. These markers and tests are crucial for clinicians in making informed decisions regarding the care and treatment of patients with liver disease, ensuring tailored and effective therapeutic interventions.

In clinical practice, directly measuring hepatic blood flow to assess liver function is often impractical due to the specialized techniques required.

Instead, clinicians estimate hepatic function through patient examination and liver function tests.

The Child–Pugh and MELD help evaluate hepatic impairment but don't directly correlate with drug pharmacokinetics.

Chronic liver disease affects drug metabolism and clearance, necessitating a tailored risk assessment before dosing.

Dosing for hepatically impaired patients remains an area of ongoing development. However, drug markers such as aminotransferases, alkaline phosphatase, bilirubin, and prothrombin time provide valuable insights into hepatic function.

For instance, elevated AST/ALT ratios suggest acute liver injury, alcoholic hepatitis, or advanced liver fibrosis, while increased AP levels may indicate hepatic tumors or biliary obstruction.

Additionally, deviations in urinary bilirubin levels and prothrombin time can help diagnose hepatobiliary disease and hepatic failure, respectively.