The spectrum of liver disease is wide. Most of the underlying pathophysiologic mechanisms relate to autoimmune diseases, viral infections and hepatotoxic agents leading to hepatitis, cirrhosis, hepatocellular carcinoma, and increased risk of bleeding. Liver disease is one of the most common causes of morbidity in patients receiving drugs and, in the presence of liver disease, most adverse drug reactions are related to altered pharmacokinetics.
The most widely accepted method to estimate the ability of the liver to metabolize drugs is to determine the patient’s Child-Pugh score (Table 2).10-12 The Child-Pugh score consists of five laboratory tests or clinical symptoms: total bilirubin, serum albumin, prothrombin time or International Normalized Ratio (INR), ascites, and hepatic encephalopathy. Each of these five areas is given a score from 1 (normal) to 3 (severely abnormal) and the scores are totaled.
|Tests/Symptoms||Score 1 point each||Score 2 points each||Score 3 points each|
|Total bilirubin in mg/dL||< 2.0||2.0-3.0||> 3.0|
|Serum albumin in mg/dL||> 3.5||2.8-3.5||< 2.8|
|Prothrombin time in seconds over control or the INR||< 4|
(INR: < 1.7)
(INR: > 2.3)
|*A score of 5 indicates normal liver function, whereas a score of 15 indicates extreme dysfunction.|
In general, for drugs metabolized by the liver, a score of ≤ 7 requires no modification of therapy; a score of 8 to 9 is grounds for a moderate decrease (≈25%) in the daily dose; and a score of ≥ 10 indicates a need for significant decrease (≈50%) in daily dosing. Information on a specific drug prescribed to patients with liver disease can be found in the “Dosage and Administration,” “Contraindications,” “Warning and Precautions” and “Adverse Effects” sections of the drug’s labeling.3