Study objectives: To compare three quantitative metabolic markers used to assess hepatic function, indocyanine green (ICG), a high-extraction marker; antipyrine, a low-extraction marker; and dextromethorphan, a P-450IID6 marker, with the clinically used Pugh's classification.
Design: Comparison of 12 healthy controls with 12 age- and sex-matched patients with different degrees of liver disease.
Setting: Research center in a university-affiliated teaching hospital.
Patients: The 12 patients had different degrees of liver disease: 4 mild (Pugh's score 6 or 7); 4 moderate (Pugh's score 8 or 9); and 4 severe (Pugh's score > or = 10). Each level had an equal number of men and women subjects.
Measurements and main results: Clearance of ICG detected mild alterations in hepatic function as efficiently as it did for moderate and severe impairment, but it lacked the specificity to distinguish among the classification groups. In contrast, antipyrine was effective in identifying moderate and severe hepatic impairment; however, its clearance was not reduced in mild liver disease. Pugh's classification appears to be a clinically useful method of assessing the global degree of hepatic impairment in patients with chronic disease, and there was a significant correlation between it and antipyrine clearance (r = 0.67, p = 0.0003) and ICG clearance (r = 0.86, p = 0.0001). Four of eight patients with a Pugh's score greater than 8 had a dextromethorphan metabolic ratio expression reflective of a poor metabolizer phenotype based on 0- to 4-hour urine collection, but only two of those eight patients were classified as poor metabolizers based on 4- to 12-hour urine collection. These percentages of poor metabolizers are substantially higher than for historical controls (8.5-10.4%) and most likely reflect a decrease in the P-450IID6 functional ability with progression of liver disease. However, due to small sample size and lack of knowledge of the patients' genotypes, these data are only suggestive.
Conclusion: Pugh's classification appears to be a reliable indicator of the degree of chronic liver disease and could be employed as a drug development research classification tool; however, it does not replace quantitative metabolic markers, especially isozyme-specific markers.