COMPARISON OF QUANTITATIVE METHODS TO ASSESS HEPATIC-FUNCTION - PUGHSCLASSIFICATION, INDOCYANINE GREEN, ANTIPYRINE, AND DEXTROMETHORPHAN

Study Objectives. To compare three quantitative metabolic markers used to assess hepatic function, indocyanine green (ICG), a high-extractio n marker; antipyrine, a low-extraction marker; and dextromethorphan, a P-450IID6 marker, with the clinically used Pugh's classification. Des ign. Comparison of 12 healthy controls with 12 age- and sex-matched pa tients with different degrees of liver disease. Setting. Research cent er in a university-affiliated teaching hospital. Patients. The 12 pati ents 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 grea ter than or equal to 10). Each level had an equal number of men and wo men subjects. Measurements and Main Results. Clearance of ICG detected mild alterations in hepatic function as efficiently as it did for mod erate and severe impairment, but it lacked the specificity to distingu ish among the classification groups. In contrast, antipyrine was effec tive in identifying moderate and severe hepatic impairment; however, i ts clearance was not reduced in mild liver disease. Pugh's classificat ion appears to be a clinically useful method of assessing the global d egree of hepatic impairment in patients with chronic disease, and ther e 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 p atients with a Pugh's score greater than 8 had a dextromethorphan meta bolic ratio expression reflective of a poor metabolizer phenotype base d on 0- to 4-hour urine collection, but only two of those eight patien ts were classified as poor metabolizers based on 4- to 12-hour urine c ollection. These percentages of poor metabolizers are substantially hi gher than for historical controls (8.5-10.4%) and most likely reflect a decrease in the P-450IID6 functional ability with progression of liv er 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 quantitativ e metabolic markers, especially isozyme-specific markers.