In addition, hepatic histology was a significant predictor of clinical outcome in these laboratory models, indicating that liver biopsy would still find more be required to optimize the prediction of risk for developing a clinical outcome. In contrast, nearly all of the patients who experienced clinical outcomes had values for QLFTs outside normal range, suggesting that QLFTs could provide greater discrimination between high- and low-risk patients in clinic populations enriched with patients who have milder disease. Indeed, in the

current study, CA Cloral, PHM, spleen volume, MBT, and, possibly, CA shunt enhanced the predictability of the HALT-C laboratory model. Although normal ALT and minimal fibrosis on liver biopsy may imply minimal disease, a proportion of these

patients have more advanced disease and are at risk for clinical outcomes.41-43 QLFTs could potentially be useful in this population by defining those with significant hepatic impairment who would be predicted to experience future clinical outcomes. Historically, clinical assessment of patients with liver disease has relied on surrogates of hepatic function (i.e., fibrosis stage or liver blood tests), as opposed to a true measurement of function. In the evaluation of disease affecting other organs, functional assessment defines prognosis and clinical management. Because fibrosis and standard blood tests have been the standards BGB324 order for assessing severity of liver disease, functional tests have been compared to these surrogates. Unfortunately, these comparisons cannot differentiate the advantages of functional testing over surrogates, or vice versa. Using a relevant, discriminating endpoint (i.e., clinical outcome), we compared QLFTs to hepatic histology and standard blood tests 上海皓元医药股份有限公司 and demonstrated that QLFTs compared favorably to hepatic histology and enhanced standard blood tests in the prediction of clinical outcome. Analyses of our battery of QLFTs suggest that CA Cl and PHM performed best in identifying patients at risk for clinical outcomes. When

used serially, these tests had the highest pooled RR, sensitivity, and negative predictive value. In contrast to CA Cl and PHM, metabolic tests may be influenced by age, gender, medications, BMI, and hepatic steatosis.19, 44-50 We conclude that QLFTs identify patients at risk for future clinical decompensation and, also, patients with adequate hepatic reserve who would have a benign clinical course. Despite these favorable characteristics, questions remain. Are QLFTs practical or ready for routine use in clinical practice, or, will any of the QLFTs gain approval by the U.S. Food and Drug Administration? It is our opinion that broader clinical application of QLFTs is not only possible, but also likely.