Given the lack
of treatment effect, treatment and control groups were combined for the analyses of QLFTs in predicting clinical outcomes. Baseline patient characteristics and standard laboratory results of patients with and without subsequent clinical outcomes are listed in Table 2. Patients who developed outcomes Trichostatin A in vivo had higher bilirubin and international normalized ratio (INR) as well as lower albumin. Although these differences were statistically significant, means for these tests were within normal range, even in patients who developed outcomes. Only 6% of patients who developed outcomes had INR >1.2, 22% had bilirubin >1.2 mg/dL, and 52% had albumin INCB024360 molecular weight <3.5 g/dL. In contrast, mean platelet count of patients who developed outcomes was below the lower limit of normal range, and 70% had a platelet count <140,000/μL. Patients with subsequent
outcomes had higher fibrosis scores and were more likely to have cirrhosis on liver histology and varices at endoscopy. QLFTs were worse at baseline in patients who subsequently experienced clinical outcomes (Table 2). Although differences varied by test, patients who in follow-up had subsequent clinical outcomes had greater hepatic impairment, including microsomal (i.e., antipyrine [AP], caffeine, and lidocaine- monoethylglycine xylidide; MEGX), mitochondrial (methionine), and cytosolic (galactose) functions, and flow-dependent clearances (galactose, cholates [CAs], and perfused hepatic mass; PHM). QLFTs are more sensitive than standard liver blood tests in identifying patients with hepatic impairment. In contrast to standard laboratory tests, baseline medchemexpress QLFTs were beyond normal range in nearly all patients who developed outcomes. Sixty-four percent had a caffeine elimination rate (kelim) <0.05 h−1, 89% had AP kelim <0.04 h−1, 80% had AP clearance (Cl) <0.4 mL min−1 kg−1, 81% had monoethylglycylxylidide
concentration at 15 minutes postlidocaine (MEGX15min) <20 ng/mL, 73% had a methionine breath test (MBT) <50, 74% had galactose elimination capacity (GEC) <5 mg min−1 kg−1, 93% had CA Cl after oral administration (Cloral) <15 mL min−1 kg−1, 89% had CA shunt >30%, and 79% had PHM <100. Figure 1 shows the relationships of tertiles of baseline metabolic QLFTs to the subsequent development of clinical outomes. MBT and AP Cl performed best. The boundaries and hazard ratios (HRs) for high-risk tertiles, which also defined QLFT cutoffs, were MBT ≤48 (HR, 5.92), AP Cl ≤0.28 mL kg−1 min−1 (HR, 3.62), caffeine kelim ≤0.04 h−1 (HR, 2.67), MEGX15min ≤9.0 ng/mL (HR, 2.50), and GEC ≤4.32 mg kg−1 min−1 (HR, 2.21) (Table 3). By ROC analyses, the c-statistic for MBT was 0.79.