Institute for Clinical and Translational Science

Risk for future clinical outcomes is proportional to the severity of liver disease in patients with chronic hepatitis C. We measured disease severity by quantitative liver function tests (QLFTs) to determine cutoffs for QLFTs that identified patients who were at low and high risk for a clinical outcome. Two hundred twenty seven participants in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial underwent baseline QLFTs and were followed for a median of 5.5 years for clinical outcomes. QLFTs were repeated in 196 patients at month 24 and in 165 patients at month 48. Caffeine elimination rate (k), antipyrine (AP) clearance (Cl), MEGX concentration, methionine breath test (MBT), galactose elimination capacity (GEC), dual cholate (CA) clearances and shunt, and perfused hepatic mass (PHM) and liver and spleen volumes (SPECT) were measured. Baseline QLFTs were significantly worse (p=0.0017 to <0.0001) and spleen volumes larger (p<0.0001) in the 54 patients who subsequently experienced clinical outcomes. QLFT cutoffs that characterized patients as “low” and “high risk” for clinical outcome yielded hazard ratios ranging from 2.21 (95%CI 1.29–3.78) for GEC to 6.52 (95%CI 3.63–11.71) for CA Cl_oral. QLFTs independently predicted outcome in models with Ishak fibrosis score, platelet count, and standard laboratory tests. In serial studies, patients with “high risk” results for CA Cl_oral or PHM had a nearly 15-fold increase in risk for clinical outcome. Less than 5% of patients with “low risk” QLFTs experienced a clinical outcome.

QLFTs independently predict risk for future clinical outcomes. By improving risk assessment, QLFTs could enhance noninvasive monitoring, counseling, and management of patients with chronic hepatitis C.