Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: results from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial.
Risk for future clinical outcomes is proportional to the severity of liver disease in patients with chronic hepatitis C virus (HCV). 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 and 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(elim)), antipyrine (AP) clearance (Cl), MEGX concentration, methionine breath test (MBT), galactose elimination capacity (GEC), dual cholate (CA) clearances and shunt, perfused hepatic mass (PHM), and liver and spleen volumes (by single-photon emission computed tomography) were measured. Baseline QLFTs were significantly worse (P = 0.0017 to P < 0.0001) and spleen volumes were 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% confidence interval [CI]: 1.29-3.78) for GEC to 6.52 (95% CI: 3.63-11.71) for CA clearance after oral administration (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.


CONCLUSIONS
QLFTs independently predict risk for future clinical outcomes. By improving risk assessment, QLFTs could enhance the noninvasive monitoring, counseling, and management of patients with chronic HCV.
Section of Hepatology, Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, CO 80045, USA. greg.everson@ucdenver.edu
Gregory T
GT
Everson
Mitchell L
ML
Shiffman
John C
JC
Hoefs
Timothy R
TR
Morgan
Richard K
RK
Sterling
David A
DA
Wagner
Shannon
S
Lauriski
Teresa M
TM
Curto
Anne
A
Stoddard
Elizabeth C
EC
Wright
D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008099:Liver / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000503:physiopathology*; D008111:Liver Function Tests; D008137:Longitudinal Studies; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a