Quantitative liver function tests as surrogate markers for end-points in controlled clinical trials: a retrospective...

Area of Science:

• Hepatology
• Clinical Trial Design
• Biomarkers

Background:

• Quantitative liver function tests, including galactose elimination capacity (GEC) and aminopyrine breath test (ABT), show potential as entry criteria and surrogate endpoints in clinical trials.
• Designing effective clinical trials requires understanding the magnitude of detectable differences and observation periods for these tests.

Purpose of the Study:

• To retrospectively analyze the time course and reproducibility of GEC and ABT changes in patients with alcoholic cirrhosis.
• To provide data for optimizing the design of future clinical trials using these liver function tests.

Main Methods:

• Retrospective analysis of GEC and ABT data from patients with alcoholic cirrhosis followed for 12 to 42 months.
• Comparison of test result changes between patients who abstained from alcohol and those who continued drinking.

Main Results:

• In patients abstaining from alcohol, GEC improved by 0.64 mg/min/kg within one year, while it deteriorated by 0.53 mg/min/kg in those who continued drinking (P < .01).
• Aminopyrine breath test (ABT) also showed significant improvement in abstinent patients and deterioration in non-abstinent patients (P < .01).
• Calculations suggest trials with n=20 per group need specific absolute differences in GEC (0.6-0.7 mg/min/kg) or ABT (0.11-0.13% dose x kg/mmol CO2) and 9-12 months of follow-up for statistical significance.

Conclusions:

• Galactose elimination capacity (GEC) and aminopyrine breath test (ABT) changes are reproducible and sensitive to alcohol consumption in patients with alcoholic cirrhosis.
• The findings provide essential data for sample size and duration calculations in controlled clinical trials, potentially reducing patient years of observation compared to survival analysis.
• These quantitative liver function tests can serve as valuable tools for planning and executing clinical trials in liver disease.