Blood Tests for Age-Related Changes in Hepatic Function
Several blood tests can measure age-related changes in hepatic function, with serum biomarker panels that incorporate age as a parameter being the most effective for assessing liver fibrosis and function in aging patients. 1
Available Serum Biomarkers That Account for Age
Several validated serum biomarker panels specifically incorporate age as a parameter to assess liver function and fibrosis:
- FibroTest® - Patented formula combining α-2-macroglobulin, γGT, apolipoprotein A1, haptoglobin, total bilirubin, age and gender 1
- Forns Index - Formula incorporating platelet count, GGT, age, and cholesterol 1
- Enhanced Liver Fibrosis (ELF) score® - Combines age, hyaluronate, MMP-3 and TIMP-1 1
- Fibrosis Probability Index (FPI) - Includes AST, age, past alcohol use, HOMA-IR, and cholesterol 1
- Hepascore® - Combines bilirubin, γGT, hyaluronate, α-2-macroglobulin, age and gender 1
- FibroMeter® - Incorporates platelet count, prothrombin index, AST, α-2-macroglobulin, hyaluronate, urea and age 1
- Virahep-C model - Includes race, age, AST, platelet count, and alkaline phosphatase 1
- Zeng score - Specifically for HBV patients, includes α-2-macroglobulin, age, GGT, and hyaluronate 1
- FIB-4 - Combines age, AST, platelets, and ALT 1
- NAFLD Fibrosis Score (NFS) - Includes age, BMI, diabetes status, AST/ALT ratio, platelet count, and albumin 1
Physiological Basis for Age-Related Changes
Age affects liver function through several mechanisms:
- Decreased liver volume - The liver volume declines with age, affecting drug metabolism capacity 2, 3
- Reduced hepatic blood flow - Blood flow to the liver decreases with age, impacting clearance of flow-limited drugs 2, 3
- Altered drug metabolism - Some specific cytochrome P450 isoenzymes may be affected by aging, particularly in men 2, 4
Standard Liver Function Tests and Age
- Standard liver function tests (AST, ALT, alkaline phosphatase, bilirubin) do not change significantly with normal aging alone 2, 5
- However, abnormal liver tests occur more commonly in elderly populations (16.1% prevalence in those aged 75 and above) 6
- The most remarkable characteristic of liver function in the elderly is increased interindividual variability 4
Clinical Application of Age-Adjusted Tests
For patients with suspected liver disease, a stepwise approach is recommended:
- Initial assessment with standard liver function tests (AST, ALT, alkaline phosphatase, bilirubin, albumin) 5
- Risk stratification using age-incorporating algorithms like FIB-4 or NAFLD Fibrosis Score 1
- For NAFLD patients: FIB-4 <1.3 (or <2.0 for those >65 years) or NFS <-1.455 (or <0.12 for those >65 years) indicate low risk of advanced fibrosis 1
- Second-line testing with serum markers such as ELF for indeterminate results 1
Limitations and Caveats
- None of these tests are liver-specific, and results may be influenced by changes in clearance and excretion of individual parameters 1
- Increased levels of hyaluronate can occur in the post-prandial state or in aged patients with chronic inflammatory processes like rheumatoid arthritis 1
- The reproducibility of some parameters included in "indirect" serum markers, such as AST levels or platelet count, may be questionable 1
- Critical interpretation is required to avoid false positive or false negative results 1
- Age-related changes in liver function may be obscured by increased interindividual variability in the elderly 4