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A
High Confidence
Cohort StudyPMC Full Text2012

Upper Limits of Normal for Alanine Aminotransferase Activity in the United States Population

Ruhl CE, Everhart JE • Hepatology

Key Finding

Optimal ALT cutoffs: men 29 IU/L (88% sens, 83% spec), women 22 IU/L (89% sens, 82% spec); 36.4% of men and 28.3% of women would show elevated ALT using these cutoffs

Key Findings

  • 1Optimal ALT cutoff men: 29 IU/L (88% sensitivity, 83% specificity)
  • 2Optimal ALT cutoff women: 22 IU/L (89% sensitivity, 82% specificity)
  • 3Using optimal cutoffs: 36.4% men and 28.3% women show elevated ALT
  • 4Traditional lab ranges (40-45 IU/L) miss significant liver disease

Original title: “Upper limits of normal for alanine aminotransferase activity in the United States population”

Plain English Summary

NHANES 1999-2008 analysis comparing HCV RNA-positive individuals (n=259) to low liver disease risk group (n=3,747) to determine optimal ALT cutoffs.

In-Depth Analysis

Study Details

Authors: Constance E Ruhl, James E Everhart
Journal: Hepatology, 2012 Feb; 55(2):447-454
PMCID: PMC3268908

Key Statistics (from original paper)

Study Population
  • •HCV RNA-positive: n = 259
  • •Low liver disease risk: n = 3,747
  • •Data source: NHANES 1999-2008
Optimal Cutoffs (Maximum Correct Classification)
SexCutoffSensitivitySpecificity
Men29 IU/L88%83%
Women22 IU/L89%82%
Alternative Thresholds

95% Sensitivity:

  • •Men: 24 IU/L (70% specificity)
  • •Women: 18 IU/L (63% specificity)

95% Specificity:

  • •Men: 44 IU/L (64% sensitivity)
  • •Women: 32 IU/L (59% sensitivity)
Population Impact

Using optimal cutoffs:

  • •36.4% of men would show elevated ALT
  • •28.3% of women would show elevated ALT

Using 95% specificity cutoffs:

  • •12.5% of men affected
  • •8.9% of women affected
Model Performance
  • •AUC (men): 0.929
  • •AUC (women): 0.915

Source: PMC full text (PMC3268908)

Paradigm Relevance

How this study applies to different clinical perspectives:

Standard Medical

Relevant

Conventional clinical guidelines used by most doctors

Why it matters:

Validates current guidelines that often use higher thresholds (40-56 U/L). Useful for ruling out overt liver disease but may miss early NAFLD.

Research Consensus

Relevant

Current scientific understanding, often ahead of guidelines

Why it matters:

Provides scientific basis for lower thresholds (29/22 U/L) that identify early liver fat accumulation before disease progression.

Metabolic Optimization

Relevant

Proactive targets for optimal health, not just disease absence

Why it matters:

Supports aggressive interpretation where lower ALT indicates better hepatic insulin sensitivity. Even values in the 20s may warrant lifestyle optimization.

Study Details

Type
Cohort Study
Methodology
NHANES 1999-2008 data. N = 259 HCV RNA-positive, N = 3,747 low-risk. ROC curve analysis. AUC: 0.929 (men), 0.915 (women).

Evidence Quality

Grade A - Large population study. PMC3268908. Establishes lower ALT thresholds than traditional lab ranges.

Topic

Liver HealthMetabolic Syndrome

Related Biomarkers

ALTLIVER ENZYMES

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ALT

Evaluator

Liver enzyme with optimal range guidance

Original Source

View on PubMedView DOIFull Text (Open Access)

DOI (Digital Object Identifier) is a permanent link to this publication. Unlike website URLs that can change, a DOI always resolves to the correct source.

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