Development and Internal Validation of a Model for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis

J Clin Gastroenterol. 2016 Feb;50(2):175-9. doi: 10.1097/MCG.0000000000000377.

Abstract

Background: Surveillance for hepatocellular carcinoma (HCC) is recommended in patients with cirrhosis; however, early detection efforts are limited by suboptimal effectiveness.

Aim: To derive and validate a model to accurately distinguish cirrhotic patients with and without HCC and compare the accuracy of the model to that of α-fetoprotein (AFP) alone.

Methods: We conducted a case-control study of cirrhotic patients with and without HCC seen at a large urban hospital system between January 2005 and June 2012. We derived multivariate logistic regression models for the presence of HCC and early-stage HCC. Discriminatory power was evaluated using receiver operating characteristic curve analysis in derivation and validation cohorts using a 10-fold cross-validation approach.

Results: We identified 1356 patients with cirrhosis, with (n=455, 147 early stage) and without (n=901) HCC. We found that AFP>20 ng/mL and FIB-4, a noninvasive marker of fibrosis, were significantly associated with the presence of HCC (OR=10.5; 95% CI, 7.9-13.9 and OR=1.05; 95% CI, 1.03-1.07, respectively) and early-stage HCC (OR=4.4; 95% CI, 2.9-6.5 and OR=1.06; 95% CI, 1.03-1.09, respectively). Models incorporating AFP and FIB-4 had good discriminatory power, with c-statistics of approximately 0.80, in both derivation and validation cohorts. The model for early-stage HCC had higher discriminatory power than AFP alone (c-statistic 0.73; 95% CI, 0.69-0.78) in derivation and validation cohorts (P=0.02 and 0.15, respectively).

Conclusions: Models including AFP and FIB-4 can accurately discriminate cirrhotic patients with early-stage HCC from those without HCC.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Validation Study

MeSH terms

  • Age Factors
  • Aged
  • Alanine Transaminase / blood
  • Area Under Curve
  • Aspartate Aminotransferases / blood
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / etiology
  • Decision Support Techniques*
  • Discriminant Analysis
  • Early Detection of Cancer / methods*
  • Female
  • Humans
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / diagnosis
  • Liver Neoplasms / blood*
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / etiology
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Odds Ratio
  • Platelet Count
  • Predictive Value of Tests
  • ROC Curve
  • Receptors, Peptide / analysis
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Factors

Substances

  • Receptors, Peptide
  • alpha-fetoprotein receptor, human
  • Aspartate Aminotransferases
  • Alanine Transaminase