Exceeding the limits of liver histology markers

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197 Scopus citations


Background/Aims: Alternatives to liver biopsy for staging liver disease caused by hepatitis C virus (HCV) have not appeared accurate enough for widespread clinical use. We characterized the magnitude of the impact of error in the "gold standard" on the observed diagnostic accuracy of surrogate markers. Methods: We calculated the area under the receiver operating characteristic curve (AUROC) for a surrogate marker against the gold standard (biopsy) for a range of possible performances of each test (biopsy and marker) against truth and a gradient of clinically significant disease prevalence. Results: In the 'best' scenario where liver biopsy accuracy is highest (sensitivity and specificity of biopsy are 90%) and the prevalence of significant disease 40%, the calculated AUROC would be 0.90 for a perfect marker (99% actual accuracy) which is within the range of what has already been observed. With lower biopsy sensitivity and specificity, AUROC determinations >0.90 could not be achieved even for a marker that perfectly measured disease. Conclusions: We demonstrate that error in the liver biopsy result itself makes it impossible to distinguish a perfect surrogate from ones that are now judged by some as clinically unacceptable. An alternative gold standard is needed to assess the accuracy of tests used to stage HCV-related liver disease.

Original languageEnglish (US)
Pages (from-to)36-41
Number of pages6
JournalJournal of Hepatology
Issue number1
StatePublished - Jan 2009


  • Biopsy
  • Hepatitis C virus
  • Liver disease
  • Surrogate markers
  • Validity

ASJC Scopus subject areas

  • Hepatology


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