It’s Not Easy to Diagnose Intermediate-Stage Liver Fibrosis

Biopsy has a low level of diagnostic performance for liver fibrosis stages F2 and F1. The recommendation for biopsy analysis, instead of non-invasive tests, for diagnosis of intermediate stages of fibrosis is therefore misleading, according to the June issue of Clinical Gastroenterology and Hepatology.

Noninvasive tests such as FibroTest are used to stage fibrosis in patients with chronic liver diseases, but there has been controversy over their accuracy. This is because it’s not clear if results from these tests can be compared with those from biopsies—no one knows if biopsy analysis is the best way to identify patients with early or intermediate-stage fibrosis.

Thierry Poynard et al. investigated the limitations of using biopsy analysis as the standard for analysis of fibrosis tests. They analyzed large surgical samples of livers from 20 consecutive patients with chronic liver diseases or normal liver (surrounding tumors). They also analyzed digitized images of 27,869 virtual biopsies of different lengths and data from 6500 patients with interpretable FibroTest results who also underwent biopsy analysis.

In statistical analyses, Poynard et al. found that the performance of biopsy was lower for the diagnosis of F2 vs F1 samples than for F1 vs F0 or F4 vs F3, even when 30-mm biopsy samples were used. The performance of FibroTest was also lower for the diagnosis of F2 vs F1 samples than for F1 vs F0 samples or F4 vs F3. However, the FibroTest had smaller percentage differences among values than biopsy analysis (see figure).

Meta-analysis of performance of biopsy and FibroTest analyses in diagnosis of adjacent fibrosis stages using AUROCs, standardized (A) and weighted (B). Horizontal lines indicate 95% confidence interval for mean difference between FibroTest and biopsy AUROCs and random (0.500). Vertical lines indicate equivalence line. When horizontal line crosses vertical line, there is no significant difference.

An increase of overall performance was observed with increasing biopsy length. However, the only comparison without a significant increase according to biopsy length was the diagnosis of F2 vs F1.

Poynard et al. conclude that because biopsy is not a perfect reference, the true performance of FibroTest and other biomarkers in evaluation of F1- and F2-stage fibrosis is unknown.

Progress in treatment of patients with hepatitis B and C virus infections has reduced the importance of identifying F2, which was the threshold for initiating treatment. However, because of the cost of these therapies, it is important to determine their efficacy in treating patients who have no progression beyond baseline stages of F0 or F1. Futhermore, in patients with HCV who are treated with pegylated interferon and ribavirin, stages of F4 vs F3 and F3 vs F2 are prognostic factors.

The authors say that the American Association for the Study of Liver Diseases guidelines from 2009, which state “These markers are useful for establishing the 2 ends of the fibrosis spectrum (minimal fibrosis and cirrhosis) but are less helpful in assessing the mid-ranges of fibrosis or for tracking fibrosis progression”, are wrong.

They acknowledge that biopsy provides much more information than just quantification of fibrosis—it is the only direct estimate of many hepatic features. But they say that the concept that there is a ‘gray zone’ for biomarkers, compared to biopsy, is misleading—because biopsy has an inherent 25% error, other methods are needed to compare accuracy of new diagnostic tools.

Read the article online.
Poynard T, Lenaour G, Vaillant JC, et al. Liver biopsy analysis has a low level of performance for diagnosis of intermediate stages of fibrosis. Clin Gastroenterol Hepatol 2012;10:657–663.e7.

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About Kristine Novak, PhD, Science Editor

Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology, both published by the American Gastroenterological Association. She has worked as an editor at biomedical research journals and as a science writer for more than 12 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.
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One Response to It’s Not Easy to Diagnose Intermediate-Stage Liver Fibrosis

  1. agungpra says:

    Have you ever tried with liver stiffness. Because it would seem also increased liver stiffness according to the degree of fibrosis

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