Transient elastography and APRI score: looking at false positives and false negatives. Diagnostic performance and association to fibrosis staging in chronic hepatitis C

Abstract

Although long regarded as the gold standard for liver fibrosis staging in chronic hepatitis C (CHC), liver biopsy (LB) implies both the risk of an invasive procedure and significant variability. The aim of this study was to evaluate the diagnostic performance for transient elastography (TE) and aspartate aminotransferase to platelet index (APRI) used alone and in combination compared to liver biopsy and to analyze false positive/negative results. Patients with CHC, and no previous clinical diagnosis of cirrhosis were enrolled to undergo liver biopsy, TE and APRI. A total of 182 adult patients with a median age of 55 years and median body mass index of 26.71 kg/m2 were analyzed. On LB, 56% of patients had significant levels of fibrosis (METAVIR F≥2) and 28% had advanced fibrosis (F3/F4). The strongest performance for both tests was observed for exclusion of advanced fibrosis with good negative predictive values (89 and 86%, respectively). Low necroinflammatory activity on LB was associated with false negative TE. False positives were associated with NASH and smaller LB fragments. Correlation between APRI and Fibroscan for F≥2 was 100% and 84% for F≥3 and remained high in both false negative and false positive instances, correctly identifying F<2 in 71% of cases and F<3 in 78% (and potentially foregoing up to 84% of LB). We concluded that low individual performance indicators could be attributable to limitations of LB. Poorer differentiation of lower levels of fibrosis is a known issue for LB and remains so for noninvasive tests. Good predictability is possible, however, for advanced fibrosis.

Figure 1. Box plot distribution of aspartate aminotransferase to platelet index (APRI) results according to METAVIR LB staging. First and third quartiles are represented as top and bottom of the boxes, and the error bars show minimum and maximal values. The vertical length of the box represents the interquartile range and the horizontal line through the middle represent the median value.

Figure 2. Box plot distribution of Fibroscan results according to METAVIR LB staging. First and third quartiles are represented as top and bottom of the boxes, and the error bars show minimum and maximal values. The vertical length of the box represents the interquartile range and the horizontal line through the middle represent the median value.

Figure 3. Receiver-operating-characteristic (ROC) curves of noninvasive tests transient elastography (TE), aspartate aminotransferase to platelet index (APRI) and a combination of both tests for significant (A) and advanced (B) fibrosis in chronic hepatitis C patients compared to histological analysis through liver biopsy.