The diagnostic accuracy of TIMP-1 alone to predict F≥2 was high, and the diagnosis of F≥2 was slightly increased when a regression model that included TIMP-1 and hyaluronic acid was applied [15]. These results disagree with those reported here. Different degrees of liver inflammation might account for this disagreement, as TIMP-1 levels correlate with liver inflammation [27]. High necro-inflammatory
activity may reduce the specificity of TIMP-1. Indeed, in previous studies in HCV monoinfection, TIMP-1 levels alone had high sensitivity, but relatively low specificity [27–29]. However, previous studies on MMP-2 in HCV monoinfection also yielded conflicting results, with some studies finding MMP-2 useful in predicting fibrosis [28,30] and other studies showing low diagnostic utility [27,29]. The reason for these contradictory results is not clear. In the present study, a regression www.selleckchem.com/Caspase.html model combining AST, platelet count and MMP-2 predicted with high certainty the buy STA-9090 absence and presence of F≥2. One-third of the study population could be spared liver biopsy by applying this model. This figure
is in agreement with that reported in a recent systematic review, in which cut-off values of biomarkers could rule out or rule in fibrosis in 35% of patients [13]. Importantly, there were a few diagnostic errors both for excluding and for detecting F≥2 in the present study. In addition, we found that using a simple index that includes in the calculation AST and platelets, as the APRI, in the first step in a diagnostic algorithm and, in the second step, a high cut-off value of MMP-2 levels increased the yield of correct F≥2 diagnoses. With this approach, it was possible to save 46% of the study group from liver biopsy. Moreover, all the classification errors were a result of patients showing F1 in the liver biopsy. The goal of the present study was to achieve maximal diagnostic accuracy with the lowest possible rate of classification errors. Thus, the very lower cut-off for the diagnosis of F≥2 yielded an NPV of 88%, and the higher cut-off yielded a PPV of 87%. The rate of misclassifications using both cut-offs was 13%. This strategy reduced the proportion of the study population who could
be classified to one-third of the patients. In a study by Larrousse et al. [15], the cut-off point with the lowest diagnostic errors derived from their model to detect F≥2 yielded a PPV of 80% and an NPV of 77% and involved 78% of the population. However, 22% of the patients were erroneously classified [15]. This high rate of misclassification precludes the application of the Larrousse and colleagues model in clinical practice. However, the selection of two cut-off values from that model with the highest predictive values would probably decrease its rate of classification errors. In the present study, cirrhosis could be detected with a higher cut-off value using the MAPI with a relatively low rate of diagnostic errors. However, only 60% of patients with cirrhosis were detected.