Background and aimThe aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are commonly used compound surrogates for advanced fibrosis in chronic hepatitis C (CHC) patients. However, the use of APRI and FIB-4 entails a risk of overestimating the fibrosis stage due to the impact of necroinflammatory activity on transaminases. We sought to investigate the optimal cutoff values of the two compound surrogates for predicting cirrhosis stratified by AST level.MethodsThis retrospective study enrolled 1716 treatment-naive CHC patients who underwent liver biopsy prior to interferon therapy from 1997–2010. Fibrosis was scored according to the modified Knodell classification. The upper limit for normal AST in our hospital is 37 IU/L. We stratified the enrolled patients into the categories of AST≤37 IU/L (N = 132), 37148 IU/L (N = 346).Results436 patients had cirrhosis (F4). The area under receiver operating characteristic (AUROC) analysis results distinguishing cirrhosis (F4) from non-cirrhosis (F0–F3) were 0.81 for APRI and 0.85 for FIB-4 in patients with AST≤37 IU/L; 0.71 for APRI and 0.72 for FIB-4 in patients with 37148 IU/L. The optimal cutoff values of APRI and FIB-4 for the diagnosis of cirrhosis were 0.6 and 1.4, respectively, in patients with AST≤37 IU/L; 1.1 and 2.2, respectively, in patients with 37148 IU/L.ConclusionsWe provide optimal cutoff values of both APRI and FIB-4 to predict cirrhosis stratified by AST levels, which should be more feasible compared with the single cutoff values proposed in previous studies.

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Our results collectively indicate that pancreatic acini-like tissue in liver represent aggregates of pancreatic acinar cells admixed with small intra-acinar terminal ductules. Given the close spatial relationship with reactive bile ductules and the apparent transition in immunophenotype from bile ductules to pancreatic acinar tissue, the latter is likely of metaplastic origin derived from a hepatic progenitor lineage.

These results indicate that computerized morphometric analysis can yield useful criteria to distinguish HB from pHCC in small biopsy specimens, and, compared with FHB, the poorer prognosis of EHB may result from its more undifferentiated (immature) and proliferative phenotype.