Optimization of the Use of APRI and FIB‐4 for Ruling Out Liver Cirrhosis in Chronic Hepatitis B Patients With Normal Alanine Aminotransferase

ABSTRACT The exclusion of cirrhosis is important in chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT). We aimed to optimise the performance of the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis score based on four factors (FIB‐4) to exclude cirrhosis in these patients. Five hundred and eighty four patients with normal ALT who underwent liver biopsy were included in the study. The patients were divided into derivation and external validation sets. A grid search method was used to identify new cut‐offs with a negative predictive value (NPV) of > 95% and a sensitivity of > 90% for detecting cirrhosis. The proportion of patients with cirrhosis in the derivation and validation sets was 19.4% and 7.5%, respectively. The conventional cut‐offs of APRI (77.6%) and FIB‐4 (41.8%) had high rates of cirrhosis misclassification. A new APRI cut‐off of 0.21 had a sensitivity of 97.0% and an NPV of 95.6%, and only two (3.0%) patients with cirrhosis were misclassified in the derivation set. Using a new FIB‐4 cut‐off of 0.53, with a sensitivity of 98.5% and NPV of 96.2%, only one (1.5%) patient with cirrhosis was misclassified. External validation showed similar results. Using the new cut‐offs of APRI and FIB‐4, cirrhosis could be completely excluded for HBeAg‐positive patients or those aged > 40 years. The conventional cut‐offs had high misclassification rates for cirrhosis. The new cut‐offs of APRI (≤ 0.21) and FIB‐4 (≤ 0.53) could be used to exclude cirrhosis in CHB patients with normal ALT levels with a low misclassification rate.