ObjectivesTo determine and validate alanine aminotransferase (ALT)-adapted dual cut-offs of liver stiffness measurements (LSMs) for assessing liver fibrosis with two-dimensional shear wave elastography (2D-SWE) in patients with chronic hepatitis B (CHB) infection.MethodsPatients with CHB infection who underwent liver biopsy to assess liver fibrosis were consecutively included. 2D-SWE confirmation thresholds with a positive likelihood ratio ≥10 and 2D-SWE exclusion thresholds with a negative likelihood ratio ≤0.1 were identified to rule in or rule out significant fibrosis and cirrhosis, respectively.ResultsThe first 515 patients (index cohort) and the next 421 patients (validation cohort) were included in the final analysis. The low and high cut-offs to rule out and rule in patients with significant fibrosis (≥ F2) were 5.4 kPa and 9.0 kPa, respectively, in patients with ALT levels ≤ 2 × the upper limit of normal (ULN) and 7.1 kPa and 11.2 kPa in patients with ALT levels > 2 × ULN. For cirrhosis (F4), the corresponding values were 8.1 kPa and 12.3 kPa in patients with ALT levels ≤ 2 × ULN and 11.9 kPa and 24.7 kPa in patients with ALT levels > 2 × ULN. The dual cut-off values showed an overall accuracy of more than 90% for diagnosis of the presence or absence of significant fibrosis and cirrhosis in the index and validation cohorts. There were no significant differences in the accuracy values between the cohorts (all p>0.05).ConclusionThe ALT-adapted dual cut-offs of LSMs showed high accuracy for diagnosis of the presence or absence of significant fibrosis and cirrhosis in patients with CHB infection.Key Points• The ALT-adapted dual cut-off values of LSMs showed high accuracy for diagnosis of the presence or absence of significant fibrosis and cirrhosis.• ALT levels did not influence the overall diagnostic accuracy for predicting significant fibrosis and cirrhosis.• The ALT-adapted dual cut-offs in patients with ALT levels > 2 × ULN were markedly higher than those in patients with ALT levels ≤ 2 × ULN.