Liver Stiffness Measurement can Predict Liver Inflammation in Chronic Hepatitis B Patients with Normal Alanine Transaminase

Background and Aims: To determine whether liver stiffness measurement (LSM) indicates liver inflammation in chronic hepatitis B (CHB) with different upper limits of normal (ULNs) for alanine aminotransferase (ALT). Methods: We grouped 439 CHB patients using different ULNs for ALT: cohort I, <= 40 U/L (439 subjects); cohort II, <= 35/25 U/L (males/females; 330 subjects); and cohort III, <= 30/19 U/L (males/females; 231 subjects). Furthermore, 84 and 96 CHB patients with normal ALT (<= 40 U/L) formed the external and prospective validation groups, respectively. We evaluated the correlation between LSM and biopsy-confirmed liver inflammation, and determined diagnostic accuracy using area under the curve (AUC). A noninvasive LSM-based model was developed using multivariate logistic regression. Results: Fibrosis-adjusted LSM values significantly increased with increasing inflamma-tion. The AUCs of LSM in cohorts I, II, and III were 0.799, 0.796, and 0.814, respectively, for significant inflammation (A>_2) and 0.779, 0.767, and 0.770, respectively, for severe inflammation (A=3). Cutoff LSM values in all cohorts for A>_2 and A=3 were 6.3 and 7.5 kPa, respectively. Internal, ex-ternal, and prospective validations showed high diagnostic accuracy of LSM for A>_2 and A=3, and no significant dif-ferences in AUCs among the four groups. LSM and globulin independently predicted A>_2. The AUC of an LSM-globulin model for A>_2 exceeded those of globulin, ALT, and AST, but was similar to that of LSM. Conclusions: LSM predicted liver inflammation and guided the indication of antiviral therapy for CHB in patients with normal ALT.