Increases and decreases in liver stiffness measurement are independently associated with the risk of liver-related events in NAFLD

Background and aims The clinical significance of change in liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in patients with NAFLD is not well-understood. We prospectively defined rates of progression to and regression from LSM-defined compensated advanced chronic liver disease (cACLD) and their associations with liver-related events (LRE). Methods Participants in the NASH Clinical Research Network NAFLD Database 2 and 3 studies were included. Progression to cACLD was defined as reaching LSM ≥10 kPa in participants with LSM < 10 kPa on initial VCTE; regression from cACLD was defined as reaching LSM < 10 kPa in participants with baseline LSM ≥ 10 kPa. LRE was defined ≥1 of the following: liver-related death, liver transplant, hepatocellular carcinoma, MELD>15, development of varices, or hepatic decompensation. Univariate and multivariable interval-censored Cox regression analyses were used to compare the cumulative LRE probability by LSM progression and regression status. Results In 1,403 participants, 89 LRE developed over a mean follow-up of 4.4 years with an LRE annual incidence rate of 1.5 (95% CI: 1.2-1.8). In participants at risk, progression to LSM ≥10 or ≥15 kPa occurred in 29% and 17%, whereas regression to LSM <10 or <15 Kpa occurred in 44% and 49%. Progressors to cACLD (≥10 kPa) experienced a higher cumulative LRE rate versus non-progressors [16% vs 4%, Adj.HR: 3.8, 95% CI [2.3-6.5], P < 0.01]. Regressors from cACLD (to LSM <10 kPA) experienced a lower LRE rate than non-regressors [7% vs 32%%, Adj.HR: 0.25, 95% CI [0.10-0.61], P < 0.01] Conclusions Change in LSM over time is independently and bi-directionally associated with risk of LRE and is a non-invasive surrogate for clinical outcomes in patients with NAFLD. (Word count: 275) Impact and Implications The prognostic value of change in LSM in patients with NAFLD is not well understood. In this large prospective study of patients with NAFLD and serial VCTE exams, baseline and dynamic changes in LSM were associated with the risk of developing liver-related events. LSM is a useful non-invasive surrogate of clinical outcomes in patients with NAFLD.