Author information
1Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, IN, United States.
2Department of Epidemiology, Johns Hopkins University, Baltimore, MD, United States.
3Department of Biostatistics and Health Data Science, Indiana University, Indianapolis, IN, United States.
4Laboratory of Pathology, National Cancer Institute, Bethesda, MD, United States.
5Division of Gastroenterology, Saint Louis University, St Louis, MO, United States.
6Division of Gastroenterology and Hepatology, Duke University, Durham, NC, United States.
7Division of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, OH, United States.
8Liver Institute Northwest, Seattle, WA, United States.
9Division of Gastroenterology and Hepatology, University of California, San Francisco, CA, United States.
10Division of Gastroenterology and Hepatology, University of California, San Diego, CA, United States.
11Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, United States.
12Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, IN, United States. Electronic address: nchalasa@iu.edu.
Abstract
Background & aims: The clinical significance of change in liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in patients with non-alcoholic fatty liver disease (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 (LREs).
Methods: Participants in the NASH Clinical Research Network-led 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. LREs were defined as 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 LREs developed over a mean follow-up of 4.4 years, with an annual incidence rate for LREs 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%, respectively, whereas regression to LSM <10 or <15 kPa occurred in 44% and 49%, respectively. Progressors to cACLD (≥10 kPa) experienced a higher cumulative LRE rate vs. non-progressors (16% vs. 4%, adjusted hazard ratio 4.0; 95% (1.8-8.9); p <0.01). Regressors from cACLD (to LSM <10 kPa) experienced a lower LRE rate than non-regressors (7% vs. 32%, adjusted hazard ratio 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.
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 vibration-controlled transient elastography 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.