Progression of MASH to cirrhosis, decompensation, and mortality, and the utility of NITs for detection and risk stratification
Philip N. Newsome, Claudio Sartini, Heather L. Morris, Derek Gazis, Andrea R. Mospan, A. Sidney Barritt, Michael W. Fried, Salvador Augustin, Mandy Fraessdorf, Bryan Rudolph, Rohit Loomba, Arun Sanyal,Background:
Recognition and management of metabolic dysfunction–associated steatohepatitis (MASH) are hindered by variability in diagnostic practices and limited real-world data on disease progression. This study assessed the use of non-invasive testing (NIT) in MASH identification and estimated incidence rates and time-to-disease progression.
Methods:
Adults in the TARGET-NASH cohort (enrolled 2016–2023) were included. MASH was confirmed via medical records, NITs, pathology reports, and imaging. Patients with MASH and significant/advanced fibrosis/cirrhosis (F2/F3/F4) were included. Outcomes included progression to cirrhosis, liver-related complications, and all-cause mortality.
Results:
Among 1964 patients (median age 59, median BMI 34), 79% had data to calculate Fibrosis-4 score (FIB-4), 36% had FibroScan, and 29% had biopsy. Among the 776 F2–F3 patients, 17% progressed to cirrhosis over a median follow-up (mFU) time of 64.6 months. In F2–F3 patients, one unit increase in FIB-4 was associated with 14% increased hazard of cirrhosis; similarly, incidence rates for cirrhosis in patients with liver stiffness measurements (LSMs) 10–15 kPa were 60.8/1000PY (per 1000 person-years; 3.5× higher than those with LSM <10 kPa). Among the 794 patients with compensated cirrhosis (cF4), 46% experienced progression events, 13% died, and 1.3% had a liver transplant (mFU=66.0 months). Among the 394 patients with decompensated cirrhosis (dF4), 29.4% died, and 9.6% had a liver transplant (mFU=62.0 months). Higher FIB-4 was associated with increased risk of decompensation and mortality in cF4 patients. Similarly, patients with LSM ≥15 kPa had a greater incidence rate of mortality (9.1/1000PY vs. 4.3/1000PY and 3.8/1000PY for LSM 10–15 kPa and <10 kPa, respectively).
Conclusions:
The burden of MASH underscores the urgency of standardizing NIT use and diagnosis. Expanding FibroScan use, automating FIB-4 calculation, and increasing awareness of NITs can improve early detection and risk stratification, thereby improving patient outcomes.