Aerobic exercise interventions lead to MASH resolution in clinical trials: Pooled analysis using the MASH resolution index

Exercise training is a core management component of metabolic dysfunction–associated steatotic liver disease (MASLD) with broad hepatic and extrahepatic benefits.1,2 Despite the benefits of hepatic steatosis, even in the absence of clinically meaningful weight loss, the effects of exercise training on histological features of metabolic dysfunction–associated steatohepatitis (MASH) are uncertain due to the relative lack of randomized controlled trials.1,2 This may, in part, be due to the need for repeat liver biopsies to accurately assess these outcomes. Since liver fibrosis is a key prognostic measure for risk of all-cause and liver-related mortality,3 examining the impact of exercise training on validated noninvasive histological surrogates is imperative.

There are several validated noninvasive tools to evaluate liver disease severity; however, most were developed and validated as screening and risk assessment tools, rather than to quantify intervention effects. We recently demonstrated that exercise training led to clinically meaningful improvements in imaging-based surrogates of liver histological change (≥30% relative reduction in MRI-measured liver fat).4 To address the ongoing need for a reliable, noninvasive assessment, with adequate sensitivity to detect the histological resolution of MASH, Loomba et al5 developed and validated the MASH resolution index (MASH-RI). This index outperformed changes in serum ALT and MRI-derived liver fat (MRI-PDFF), and provides an alternative endpoint to determine MASH resolution post-intervention, removing the need for paired liver biopsy in intervention studies. MASH-RI is comprised of baseline/change in MRI-PDFF, baseline/change in ALT, and baseline AST. We examined the efficacy of exercise training on the MASH-RI compared with standard care control.