Identifying suitable biomarkers that can be used to replace liver biopsy or to determine patients who would benefit from one is garnering interest in both the clinical management of MASH and drug development.
Research published in the Journal of Hepatology investigated two MRI-derived noninvasive tests—iron corrected T1 mapping (cT1) and liver fat content from proton density fat fraction (PDFF)—to predict histologic improvement in patients who had undergone experimental treatment for MASH.
“Monitoring of patients and assessing the efficacy of interventions is critical to reducing the prevalence of MASH. Non-invasive tests that provide precise measurement and the ability to detect any changes in the disease-driving features dynamically are of prime interest in the management of patients as well as for the efficacy assessment in clinical trials,” Naim Alkhouri, MD, FAASLD, and coauthors wrote.
Emerging data suggest that absolute reduction in cT1 of at least 80 ms and relative reduction in liver fat content of 30% demonstrates histological improvement.
Predicting Histologic Response
For the retrospective analysis, the researchers pooled data from three interventional MASH phase 2 clinical trials to assess the differences in the magnitude of change in cT1 and liver fat content between responders and non-responders. Responders were defined as those achieving resolution of steatohepatitis without worsening fibrosis. A total of 150 patients were included in the analysis.
The researchers found that cT1 and liver fat content from PDFF are effective at identifying those likely to respond to drug interventions. A significant decrease in liver cT1 (-119 ms vs -49 ms) and liver fat content (-65% vs -29%) in responders compared with non-responders (P<0.001), respectively, was observed. The area under the curve for cT1 identifying responders was 0.72. The Youden’s index (optimal threshold) for cT1 to distinguish responders from non-responders was -82 ms, and the relative reduction in liver fat content indicates the likelihood for resolution of MASH was 58%.
Additionally, a reduction of at least 80 ms in cT1 was associated with a five-fold increase in the odds of achieving resolution of steatohepatitis (sensitivity 0.68; specificity 0.70). The cohort having a 30% relative reduction in liver fat was 3.8 times more likely to achieve a histological response (sensitivity 0.77; specificity 0.53).
“These results, from three combined drug trials, demonstrate that changes in multiparametric MRI markers of liver health (cT1 and PDFF) can predict histological response for steatohepatitis following therapeutic intervention,” the investigators concluded.
