Refined liver MRI-derived cT1 thresholds capturing hepatic fat fraction enhance mortality risk prediction

Corrected T1 (cT1), measured by liver MRI, enables non-invasive assessment of hepatic water content. Although a threshold of ≥800 ms has been proposed to identify individuals at risk of metabolic dysfunction-associated steatohepatitis (MASH) and adverse outcomes, it identifies only a small proportion of individuals (∼5%) and may fail to capture risk below this threshold. We aimed to evaluate whether cT1 values below 800 ms are associated with mortality and whether hepatic steatosis, assessed by MRI-derived proton density fat fraction (PDFF), modifies this association.

We analyzed 29,597 UK Biobank participants with liver MRI-derived cT1 measurements. Participants were categorized into three groups (<700, 700-799, and ≥800 ms) based on penalized spline analysis. Outcomes included all-cause mortality, cause-specific mortality, and liver-related events. Cox proportional hazards models were adjusted for demographic, lifestyle, and cardiometabolic factors.

Approximately 40% of participants had cT1 values of 700-799 ms, and 5% had cT1 values ≥800 ms. Over a median follow-up of 5.3 years, participants with cT1 values of 700-799 ms had higher risks of all-cause mortality (adjusted hazard ratio [aHR] 1.21; 95% CI 1.02-1.43) and cardiovascular mortality (aHR 1.54; 95% CI 1.04-2.28) than those with cT1 values <700 ms. Risks were even higher among participants with cT1 values ≥800 ms. Clinically significant hepatic steatosis (PDFF ≥10%) significantly modified the association between cT1 and all-cause mortality (p for interaction <0.05). Higher cT1 was associated with increased all-cause mortality only among participants with PDFF <10% (aHR 1.25 [95% CI 1.06-1.49] for cT1 700-799 ms and 2.20 [95% CI 1.40-3.48] for cT1 ≥800 ms, compared with cT1 <700 ms), but not among those with PDFF ≥10%.

cT1 values between 700 and 799 ms were independently associated with an increased risk of mortality. Notably, this association was modified by the presence of clinically significant hepatic steatosis as assessed by PDFF.

Using liver MRI to measure cT1, we demonstrated that cT1 values of 700-799 ms, below the conventional threshold of 800 ms, were independently associated with an increased risk of all-cause and cardiovascular mortality. We also found that this association was present only among participants with PDFF <10%, indicating that clinically significant hepatic steatosis modifies the relationship between cT1 and mortality. These findings suggest that lower cT1 thresholds may improve risk stratification and that the prognostic significance of cT1 should be interpreted in the context of hepatic steatosis.