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

BACKGROUND & AIMS: Corrected T1 (cT1), measured by liver MRI, enables non-invasive evaluation of hepatic water content. Although a threshold of ≥800 ms has been proposed to identify individuals at risk of MASH with poor outcomes, it captures only a small proportion (∼5%) and may fail to account for risk below this level. We aimed to evaluate whether cT1 values below 800ms are associated with mortality and whether hepatic steatosis, assessed by MRI-derived proton density fat fraction (PDFF), modifies this relationship. METHODS: We analyzed 29,597 UK Biobank participants with liver MRI-derived cT1 values. Participants were categorized into three groups (<700, 700-799, and ≥800 ms) based on penalized spline analysis. Outcomes included all-cause, cause-specific mortality, and liver-related events. Cox models were adjusted for demographic, lifestyle, and cardiometabolic factors. RESULTS: Approximately 40% of participants had cT1 700-799 and 5% had ≥800ms. Over a median follow-up of 5.3 years, the 700-799ms group showed increased risks of all-cause mortality (adjusted hazard ratio 95% CI: 1.21 1.02-1.43) and cardiovascular mortality (1.54 1.04-2.28) compared with <700ms. The risks were even higher in the cT1 ≥800ms group. Clinically significant hepatic steatosis (PDFF≥10%) had interaction on the association between cT1 and all-cause mortality (P<0.05). cT1 significantly increased all-cause mortality only in participants with PDFF<10% (1.25 1.06-1.49 in the cT1 700-799ms group and 2.20, 1.40-3.48 in the cT1 ≥ 800ms group, compared to the cT1 < 700ms group), but not in those with PDFF ≥ 10%. CONCLUSION: cT1 values between 700 and 799ms were independently associated with increased mortality risk. Notably, this association was modified by the presence of significant hepatic steatosis as assessed by PDFF. IMPACT AND IMPLICATIONS: Using liver MRI to measure cT1, we demonstrated that a cT1 value of 700-799 ms (lower than the traditional cut-off value of 800 ms) was associated with an increased risk of all-cause and cardiovascular mortality. Additionally, the association between cT1 and mortality was evident only among participants with PDFF <10%, not in those with PDFF ≥ 10%. These findings suggest that cT1 can predict all-cause and cardiovascular mortality only in participants without clinically significant hepatic steatosis. In participants with clinically significant hepatic steatosis, cT1 was not associated with increased mortality.