IDDF2024-ABS-0160 Evidence for a causal link between MRI-determined early liver disease and cataracts: a prospective study and mendelian randomization analysis

<h3>Background</h3> Chronic liver disease (CLD) can lead to various severe extrahepatic multisystem complications. However, little is known about the association between early liver disease determined by corrected T1 (cT1) and cataracts, the leading cause of blindness worldwide. This study aimed to explore the association of cT1 with cataracts using observational and Mendelian randomization designs. <h3>Methods</h3> The prospective cohort included 30,693 participants aged 45–81 years from the UK Biobank. Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured by MRI. In the Mendelian randomization, we utilized six single nucleotide polymorphisms associated with cT1 (<i>P</i> &lt; 5*10^-8) from Europeans (<i>n</i> = 14,440); we also obtained the summarized statistics of genome-wide association studies for cataracts from Europeans (10,475 cataract cases and 98,342 noncases). <h3>Results</h3> In the prospective study with a median follow-up of 4.3 years, 870 participants developed cataracts. The cumulative incidence of cataracts increased as cT1 values rose, climbing from 2.25% in the quartile 1 to 3.75% in the quartile 4 subgroup. Cox regression analysis revealed that liver disease activity (cT1), but not liver fat (PDFF), was independently associated with the risk of incident cataracts (adjusted hazard ratio: 1.14, 95% CI: 1.04-1.26, per 1-SD increase). Our Mendelian randomization analysis showed that genetically determined cT1 was also significantly associated with cataracts (odds ratio: 1.99, 95% CI: 1.22–3.24, per 1-SD increase). <h3>Conclusions</h3> This study suggested a causal role of early liver disease (cT1) in the development of cataracts.