Correlations between metal ion transporters, liver MRIs identify mechanism of steatohepatitis

The link between two metal ion transporters and MRI based corrected Tl demonstrated a new mechanism in steatohepatitis, according to a recently published article.

“Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at risk individuals,” Constantinos A. Parisinos, MD, from the Institute of Health Informatics, Faculty of Population Health Sciences, University College London, and colleagues wrote.

Parisinos and colleagues performed a genome-wide association study of 14,440 European patients in the UK Biobank with liver MRI based corrected Tl (cTl) measures. The impact of cTl variants on the liver blood tests and the range of metabolic traits and diseases were assessed. The causal effects of 24 predominantly metabolic traits on liver cTl measures were tested with the Mendelian randomization.

“Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and BMI were causally associated with elevated cT1 whilst favorable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective,” the researchers wrote.

Investigators found six independent genetic variants correlated with liver cTl that reached the genome-wide association significance threshold. There were four variants correlated with elevated transaminases (rs75935921 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3), which had a variable impact on liver fat and metabolic traits.

“While cT1 has demonstrated excellent repeatability and good correlation with fibro-inflammation and clinical outcomes, other histological phenomena such as simple steatosis and ballooning have been shown to contribute to an increased T1 signa,” the investigators wrote. “Only two of the six cT1 variants were associated with liver steatosis, which highlights the complementarity of cT1 and liver fat [proton density fat fraction] PDFF as biomarkers of liver status, and their potential to recognize different mechanisms predisposing to liver disease.” – by Monica Jaramillo

Disclosure: Parisinos reports he receives funding by a Wellcome Trust Clinical PhD Programme (206274/Z/17/Z). Please see the full study for all other authors’ relevant financial disclosures.