{Reference Type}: Journal Article
{Title}: Use of PNPLA3, TM6SF2, and HSD17B13 for detection of fibrosis in MASLD in the general population.
{Author}: Rashu EB;Werge MP;Hetland LE;Thing M;Nabilou P;Kimer N;Junker AE;Jensen AH;Nordestgaard BG;Stender S;Gluud LL;
{Journal}: Clin Res Hepatol Gastroenterol
{Volume}: 48
{Issue}: 7
{Year}: 2024 Jun 1
{Factor}: 3.189
{DOI}: 10.1016/j.clinre.2024.102389
{Abstract}: <B>BACKGROUND: </B>Genetic testing can be used to evaluate disease risk. We evaluated if the use of three Single Nucleotide Polymorphisms (SNPs), alone or combined into a genetic risk score (GRS), can aid identify significant fibrosis in subjects with metabolic dysfunction-associated steatotic liver disease (MASLD).<BR><B>METHODS: </B>We assessed three known risk variants: PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567. The study included 414 adult individuals invited from the Danish population, who were defined as at-risk of MASLD due to elevated ALT and body mass index (BMI) >25 kg/m2. Participants were assessed clinically and by the Fibrosis-4 (FIB-4) index and Fibroscan.<BR><B>RESULTS: </B>In total, 17 participants (4.1 %) had alcohol-related liver disease, 79 (19.1 %) had no evidence of liver disease, and four (1.0 %) were diagnosed with other liver diseases, including malignant disease. The remaining 314 participants (75.8 %) were diagnosed with MASLD. Of the 27 who underwent a liver biopsy for suspected fibrosis, 15 had significant fibrosis (≥F2) and 12 had no/mild fibrosis (F0/F1). The GRS was not associated with significant fibrosis (p = 0.09) but PNPLA3 was with an odds ratio of 6.75 (95 % CI 1.29 - 50.7; p = 0.039) risk allele CG/GG versus CC. The diagnostic accuracy of PNPLA3 combined with an increased Fib-4 (>1.3) was excellent for detecting significant fibrosis with a sensitivity of 1.00 (95 % CI 0.72-1.00), but the specificity was no better than for FIB-4 alone.<BR><B>CONCLUSIONS: </B>This study found no evidence to support the use of GRS for diagnosing significant fibrosis in MASLD. However, the combination of PNPLA3 and Fib-4 increased sensitivity considerably. In addition, ALT remains a useful tool for screening diagnosing other liver diseases than MASLD.