Use of PNPLA3, TM6SF2, and HSD17B13 for detection of fibrosis in MASLD in the general population - 06/06/24
, Mikkel Parsberg Werge a, Liv Eline Hetland a, Mira Thing a, Puria Nabilou a, Nina Kimer a, Anders Ellekaer Junker a, Anne-Sofie Houlberg Jensen a, b, Børge Grønne Nordestgaard c, d, Stefan Stender d, e, Lise Lotte Gluud a, dHighlights |
• | 414 individuals at risk of MASLD from the Danish general population agreed to participate to a hepatological assessment at Gastro Unit, Hvidovre Hospital, Copenhagen Denmark. |
• | Four patients screened turned out to have malignant diseases or autoimmune liver diseases. |
• | 27 participants underwent a liver biopsy due to risk of significant liver fibrosis. |
• | The combination of Fib-4 and PNPLA3 (CC/CG) increased diagnostic accuracy and had excellent sensitivity. |
• | The study found no evidence to support the use of a 3-SNP genetic risk score. |
Abstract |
Background |
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).
Methods |
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.
Results |
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.
Conclusions |
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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Keywords : Metabolic dysfunction-associated liver disease, Masld, Non-alcoholic fatty liver disease, Steatohepatitis, Cirrhosis, Fibrosis, PNPLA3
Abbreviations : MASLD, SNP, ALT, CI
Plan
Vol 48 - N° 7
Article 102389- août 2024 Retour au numéro
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