Use of PNPLA3, TM6SF2, and HSD17B13 for detection of fibrosis in MASLD in the general population
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Use of PNPLA3, TM6SF2, and HSD17B13 for detection of fibrosis in MASLD in the general population. / Rashu, Elias Badal; Werge, Mikkel Parsberg; Hetland, Liv Eline; Thing, Mira; Nabilou, Puria; Kimer, Nina; Junker, Anders Ellekaer; Jensen, Anne Sofie Houlberg; Nordestgaard, Børge Grønne; Stender, Stefan; Gluud, Lise Lotte.
I: Clinics and Research in Hepatology and Gastroenterology, Bind 48, Nr. 7, 102389, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Use of PNPLA3, TM6SF2, and HSD17B13 for detection of fibrosis in MASLD in the general population
AU - Rashu, Elias Badal
AU - Werge, Mikkel Parsberg
AU - Hetland, Liv Eline
AU - Thing, Mira
AU - Nabilou, Puria
AU - Kimer, Nina
AU - Junker, Anders Ellekaer
AU - Jensen, Anne Sofie Houlberg
AU - Nordestgaard, Børge Grønne
AU - Stender, Stefan
AU - Gluud, Lise Lotte
N1 - Publisher Copyright: © 2024 Elsevier Masson SAS
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Cirrhosis
KW - Fibrosis
KW - Masld
KW - Metabolic dysfunction-associated liver disease
KW - Non-alcoholic fatty liver disease
KW - PNPLA3
KW - Steatohepatitis
U2 - 10.1016/j.clinre.2024.102389
DO - 10.1016/j.clinre.2024.102389
M3 - Journal article
C2 - 38830575
AN - SCOPUS:85195061861
VL - 48
JO - Clinics and Research in Hepatology and Gastroenterology
JF - Clinics and Research in Hepatology and Gastroenterology
SN - 2210-7401
IS - 7
M1 - 102389
ER -
ID: 394434235