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Combined effects of PNPLA3, TM6SF2 and HSD17B13 variants on severity of biopsy-proven non-alcoholic fatty liver disease.

cris.virtualsource.author-orcid64e361eb-bc8e-4d57-acdb-203725b21e94
datacite.rightsopen.access
dc.contributor.authorPaternostro, Rafael
dc.contributor.authorStaufer, Katharina
dc.contributor.authorTraussnigg, Stefan
dc.contributor.authorStättermayer, Albert-Friedrich
dc.contributor.authorHalilbasic, Emina
dc.contributor.authorKeritam, Omar
dc.contributor.authorMeyer, Elias L
dc.contributor.authorStift, Judith
dc.contributor.authorWrba, Fritz
dc.contributor.authorSipos, Bence
dc.contributor.authorCanbay, Ali
dc.contributor.authorSchlattjan, Martin
dc.contributor.authorAigner, Elmar
dc.contributor.authorDatz, Christian
dc.contributor.authorStickel, Felix
dc.contributor.authorSchafmayer, Clemens
dc.contributor.authorHampe, Jochen
dc.contributor.authorBuch, Stephan
dc.contributor.authorPrager, Gerhard
dc.contributor.authorMunda, Petra
dc.contributor.authorMandorfer, Mattias
dc.contributor.authorFerenci, Peter
dc.contributor.authorTrauner, Michael
dc.date.accessioned2024-10-05T06:50:33Z
dc.date.available2024-10-05T06:50:33Z
dc.date.issued2021-08
dc.description.abstractOBJECTIVE Several single-nucleotide polymorphisms have been identified to be disadvantageous or protective in regard to disease severity in patients with non-alcoholic fatty liver disease (NAFLD). However, it is unclear, whether including genetic risk factor(s) either alone or combined into risk stratification algorithms for NAFLD actually provides incremental benefit over clinical risk factors. DESIGN Patients with biopsy-proven NAFLD were genotyped for the PNPLA3-rs738409(minor allele:G), TM6SF2-rs58542926(minor allele:T) and HSD17B13- rs72613567 (minor allele:TA) variants. The NAFLD activity score (NAS) and fibrosis stage (F0-F4) were used to grade and stage all liver biopsy samples. Patients from seven centers throughout Central Europe were considered for the study. RESULTS 703 patients were included: NAS ≥ 5:173(24.6%); Fibrosis: F3-4:81(11.5%). PNPLA3 G/G genotype was associated with a NAS ≥ 5(aOR 2.23, p = 0.007) and advanced fibrosis (aOR-3.48, p < 0.001).TM6SF2 T/- was associated with advanced fibrosis (aOR 1.99, p = 0.023). HSD17B13 TA/- was associated with a lower probability of NAS ≥ 5(TA/T: aOR 0.65, p = 0.041, TA/TA: aOR 0.40, p = 0.033). Regarding the predictive capability for NAS ≥ 5, well-known risk factors (age, sex, BMI, diabetes, and ALT; baseline model) had an AUC of 0.758, Addition of PNPLA3(AUC 0.766), HSB17B13(AUC 0.766), and their combination(AUC 0.775), but not of TM6SF2(AUC 0.762), resulted in a higher diagnostic accuracy of the model. Addition of genetic markers for the prediction of advanced fibrosis (baseline model: age, sex, BMI, diabetes: AUC 0.777) resulted in a higher AUC if PNPLA3(AUC 0.789), and TM6SF2(AUC 0.786) but not if HSD17B13(0.777) were added. CONCLUSION In biopsy-proven NAFLD, PNPLA3 G/-, TM6SF2 T/- and HSD17B13 TA/- carriage are associated with severity of NAFLD. Incorporating these genetic risk factors into risk stratification models might improve their predictive accuracy for severity of NAFLD and/or advanced fibrosis on liver biopsy.
dc.description.numberOfPages12
dc.description.sponsorshipUniversitätsklinik für Viszerale Chirurgie und Medizin
dc.identifier.doi10.48350/160158
dc.identifier.pmid34076851
dc.identifier.publisherDOI10.1007/s12072-021-10200-y
dc.identifier.urihttps://boris-portal.unibe.ch/handle/20.500.12422/53726
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofHepatology international
dc.relation.issn1936-0541
dc.relation.organizationDCD5A442C1F6E17DE0405C82790C4DE2
dc.subjectAdvanced fibrosis Cirrhosis Fibrosis Genetic risk factors HSD17B13 Liver biopsy NAFLD NASH PNPLA3 TM6SF2
dc.subject.ddc600 - Technology::610 - Medicine & health
dc.titleCombined effects of PNPLA3, TM6SF2 and HSD17B13 variants on severity of biopsy-proven non-alcoholic fatty liver disease.
dc.typearticle
dspace.entity.typePublication
dspace.file.typetext
oaire.citation.endPage933
oaire.citation.issue4
oaire.citation.startPage922
oaire.citation.volume15
oairecerif.author.affiliationUniversitätsklinik für Viszerale Chirurgie und Medizin
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unibe.date.licenseChanged2021-10-26 15:46:19
unibe.description.ispublishedpub
unibe.eprints.legacyId160158
unibe.refereedtrue
unibe.subtype.articlejournal

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