Effect of common genetic variants on the risk of cirrhosis in non-alcoholic fatty liver disease during 20 years of follow-up

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Effect of common genetic variants on the risk of cirrhosis in non-alcoholic fatty liver disease during 20 years of follow-up

Holmer, Magnus (author): Karolinska Institutet

Ekstedt, Mattias (author): Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Mag- tarmmedicinska kliniken

Nasr, Patrik (author): Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Mag- tarmmedicinska kliniken,Karolinska Inst, Sweden

Zenlander, Robin (author): Karolinska Institutet

Wester, Axel (author): Karolinska Institutet

Tavaglione, Federica (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine

Romeo, Stefano, 1976 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine

Kechagias, Stergios (author): Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Mag- tarmmedicinska kliniken

Stål, Per (author): Karolinska Institutet

Hagström, Hannes (author): Karolinska Institutet

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2022-10-11
2022
English.
In: Liver international (Print). - : Wiley. - 1478-3223 .- 1478-3231. ; 42:12, s. 2769-2780

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Journal article (peer-reviewed)

Abstract Subject headings

Background and Aims Several genotypes associate with a worse histopathological profile in patients with non-alcoholic fatty liver disease (NAFLD). Whether genotypes impact long-term outcomes is unclear. We investigated the importance of PNPLA3, TM6SF2, MBOAT7 and GCKR genotype for the development of severe outcomes in NAFLD. Method DNA samples were collected from 546 patients with NAFLD. Advanced fibrosis was diagnosed by liver biopsy or elastography. Non-alcoholic steatohepatitis (NASH) was histologically defined. Additionally, 5396 controls matched for age, sex and municipality were identified from population-based registers. Events of severe liver disease and all-cause mortality were collected from national registries. Hazard ratios (HRs) adjusted for age, sex, body mass index and type 2 diabetes were estimated with Cox regression. Results In NAFLD, the G/G genotype of PNPLA3 was associated with a higher prevalence of NASH at baseline (odds ratio [OR] 3.67, 95% CI = 1.66-8.08), but not with advanced fibrosis (OR 1.81, 95% CI = 0.79-4.14). After up to 40 years of follow-up, the PNPLA3 G/G genotype was associated with a higher rate of severe liver disease (adjusted hazard ratio [aHR] 2.27, 95% CI = 1.15-4.47) compared with the C/C variant. NAFLD patients developed cirrhosis at a higher rate than controls (aHR 9.00, 95% CI = 6.85-11.83). The PNPLA3 G/G genotype accentuated this rate (aHR 23.32, 95% = CI 9.14-59.47). Overall mortality was not affected by any genetic variant. Conclusion The PNPLA3 G/G genotype is associated with an increased rate of cirrhosis in NAFLD. Our results suggest that assessment of the PNPLA3 genotype is of clinical relevance in patients with NAFLD to individualize monitoring and therapeutic strategies.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Keyword

NAFLD; NASH; PNPLA3; TM6SF2

Publication and Content Type

ref (subject category)
art (subject category)

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By the author/editor: Holmer, Magnus; Ekstedt, Mattias; Nasr, Patrik; Zenlander, Robin; Wester, Axel; Tavaglione, Fede ...; show more...; Romeo, Stefano, ...; Kechagias, Sterg ...; Stål, Per; Hagström, Hannes; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Gastroenterology ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cardiac and Card ...

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By the university: Linköping University; Karolinska Institutet; University of Gothenburg

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