Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

High Risk of Fatty Liver Disease Amplifies the Alanine Transaminase-Lowering Effect of a HSD17B13 Variant

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Letter to the Editor: Glucocorticosteroids for Alcohol-Associated Hepatitis

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. PNPLA3 genotype and risk of liver and all-cause mortality

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Identification and Replication of Six Loci Associated With Gallstone Disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Impact of cardiovascular risk factors and genetics on 10-year absolute risk of dementia: risk charts for targeted prevention

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Apolipoprotein M and risk of type 2 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. The European Heart Journal: leading the fight to reduce the global burden of cardiovascular disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Autosomal recessive hypercholesterolemia in a kindred of Syrian ancestry

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

A common loss-of-function variant in HSD17B13 (rs72613567:TA) was recently found to protect from chronic liver disease. Whether the variant confers protection from specific risk factors for liver disease is unclear. We tested the association of rs72613567 with plasma levels of alanine transaminase (ALT) and clinical liver disease and mortality in 111,612 individuals from the Danish general population, including 497 with cirrhosis and 113 with hepatocellular carcinoma. HSD17B13 rs72613567:TA was associated with stepwise lower levels of plasma ALT of up to 1.3 U/L in TA/TA homozygotes versus T/T homozygotes. For each TA-allele, the risk of cirrhosis and hepatocellular carcinoma was reduced by 15% and 28%, respectively. In prospective analyses, the TA-allele was associated with up to 33% lower rates of liver-related mortality in the general population, and with up to 49% reduced liver-related mortality in patients with cirrhosis. The ALT-lowering effect of rs72613567:TA was amplified by increasing adiposity, alcohol consumption, and genetic risk of fatty liver disease. The TA-allele was associated with only marginally lower ALT in lean nondrinkers with low genetic risk of hepatic steatosis. In contrast, compared with T/T homozygotes, TA/TA homozygotes had 12% to 18% lower plasma ALT among the most obese, in heavy drinkers, and in individuals carrying three or four steatogenic alleles in patatin-like phospholipase domain-containing protein 3 (PNPLA3) and transmembrane 6 superfamily 2 (TM6SF2). Conclusion: High risk of fatty liver disease amplifies the ALT-lowering effect of HSD17B13 rs72613567:TA in the Danish general population.

Original languageEnglish
JournalHepatology (Baltimore, Md.)
Volume71
Issue number1
Pages (from-to)56-66
Number of pages11
ISSN0270-9139
DOIs
Publication statusPublished - Jan 2020

ID: 59309547