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Impact of HSD17B13 rs72613567 genotype on hepatic decompensation and mortality in patients with portal hypertension
Author(s) -
Scheiner Bernhard,
Stättermayer Albert F.,
Schwabl Philipp,
Bucsics Theresa,
Paternostro Rafael,
Bauer David,
Simbrunner Benedikt,
Schmidt Ralf,
Marculescu Rodrig,
Ferlitsch Arnulf,
PeckRadosavljevic Markus,
Pinter Mathias,
Trauner Michael,
Reiberger Thomas,
Ferenci Peter,
Mandorfer Mattias
Publication year - 2020
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.14304
Subject(s) - medicine , gastroenterology , portal hypertension , portal venous pressure , cirrhosis , decompensation , alcoholic liver disease , fatty liver , hazard ratio , liver disease , confidence interval , chronic liver disease , endocrinology , disease
Background & Aims The loss‐of‐function rs72613567 T > TA ‐variant in the 17β‐hydroxysteroid dehydrogenase 13 ( HSD17B13 ) gene might protect from alcoholic and non‐alcoholic fatty liver disease (ALD/NAFLD) and associated fibrosis/cirrhosis. We investigated the impact of the T > TA ‐variant on hepatic decompensation and mortality and investigated its implications on retinol and sex steroid metabolism in patients who had already developed advanced chronic liver disease (ACLD). Methods Retrospective analysis in prospectively characterized patients with viral hepatitis‐ and ALD/NAFLD‐induced portal hypertension (hepatic venous pressure gradient (HVPG) ≥ 6 mmHg) diagnosed at the Medical University of Vienna. Results Among 487 patients who were followed longitudinally, 166 (34%) were heterozygous and 24 (5%) were homozygous for the ‘protective’ TA ‐allele. Patients harbouring at least one TA ‐allele had a lower MELD (9 (8‐12) vs 10 (8‐13) points; P = .003) and showed a trend towards lower HVPG (16 ± 6 vs 17 ± 7 mmHg; P = .067). Interestingly, in competing risk analyses adjusted for age, HVPG and MELD, harbouring the TA ‐allele was associated with numerically increased risks for mortality (adjusted subdistribution hazard ratio (aSHR): 1.3 (95% confidence interval (95% CI): 0.888‐1.91); P = .18), liver‐related death (aSHR: 1.34 (95% CI: 0.9‐1.98); P = .15) and hepatic decompensation (aSHR: 1.29 (95% CI: 0.945‐1.77); P = .11). This might be explained by trends towards worse outcomes (eg liver‐related death: aSHR: 1.64 (95% CI: 0.95‐2.84); P = .076) in patients with viral hepatitis‐induced ACLD. In a cross‐sectional analysis of 211 additional patients, serum retinol levels were comparable between HSD17B13 genotypes, but in males, serum testosterone levels numerically decreased with an increasing number of TA ‐alleles. Conclusion In patients with viral hepatitis‐ and ALD‐induced portal hypertension, the T > TA ‐variant was not protective of hepatic decompensation and mortality. Further studies should investigate the pathophysiological mechanisms underlying the effects of HSD17B13 genotype at different stages of liver disease.