Impact of HSD17B13 rs72613567 genotype on hepatic decompensation and mortality in patients with portal hypertension

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.