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 protects from alcoholic and non-alcoholic liver disease (ALD/NAFLD) and associated fibrosis/cirrhosis.

We investigated the impact of the T>TA-variant on hepatic decompensation and mortality in patients who had already developed advanced chronic liver disease (ACLD).

Methods:

We performed a retrospective analysis in prospectively characterized patients with viral and ALD/NAFLD-induced portal hypertension (hepatic venous pressure gradient [HVPG]≥6 mmHg) diagnosed at the Medical University of Vienna.

Results:

Among 487 patients, 166 (34%) were heterozygous and 24 (5%) were homozygous for the 'protective' TA-allele. Patients harboring at least one TA-allele had a lower MELD (9 [8 – 12] vs. 10 [8 – 13] points; P= 0.003) and showed a trend towards lower HVPG (16 ± 6 vs. 17 ± 7 mmHg; P= 0.067). Moreover, TA-allele carriers with ALD/NAFD tended to be older at the time of HVPG-measurement.

Interestingly, in competing risk analyses adjusted for age, HVPG, and MELD, harboring 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= 0.18), liver-related death (aSHR: 1.34 [95%CI: 0.9 – 1.98]; P= 0.15), and hepatic decompensation (aSHR: 1.29 [95%CI: 0.945 – 1.77]; P= 0.11). This might be explained by trends towards worse outcomes (e.g., liver-related death: aSHR: 1.64 [95%CI: 0.95 – 2.84]; P= 0.076) in patients with viral hepatitis-induced ACLD.

Conclusion:

In line with previous observations, patients exhibiting at least one TA-allele showed less pronounced liver disease and tended to be older (ALD/NAFLD) at the time of HVPG-measurement. Interestingly, the T>TA-variant was not protective of hepatic decompensation and mortality and even tended to increase risks in patients with viral hepatitis-induced ACLD. Further studies should investigate the pathophysiological mechanisms underlying the partially opposing effects of HSD17B13 genotype within different stages of liver disease.