Acute hemodynamic response to propranolol predicts bleeding and nonbleeding decompensation in patients with cirrhosis

Benedikt S Hofer, Benedikt Simbrunner, David J M Bauer, Rafael Paternostro, Philipp Schwabl, Bernhard Scheiner, Georg Semmler, Lukas Hartl, Mathias Jachs, Barbara Datterl, Albert F Staettermayer, Michael Trauner, Mattias Mandorfer, Thomas Reiberger, Benedikt S Hofer, Benedikt Simbrunner, David J M Bauer, Rafael Paternostro, Philipp Schwabl, Bernhard Scheiner, Georg Semmler, Lukas Hartl, Mathias Jachs, Barbara Datterl, Albert F Staettermayer, Michael Trauner, Mattias Mandorfer, Thomas Reiberger

Abstract

Nonselective beta-blockers are used as prophylaxis for variceal bleeding in patients with advanced chronic liver disease (ACLD). The acute hemodynamic response to intravenous propranolol (i.e., ≥10% reduction in hepatic venous pressure gradient [HVPG]) is linked to a decreased risk of variceal bleeding. In this study, we aimed to investigate the overall prognostic value of an acute response in compensated and decompensated ACLD. We analyzed the long-term outcome of prospectively recruited patients with ACLD following a baseline HVPG measurement with an intraprocedural assessment of the acute hemodynamic response to propranolol. Overall, we included 98 patients with ACLD (mean ± SD age, 56.4 ± 11.5 years; 72.4% decompensated; 88.8% varices; mean ± SD HVPG, 19.9 ± 4.4 mm Hg) who were followed for a median of 9.6 (interquartile range, 6.5-18.2) months. Fifty-seven patients (58.2%) demonstrated an acute hemodynamic response to propranolol that was associated with a decreased risk of variceal bleeding (at 12 months, 3.6% vs. 15% in nonresponder; log-rank, p = 0.038) and hepatic decompensation (at 12 months, 23% vs. 33% in nonresponder; log-rank, p = 0.096). On multivariate analysis, the acute response was an independent predictor of first/further hepatic decompensation (adjusted hazards ratio, 0.31; 95% confidence interval [CI], 0.13-0.70; p = 0.005). Importantly, there was a tendency toward a prolonged transplant-free survival in acute responders compared to nonresponders (34.2; 95% CI, 29.2-39.2 vs. 25.2; 95% CI, 19.8-30.6 months; log-rank, p = 0.191). Conclusions: Patients with ACLD who achieve an acute hemodynamic response to intravenous propranolol experience a lower risk of variceal bleeding and nonbleeding hepatic decompensation events compared to nonresponders. An assessment of the acute hemodynamic response to intravenous propranolol provides important prognostic information in ACLD.

Trial registration: ClinicalTrials.gov NCT03267615.

Conflict of interest statement

Benedikt Simbrunner received travel support from AbbVie and Gilead. Bernhard Scheiner received travel support from Gilead, AbbVie, and Ipsen. Albert F. Staettermayer served as a speaker and/or consultant and/or advisory board member for Boehringer Ingelheim, Gilead, and MSD. Michael Trauner received grant support from Albireo, Alnylam, Cymabay, Falk, Gilead, Intercept, MSD, Takeda, and UltraGenyx; he received honoraria for consulting from Albireo, Boehringer Ingelheim, BiomX, Falk, Genfit, Gilead, Intercept, MSD, Novartis, Phenex, Pliant, Regulus, and Shire; he received speaker fees from Bristol‐Myers Squibb, Falk, Gilead, Intercept, and MSD as well as travel support from AbbVie, Falk, Gilead, and Intercept; he is coinventor of patents on the medical use of 24‐noursodeoxycholic acid. Mattias Mandorfer served as a speaker and/or consultant and/or advisory board member for AbbVie, Collective Acumen, Gilead, and W. L. Gore & Associates and received travel support from AbbVie and Gilead. Thomas Reiberger received grant support from AbbVie, Boehringer‐Ingelheim, Gilead, Philips Healthcare, Siemens, Pliant, and Gore; he received speaking honoraria from AbbVie, Gilead, Gore, Intercept, Roche, and MSD; he received consulting/advisory board fees from AbbVie, Boehringer‐Ingelheim, Gilead, and Siemens and travel support from Gilead and AbbVie. The other authors declare no conflict of interest.

© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.

Figures

FIGURE 1
FIGURE 1
Variceal (re‐)bleeding stratified by acute hemodynamic response. *, significant.
FIGURE 2
FIGURE 2
Hepatic decompensation stratified by acute hemodynamic response. (A) Overall cohort. (B) Patients with previous decompensation. *, significant.
FIGURE 3
FIGURE 3
Survival stratified by acute hemodynamic response. (A) Overall cohort. (B) Patients with previous decompensation.

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