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. 2021 Sep;70(9):1758-1767.
doi: 10.1136/gutjnl-2020-322712. Epub 2020 Nov 16.

Amelioration of systemic inflammation in advanced chronic liver disease upon beta-blocker therapy translates into improved clinical outcomes

Mathias Jachs  1   2 , Lukas Hartl  1   2 , Dunja Schaufler  1   2 , Christopher Desbalmes  1   2 , Benedikt Simbrunner  1   2   3 , Ernst Eigenbauer  4 , David Josef Maria Bauer  1   2 , Rafael Paternostro  1   2 , Philipp Schwabl  1   2   3 , Bernhard Scheiner  1   2 , Theresa Bucsics  1   2 , Albert Friedrich Stättermayer  1 , Matthias Pinter  1 , Michael Trauner  1 , Mattias Mandorfer  1   2 , Thomas Reiberger  5   2   3
Affiliations

Amelioration of systemic inflammation in advanced chronic liver disease upon beta-blocker therapy translates into improved clinical outcomes

Mathias Jachs et al. Gut. 2021 Sep.

Abstract

Objective: Systemic inflammation promotes the development of clinical events in patients with advanced chronic liver disease (ACLD). We assessed whether (1) non-selective beta blocker (NSBB) treatment initiation impacts biomarkers of systemic inflammation and (2) whether these changes in systemic inflammation predict complications and mortality.

Design: Biomarkers of systemic inflammation, that is, white blood cell count (WBC), C reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT) were determined at sequential hepatic venous pressure gradient (HVPG) measurements without NSBB and under stable NSBB intake. The influence of NSBB-related changes in systemic inflammation on the risk of decompensation and liver-related death was analysed using competing risk regression.

Results: Our study comprised 307 stable patients with ACLD (Child-A: 77 (25.1%), Child-B: 161 (52.4%), Child-C: 69 (22.5%), median HVPG: 20 (IQR 17-24) mm Hg) including 231 (75.2%) with decompensated disease.WBC significantly decreased upon NSBB therapy initiation (median: -2 (IQR -19;+13)%, p=0.011) in the overall cohort. NSBB-related reductions of WBC (Child-C: -16 (-30;+3)% vs Child-B: -2 (-16;+16)% vs Child-A: +3 (-7;+13)%, p<0.001) and of CRP (Child-C: -26 (-56,+8)% vs Child-B: -16 (-46;+13)% vs Child-A: ±0 (-33;+33)%, p<0.001) were more pronounced in advanced stages of cirrhosis. The NSBB-associated changes in WBC correlated with changes in CRP (Spearman's ρ=0.228, p<0.001), PCT (ρ=0.470, p=0.002) and IL-6 (ρ=0.501, p=0.001), but not with changes in HVPG (ρ=0.097, p=0.088).An NSBB-related decrease in systemic inflammation (ie, WBC reduction ≥15%) was achieved by n=91 (29.6%) patients and was found to be an independent protective factor of further decompensation (subdistribution HR, sHR: 0.694 (0.49-0.98), p=0.038) in decompensated patients and of liver-related mortality in the overall patient cohort (sHR: 0.561 (0.356-0.883), p=0.013).

Conclusion: NSBB therapy seems to exert systemic anti-inflammatory activity as evidenced by reductions of WBC and CRP levels. Interestingly, this effect was most pronounced in Child-C and independent of HVPG response. An NSBB-related WBC reduction by ≥15% was associated with a decreased risk of further decompensation and death.

Keywords: cirrhosis; inflammation; portal hypertension.

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Conflict of interest statement

Competing interests: BSim received travel support from AbbVie and Gilead, DJMB has received travel support from AbbVie and Gilead, PS received speaking honoraria from Bristol-Myers Squibb and Boehringer-Ingelheim, consulting fees from PharmaIN and travel support from Falk. BSch received travel support from Gilead, AbbVie and Ipsen. TB received travel support from AbbVie, Bristol-Myers Squibb and Medis, as well as speaker fees from Bristol-Myers Squibb. AFS has served as a speaker and/or consultant and/or advisory board member for Boehringer Ingelheim, Gilead and MSD. MP is an investigator for Bayer, BMS, Lilly and Roche; served as a speaker and/or consultant for Bayer, BMS, Ipsen, Eisai, Lilly, MSD and Roche; and received travel support from Bayer and BMS. MT received grant support from Albireo, Cymabay, Falk, Gilead, Intercept, MSD and Takeda; honoraria for consulting from Albireo, Boehringer-Ingelheim, BiomX, Falk, Genfit, Gilead, Intercept, MSD, Novartis, Phenex and Regulus; speaker fees from Bristol-Myers Squibb, Falk, Gilead, Intercept and MSD; as well as travel support from AbbVie, FalkGilead and Intercept. MM served as a speaker and/or consultant and/or advisory board member for AbbVie, Bristol-Myers Squibb, Gilead and W. L. Gore & Associates and received travel support from AbbVie, Bristol-Myers Squibb and Gilead. TR received grant support from AbbVie, Boehringer-Ingelheim, Gilead, MSD, Philips Healthcare and Gore; speaking honoraria from AbbVie, Gilead, Gore, Intercept, Roche and MSD; consulting/advisory board fee from AbbVie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD and Siemens; and travel support from Boehringer-Ingelheim, Gilead and Roche.

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