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.
- portal hypertension
Statistics from Altmetric.com
Correction notice This article has been corrected since it published Online First. The results, patient characteristics section, has been corrected.
Contributors MJ, MM and TR designed the study. All authors contributed to the data acquisition, which was then statistically analysed and interpreted by MJ, DJMB, MM and TR. MJ and TR drafted the original version of the manuscript that was critically revised by all authors.
Funding This study was supported by a Gilead International Liver Disease Research Scholarship (2018-FA716E0930) granted to Thomas Reiberger.
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.
Patient consent for publication Obtained.
Ethics approval The study was conducted in accordance with the declaration of Helsinki and approved by the local ethics committee of the Medical University of Vienna (No. 1493/2016). No written consent was required for this retrospective analysis.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request. This retrospective analysis is based on data from a deidentified patient database that includes data on patients of the Vienna haemodynamic laboratory who are treated at our specialised outpatient clinic. For any inquiries about the data, please contact the corresponding author TR (mail: firstname.lastname@example.org).
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.