The initiation of nonselective beta-blocker (NSBB) therapy may ameliorate systemic inflammation in patients with advanced chronic liver disease (ACLD), according to study data published in Gut. In turn, NSBB-associated reductions in inflammation were associated with improved clinical outcomes and liver-related survival.

Systemic inflammation in ACLD is associated with significant morbidity and mortality. The present study sought to assess the capacity of NSBB to reduce inflammation in ACLD and improve long-term outcomes. Patients with ACLD who were diagnosed with clinically significant portal hypertension between 2004 and 2018 at participating medical centers in Austria were enrolled. Patients underwent sequential hepatic venous pressure gradient (HVPG) measurements before and after initiation of NSBB therapy. Biomarkers of systemic inflammation — including white blood cell (WBC) count, C-reactive protein (CRP), interleukin 6 (IL-6), and procalcitonin (PCT) — were determined at each HVPG assessment. The primary outcome was change in inflammatory biomarkers following stable exposure to NSBBs. Competing risk regression was performed to assess the influence of NSBB-induced changes on the risk of decompensation and death.

The study cohort comprised 307 patients with ACLD (men, 74.6%; median age, 55 y). Median (interquartile range [IQR]) baseline HVPG was 20 mm Hg (IQR, 17-24). The distribution of Child-Turcotte-Pugh score (Child) stages was as follows: 77 (25.1%) Child stage A; 161 (52.4%) Child stage B; and 69 (22.5%) Child stage C. The majority of patients (75.2%) had decompensated disease at baseline. In the total cohort, NSBB therapy was associated with substantial reductions in median WBC count and CRP level. Specifically, median (IQR) WBC count decreased from 4.78 (3.36-6.48) at baseline to 4.65 (3.38-6.33) at follow-up, and median CRP levels declined from 0.48 (0.17-1.16) to 0.35 (0.15-0.87) mg/dL. Patients with more advanced cirrhosis experienced greater declines in WBC count (P <.001) and CRP level (P =.016) compared with patients with earlier stages. However, HVPG decreases under NSBB therapy were similar across all Child stages (P =.688).


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NSBB-associated changes in WBC count were significantly correlated with changes in CRP (P <.001), PCT (P =.002), and IL-6 (P =.088). However, changes in WBC count were not substantially correlated with changes in HVPG. Overall, 91 patients (29.6%) achieved an NSBB-related decrease in systemic inflammation, defined as a reduction in WBC count of at least 15%. In risk-regression models, this NSBB-related decrease in systemic inflammation was an independent protective factor against further decompensation in patients with decompensation (subdistribution hazard ratio [HR], 0.694; P =.038). Decreased systemic inflammation also predicted lower mortality in the total patient cohort (subdistribution hazard ratio, 0.561; P =.013).

Per these data, NSBB therapy appears to have systemic anti-inflammatory effects in patients with ACLD. These anti-inflammatory effects appeared to be independent of HVPG response. NSBB-related reduction in WBC count was significantly associated with reduced risk of further decompensation and liver-related mortality. As study limitations, investigators noted the retrospective design and significant attrition rate; patients lost to follow-up may have had more severe disease or poorer response to NSBB therapy. Additionally, potential confounding factors of WBC response (eg, hydration status) were not measured. Even so, “[m]onitoring WBC dynamic under NSBB therapy…may [be] a readily available and clinically useful parameter to identify patients with ACLD who may benefit most from NSBB therapy,” the investigators wrote. “[I]n Child-C patients — in whom systemic inflammation is more pronounced — a decrease in WBC under NSBB therapy may prompt physicians to keep the patient on NSBB.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Reference

Jachs M, Hartl L, Schaufler D, et al. Amelioration of systemic inflammation in advanced chronic liver disease upon beta-blocker therapy translates into improved clinical outcomes. Published online November 16, 2020. Gut. doi:10.1136/gutjnl-2020-322712