Use of beta-blockers linked to acute kidney injury, mortality in decompensated cirrhosis
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Key takeaways:
- Use of nonselective beta-blockers was associated with stage 2 acute kidney injury in decompensated cirrhosis.
- NSBB use also was significantly associated with waitlist mortality in Child B and Child C cirrhosis.
Use of nonselective beta-blockers was associated with stage 2 acute kidney injury and all-cause mortality among patients with decompensated cirrhosis waitlisted for liver transplantation, data showed.
“While NSBBs have been firmly established in the treatment of patients with compensated cirrhosis, whether NSBBs confer similar benefits among decompensated cirrhosis patients is less clear,” Mason Lai, an internal medicine resident at the University of California, San Francisco, and colleagues wrote in Hepatology Communications. “The concern is that once patients decompensate, the ‘therapeutic window’ may close, predisposing patients to unwanted hemodynamic changes.”
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They continued, “Given the potential negative downstream consequences of NSBBs, we hypothesized that the utilization of NSBBs in patients with decompensated cirrhosis is associated with an increased risk of AKI and waitlist mortality.”
To test this hypothesis, Lai and colleagues analyzed data from 1,816 patients (mean age, 58 years; 35% women) with decompensated cirrhosis listed for LT at UCSF from June 2012 to April 2022. Most patients were Child-Pugh score B (40%) at time of enrollment, followed by Child C (39%) and Child A (21%).
During a median follow-up of 1.5 years, 45% of patients received nonselective beta-blockers (NSBBs) at one or more time points, including propranolol (76%), nadolol (16%) and carvedilol (8%).
Time-dependent Cox regression models demonstrated a significant association between NSBB use and stage 2 AKI (HR = 1.57; 95% CI, 1.24-1.99), which remained significant after adjusting for confounders (HR = 1.53; 95% CI, 1.19-1.97).
Among those with Child C cirrhosis, 21% experienced stage 2 AKI, with development associated with NSBB use in both univariate (HR = 1.62; 95% CI, 1.16-2.24) and adjusted models (adjusted HR = 1.8; 95% CI, 1.26-2.57). Researchers reported no significant association with NSBB use among patients with Child A and Child B cirrhosis who experienced at least stage 2 AKI (7% and 17%, respectively).
Results also showed that 26% of the cohort died or were removed from the waitlist because of illness during follow-up, with NSBB use associated with waitlist mortality in time-dependent Cox regression (HR = 1.4; 95% CI, 1.17-1.67) and multivariate models (aHR = 1.3; 95% CI, 1.07-1.59).
Among those with Child B and Child C cirrhosis, NSBB use and waitlist mortality were significantly associated (aHR = 1.38; 95% CI, 1.04-1.85 and aHR = 1.45; 95% CI, 1.03-2.03, respectively), while no significant association was reported in patients with Child A cirrhosis.
“Our findings that the use of NSBB is independently associated with stage 2 AKI or greater and waitlist mortality among patients with decompensated cirrhosis listed for liver transplant is significant,” Lai and colleagues wrote. “Our data suggests that clinicians should exercise caution when considering the use of NSBBs in patients with decompensated cirrhosis awaiting a liver transplant, particularly those with Child C cirrhosis.”
Perspective
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William Carey, MD
Years ago, it was thought the “window of benefit” from nonselective beta-blockers (and carvedilol) closes as the degree of cirrhotic decompensation advances. Current guidance, on the other hand, states that in patients with ascites, traditional NSBBs or carvedilol should be dose-reduced or discontinued in cases of persistently low blood pressure and/or hepatorenal syndrome (HRS-AKI).
Once blood pressure returns to baseline and/or HRS-AKI resolves, NSBBs can be reinitiated or retitrated (Baveno VII). However, this data suggest that current guidance may be harmful. If duplicated, clinical practice will once again revert to a “closed window” approach to use these medications in decompensated cirrhosis.
More studies are needed with careful attention to dosage adjustments, monitoring frequency, compliance and more. A randomized prospective study will be needed to answer this important question with confidence.
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