Terlipressin should be used with caution in hepatorenal syndrome type 1, grade 3 ACLF
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Patients with hepatorenal syndrome type 1 and advanced acute-on-chronic liver failure had significantly greater incidence of respiratory failure and 90-day mortality when treated with terlipressin vs. placebo, according to research.
“Terlipressin is the most widely used splanchnic vasoconstrictor for the treatment of [hepatorenal syndrome type 1] worldwide,” Florence Wong, MD, FRACP, FRCPC, professor of medicine at the University of Toronto and staff hepatologist at Toronto General Hospital in Canada, and colleagues wrote in Alimentary Pharmacology & Therapeutics. “The use of terlipressin, which increases the systemic vascular resistance and cardiac afterload, may affect cardiac and respiratory function, especially in cirrhotic patients with advanced ACLF and who may have underlying cirrhotic cardiomyopathy.”
In a post-hoc analysis of data from the placebo-controlled CONFIRM trial, Wong and colleagues assessed 90-day mortality and incidence of respiratory failure in 299 adults with hepatorenal syndrome type 1 (HRS1) and ACLF ranging from grade 1 to 3. Patients were randomized to receive either terlipressin or placebo, along with albumin, and were assessed at enrollment for organ failure using the ACLF grading system. Investigators compared outcomes of patients with grades 1 and 2 ACLF vs. patients with grade 3 ACLF.
Among 200 patients treated with terlipressin, significantly more patients with grade 3 ACLF developed respiratory failure vs. patients with grades 1 and 2 ACLF (30% vs. 9.4%). Conversely, of 99 patients in the placebo group, 6.2% of those with grades 1 and 2 ACLF developed respiratory failure compared with 0% of those with grade 3 ACLF, a statistically significant difference in the incidence of respiratory failure in patients with grade 3 ACLF treated with terlipressin vs. placebo (30% vs. 0%).
Results of a multivariate logistic regression analysis also showed baseline international normalized ratio, mean arterial pressure and pulse oximeter oxygen saturation were predictors of respiratory failure with terlipressin treatment. However, prior albumin as a continuous variable was not a predictor of this outcome.
Researchers further reported that 101 patients in the terlipressin group and 45 patients in the placebo group died within 90 days after completion of treatment. Patients with grades 1 and 2 ACLF who were treated with terlipressin or placebo had similar 90-day survival rates (55.5% vs. 56.6%, respectively), while patients with grade 3 ACLF who were treated with terlipressin had significantly lower survival rates than those in the placebo group (27.55% vs. 50%), mainly due to respiratory failure.
“The use of terlipressin, together with albumin, in the treatment of HRS1 with cirrhosis can lead to the development of respiratory failure,” Wong and colleagues concluded. “This is especially true in patients with advanced grade 3 ACLF. All patients receiving terlipressin need to be monitored closely for the development of respiratory failure; excessive use of albumin should be avoided.”
They added, “Future studies should focus on elucidating the precise mechanisms involved in the development of respiratory failure associated with terlipressin treatment, the inflammatory components that may be active, treatment algorithms to mitigate adverse events and the evaluation of new treatments for these severely ill patients.”
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