In a subgroup of patients with hepatorenal syndrome type 1 (HRS) who received a liver transplant, terlipressin treatment appears to reduce the need for renal replacement therapy (RRT) through 12 months of follow-up, according to a study presented at the annual meeting of the American College of Gastroenterology.
Among transplant recipients, overall 12-month survival was 11% higher for those treated with terlipressin compared with placebo, said K. Rajender Reddy, MD, director of hepatology and medical director of liver transplantation at the University of Pennsylvania, Philadelphia.
“Hepatorenal syndrome type 1 is a potentially reversible form of acute kidney injury that occurs in the setting of end-stage liver disease,” he said.
Liver transplantation, which eliminates end-stage liver disease, is the only definitive treatment for HRS. However, renal replacement therapy is common and associated with poor clinical outcomes and low patient survival rates in both the pretransplant and posttransplant settings, he noted.
Terlipressin, an injectable synthetic vasopressin analogue, restores renal blood flow and reverses HRS in 20%-40% of patients, Dr. Reddy said. In September, the U.S. Food and Drug Administration approved terlipressin (Terlivaz) for patients with HRS type 1. The label has a boxed warning for serious or fatal respiratory failure.
The safety and efficacy were assessed in the phase 3 CONFIRM trial, which Dr. Reddy and colleagues previously published. The randomized, placebo-controlled study demonstrated that terlipressin reversed HRS and reduced the need for RRT through day 30. The reversal of HRS with terlipressin did not improve 90-day survival as compared with placebo, which researchers attributed to a higher death rate within 90 days after the first dose despite improved kidney function.
A closer look at the liver transplant patients
In the subgroup analysis of the CONFIRM study, Dr. Reddy and colleagues analyzed the clinical outcomes through 12 months of follow-up in patients with HRS who received a liver transplant. They looked at the incidence of verified HRS reversal, HRS reversal, need for RRT, and overall survival.
Verified HRS reversal was defined as two consecutive serum creatinine measurements of 1.5 mg/dL or less at least 2 hours apart up to day 14 and survival without RRT for at least 10 days. HRS reversal was defined as a serum creatinine level of 1.5 mg/dL or less while on treatment. In addition, the need for RRT and overall survival were assessed at days 30, 60, 90, 180, and 365.
RRT was defined as any procedure that replaced nonendocrine kidney function, including continuous hemofiltration and hemodialysis, intermittent hemodialysis, peritoneal dialysis, ultrafiltration, or other dialysis and filtration techniques.
In the CONFIRM study, 199 patients with HRS were treated with terlipressin plus albumin, and 101 patients were treated with placebo plus albumin for up to 14 days. In the terlipressin group, 46 patients received liver transplants within the first 2 months of the study, as did 29 in the placebo group. Two patients in the terlipressin group and one in the placebo group received a simultaneous liver-kidney transplant.