Author information

¹Division of Hepatology, Annette C. and Harold C. Simmons Transplant Institute, Baylor Scott & White All Saints Medical Center Fort Worth, TX.

²Department of Medicine, Burnett School of Medicine at TCU, Fort Worth, TX.

³OPEN Health, Parsippany, NJ.

⁴Mallinckrodt Pharmaceuticals, Hampton, NJ.

⁵Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN.

Abstract

Objectives: Evidence on the comparison of treatments for hepatorenal syndrome-acute kidney injury (HRS-AKI) in a US population is limited. An indirect comparison of terlipressin plus albumin versus midodrine and octreotide plus albumin (MO) may provide further insight into treatment efficacy.

Methods: Cohorts of patients treated for HRS-AKI characterized by serum creatinine [SCr] < 5 mg/dL, baseline acute-on-chronic liver failure (ACLF) grades 0-2, and exclusion of patients listed for transplant if MELD ≥ 35 were pooled from 1) the CONFIRM and REVERSE randomized controlled trials (N=159 meeting eligibility criteria from N=216 overall treated with terlipressin) and 2) a retrospective review of medical records from 10 US tertiary hospitals (2016-2019; N=55 treated with MO meeting eligibility criteria from N=200 overall). The primary endpoint comparing the two cohorts was HRS reversal defined as achieving SCr ≤1.5 mg/dL at least once during the treatment. Covariate balancing propensity scoring was used to adjust for differences in baseline characteristics.

Results: HRS-AKI reversal was achieved in 52.35% of terlipressin-treated patientscompared to 20% of MO-treated patients [adjusted mean difference (95% confidence interval)= 32.35% (17.40, 47.30), p<.0001]. Terlipressin patients had increased overall survival (adjusted HR=0.57 (0.35,0.93), p=0.02) but similar transplant-free survival (adjusted HR= 0.79 (0.53,1.17), p=0.24). Achievement of HRS-AKI reversal was associated with increased OS and TFS regardless of treatment (p <0.001).

Conclusions: Consistent with prior reports, terlipressin plus albumin is more effective in improving kidney function and achieving HRS-AKI reversal than MO plus albumin based on indirect comparison in a US population.