Wang, Wei‐Jhih

INTRODUCTION: Evidence on the comparative real-world effectiveness of terlipressin vs midodrine plus octreotide (MO) for hepatorenal syndrome-acute kidney injury (HRS-AKI) in the United Kingdom and the United States is limited. METHODS: Using individual-level chart review data for patients across the United Kingdom (2013–2017) and the United States (2016–2019), an indirect treatment comparison was conducted comparing the efficacy of terlipressin (UK cohort) with MO (US cohort). Covariate balancing propensity scoring matched the cohorts on baseline serum creatinine (SCr), presence of encephalopathy and/or ascites, albumin use and duration, age, and sex. The primary endpoint was HRS reversal, defined as achieving SCr ≤1.5 mg/dL by the last day of treatment. RESULTS: At treatment initiation, 90.2% of UK patients received terlipressin (194/215), while 89.2% of US patients received MO (140/157). Concomitant albumin was administered in 67.9% of UK and 98.7% of US patients. In a covariate balancing propensity score-adjusted cohort, HRS reversal was achieved in 53.2% of terlipressin-treated patients (the United Kingdom, weighted effective sample size of 75) compared with 16.9% of MO-treated patients (the United States, n = 89) (adjusted mean difference (95% CI) 36.3% (22.4, 50.2), P < 0.0001). In adjusted analysis, individuals treated with terlipressin experienced an overall reduction in SCr at completion of treatment (SCr decrease 1.00 mg/dL vs increase of 0.08 mg/dL for MO-treated patients, P < 0.0001). DISCUSSION: HRS-AKI treatment and outcomes differ between the United Kingdom and the United States, attributed to the historical standard of care MO in the United States. In adjusted analyses, real-world use of terlipressin was more effective than MO at improving kidney function and achieving HRS-AKI reversal.

INTRODUCTION: 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 vs midodrine and octreotide plus albumin (MO) may provide further insight into treatment efficacy. METHODS: Cohorts of patients treated for HRS-AKI characterized by inclusion of patients with serum creatinine (SCr) <5 mg/dL and baseline acute-on-chronic liver failure grades 0–2 and exclusion of patients listed for transplant if model for end-stage liver disease scores ≥35 were pooled from (i) the CONFIRM and REVERSE randomized controlled trials (N = 159 meeting eligibility criteria from N = 216 overall, treated with terlipressin) and (ii) 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 end point comparing the 2 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 patients compared with 20% of MO-treated patients (adjusted mean difference 32.35%, 95% confidence interval [CI] 17.40–47.30, P < 0.0001). Terlipressin-treated patients had increased overall survival (adjusted hazard ratio 0.57, 95% CI 0.35–0.93, P = 0.02) but similar transplant-free survival (adjusted hazard ratio 0.79, 95% CI 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). DISCUSSION: 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.