(1311) Terlipressin Improves Outcomes in Patients With HRS and Alcoholic Hepatitis: The CONFIRM Study

Introduction: Alcoholic hepatitis (AH) may lead to liver cirrhosis, hepatorenal syndrome (HRS) and subsequently acute-on-chronic liver failure (ACLF). Terlipressin (terli) is FDA-approved to treat HRS, with greater benefit if treatment is initiated when serum creatinine (SCr) is < 5 mg/dL; patients (pts) with ACLF grade 0–2 have a lower risk of respiratory failure. In pts with AH complicated by HRS, terli is associated with a greater rate of HRS reversal versus placebo (pbo). This post hoc analysis of the pbo-controlled CONFIRM study evaluated the efficacy of terli in the subgroup of pts with HRS, ACLF grade 0–2 and SCr < 5 mg/dL, excluding any pts with contraindications or warnings (i.e., ACLF grade 3 or SCr >5 mg/dL) as listed in the US prescribing information (USPI).

Methods: The incidence of verified HRS reversal—defined as 2 consecutive SCr values ≤1.5 mg/dL at least 2 hours apart while on treatment and alive without RRT for at least 10 days—and HRS reversal—defined as SCr ≤1.5 mg/dL while on treatment, overall survival up to 90 days, and renal replacement therapy (RRT)-free survival up to Day 90 were assessed. Statistical analyses were performed using a Cochran-Mantel-Haenszel test or a 2-sample log-rank test to compare treatment arms.

Results: From the CONFIRM intent-to-treat population (N=300), 117 pts had HRS associated with AH, ACLF grade 0–2, and SCr < 5 mg/dL (terli n=78; pbo n=39). Baseline demographics were comparable across treatment arms. The incidence of verified HRS reversal was significantly higher in pts treated with terli (25/78 [32%]) versus pbo (3/39 [8%], P=0.004), as was the incidence of HRS reversal (terli: 29/78 [37%] vs pbo: 4/39 [10.3%], P=0.002). Overall survival up to 90 days was similar between the terli and pbo arms (log rank P=0.450). The number of pts alive at Day 90 was also similar (37/78 [47%] vs 18/39 [46%]. RRT-free survival was numerically longer in the terli arm compared with pbo (median RRT-free survival: 21 days vs 12 days, log rank P=0.110).

Conclusions: In CONFIRM, the largest prospective pbo-controlled study of terli to date, pts with AH and HRS, who met the current USPI criteria (i.e., ACLF grade 0–2 and SCr < 5 mg/dL) had a significantly better response rate than pbo, highlighting the utility of terli in reversing acute kidney injury in pts with AH.