Early treatment with terlipressin in patients with hepatorenal syndrome yields improved clinical outcomes in North American studies

• Published in: Hepatology communications Vol. 7; no. 1; p. e1307
• Main Authors: Curry, Michael P, Vargas, Hugo E, Befeler, Alex S, Pyrsopoulos, Nikolaos T, Patwardhan, Vilas R, Jamil, Khurram
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins 01.01.2023; Wolters Kluwer Health/LWW
• Subjects: Creatinine - therapeutic use; Hepatorenal Syndrome - drug therapy; Hepatorenal Syndrome - etiology; Humans; Lypressin - therapeutic use; North America; Original; Terlipressin - therapeutic use; Treatment Outcome; Vasoconstrictor Agents - therapeutic use; North America
• ISSN: 2471-254X; 2471-254X
• DOI: 10.1097/01.HC9.0000897228.91307.0c

Hepatorenal syndrome type 1 (HRS-1) is a serious complication of advanced cirrhosis and a potentially reversible form of acute kidney injury that is associated with rapidly deteriorating kidney function. Liver transplantation remains the only curative treatment for decompensated cirrhosis. However, terlipressin, a vasopressin analog, successfully reverses HRS-1, and may improve patient survival while awaiting liver transplantation. Patients with higher baseline serum creatinine have a reduced response to treatment with terlipressin. These post hoc analyses examined pooled data from 352 patients with HRS-1 treated with terlipressin in 3 North American-centric, Phase III, placebo-controlled clinical studies (i.e. OT-0401, REVERSE, and CONFIRM)-across 3 serum creatinine subgroups (i.e. <3, ≥3-<5, and ≥5 mg/dL)-to further delineate their correlation with HRS reversal, renal replacement therapy-free survival, and overall survival. Serum creatinine was significantly associated with HRS reversal in univariate and multivariate logistic regression analyses (P<0.001). The incidence of HRS reversal inversely correlated with serum creatinine subgroup (<3 mg/dL, 49.2%; ≥3-<5 mg/dL, 28.0%; ≥5 mg/dL, 9.1%). At Day 30 follow-up, renal replacement therapy-free survival was significantly higher for patients with HRS-1 in the lower serum creatinine subgroups than in the higher subgroup (<5 vs. >5 mg/dL; p=0.01). Terlipressin-treated patients with HRS-1, with a lower baseline serum creatinine level, had a higher overall survival (p<0.001) and higher transplant-free survival at Day 90 (p=0.04). Patients with HRS-1 and lower serum creatinine levels who were treated with terlipressin had higher HRS reversal and survival outcomes, highlighting the significant need to identify and treat patients with HRS-1 early when they often have lower serum creatinine levels, and likely a greater response to terlipressin.