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.