Terlipressin is superior to midodrine/octreotide for hepatorenal syndrome type 1

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Hepatorenal syndrome type 1 (HRS-1) is a potentially devastating form of renal injury in cirrhosis with high mortality 1. Renal function improvement is a major determinant of survival in patients with HRS-1 2,3, which necessitates prompt initiation of potent pharmacological treatment. Among vasoactive drugs, intravenous terlipressin and the combination of oral midodrine and subcutaneous octreotide (both regimens plus albumin) are first choice treatments worldwide, although terlipressin is not available in the USA 4,5. Interestingly, only one study compared terlipressin (given as continuous infusion) with midodrine/octreotide showing a higher rate of renal function recovery (70.4 vs. 28.6%; P=0.01) and 3-month survival (55.6 vs. 28.6%; P=0.06) in the terlipressin group 2. Herein, we present retrospective data from our center on the outcome of patients with HRS-1, treated with bolus terlipressin or midodrine/octreotide-based regimens.
We evaluated 45 patients with HRS-1, defined by occasionally recommended criteria 1, who received terlipressin plus albumin (TERLI group; n=28) or midodrine/octreotide plus albumin (MID/OCT group; n=17) between 2003 and 2014. No patient had alcoholic hepatitis, neoplasia, or contraindications to treatment administered. Terlipressin was administered as an intravenous bolus of 0.5–1 mg per 4 h and 2 mg per 4 h every 3 days if a significant reduction in serum creatinine (≥1 mg/dl) was not observed during each 3-day period. Midodrine and octreotide were administered at a dose of 7.5–12.5 mg orally thrice daily and 100–200 μcg subcutaneously thrice daily, respectively. Ιn our center, intravenous albumin (60–80 g/day for 2 days) was always used in the diagnosis of HRS-1 since 2002 3. Both treatments were given until serum creatinine decreased to less than or equal to 1.5 mg/dl or for a maximum of 14 days. Complete, partial, and no response were defined as a serum creatinine decrease: to 1.5 mg/dl, of 50% or more from baseline to a final value of more than 1.5 mg/dl, and of less than 50% from baseline, respectively. For survival analysis, censoring was performed for death related to progressive/recurrent HRS-1, initiation of dialysis, and liver transplantation.
Causes of HRS-1, baseline serum creatinine, and Child–Pugh/Model for End-Stage Liver Disease scores were similar in both the groups. A significantly greater number of patients in the TERLI group experienced combined partial/complete and complete improvement of renal function than in patients in the MID/OCT group (60.7 vs. 23.5%; P=0.004 and 39.2 vs. 0%; P=0.002, respectively). Responders (partial and full) showed a significantly higher 3-month survival than nonresponders in both the groups (Fig. 1a and b). However, cumulative survival was significantly higher in the TERLI group compared with MID/OCT group (Fig. 1c). No patient discontinued either treatment because of adverse effects.
In line with recent observations, our findings indicate that terlipressin is far more effective than midodrine/octreotide in improving renal function in patients with HRS-1 thus offering a survival benefit.
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