#VisualAbstract: Terlipressin improved renal function in patients with type 1 hepatorenal syndrome

1. Administration of intravenous terlipressin was shown to improve kidney function in hospitalized patients with type 1 hepatorenal syndrome.

2. Patients treated with terlipressin were associated with serious adverse events such as respiratory failure.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Hemodynamic abnormalities of type 1 hepatorenal syndrome (HRS-1), a condition consisting of rapidly progressing renal failure, occurs in patients with decompensated cirrhosis. A synthetic vasopressin analog, terlipressin, has the ability to decrease portal blood inflow, consequently reducing portal hypertension, which is the main cause of hemodynamic abnormalities associated with advanced cirrhosis. This study examines the safety and efficacy of intravenous (IV) terlipressin in hospitalized patients with HRS-1. The study determined terlipressin as an effective treatment option for patients with HRS-1 compared to the placebo group. Although reversal of HRS-1 was more common among participants that received the study drug, complications such as respiratory failure leading to death were also more common in this group. This study was strengthened by its double-blind design; however, the study was conducted over a short period, thus limiting the outcomes measured. Nonetheless, the study results were significant as IV terlipressin could be a potential therapeutic to reverse the renal effects of HRS-1.

Click to read the study in NEJM

Relevant Reading: In vitro binding and receptor-mediated activity of terlipressin at vasopressin receptors V 1 and V 2

In-Depth [randomized controlled trial]: In this randomized control trial 300 patients were enrolled in the study. Patients with a confirmed diagnosis of HRS-1, have cirrhosis, ascites, and kidney failure were included in the study. Patients with a high creatinine level (>7.0mg/dL) or large-volume paracenteses (4L or more) two days prior to randomization were excluded from the study. Patients were randomized in a 2:1 ratio into the terlipressin group or place group, respectively. All patients were administered albumin alongside their study treatment. This primary outcome was HRS reversal following drug administration. During analysis, 17% of the patients from the placebo group and 32% from the treatment group had HRS reversal (P=0.006). The mean follow-up duration was for 55.3 days, and 23% of the terlipressin patients received a liver transplant. In the placebo group, the mean duration of follow-up was 56.1 days, and 29% of the patients received a liver transplant. At 90 days, 51% of patients had died in the terlipressin group, and 45% of patients died in the placebo group (difference, 6 percentage points; 95% confidence interval [CI], -6 to 18). In conclusion, the reversal of HRS was significantly greater in the treatment group compared to the placebo group. Moreover, patients were more likely to die following respiratory failure in the treatment group as compared to the control group.

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