Systematic review of randomized trials on vasoconstrictor drugs for hepatorenal syndrome

Vasoconstrictor drugs may improve renal function in hepatorenal syndrome (HRS), but the effect on mortality has not been established. We therefore performed a systematic review of randomized trials on vasoconstrictor drugs for type 1 or type 2 HRS. Mortality was the primary outcome measure. Eligible trials were identified through electronic and manual searches. Intention-to-treat random effects meta-analyses were performed. Ten randomized trials on terlipressin alone or with albumin, octreotide plus albumin, and noradrenalin plus albumin were included. The total number of patients was 376. Overall, vasoconstrictor drugs used alone or with albumin reduced mortality compared with no intervention or albumin (relative risk [RR], 0.82; 95% confidence interval [CI], 0.70-0.96). In subgroup analyses, the effect on mortality was seen at 15 days (RR, 0.60; 95% CI, 0.37-0.97) but not at 30 days (RR, 0.74; 95% CI, 0.40-1.39), 90 days (RR, 0.89; 95% CI, 0.66-1.22), or 180 days (RR, 0.83; 95% CI, 0.65-1.05). Subgroup analyses stratified by the treatments assessed showed that terlipressin plus albumin reduced mortality compared with albumin (RR, 0.81; 95% CI, 0.68-0.97). The effect was seen in subgroup analyses of type 1 but not type 2 HRS. The remaining trials were small and found no beneficial or harmful effects of the treatments assessed.

Terlipressin plus albumin may prolong short-term survival in type 1 HRS. The duration of the response should be considered when making treatment decisions and in the timing of potential liver transplantations. Considering the small number of patients included, the evidence does not allow for treatment recommendations regarding type 2 HRS or any of the remaining treatment comparisons assessed.