Meta-analysis: Terlipressin therapy for the hepatorenal syndrome

Background: The hepatorenal syndrome is a severe and well-known complication of end-stage liver disease, but its management is controversial. Recent reports have shown the efficacy of terlipressin therapy, a vasopressin analogue, in hepatorenal syndrome patients. Aim: To evaluate the efficacy and safety of terlipressin in the treatment of hepatorenal syndrome. Methods: We performed a systematic review of the literature with a meta-analysis of clinical trials. The primary outcome (as a measure of efficacy) was the rate of responder patients (i.e. patients who had hepatorenal syndrome reversal after terlipressin therapy). The secondary outcomes were the rate of responders who had hepatorenal syndrome recurrence after terlipressin withdrawal, and the drop-out rate (as a measure of tolerability). We used the random effects model of DerSimonian and Laird with heterogeneity and sensitivity analysis. Results: We identified 10 clinical trials (154 unique patients); two (20.0%) were randomized, controlled trials. The pooled rate of patients who reversed hepatorenal syndrome after terlipressin therapy was 0.52 (95% CI, 0.42; 0.61), P = 0.0001; I2 = 24.6%. The pooled frequency of responder patients who showed hepatorenal syndrome recurrence after terlipressin withdrawal was 0.55 (95% CI, 0.40; 0.69), P = 0.00001; I2 = 44.3%. The pooled rate of patients who showed side-effects to terlipressin therapy was 0.29 (95% CI, 0.17; 0.42), P < 0.0001, I2 = 66.6%. The drop-out rate was 0%. The pooled OR for mortality rate in hepatorenal syndrome patients who were not responders to terlipressin vs. responder patients was 5.746 (95% CI, 1.5; 21.9). We did not find any predictive factor of response to terlipressin therapy. Conclusions: This meta-analysis shows efficacy and safety of terlipressin in the treatment of hepatorenal syndrome. However, a significant number of responder patients relapsed after terlipressin withdrawal. Further studies are in progress to address the link between terlipressin and survival in hepatorenal syndrome patients.