Terlipressin for hepatorenal syndrome: A meta-analysis of randomized trials.
BACKGROUND
Hepatorenal syndrome (HRS) is a severe complication of end-stage renal disease whose management still constitutes a big challenge. Various approaches have been used for hepatorenal syndrome treatment, including vasoconstrictor therapy. Terlipressin, a vasopressin analogue, has frequently been used.


OBJECTIVE
To evaluate the efficacy and safety of terlipressin in patients with HRS by performing a systematic review with a meta-analysis of controlled, clinical trials.


METHODS
Only prospective, placebo-controlled, randomized clinical trials (RCTs) were included. We used the random effects model of DerSimonian and Laird, with heterogeneity and subgroups analyses. The primary end-point of interest was the HRS reversal after terlipressin (or placebo) therapy in study patients vs. control patients (as a measure of efficacy). The secondary outcome was the rate of ischemic side-effects in study patients vs. placebo patients (as a measure of tolerability). The additional end-point was the impact of terlipressin on survival in the HRS population.


RESULTS
We identified five studies involving 243 unique patients with HRS. Pooling of study results showed a significant increase in HRS reversal among study (terlipressin) versus control (placebo) patients; the pooled odd ratio (OR) of HRS reversal was 8.09; 95% CI, 3.521; 18.59; p=0.0001. The p-value was 0.5 for our test of study heterogeneity. In a subgroup analysis excluding case-control trials these results did not change. The rate of severe ischemic events was higher in study than control patients, pooled OR=2.907; 95% CI, 1.094; 7.723 (p=0.032). The test for heterogeneity was not significant. Terlipressin use had no significant impact upon survival (pooled OR for survival rate, 2.064; 95% CI, 0.939; 4.538; p=0.07). No significant heterogeneity (NS) was found.


CONCLUSIONS
Our meta-analysis shows that terlipressin has higher efficacy than placebo in reversing renal function in the HRS population. There was no apparent impact of terlipressin therapy on survival in HRS patients but further large-size trials are needed. Terlipressin use in the HRS population requires careful selection of patients and close clinical surveillance. These results support the use of terlipressin for reversal of renal function in the HRS population.
Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS Foundation, Milan - Italy. fabrizi@policlinico.mi.it
Fabrizio
F
Fabrizi
Vivek
V
Dixit
Piergiorgio
P
Messa
Paul
P
Martin
D000418:Albumins / Q000627:therapeutic use; D019317:Evidence-Based Medicine; D005260:Female; D006530:Hepatorenal Syndrome / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D008236:Lypressin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010952:Plasma Substitutes / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D000077585:Terlipressin; D013997:Time Factors; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000009:adverse effects / Q000627:therapeutic use*
D000418:Albumins; D010952:Plasma Substitutes; D014662:Vasoconstrictor Agents; D008236:Lypressin; D000077585:Terlipressin