Clinical

Terlipressin may improve hepatorenal syndrome, but ischemic risks seen

Last Updated: 2008-06-23 12:23:53 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Combination treatment with albumin and the vasopressin analogue terlipressin can improve renal function in patients with hepatorenal syndrome and advanced liver disease, according to new research. Unfortunately, terlipressin does not improve short-term mortality and carries a risk of ischemic complications.

Hepatorenal syndrome, a form of renal failure seen in patients with end-stage liver disease, is associated with high mortality, in large part because effective treatments are lacking.

Because arterial vasodilatation is thought to play a key role in hepatorenal syndrome, treatment with various vasoconstrictors, including terlipressin, has been attempted in small, retrospective, nonrandomized studies. Finally, two randomized multicenter trials of vasoconstrictor therapy for hepatorenal syndrome have been published, in the May issue of Gastroenterology.

In the first study, Dr. Pere Gines, from the University of Barcelona, Spain, and colleagues assessed renal function and survival in 46 patients who received IV terlipressin (1 to 2 mg/4 hours) or placebo in combination with albumin (1 g/kg followed by 20 to 40 g/day) for up to 15 days.

Ten of the 23 terlipressin-treated patients (43.5%) showed improved renal function at 3 months compared with 2 of 23 control patients (8.7%), the report indicates (p = 0.017). Baseline urine volume, serum creatinine and leukocyte count, and treatment with terlipressin plus albumin were all independent predictors of enhanced renal function.

Survival was higher, but not significantly, in the terlipressin group: 27% vs. 19%. The end-stage liver disease score at baseline and the improvement in renal function both correlated with survival at 3 months.

Cardiovascular complications were more common in the terlipressin group than in controls (10 vs. 4 patients). Permanent terlipressin withdrawal was needed in 3 patients.

The second study, which was similar in design to the first, involved 112 patients. The main outcome, treatment success, was defined as a drop in serum creatinine to 1.5 mg/dL or less for at least 48 hours by day 14 without syndrome relapse, dialysis, or death.

Dr. Arun Sanyal of Virginia Commonwealth University in Richmond and colleagues report that the treatment success rate in the terlipressin group was double that in the control group (25% vs. 12.5%), although the difference was not statistically significant. Terlipressin therapy was, however, associated with significant reductions in serum creatinine (p < 0.009) and greater likelihood of syndrome reversal (p = 0.008).

No significant differences in overall or transplantation-free survival were achieved, however.

Dr. Roberto J. Groszmann and Dr. Joseph K. Lim from Yale University in New Haven, Connecticut note that while these two papers provide important data that warrant further study, industry support is unlikely because terlipressin is an "orphan" drug that is already widely used in Europe and Asia. "Institutional and foundation support for collaborative studies will be needed" to clarify the role of terlipressin and other vasoconstrictors as a bridge to liver transplantation, the editorialists say.

Gastroenterology 2008;134:1352-1359,1360-1368,1608-1611.