Non-hemodynamic Effects of Terlipressin in Patients with Acute Variceal Bleeding: A Prospective Pilot Study

Abstract

Background: While the hemodynamic effects of terlipressin on reduction of hepatic venous pressure gradient are well known, there is a limited information available on the non- hemodynamic effects of this drug in patients with acute variceal bleeding (AVB). The present study evaluated the effects of terlipressin on systemic inflammation and on endotoxemia in patients with cirrhosis during an episode of AVB. Methods: In this prospective pilot study, peripheral blood sample was withdrawn from patients presenting with AVB on Day-2. Terlipressin was administered as 1mg intravenously every 6 hours as a bolus dose. Prior to next dose, repeat blood sample was withdrawn. In both pre- and post-terlipressin samples, interleukin-6 (IL-6), interleukin-1 (IL-1), tumor necrosis factor alpha (TNF α), C-reactive protein (CRP) and endotoxemia (assessed indirectly by IgM anti- endotoxin antibody) were estimated and compared in individual patients. Results: 24 patients of AVB (mean Age- 45±12 years, 62.5%males) with median Child- turcotte pugh score and model for end stage liver disease score of 8±2 and 13.7±4.1 respectively were studied. Upon terlipressin administration, there was a significant decline in serum IL-1 levels [ pre-terlipressin- (928.84± 363.14) pg/ml vs post-terlipressin- (754.74 ±289.61) pg/ml P= 0.003), serum IL6 levels [ pre-terlipressin-143.75 ng/ml (121.20-166.84) vs post-terlipressin-123ng/ml (99.5 -152.5), P<0.001), serum TNF-α levels [ pre-terlipressin- (1.48± 0.35) pg/ml vs post terlipressin- (1.22± 0.42) pg/ml, P=0.004] and serum CRP levels [ Pre- terlipressin- (5.82 ± 1.44) ng/ml vs post- terlipressin- 4.41± 1.21) ng/ml, P= 0.006]). Endotoxemia assessed by IgM anti-endotoxin antibody showed a significant fall (rise in antibody concentration) after terlipressin administration [ Pre-terlipressin- IgM anti-endotoxin antibody -27.14 (23.05 - 39.3) MMU/mL vs 31.98 (20.95 - 47.08) MMU/mL, P=0.02]. Conclusions: Terlipressin administration in AVB is associated with decline in systemic inflammation and endotoxemia. Further studies with larger sample size and an appropriate control group are required to demonstrate the clinical relevance of these non-hemodynamic effects of terlipressin.