Endothelin-1/Nitric Oxide Ratio as a Predictive Factor of Response to Therapy With Terlipressin and Albumin in Patients With Type-1 Hepatorenal Syndrome

Ahmed Abdel-Razik; Nasser Mousa; Mostafa Abdelsalam; Ahmed Abdelwahab; Mona Tawfik; Ahmed M Tawfik; Ahmad S Hasan; Rania Elhelaly; Niveen El-Wakeel; Waleed Eldars

doi:10.3389/fphar.2020.00009

Endothelin-1/Nitric Oxide Ratio as a Predictive Factor of Response to Therapy With Terlipressin and Albumin in Patients With Type-1 Hepatorenal Syndrome

Front Pharmacol. 2020 Jan 31:11:9. doi: 10.3389/fphar.2020.00009. eCollection 2020.

Authors

Affiliations

¹ Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
² Nephrology and Dialysis Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
³ Diagnostic & Interventional Radiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
⁴ Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
⁵ Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

Abstract

Background and purpose: Predictors of response to type-1 hepatorenal syndrome (HRS) therapy are urgently needed. This study's purpose is to evaluate the proposed predictors in these patients.

Methods: Forty-two type-1 HRS patients with cirrhosis were treated with albumin and terlipressin. Clinical, biochemical, and demographic parameters taken at the onset of therapy and changes in endothelin-1/nitric oxide (ET-1/NO) ratio during therapy were analyzed to check their predictive value.

Results: Response to treatment (serum creatinine level <1.5 mg/dL at the end of therapy) was shown in 20 patients (48%). Independent predictive variables of response to therapy were early reduction of ET-1/NO ratio ≥0.15 at day 3 of therapy and serum bilirubin baseline <8 mg/dL (area under the receiver operating characteristic curve, 0.751; P < 0.001; specificity, 55%; sensitivity, 85%). Response rates in patients with serum bilirubin level <8 and ≥8 mg/dL were 63% and 20%, respectively (P = 0.008). The corresponding values in patients with an early reduction of ET-1/NO ratio ≥0.15 and <0.15 on day 3 were 85% and 13.6%, respectively (P < 0.001).

Conclusions: Early reduction of ET-1/NO ratio and lower serum bilirubin baseline can predict response to type-1 HRS therapy with albumin and terlipressin. Alternative therapy should be investigated for nonresponder type-1 HRS patients.

Keywords: albumin; endothelin-1; endothelin-1/nitric oxide ratio; hepatorenal syndrome; liver cirrhosis; nitric oxide; terlipressin.