Introduction

Terlipressin infusion is effective in treatment of hepatorenal syndrome (HRS-AKI). However, its efficacy in HRS-AKI in acute-on-chronic liver failure (ACLF) patients has been suboptimal. Progression of AKI is rapid in ACLF patients. Response to terlipressin correlates with stage of AKI and ACLF. We investigated whether early initiation of terlipressin (eTerli) therapy can improve response in HRS-AKI patients.

Aims & Methods

Consecutive ACLF patients with stage II/III AKI despite albumin resuscitation (40g) for 12 hours were randomized to receive early terlipressin at 2mg/24 hour plus albumin (ET, n=35) or standard therapy (ST, n=35) with albumin alone for 48 hours followed by terlipressin. The primary end-point was AKI reversal by day 7. Secondary end-points included need for dialysis, treatment-related adverse effects and mortality at day 28 and Day 90.

Results

Baseline parameters including AKI stage and ACLF AARC scores in two arms were comparable. Full AKI response at day 7 was observed in 24/35 (68.6%) patients in ET arm compared to 11/35(31.4%) in ST arm [P-0.03]. Full AKI response at day 3 was observed in 11/35 (31.4%) patients in ET group vs. 4/35(11.4%) in ST group [P-0.04]. ST compared to ET [HR: 4.321(95%CI: 1.189-15.702); P-0.026] and day 3 serum creatinine >1.6 [HR: 9.143(95% CI:2.568-32.551); AUROC-0.866; P <0.001] were independent predictors of HRS non-response at day 7. Patients in ET arm showed significant improvement in ACLF grade (ACLF grade II to I – 16 patients), mean arterial pressure (68.2 ± 1.2 to 82.3 ± 1.4 mm Hg; P-0.05) and urine output (26.4 ± 0.9 to 52.4 ± 1.2 ml/h; P-0.001) at day 3. Five patients in each arm developed progressive AKI requiring dialysis. The total dose of albumin (baseline to day 7) was higher in ST (177.5 ± 40.3g) than ET arm (149.1 ± 41.8g)[P-0.006]. Significantly more patients died within 28 days in ST than ET arm [23/35; 65.7 % vs. 14/35, 40%, P-0.031] and ST compared to ET [HR: 2.079(95%CI: 1.042-4.149); P-0.038], HE at presentation [HR: 2.929(95% CI:1.201-7.142); P-0.018] and Day 3 serum creatinine >1.46 [HR:1.369 (95%CI: 1.075-1.743); P-0.011] were independent predictors of mortality. Overall, 15(21.4%) patients had terlipressin related adverse effects, none was life threatening.

Conclusion

In patients with ACLF, early initiation of terlipressin for AKI persisting despite 12 hours of volume expansion with albumin helps in significant short-term mortality benefit along with early reversal of AKI, improvement in hemodynamic parameters and regression of ACLF stage.

References

Jindal A, Bhadoria AS, Maiwall R, Sarin SK. Evaluation of acute kidney injury and its response to terlipressin in patients with acute-on-chronic liver failure. Liver Int 2016;36:59-67.
Maiwall R, Kumar S, Sarin SK, Kumar G, Rastogi A, Bihari C, et al. AKI in patients with acute on chronic liver failure is different from acute decompensation of cirrhosis. Hepatol Int 2015;9:627-639.
Piano S, Schmidt HH, Ariza X, Amoros A, Romano A, Husing-Kabar A, et al. Association between grade of acute on chronic liver failure and response to terlipressin and albumin in patients with hepatorenal syndrome. Clin Gastroenterol Hepatol. 2018; 16(1792–1800):e1793.

Disclosure

Part of abstract was presented as a oral plenary presentation at the AASLD 2022.
No other conflict of interest