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Early Versus Standard Initiation of Terlipressin for Acute Kidney Injury in ACLF: A Randomized Controlled Trial (eTerli Study)

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Abstract

Background and Aims

Terlipressin infusion is effective in hepatorenal syndrome (HRS-AKI). However, its efficacy for HRS-AKI resolution in acute-on-chronic liver failure (ACLF) patients has been suboptimal. Progression of AKI is rapid in ACLF. We investigated whether early initiation of terlipressin(eTerli) can improve response rates.

Methods

Consecutive ACLF patients with stage II/III AKI despite albumin resuscitation (40 g) were randomized to receive terlipressin at 2 mg/24 h plus albumin at 12 h (ET, n = 35) or at 48 h as standard therapy (ST, n = 35). (June 22, 2020 to June 10, 2022). The primary end-point was AKI reversal by day7.

Results

Baseline parameters including AKI stage and ACLF-AARC scores in two arms were comparable. Full AKI response at day 7 was higher in ET [24/35 (68.6%)] than ST arm [11/35 (31.4%; P 0.03]. Day3 AKI response was also higher in ET arm [11/35 (31.4%) vs. 4/35 (11.4%), P 0.04]. Using ST compared to ET [HR 4.3; P 0.026] and day 3 serum creatinine > 1.6 mg/dl [HR 9.1; AUROC-0.866; P < 0.001] predicted HRS-AKI non-response at day 7. ET patients showed greater improvement in ACLF grade, mean arterial pressure, and urine output at day 3, and required lower albumin within 7 days than ET arm (149.1 ± 41.8 g vs. 177.5 ± 40.3 g, P 0.006) and had lower 28-day mortality: 40% vs. 65.7%, P 0.031]. Early use of terlipressin than ST [HR 2.079; P 0.038], baseline HE [HR 2.929; P 0.018], and AKI persistence at day 3 [HR 1.369; P 0.011] predicted 28-day mortality. Fifteen (21.4%) patients had treatment related adverse effects, none was life threatening.

Conclusion

In ACLF patients, early initiation of terlipressin for AKI persisting after 12 h of volume expansion with albumin helps in reduced short-term mortality and early AKI reversal with regression of ACLF stage. These results indicate need for change in current practice for terlipressin usage in HRS-AKI.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

ACLF:

Acute on chronic liver failure

AKI:

Acute kidney injury

CI:

Confidence interval

CVP:

Central venous pressure

DC:

Decompensated cirrhosis

HE:

Hepatic encephalopathy

HR:

Hazard ratio

HRS:

Hepatorenal syndrome

ICA:

International Club of Ascites

IL:

Interleukin

IQR:

Interquartile range

IVC:

Inferior vena cava

MAP:

Mean arterial pressure

MELD:

Model for End-Stage Liver Disease

OR:

Odds ratio

PPA:

Per-protocol analysis

RCT:

Randomized controlled trial

RRT:

Renal replacement therapy

SBP:

Spontaneous bacterial peritonitis

sCr:

Serum creatinine

ET:

Early terlipressin

ST:

Standard terlipressin

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Acknowledgments

The paper was presented as a plenary presentation at the AASLD 2022.

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Authors and Affiliations

  1. Department of Hepatology, Institute of Liver and Biliary Sciences, D – 1, Vasant Kunj, New Delhi, 110070, India

    Ankur Jindal, Hitesh Singh, Vinod Arora, Manoj Kumar Sharma, Rakhi Maiwall, V. Rajan, Harsh Vardhan Tewathia, Chitranshu Vasishtha & Shiv Kumar Sarin

  2. Department of Clinical Research and Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India

    Guresh Kumar

Authors
  1. Ankur Jindal
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  2. Hitesh Singh
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Contributions

AJ, SKS: Conceptualization (lead); writing—original draft (lead); writing—review and editing (equal). AJ: Data analysis (equal) HT: Patient enrollment (lead) GK: Data analysis (equal) VA, RV, RM, HT, CV: review and editing (equal).

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Correspondence to Shiv Kumar Sarin.

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Jindal, A., Singh, H., Kumar, G. et al. Early Versus Standard Initiation of Terlipressin for Acute Kidney Injury in ACLF: A Randomized Controlled Trial (eTerli Study). Dig Dis Sci (2024). https://doi.org/10.1007/s10620-024-08423-8

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