Abstract
Hepatorenal syndrome–acute kidney injury (HRS-AKI) is a life-threatening complication of decompensated cirrhosis and carries significant implications for liver transplantation (LT) candidacy and outcomes. Terlipressin, a synthetic vasopressin analogue, has emerged as a first-line pharmacologic therapy for HRS-AKI. We conducted a systematic review of practice guidelines and studies published between 2020 and 2025 evaluating the role of terlipressin in adult patients with HRS-AKI, with a focus on those undergoing evaluation or listed for LT. Databases including PubMed, MEDLINE, and Scopus were included, and 127 studies met inclusion criteria. Current evidence supports early initiation of terlipressin in appropriately selected patients with HRS-AKI who do not respond to volume resuscitation, with concurrent albumin administration. However, heterogeneity exists across professional society guidelines regarding diagnostic criteria, albumin use, and timing of therapy. In LT candidates, additional complexities arise due to the impact of HRS-AKI reversal on Model for End-Stage Liver Disease (MELD) prioritization. Adjunctive tools such as point-of-care ultrasound and emerging biomarkers may improve diagnostic accuracy and guide individualized management. Terlipressin therapy, as compared to placebo and other vasoconstrictors, is associated with higher rates of HRS reversal, reduced need for renal replacement therapy, and improved short-term outcomes, including patients awaiting LT. However, careful patient selection and monitoring are essential due to risks of ischemic and cardiopulmonary complications. This systematic review provides literature-based considerations to guide the management of HRS-AKI with terlipressin in LT candidates, emphasizing individualized care, early intervention, and integration with LT planning.