Liver-HERO: hepatorenal syndrome-acute kidney injury (HRS-AKI) treatment with transjugular intrahepatic portosystemic shunt in patients with cirrhosis-a randomized controlled trial

Trials. 2023 Apr 5;24(1):258. doi: 10.1186/s13063-023-07261-9.

Abstract

Background: Patients with cirrhosis and ascites (and portal hypertension) are at risk of developing acute kidney injury (AKI). Although many etiologies exist, hepatorenal AKI (HRS-AKI) remains a frequent and difficult-to-treat cause, with a very high mortality when left untreated. The standard of care is the use of terlipressin and albumin. This can lead to reversal of AKI, which is associated to survival. Nevertheless, only approximately half of the patients achieve this reversal and even after reversal patients remains at risk for new episodes of HRS-AKI. TIPS is accepted for use in patients with variceal bleeding and refractory ascites, which leads to a reduction in portal pressure. Although preliminary data suggest it may be useful in HRS-AKI, its use in this setting is controversial and caution is recommended given the fact that HRS-AKI is associated to cardiac alterations and acute-on-chronic liver failure (ACLF) which represent relative contraindications for transjugular intrahepatic portosystemic shunt (TIPS). In the last decades, with the new definition of renal failure in patients with cirrhosis, patients are identified at an earlier stage. These patients are less sick and therefore more likely to not have contraindications for TIPS. We hypothesize that TIPS could be superior to the standard of care in patients with HRS-AKI.

Methods: This study is a prospective, multicenter, open, 1:1-randomized, controlled parallel-group trial. The main end-point is to compare the 12-month liver transplant-free survival in patients assigned to TIPS compared to the standard of care (terlipressin and albumin). Secondary end-point include reversal of HRS-AKI, health-related Quality of Life (HrQoL), and incidence of further decompensation among others. Once patients are diagnosed with HRS-AKI, they will be randomized to TIPS or Standard of Care (SOC). TIPS should be placed within 72 h. Until TIPS placement, TIPS patients will be treated with terlipressin and albumin. Once TIPS is placed, terlipressin and albumin should be weaned off according to the attending physician.

Discussion: If the trial were to show a survival advantage for patients who undergo TIPS placement, this could be incorporated in routine clinical practice in the management of patients with HRS-AKI.

Trial registration: Clinicaltrials.gov NCT05346393 . Released to the public on 01 April 2022.

Keywords: Acute kidney injury; Cirrhosis; Hepatorenal syndrome; Randomized controlled trial; TIPS.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Acute Kidney Injury* / etiology
  • Albumins / therapeutic use
  • Ascites / etiology
  • Esophageal and Gastric Varices* / complications
  • Esophageal and Gastric Varices* / drug therapy
  • Gastrointestinal Hemorrhage
  • Hepatorenal Syndrome* / drug therapy
  • Hepatorenal Syndrome* / etiology
  • Humans
  • Liver Cirrhosis / complications
  • Portasystemic Shunt, Transjugular Intrahepatic* / adverse effects
  • Prospective Studies
  • Quality of Life
  • Terlipressin

Substances

  • Terlipressin
  • Albumins

Associated data

  • ClinicalTrials.gov/NCT05346393