麻豆传媒

Starting terlipressin (Terlivaz) well before the 48-hour period to establish a diagnosis of hepatorenal syndrome acute kidney injury (HRS-AKI) led to better outcomes for patients with acute-on-chronic liver failure (ACLF), according to a small randomized trial.

In the study, AKI reversals at 7 days were twice as frequent when patients started terlipressin after 12 hours of albumin infusion compared to the standard initiation at 48 hours (68.6% vs 31.4%, P=0.03), reported Hitesh Singh, MD, of the Institute of Liver and Biliary Sciences in New Delhi.

Significantly more reversals were seen as early as 3 days with terlipressin (31.4% vs 11.4%), he said at the annual Liver Meeting sponsored by the American Association for the Study of Liver Diseases.

In addition, starting the vasopressor at 12 hours also led to improvements in mean arterial pressure and urine output, as well as significantly greater survival at both 28 days (60% vs 34%) and 90 days (70% vs 34%).

The observed benefit in the trial could be "because of early splanchnic vasoconstriction and redistribution of blood to the kidneys," said Singh.

He explained that the diagnosis of HRS-AKI requires 48 hours of volume repletion with albumin and diuretic withdrawal, but that waiting this long has been linked to disease worsening and an increased risk for death. The vasopressor was recently approved in the U.S. for patients with HRS and rapid declines in kidney function, but has been used in other parts of the world for decades.

"These early results are promising," said Christina Lindenmeyer, MD, of the Cleveland Clinic in Ohio, who was not involved in the study.

"More data is needed to better understand: 1) the definition of AKI in patients with ACLF given the dynamic natural history of the syndrome, 2) the impact of early terlipressin in patients with severe ACLF and volume overload and/or respiratory failure, and 3) consensus regarding early intervention in relationship to a patient's candidacy for liver transplantation," Lindenmeyer told 麻豆传媒.

Reached for comment, Andrew Talal, MD, MPH, of the University at Buffalo in New York, highlighted the findings that early terlipressin initiation improved "short-term mortality by improving hemodynamic function, while also diminishing the severity of acute kidney injury and stage of [ACLF]."

"While a relatively small number of participants were included in this trial, the results do look promising in an area where data have been lacking," said Talal, who was not involved in the research.

From June 2020 to May 2022, the open-label study included 70 ACLF patients with stage II or III AKI despite receiving 40 g of albumin resuscitation for 12 hours. Participants were randomized 1:1 to receive terlipressin at 12 hours (2 mg/every 24 hours; early group) plus albumin or continue on albumin and start terlipressin at 48 hours (2 mg/every 24 hours; standard group).

Baseline clinical characteristics were similar between the study arms, said Singh.

At 3 days, mean arterial pressure showed more improvement in the early group (62.2 to 82.4 mm Hg) than in the standard group (63.4 to 76.4 mm Hg). And urine output at this point also showed more improvement in the early group (26.4 to 52.4 mL/hour) compared with the standard group (24.2 to 44.6 mL/hour).

A higher proportion of patients in the early group no longer had AKI at day 3 as well (31.4% vs 8.6%, P<0.01)

From baseline to 7 days, a lower total intravenous albumin dose was required in the early group than the standard group (149.1 vs 177.5 g, P<0.01), said Singh.

Overall, five patients from each group experienced progressive AKI and required dialysis. Nine patients developed treatment-related adverse events, but none were life threatening. The study is currently ongoing and further data are required, Singh acknowledged.

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