Kevin Moore, MD UCL Institute of Liver and Digestive Health Royal Free Hospital, University College London

Hepatorenal Syndrome-Acute Kidney Injury: Predictors of Response to Terlipressin Interview with:

Kevin Moore, MD UCL Institute of Liver and Digestive Health Royal Free Hospital, University College London

Dr. Moore

Kevin Moore, MD
UCL Institute of Liver and Digestive Health
Royal Free Hospital, University College London What is hepatorenal syndrome – acute kidney injury (HRS-AKI) and how does terlipressin fit into the treatment landscape? 

Response: HRS-AKI, also known as hepatorenal syndrome type 1 (HRS-1), is an acute and life-threatening syndrome involving acute kidney failure in people with cirrhosis.[i] HRS-1 can progress to life-threatening renal failure within daysi and has a median survival time of approximately two weeks and greater than 80 percent mortality within three months if left untreated.[ii],[iii]

Terlipressin, a potent vasopressin analogue selective for V1 receptors, is an investigational agent, and its safety and effectiveness have not yet been established by the U.S. Food and Drug Administration. In the U.S., there are currently no approved pharmacologic treatments for HRS-1; however, terlipressin is approved in most other countries, where it has been a standard of care for the last 20 years in the treatment of patients with HRS-1.[iv],[v]

The current standard of care for HRS-1 in the U.S. includes other vasoconstrictors such as midodrine (a drug which can increase blood pressure and potentially improve blood flow into the kidneys) along with concomitant albumin and frequent monitoring, but current data do not support good efficacy.2 Dialysis (a type of renal replacement therapy) is sometimes used in hepatorenal syndrome, but dialysis is not curative and it can be costly. What are the main findings?

Response: Results from a post-hoc analysis of a retrospective chart review study of terlipressin in patients HRS-AKI from 26 hospitals in the United Kingdom were presented at The Liver Meeting Digital Experience, the annual meeting of the American Association for the Study of Liver Diseases in a poster presentation titled, “Predictors of Response to Terlipressin in Patients with Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI): A Multicenter Study.”

The retrospective chart review study included 250 adult patients hospitalized with a diagnosis of HRS-AKI over a four-year period – between January 1, 2013 and December 31, 2017 – who received terlipressin or other vasopressors. The objective was to identify predictors of response to terlipressin and mortality in these patients.

The majority of patients were treated with terlipressin (n=203) and were evenly distributed by baseline AKI severity: mild, 33 percent (SCr <2.25 mg/dL); moderate, 36 percent (SCr ≥2.25 mg/dL and <3.5 mg/dL); severe, 31 percent (SCr ≥3.5 mg/dL).

The chart review found that the overall response rate among patients treated with terlipressin, including complete responses (SCr ≤1.5 mg/dL) and partial responses (SCr reduction ≥20 percent but SCr >1.5 mg/dL), was 73 percent and differed minimally between the mild and moderate groups compared to the severe group (60 percent). In addition, the analysis identified predictors of overall response as: an absence of a precipitating event, concomitant use of albumin and mild or moderate baseline AKI severity. The presence of encephalopathy was the only predictor of mortality (hazard ratio, 2.77; 95 percent confidence interval, 1.56 to 4.92) identified by the study.

The limitations of this analysis include a more heterogeneous HRS population than those in randomized clinical trials, diagnosis based on reporting, sampling bias from conveniently selected centers, potential selection bias towards patients with known outcomes to the providers, and under reporting of less severe adverse events. What should readers take away from your report?

Response: As a physician treating patients with difficult conditions like HRS-1, I am committed to continuing to build on decades of research of investigational products like terlipressin that can advance our scientific understanding of potential treatment options for these very sick patients who often rapidly decline and experience significant mortality rates if left untreated. The results of this U.K. analysis represent the largest real-world population experience of terlipressin for HRS-1. 

Mallinckrodt Pharmaceuticals
Any disclosures?
Mallinckrodt Pharmaceuticals funded the studies. 



AASLD 2020 abstracts:

  • Abstract 650: “Hepatorenal Syndrome and Acute Kidney Injury in Patients with Liver Disease: National Practice Patterns and Outcomes from a Large U.S. Database”
  • Abstract 1831“Predictors of Response to Terlipressin in Patients With Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI): A Multicenter Study”


[i] National Organization for Rare Disorders. Hepatorenal Syndrome. Available at: Accessed December 10, 2020.

[ii] Colle I and Laterre PF. Hepatorenal syndrome: the clinical impact of vasoactive therapy. Expert Review of Gastroenterology & Hepatology. (2018) 12:2, 173-188, DOI: 10.1080/17474124.2018.1417034.

[iii] Gines P, Sola E, Angeli P, et al. Hepatorenal syndrome. Nature Reviews. (2018) 4:23.

[iv] De Franchis R. Evolving Consensus in Portal Hypertension Report of the Baveno IV Consensus Workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2005;43:167-176.

[v] Ioannou GN, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database of Systematic Reviews. 2003;1. doi: 10.1002/14651858.CD002147.[wysija_form id=”3″]


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Last Updated on December 21, 2020 by Marie Benz MD FAAD