In this video, Michael Curry, MD, from Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, reviews presentations from the American Association for the Study of Liver Diseases on managing hepatorenal syndrome. 

Michael Curry, MD, is chief of Hepatology at Beth Israel Deaconess Medical Center and associate professor of medicine at Harvard Medical School.

TRANSCRIPT

Hello, I am Dr. Michael Curry, Chief of Hepatology at Beth Israel Deaconess Medical Center and Associate Professor of Medicine at Harvard Medical School. This year at AASLD, I reviewed the data that was presented on hepatorenal syndrome this year.

This year, there was very little data presented on hepatorenal syndrome. It amounted to a total of approximately two or three posters -- one oral presentation and a webinar. The posters this year focused on epidemiology and risk factors for development of hepatorenal syndrome (HRS).

In "Poster 650" by Allegretti and colleagues from Mass General Hospital, they looked at nationwide US hospital-based data using ICD-10 coding and identified patients with hepatorenal syndrome admitted to hospitals here in the United States.

Over the time period of the study, there were approximately 13,000 patients admitted with hepatorenal syndrome and a comparative group of about 42,000 patients admitted with liver cirrhosis and acute kidney injury.

What they saw from their data was that 90% of patients with hepatorenal syndrome or acute kidney injury in the setting of liver cirrhosis were admitted through the emergency room or through an urgent care setting.

Not surprisingly, the in-hospital mortality was higher for patients with hepatorenal syndrome at 26%. as opposed to 9% for patients with liver cirrhosis and acute kidney injury. This was despite the fact that on average, patients with hepatorenal syndrome were about 5 years younger than those admitted with acute kidney injury.

Discharged to home in those individuals who have hepatorenal syndrome was far less common than those that have acute kidney injury. Unfortunately, as we are aware, discharge to hospice was higher in patients with hepatorenal syndrome as compared to those individuals with acute kidney injury.

This really highlights the severity and seriousness of hepatorenal syndrome, which we all know has a poor prognosis with virtually 85% of individuals passing away from renal failure, liver failure, or multiorgan dysfunction syndrome within a period of 3 months, prompting the urgent need, I would say, for an appropriate treatment for hepatorenal syndrome here in the United States.

In the second poster that was presented by Kevin Moore and colleagues looked at the largest real-world experience of terlipressin for the treatment of hepatorenal syndrome in patients admitted to community or academic medical centers in the United Kingdom.

This study, which was 203 patients, identified precipitating factors and looked at resolution of hepatorenal syndrome in response to the use of terlipressin and albumin therapy. What they identified was that 84% of individuals presenting with HRS had a precipitating event, and 33% of patients had concomitant hepatic encephalopathy.

They divided their patients into those with mild hepatorenal syndrome, which was considered to be presenting serum creatinine of less than 2.25, moderate hepatorenal syndrome, which was between 2.25 and 3.5, and severe hepatorenal syndrome, which was a creatinine defined as greater than 3.5 grams per deciliter.

In their study, unlike data from the US, 73% of patients responded to the combination of terlipressin and albumin. The higher response rate is likely related to the adoption of the most recent acute kidney injury-HRS definitions, which are different to what we have conventionally used here in the US in clinical trials.

The study also looked to identify predictors of response to terlipressin therapy and showed that the absence of a precipitating factor, the concomitant use of albumin in association with terlipressin and the presence of either mild or moderate acute kidney injury as opposed to severe hepatorenal syndrome were independent predictors of response.

Again, this study highlights the need for an appropriate treatment to treat patients with hepatorenal syndrome. When used early in patients with early kidney dysfunction, it provides a more robust and more significant response ratio.

The third study that I reviewed was an oral presentation from India given by Dr. Gupta, which looked at a comparison of continuous infusion of terlipressin versus a bolus-dose injection of terlipressin on a Q6-hour basis.

Essentially, what they showed was that with a continuous infusion of terlipressin, the total dose of terlipressin administered is lower than those seen in individuals who receive bolus dosing of terlipressin. The response rates in reversing hepatorenal syndrome were similar regardless of the mode of administration.

What was shown in this study, which was similar to that what has already been published by Dr. Cavallin and colleagues a few years ago in Hepatology, was that a continuous infusion of terlipressin was better tolerated by patients in the treatment of hepatorenal syndrome, with a lower incidence of adverse events.

Finally, at AASLD this year a webinar, which was held on Saturday evening, was delivered by my colleagues, Dr. Todd Frederick from San Francisco, Dr. Hugo Vargas from Arizona, and myself, where we discussed the new definitions of hepatorenal syndrome and the treatment of hepatorenal syndrome with terlipressin and other agents that are available to us here in the United States, including norepinephrine, octreotide, and midodrine.

This was a summary that provided knowledge about the definitions of acute kidney injury-HRS, which are different from the standard International Club of Ascites definitions of HRS, which require patients to have a serum creatinine of 2.5 for type 1 HRS.

The adaptation of these new definitions will allow us to be able to treat patients at an earlier stage of their acute kidney injury, and potentially reverse HRS in a larger population of patients, improving potentially the outcome for these individuals.

Terlipressin, while not approved here in the United States at this time point, is under consideration by the FDA. The FDA are working with the sponsor of the largest clinical trial, called the CONFRIM trial, for treating hepatorenal syndrome, the sponsor being Mallinckrodt, to try and bring this to approval here in the United States.

In the CONFIRM trial, we highlighted at the webinar that terlipressin was more effective than placebo in achieving confirmed or verified reversal of hepatorenal syndrome in patients with type 1 HRS. The study did not show a survival advantage.

However, other secondary endpoints showed a reduction in the need for renal replacement therapy in patients who were treated with terlipressin and also a reduction in the need for a post-transplant renal replacement therapy in patients treated with terlipressin.

In a separate study, which I highlighted at that webinar, from Dr. Piano and colleagues in Italy, it has been shown that individuals who are listed for liver transplantation, who developed hepatorenal syndrome, who go on and have that hepatorenal syndrome treated with terlipressin, are far less likely to develop chronic kidney disease after liver transplantation than those individuals who do not receive terlipressin going into liver transplantation with HRS.

That completes the presentations given at this year's AASLD on the topic of hepatorenal syndrome. We look forward, hopefully, to FDA approval for terlipressin here in the United States so that we can adequately treat these individuals for this devastating, life-threatening complication of end-stage renal disease and end-stage liver disease. Thank you very much.