Mallinckrodt presents results from two retrospective studies on real world characteristics and outcomes of patients with hepatorenal syndrome type-1 (HRS-1) at The Liver Meeting Digital Experience.

HRS-1, also known as HRS-acute kidney injury (HRS-AKI), is a life-threatening complication in patients with advanced liver disease. The data were highlighted in poster presentations at the Liver Meeting Digital Experience, the annual meeting of the American Association for the Study of Liver Diseases (AASLD), being held virtually from November 12-15.

The first poster presentation titled "Hepatorenal Syndrome Patient Characteristics, Treatment, and Clinical Response by Disease Severity: Real-world Practice Patterns from 11 U.S. Hospitals," is a retrospective, observational study based on medical chart data from 132 hospitalized adult patients across 11 hospitals in the U.S. between January 1, 2016, and June 30, 2019. The objective of the study was to describe characteristics of HRS-1 patients in the United States and assess real-world treatment patterns and clinical outcomes based on disease severity.

Patients were classified as standard presentation (i.e., baseline serum creatinine [SCr] <5 mg dl, acute on chronic liver failure [aclf] grade 0-2, and model for end-stage liver disease [meld] score><35) or severe presentation (i.e., baseline scr greater than 5 mg dl or aclf>2 or MELD score greater than 35). Data were collected from hospital admission up to 90 days post-discharge or until death using an electronic case report form.</35)></5>

A total of 65 patients (49.2 percent) had standard disease severity and 67 (50.8 percent) had severe disease. The analysis showed that initial use of vasopressor therapies was similar between the two groups with midodrine/octreotide monotherapy being the most widely used (89.2 percent in standard cases versus 82.1 percent in severe cases). Overall response to therapy (N=132) was low in patients initiating existing treatment regimens irrespective of disease severity (Complete Response: 13.8 percent versus 17.9 percent and Partial Response: 9.2 percent versus 16.4 percent in the standard and severe groups, respectively, p=0.324).

The limitations of this post hoc analysis of a retrospective chart review may include a more heterogeneous HRS population than those in randomized clinical trials, 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.

"Hepatorenal syndrome is very difficult to diagnose and typically met with high mortality rates if left untreated. Our analysis showed that overall response rate was low in patients initiating existing treatment regimens irrespective of disease severity, indicating a high unmet medical need in people with HRS-1, and need for alternate therapies," said Arun Sanyal, M.D., Lead Study Investigator And Reno Vlahcevic Professor Of Medicine, Physiology And Molecular Pathology At Virginia Commonwealth University.

The second poster presentation, titled "Serum Creatinine ?5 mg/dL is Associated with Decreased Safety and Efficacy in Patients Treated with Terlipressin for Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI) in the United Kingdom," is a post hoc analysis of a medical chart review study with data from 203 hospitalized adult patients treated with terlipressin collected across 26 hospitals in the UK (where terlipressin is approved and available) between January 1, 2013, and December 31, 2017. The objective of the analysis was to describe efficacy and safety outcomes in patients with a SCr ?5 mg/dL at the time of vasopressor initiation. Data were collected from hospital admission up to 90 days post-discharge or until death using an electronic case report form.

The results showed that among 203 patients who received terlipressin, 181 (89 percent) had a SCr <5 mg dl at presentation and 22 (11 percent) had a scr greater than 5 mg dl. the overall response rate was 74.0 percent in patients with presenting scr><5 mg dl and 63.6 percent in patients with presenting scr greater than 5 mg dl. patients with a presenting scr><5 mg dl were more likely to achieve complete response compared with those with presenting scr greater than 5 mg dl (54.7 versus 13.6 percent, respectively; p><.001). the overall survival was longer in patients with presenting scr><5 mg dl than in patients with presenting scr greater than 5 mg dl (p=".041)." additionally, patients with presenting scr greater than 5 mg dl were more likely to develop fluid overload or pulmonary edema (27.3 percent) and multi-organ failure (31.8 percent) compared to patients with a scr><5 mg dl (14.4 and 6.1 percent, respectively).the limitations of this post hoc analysis of a retrospective chart review may include a more heterogeneous hrs population than those in randomized clinical trials, 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.></5></5></.001).></5></5></5>

"Our analysis supports previous studies linking higher presenting SCr to poorer outcomes in patients with HRS-1.Importantly, these findings highlight significant unmet need for effective medical therapy for HRS-AKI and suggest that earlier initiation of vasoconstrictors may optimize patient outcomes," said Andrew Allegretti, M.D. MSc, Lead Study Investigator And Director Of Critical Care Nephrology, Massachusetts General Hospital.