The Liver Meeting
Hepatorenal syndrome-acute kidney injury (HRS-AKI) is characterized by rapid deterioration in renal function in patients with cirrhosis. HRS-AKI is the result of portal hypertension that leads to decreased effective circulating arterial volume and renal vasoconstriction. Patients with HRS-AKI face poor prognosis; results of studies in multiple cohorts demonstrated ~50% survival at 1 month.
Other previous studies have shown associations between vasoconstrictors and improvement in outcomes in patients with HRS-AKI. In the United States, treatment primarily involves use of vasoactive medications such as midodrine with octreotide, norepinephrine, and vasopressin, in combination with albumin. Critical factors that can aid in predicting clinical outcome and treatment response among patients with HRS-AKI include Model of Endstage Liver Disease (MELD) score that incorporated serum bilirubin, creatinine, and the international normalized ratio, along with acute-on-chronic liver failure (ACLF).
Arun J. Sanyal, MD, and colleagues conducted a retrospective, observational study designed to identify characteristics of patients with HRS-AKI in the United States and to assess treatment patterns and clinical outcomes based on disease severity. Results of the study were reported during a virtual poster session at the AASLD Liver Meeting in a poster titled Hepatorenal Syndrome Patient Characteristics, Treatment, and Clinical Response by Disease Severity: Real-World Practice Patterns from 11 US Hospitals.
The study utilized medical chart data extracted by physicians from adult patients hospitalized at 11 tertiary care centers in the United States. Data were collected from hospital admission up to 90 days post-discharge or until death.
International Classification of Diseases (ICD), Ninth Revision, and ICD-Tenth Revision codes were used to identify eligible patients; patient eligibility was also determined using chart documentation of diagnosis of HRS-AKI. Patients were selected based on a random number generated by the study sponsor.
Inclusion criteria were age >18 years, alive, or deceased at the time of data collection, and first hospital admission for HRS-AKI episode between January 1, 2016, and June 30, 2019. Patients were excluded if they were enrolled in any clinical trial during hospitalization, had incomplete laboratory data for assessment of treatment response (defined as a serum creatinine ]SCr] on the day of vasopressor initiation and discontinuation), or had hospital stay ≤2 days.
The analysis included data on 132 patients at 11 tertiary care centers. Of the total cohort, 49.2% (n=65) had standard disease severity (baseline SCr <5 mg/dL, ACLF grade 0-2, and MELD score <35) and 50.8% (n=67) had severe disease (baseline SCr ≥5 mg/dL or ACLF >2 or MELD score ≥35). At admission, mean patient age was 57 years, 45.5% were female, and 68.2% were White. The most common precipitating events were treatment with diuretics (42.4%) and large-volume paracentesis (41.7%). The primary underlying cause of cirrhosis was acute alcoholic cirrhosis (55.3%), which was more common in the group with severe disease at presentation than in the standard disease group (67.2% vs 43.1%; P=.005).
The two groups were similar in initial vasopressor therapies: midodrine/octreotide monotherapy (89.2% vs 82.1%), norepinephrine monotherapy (1.5% vs 6.0%), and other combination therapies (9.2% vs 11.9%). Median duration of treatment was norepinephrine, 3 days in the standard presentation group and 6.5 days in the severe disease group; midodrine/octreotide, 5 days in the standard group and 6 days in the severe disease group; and other therapy, 12 days in the standard group and 5.5 days in the severe group. Nearly all (99%) patients received concurrent treatment with albumin (100% of patients in the standard presentation group and 98.5% of those in the severe disease presentation group).
Mean change in SCr from baseline to day 14 was –0.2 mg/dL in the standard presentation group and +0.7 in the severe presentation group (P=.006). Overall response was 23.0% (complete response [CR], 13.8% and partial response [PR], 9.2%) in the standard disease presentation group and 34.3% (CR, 17.9% and PR, 16.4%) in the severe disease presentation group (P=.3). Median time from initiation of vasopressor treatment to response was 14 days in both groups.
In the standard group, median overall survival from initiation of vasopressor treatment was 1.5 months compared with 0.6 months in the severe disease group.
In conclusion, the authors said, “Midodrine/octreotide was the most prescribed vasopressor for HRS-AKI in the United States. The results of the study do not support a link between disease severity at presentation and response to vasopressor treatment or mortality. Overall response rate was low in patients initiating existing treatment regimens irrespective of disease severity, indicating an unmet need in HRS-AKI patients and need for alternate therapies that will improve response and survival outcomes.”
The study was supported by Mallinckrodt Pharmaceuticals.
Source: Sanyal AJ, Reddy R, Brown KA, et al. Hepatorenal syndrome patient characteristics, treatment, and clinical response by disease severity: Real-world practice patterns from 11 US hospitals. Poster presented at the American Association for the Study of Liver Disease virtual Liver Meeting, November 12-15, 2021.