Q&A: ‘Strong’ incidence of IFALD in patients dependent on parenteral nutrition
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Protara Therapeutics announced results of a study designed to further understand the incidence of intestinal failure-associated liver disease in patients dependent on parenteral nutrition.
Healio Gastroenterology spoke with Alan Buchman, MD, professor of clinical surgery and medical director, Intestinal Rehabilitation and Transplant Center, University of Illinois at Chicago, about the results and the future research to come.
Healio: Can you describe the purpose and design of the study?
Buchman: We hypothesized that a significant number of patients dependent on parenteral nutrition (PN) suffer from intestinal failure-associated liver disease (IFALD), and the purpose of this study was to deepen our understanding of this correlation. In order to do this, we sought to understand the incidence of cholestasis, a hallmark pathology of IFALD, in this patient population. The study was designed as a retrospective, observational study that examined data from 468 patients dependent on PN for 6 months or more.
The primary endpoint of the study was to identify the proportion of patients dependent on PN with suspected liver disease, which we defined as alkaline phosphatase (ALP) levels greater than 1.5 times the upper limit of normal (ULN). ALP is an established biomarker for cholestasis and a clinically meaningful indicator of IFALD severity and progression. The study evaluated ALP levels from baseline up to 36 months to determine if there is a progressive component to cholestasis in IFALD and the degree to which medical management affected ALP levels.
Healio: What were the results of the study?
Buchman: The study found that approximately 30% of patients who are dependent on PN have cholestasis despite the use of current medical management in these patients.
Approximately 31% of all patients, irrespective of baseline levels, presented with ALP levels greater than 1.5 times the ULN at any given time over a 30-month period.
Approximately 28% of all patients had persistent ALP elevations greater than 1.5 times the ULN at 36 months. At baseline, approximately 23% of patients presented with ALP levels greater than 1.5 times the ULN. In these patients, approximately 76% presented with greater than 1.5 times the ULN at any given time over a 30-month period and approximately 59% had persistent ALP elevations greater than 1.5 times the ULN at 36 months. While medical management demonstrated some improvement in ALP levels, it was not sufficient for managing ALP levels over the long term in patients on PN.
Healio: What is the take-home message of the study?
Buchman: These study findings validated our initial thinking that there is a strong incidence of IFALD in patients dependent on PN. Further, these data show that current medical management of IFALD is largely insufficient in improving ALP levels and cholestasis.
Healio: What is the conclusion?
Buchman: Importantly, these data underscore the fact that there is a significant need for an effective intervention for patients with IFALD, which carries a particularly poor prognosis in the absence of an intestine-liver transplant.
Healio: What is the next step in research?
Buchman: In terms of next steps, in order to further characterize the prevalence and needs of IFALD patients dependent on PN, a prospective, multicenter, cross-sectional observational study has been initiated to assess the prevalence of choline deficiency, as well as cholestasis and steatosis, in approximately 300 patients dependent on PN.
As background, patients who are dependent on PN are unable to absorb sufficient levels of choline, an essential component of several metabolic processes, ultimately resulting in the development of IFALD.
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