Metabolomic Biomarkers for the Diagnosis of NASH in Liver Transplant Population

Project: Research project

Project Details

Description

Nonalcoholic fatty liver disease is the most common cause of liver injury in the United States. NASH, the progressive subtype of nonalcoholic fatty liver disease (NAFLD) has become the second most common indication for liver transplantation, on pace to become the most common. (1) Liver biopsy is the gold standard for the diagnosis of NASH, however it is not feasible to perform liver biopsies in all patients. There is a tremendous clinical need for biomarkers to diagnose, monitor, and assess the prognosis of patients with NASH. Emerging data demonstrate that some serum based biomarker panels can have reliable accuracy in the diagnosis of NASH in the non-transplant setting.
Participants in this pilot study will consist of patients who have undergone liver
transplantation at Northwestern Memorial Hospital (Chicago, IL, USA) from 1987 to present. Participants will be drawn from the “Mini-Liver” cohort, which is an established protocol that accrues patients on an ongoing basis who come in for a for-cause or protocol liver biopsy posttransplantation, several of whom have recurrent NASH. Biopsy specimens will be independently evaluated by Dr. Anthony Demetris at the University of Pittsburgh and include all relevant histological determinants. Histological data of interest will include, but are not limited to, NASH diagnosis (definite versus borderline or absent), Fibrosis stage (0-4), steatosis grade (0-3), hepatic ballooning (0-2), and lobular inflammation grade (0-3). Biopsy samples are stored and available for additional testing.
Expected Outcomes: Upon completion of data collection, the accuracy of the OWLiver assay to correctly identify those with NASH will be statistically analyzed and ROC curves generated. Previous work has suggested the OWLiver assay can differentiate between NASH, simple steatosis, and healthy liver (ROC > .90).(2, 3) It is anticipated that the OWLiver test will perform well in the liver transplant population and an ROC > 0.90 is the primary goal, differentiating recurrent NASH from normal liver function and non-NASH abnormal liver function. If successful, this assay could be used as a platform for monitoring liver transplant patients and developing a treatment plan to prevent NASH recurrence.
StatusFinished
Effective start/end date9/1/178/31/19

Funding

  • Northwestern Memorial Hospital (Agmt 12 Sgnd 10/9/17)
  • Digestive Health Foundation (Agmt 12 Sgnd 10/9/17)

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