# Multi-parametric MRI of ARPKD liver disease

> **NIH NIH R03** · CHILDREN'S HOSP OF PHILADELPHIA · 2022 · $126,193

## Abstract

PROJECT SUMMARY/ABSTRACT
Liver involvement in autosomal recessive polycystic kidney disease (ARPKD) consists of intrahepatic biliary duct
dilatation, congenital hepatic fibrosis, and portal hypertension. Some patients require liver transplantation or
portosystemic shunting due to severe complications such as recurrent ascending cholangitis or refractory
variceal bleeding. Despite this substantial burden of morbidity, there are currently no approved disease-
modifying therapies for ARPKD. Although several agents have shown promising results in pre-clinical studies, a
critical barrier to advancing clinical trials is the lack of sensitive biomarkers of ARPKD progression for use as
efficacy endpoints. Current clinical methods to measure ARPKD liver disease severity are inadequate, because
standard blood tests of liver inflammation and synthetic function are generally normal even in severely affected
individuals. Patients with portal hypertension may develop an enlarged spleen or low platelet counts, but these
findings cannot detect earlier stages of liver fibrosis. Liver biopsies are invasive and lack prognostic value, and
would not be feasible or acceptable as a clinical trial endpoint. New non-invasive imaging biomarkers of ARPKD
liver disease progression are therefore needed, and will be a prerequisite for advancing potential clinical trials.
In the applicant's K23-supported work, ultrasound (US) elastography and two-dimensional (2D) magnetic
resonance elastography (MRE) appeared to be helpful to quantify the severity of ARPKD liver disease. However,
both of these methods can only measure liver fibrosis, and do not directly capture other important elements of
ARPKD-related liver disease, namely biliary duct dilatation and portal hypertension. Therefore, this proposal
seeks to investigate two novel non-contrast MR methods to provide a more comprehensive assessment of
ARPKD liver disease severity: quantitative magnetic resonance cholangiopancreatography (MRCP+), which can
quantify biliary duct dilatation, and three-dimensional MRE (3D-MRE) of the liver and spleen, which measures
multiple tissue mechanical properties to quantify tissue fibrosis and portal hypertension. Findings from this study
will inform the design of future proposals for a larger multicenter investigation of imaging biomarkers of ARPKD
progression, with a long-term goal of developing validated biomarkers for use as surrogate endpoints in ARPKD
clinical trials to advance the development of ARPKD therapies.

## Key facts

- **NIH application ID:** 10380806
- **Project number:** 5R03DK127132-02
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Erum Aftab Hartung
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $126,193
- **Award type:** 5
- **Project period:** 2021-04-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380806

## Citation

> US National Institutes of Health, RePORTER application 10380806, Multi-parametric MRI of ARPKD liver disease (5R03DK127132-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10380806. Licensed CC0.

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