# Michigan Hepatotoxicity Clinical Research Network Renewal 2018

> **NIH NIH U01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $346,443

## Abstract

Michigan Hepatotoxicity Research Network 2018 Renewal
ABSTRACT
In the past 5 years, the Drug Induced Liver Injury Network (DILIN) has increased cumulative enrollment
to over 2000 adult and pediatric patients in the ongoing Prospective and Retrospective registry studies.
In addition, an “Acute” DILI protocol with collection of serial early biological samples for mechanistic
biomarker studies was developed and implemented. Other network aims included investigation of the
role of genetic polymorphisms in DILI susceptibility and outcome, development of improved causality
assessment methods, and expansion of the LiverTox website. The University of Michigan team led by
Dr. Fontana has played an important role in the design, implementation, and analysis of the primary and
ancillary DILIN studies since its inception in 2003. Michigan has not only been a leading enroller in all of
the ongoing Registry studies but also provided important leadership in multiple DILIN committees and
initiatives. The Michigan team now proposes a series of novel and feasible study aims for the DILIN
renewal. The PRIMARY AIM of this proposal is to continue to recruit and enroll high causality adult and
pediatric DILI cases into the registry studies for genetic, immunologic, biomarker and mechanistic
studies. The Michigan Hepatotoxicity Network has specific plans to increase the enrollment of ethnic
minorities via the engagement of hepatologists/ collaborators in southeastern Michigan and elsewhere
that care for a large number of African American, Hispanic, and Asian patients. In addition, further
development of natural language processing algorithms to search the EMR at the University of Michigan
are proposed to facilitate enrollment. Qualitative, quantitative and toxicological studies of the chemical
constituents in the herbal and dietary supplement (HDS) products implicated in a growing proportion of
DILI cases will be expanded via an ongoing collaboration with the National Center for National Products
Research. The SECOND AIM of this proposal is to conduct pilot/ feasibility clinical trials to improve the
outcomes of patients with severe acute DILI and those at risk for developing chronic DILI. Proposed
study designs include a 12 week course of a simple and safe, orally administered anti-inflammatory or
anti-oxidant agent (e.g. budesonide, SAMe, vitamin E) in selected patients with severe acute DILI at risk
for adverse outcomes. In addition, 12 to 24 week studies of a safe and effective orally administered anti-
cholestatic agent such as an ileal apical bile salt transport inhibitor that may reduce serum bile acids are
proposed for subjects at risk of chronic DILI. Lastly, prospective studies of magnetic resonance
elastography and MRCP imaging are proposed to improve our understanding of the severity and natural
history of DILI. The THIRD AIM of this proposal is to further expand the LiverTox website to include
additional chapters on HDS DILI, develop and implement a compute...

## Key facts

- **NIH application ID:** 10234116
- **Project number:** 5U01DK065184-19
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** ROBERT J FONTANA
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $346,443
- **Award type:** 5
- **Project period:** 2003-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234116

## Citation

> US National Institutes of Health, RePORTER application 10234116, Michigan Hepatotoxicity Clinical Research Network Renewal 2018 (5U01DK065184-19). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10234116. Licensed CC0.

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