# Liver Cirrhosis Network: Clinical Research Center - Mayo Clinic

> **NIH NIH U01** · MAYO CLINIC ROCHESTER · 2021 · $366,103

## Abstract

PROJECT SUMMARY/ABSTRACT
Therapies aimed at preventing development of cirrhosis-related complications are lacking. Statins have been
shown to improve liver function and attenuate portal hypertension although definitive studies are lacking. Our
investigative team has deep expertise in cirrhosis and portal hypertension including clinical, translational, and
laboratory aspects of disease. Our aims in this proposal are: Aim 1. To conduct a prospective, multicenter,
observational study of patients with compensated cirrhosis that will serve as the foundation for
discovery of novel mechanistic and therapeutic targets. We will consolidate a longitudinal database to (a)
provide unique information on the natural history and outcomes of cirrhosis and (b) support translational
research (proposed in Aim 3). This robust multicenter dataset will be used for the development and validation
of an artificial intelligence-derived algorithm for prediction of decompensation combining extensive clinical,
laboratory and radiographic data, including magnetic resonance elastography and electrocardiogram. Aim 2.
To perform a multicenter prospective randomized phase 3 clinical trial of simvastatin versus placebo
to improve outcomes in patients with compensated cirrhosis. This aim will test the hypothesis that
simvastatin is superior to placebo for reducing complications of cirrhosis and overall mortality. This phase 3
efficacy trial will randomize patients to Simvastatin 20 mg or placebo daily with median follow up of 36 months.
The primary endpoint will be development of varices, decompensating events or death analyzed as ordinal
outcomes based six prognostic stages. Secondary endpoints will include fibrosis regression, incidence of
hepatocellular carcinoma, and cardiovascular complications. Aim 3. To identify novel pathogenic targets in
cirrhosis progression through 2 Sub-aims: Sub-Aim 3a. To investigate the rate of telomere attrition in
cirrhosis progression and decompensation. Telomere shortening has been observed in advanced cirrhosis
and preclinical studies have shown reduced fibrosis with telomere length restoration. However, the rate of
telomere attrition in cirrhosis and its association with disease progression remain unknown. Our proposal will
serve as the basis for future studies assessing new therapies aimed at telomere length preservation in
cirrhosis and effects of statins. Sub-Aim 3b. To measure circulating markers of neutrophil extracellular
traps (NETs) and its correlation to development of hepatic decompensation. Anticoagulation has been
shown to reduce hepatic decompensation in a small trial of patients with cirrhosis. Our group has recently
shown that NETs drive intrahepatic thrombosis, and inhibition of NETs reduces portal pressure in preclinical
studies. Thus, the results of this sub-aim will serve as the foundation for future human studies investigating
novel therapies aimed at disrupting NETs in the liver. Our center and team have substantial experti...

## Key facts

- **NIH application ID:** 10310667
- **Project number:** 1U01DK130181-01
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** VIJAY H. SHAH
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $366,103
- **Award type:** 1
- **Project period:** 2021-09-13 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10310667

## Citation

> US National Institutes of Health, RePORTER application 10310667, Liver Cirrhosis Network: Clinical Research Center - Mayo Clinic (1U01DK130181-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10310667. Licensed CC0.

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