# Liver Cirrhosis Network: Clinical Research Centers

> **NIH NIH U01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2022 · $375,370

## Abstract

The population burden of cirrhosis is rising especially related to nonalcoholic steatohepatitis (NASH), alcohol-
induced liver disease (ALD) and in those living with HIV. The progression of cirrhosis to liver-associated clinical
events (LACE) and death is related to a diverse set of systemic and hepatic factors which may be etiology-
specific or agnostic. There remain gaps in knowledge in assessing how these factors interact to cause cirrhosis-
progression to outcomes. This limits rational development of non-invasive tools for risk-stratification and
disease-monitoring purposes as well as the ability to holistically model the development of outcomes. There is
also no established etiology-agnostic approach to reduce the risk of outcomes and death. This proposal, in
response to RFA-DK-20-003, addresses these unmet needs with two specific aims: Aim 1: To conduct a
prospective, multicenter, observational study of patients with cirrhosis of varying etiology that serves as the
foundation for conducting novel mechanistic and therapeutic studies. Patients with compensated cirrhosis of
varying etiology inclusive of NASH, ALD with and without HIV will be enrolled and followed prospectively with
protocol-driven data and bio-sample collection. Outcomes will be assessed prospectively by a pre-specified
adjudication process. Through collaboration with external partners, we will evaluate several promising tools
(e.g. spleen-stiffness measurement), circulating biomarkers (PROC3-6, ELF test) and machine-learned
approaches to obtain novel insights on fibrosis, factors driving outcomes and to model outcomes. The cohort
data and bio-samples will further support mechanistic studies of factors driving fibrosis and outcomes. Aim 2:
To perform a multi-center prospective randomized, double-blind placebo-controlled clinical trial to evaluate the
clinical utility of atorvastatin (10 mg/day x 2 yrs) in patients with compensated cirrhosis. Patients with
compensated cirrhosis of varying etiology, stratified by varices and CTP score (5 or 6) will be enrolled. The trial
design uses the estimand framework proposed by the FDA (ICH E9 R1). The primary endpoint captures benefit
from a patient-perspective and is defined by survival without LACE or major adverse cardiac event or need for
drug withdrawal for toxicity. The primary analysis will be a comparison of proportions of patients meeting the
primary endpoint. The secondary analysis of benefit is a time-to-event analysis of clinical outcomes. Several
measures to track safety and de-risk the study are proposed. A benefit-risk analyses using state of the art
approach is proposed. Together, they will provide robust information on the utility of atorvastatin to improve
outcomes in compensated cirrhosis. The feasibility of the studies is supported by a strong and extensive referral
network, a robust tele-medicine program for liver disease and research infrastructure. The studies will have a
major positive impact by: (1) providing robu...

## Key facts

- **NIH application ID:** 10487561
- **Project number:** 5U01DK130134-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Jasmohan S Bajaj
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $375,370
- **Award type:** 5
- **Project period:** 2021-09-13 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10487561

## Citation

> US National Institutes of Health, RePORTER application 10487561, Liver Cirrhosis Network: Clinical Research Centers (5U01DK130134-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10487561. Licensed CC0.

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