# Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis

> **NIH VA I01** · PHILADELPHIA VA MEDICAL CENTER · 2020 · —

## Abstract

Background: Cirrhosis is the final common pathway of hepatic inflammation and fibrosis caused most
commonly by alcohol or viral infection with hepatitis C and/or B. HMG-coA reductase inhibitors (statins) are
thought to be beneficial in liver disease by ameliorating intrahepatic endothelial dysfunction, inflammation
and fibrosis, thereby leading to a reduction in portal pressure. Because clinically significant portal
hypertension is the main driver of decompensation, a reduction in portal pressure (demonstrated in both
experimental and human cirrhosis) will prevent hepatic decompensation.
Objectives: This phase III, randomized, double-blind, placebo-controlled, multi-center study will assess
whether simvastatin can delay/prevent hepatic decompensation, hepatocellular carcinoma (HCC), need for
liver transplantation or death in Veterans with compensated cirrhosis at a high-risk of decompensation.
Specific Aims: 1) To demonstrate that statin therapy in patients with cirrhosis at high-risk for hepatic
decompensation will reduce the incidence of hepatic decompensation, hepatocellular carcinoma, all-cause
mortality and need for liver transplantation; 2) to assess the impact of statin exposure on health-related
quality of life in patients with compensated cirrhosis; and 3) to explore the impact of chronic simvastatin on
portal hypertension in patients with compensated cirrhosis.
Study Design: Patients with compensated cirrhosis at high-risk for hepatic decompensation will be
stratified based upon the presence or absence of varices and randomized to simvastatin 40mg/day or
placebo for up to 24 months. Patients will be observed for the development of hepatic decompensation
(variceal hemorrhage, ascites, encephalopathy), HCC, liver-related death, death from any cause, and/or
complications of statin therapy. The primary study endpoint is the effect of statin therapy on reducing the
incidence of hepatic decompensation and HCC. Secondary endpoints are to assess the effect of statin
therapy on mortality, need for liver transplantation, health related quality of life in patients with
decompensated cirrhosis, to assess the impact of statins on portal hypertension, and to explore the
interaction of SLCO1B1 and KIF6 polymorphisms on safety and clinical efficacy of statin therapy.
Clinical Impact: There are an estimated 35,000 individuals with cirrhosis receiving ongoing medical care
within the VA healthcare system. Approximately 15,000 liver decompensation-related hospitalizations occur
annually in the VA with a mean length of stay of 9 days. The current estimated total healthcare expenditure
for an ‘average’ Veteran with cirrhosis approximates $23,000 per year, three times greater than age-
matched controls. Patients with decompensated cirrhosis have nearly double the annual costs,
predominantly related to hospitalizations. Simvastatin, at a cost of $25-50 per year, if proven to safely
reduce liver decompensation and death, would have tremendous health benefits fo...

## Key facts

- **NIH application ID:** 10008481
- **Project number:** 1I01CX002010-01A1
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** David E Kaplan
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-09-30 → 2025-10-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10008481

## Citation

> US National Institutes of Health, RePORTER application 10008481, Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis (1I01CX002010-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10008481. Licensed CC0.

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