# Atorvastatin reduces recurrent decompensation events in advanced cirrhosis in a randomized placebo-controlled trial

## TL;DR

Atorvastatin reduced cirrhosis complications and improved gut-liver health in a clinical trial, showing promise as a treatment for advanced cirrhosis.

## Contribution

This is the first randomized placebo-controlled trial showing atorvastatin reduces decompensation events and hepatorenal syndrome in decompensated cirrhosis.

## Key findings

- Atorvastatin reduced recurrent decompensation events by 50% compared to placebo.
- Atorvastatin completely prevented hepatorenal syndrome in the treatment group.
- The drug improved biomarkers of inflammation and gut barrier function.

## Abstract

Statins exhibit pleiotropic anti-inflammatory and antifibrotic properties that may attenuate the progression of cirrhosis. This study aimed to evaluate the efficacy and safety of atorvastatin in preventing recurrent decompensation events (DDs) and in modulating the gut–liver axis among patients with decompensated cirrhosis. In this randomized, double -blind, placebo-controlled trial, 100 adults with decompensated cirrhosis were randomly assigned in a 1:1 ratio to receive either atorvastatin (20 mg/day) or placebo for six months. The primary endpoint was the incidence of recurrent decompensation events (DDs). Secondary outcomes included changes in biomarkers of oxidative stress (malondialdehyde [MDA]), systemic inflammation (nuclear factor kappa B [NF-κB], C-reactive protein [CRP], and erythrocyte sedimentation rate [ESR]), intestinal permeability (zonulin), and endotoxemia (lipopolysaccharide [LPS]). Atorvastatin treatment significantly reduced the cumulative recurrence of cirrhosis-related complications compared to placebo (36% vs. 72%; HR 0.50; 95% CI, 0.33–0.75; P < 0.001). Notably, atorvastatin conferred complete protection against hepatorenal syndrome (HRS) (0% vs. 20% in the placebo group; all Type 2). These clinical improvements were mirrored by significant reductions in MDA, NF-κB, LPS, and zonulin levels (P < 0.05), indicating a robust attenuation of systemic inflammation and restoration of intestinal barrier integrity. Atorvastatin was well-tolerated; while mild myalgia was more frequent in the intervention group (14% vs. 2%), elevations in transaminases were transient and clinically insignificant. In this randomized trial, atorvastatin was associated with a lower recurrence of decompensation events and a reduced incidence of hepatorenal syndrome compared with placebo. These effects were accompanied by improvements in biomarkers related to systemic inflammation and gut–liver axis dysfunction. Atorvastatin was generally well tolerated, although mild myalgia occurred more frequently and warrants clinical monitoring. While these findings suggest a potential role for atorvastatin as an adjunctive therapy in decompensated cirrhosis, confirmation in larger, multicenter studies is required before broader clinical application. Clinical trial number: NCT05563389 (https://register.clinicaltrials.gov/prs/beta/studies/S000CHKM00000052/recordSummary).

The online version contains supplementary material available at 10.1038/s41598-026-41326-4.