A groundbreaking study by researchers at Harvard Medical School has revealed that statins, commonly prescribed cholesterol-lowering drugs, significantly reduce the risk of hepatocellular carcinoma (HCC) and hepatic decompensation in patients with chronic liver disease (CLD). The findings, published in JAMA Internal Medicine, add to the growing body of evidence suggesting that statins provide not only cardiovascular benefits but also substantial protective effects against liver disease progression.
Why This Study Matters: The Growing Burden of Liver Cancer
Hepatocellular carcinoma is among the leading causes of cancer-related deaths worldwide, and its prevalence continues to rise. While viral hepatitis has historically been the dominant cause of HCC, advancements in antiviral therapies have dramatically reduced hepatitis B and C-related liver cancer cases. Today, metabolic dysfunction-associated liver disease (MASLD, formerly NAFLD), alcohol-related liver disease (ALD), and other metabolic conditions have emerged as the primary risk factors.
With limited effective therapies available for preventing the progression of CLD to liver cancer, researchers have been exploring alternative strategies. Statins—widely used to lower cholesterol—have been of particular interest due to their anti-inflammatory, antifibrotic, and antioxidant properties. While past studies have hinted at their potential role in reducing liver disease progression, the latest Harvard research provides the most comprehensive and compelling evidence to date.
Study Design: A Large-Scale Historical Cohort Analysis
To investigate the impact of statins on liver disease progression, researchers conducted a historical cohort study using data from the Mass General Brigham health care system, covering 23 years (2000-2023). The analysis included:
- 16,501 adult patients (aged 40 or older) diagnosed with chronic liver disease
- Baseline Fibrosis-4 (FIB-4) scores of ≥1.3, indicating at least mild fibrosis
- Comparison groups: Statin users vs. nonusers
- Key outcomes: Incidence of hepatocellular carcinoma, hepatic decompensation, and changes in liver fibrosis severity
- Advanced statistical adjustments: Inverse probability of treatment weighting (IPTW) to account for potential confounding factors
Key Findings: Statins Reduce Liver Cancer Risk by 33%
The results of the study showed statistically significant reductions in the risks of liver cancer and complications among statin users:
1. Reduced Risk of Hepatocellular Carcinoma (HCC)
- Statin users had a 33% lower risk of developing liver cancer compared to nonusers.
- The 10-year cumulative incidence of HCC was 8.0% among nonusers vs. 3.8% among statin users.
- This translated to an absolute risk reduction of 4.2% (95% confidence interval: −5.3% to −3.1%).
2. Lower Risk of Hepatic Decompensation
Hepatic decompensation refers to severe complications of advanced liver disease, including ascites, variceal bleeding, and hepatic encephalopathy.
- Statin users had a 22% lower risk of hepatic decompensation compared to nonusers.
- The 10-year cumulative incidence was 19.5% among nonusers vs. 10.6% among statin users.
- The absolute risk reduction was 9.0% (95% CI: −10.6% to −7.3%).
3. Lipophilic Statins Offer Greater Protection
Not all statins provided the same level of benefit. Lipophilic statins, such as atorvastatin and simvastatin, demonstrated stronger protective effects than hydrophilic statins (e.g., rosuvastatin, pravastatin):
- Lipophilic statins lowered HCC risk by 36% (adjusted hazard ratio [aSHR] 0.64).
- Hydrophilic statins had a more modest 21% reduction (aSHR 0.79).
4. Longer Statin Use = Greater Benefits
Duration of statin use played a crucial role in enhancing liver protection:
- Patients prescribed at least 600 cumulative daily doses (approximately 1.6 years of daily use) experienced:
- 40% lower risk of liver cancer (aSHR 0.60)
- 36% lower risk of hepatic decompensation (aSHR 0.64)
5. Slower Liver Fibrosis Progression
Among a subset of 7,038 patients with repeated FIB-4 measurements, statin users showed better liver health outcomes:
- Fewer patients progressed to advanced fibrosis stages.
- More patients improved from high-risk to lower-risk fibrosis categories.
The Science Behind Statins’ Liver-Protective Effects
The beneficial effects of statins on liver health likely stem from their multiple biological properties:
- Anti-inflammatory effects: Chronic inflammation is a key driver of liver fibrosis and cancer. Statins reduce pro-inflammatory cytokines and immune activation.
- Antifibrotic properties: Statins inhibit hepatic stellate cell activation, the primary driver of liver scarring (fibrosis).
- Antioxidant activity: Oxidative stress is a major contributor to liver damage, and statins help mitigate this by reducing reactive oxygen species (ROS) production.
- Tumor-suppressing mechanisms: Statins may interfere with cancer cell proliferation and angiogenesis, slowing down liver cancer development.
Implications for Clinical Practice
The study’s findings strongly support the consideration of statins as a preventive strategy for patients with chronic liver disease, particularly those at high risk of hepatocellular carcinoma. This could have major implications for clinical guidelines, as statins are already widely available, affordable, and well-tolerated.
However, not all CLD patients are currently recommended statins due to concerns about potential liver toxicity, especially in those with advanced cirrhosis. The latest evidence challenges this notion, suggesting that statins are not only safe for most CLD patients but also highly beneficial.
Looking Ahead: Future Research and Clinical Trials
While observational studies like this provide compelling data, randomized controlled trials (RCTs) are needed to confirm causality and optimize dosing strategies. Several ongoing trials aim to determine whether statins should be actively prescribed for CLD prevention, even in patients without cardiovascular indications.
Additionally, further research is needed to explore:
- The optimal duration and intensity of statin therapy for liver disease prevention.
- Potential synergistic effects when combined with other antifibrotic agents.
- Whether statins can be safely used in cirrhotic patients with advanced liver disease.
Conclusion: A Paradigm Shift in Liver Disease Prevention
The Harvard study represents a significant breakthrough in the field of liver disease research. It provides strong evidence that statins can substantially reduce the risk of hepatocellular carcinoma and hepatic decompensation, particularly when using lipophilic statins for extended periods.
These findings suggest that statins could become an important tool in liver disease management, offering a new, effective strategy to combat rising rates of metabolic and alcohol-related liver diseases. As further research unfolds, we may soon see a shift in clinical practice, where statins are routinely considered for liver disease prevention alongside traditional treatments.
For patients with chronic liver disease, particularly those at high risk for liver cancer, discussing the potential benefits of statin therapy with healthcare providers may be an important next step toward better long-term health outcomes.
Reference: Jonggi Choi et al, Statin Use and Risk of Hepatocellular Carcinoma and Liver Fibrosis in Chronic Liver Disease, JAMA Internal Medicine (2025). DOI: 10.1001/jamainternmed.2025.0115