In Brief | Oncology | Hepatocelluarl Carinoma
Evaluating the Protective Effect of Statins on Hepatocellular Carcinoma and Liver Fibrosis
Time to read: 03:57Time to listen: 07:06
Originally Published: 17 March 2025
Source: JAMA Internal Medicine
Type of article: In Brief
MedED Catalogue Reference: MOCiB003
Category: Oncology
Cross Reference: Hepatic Cancers
Keywords: chronic liver diseases, hepatocellular carcinoma, fibrosis, statins
In adults aged 40 years and older with chronic liver disease, statin use was significantly associated with a reduced 10-year cumulative incidence of hepatocellular carcinoma and hepatic decompensation
This article is a review of recent studies originally published in JAMA Internal Medicine, 17 March 2025. This article does not represent the original research, nor is it intended to replace the original research. Access the full Disclaimer Information.
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In Context
Liver cancer is a major global health concern, with over 800,000 new cases diagnosed annually. In South Africa, liver cancer is a growing burden, contributing significantly to cancer-related deaths. The five-year survival rate remains below 20%, highlighting the urgent need for effective prevention and treatment strategies.1,2
With limited options for liver disease prevention, drug repurposing has gained attention. Statins, widely used for lowering cholesterol, have shown promise beyond their primary function. They exert multiple beneficial effects, including reducing cell proliferation, inflammation, and oxidative stress while also enhancing immune response.
Previous research has found that statins lower the risk of hepatocellular carcinoma through these mechanisms. One large cohort study, which included over 1.7 million individuals, found that regular statin use was linked to a 15% reduction in new-onset liver disease, a 28% lower risk of liver-related death, and up to a 74% reduction in HCC incidence compared to non-users.. 2
These findings suggest that statins could play a role in liver disease prevention. However, further studies, including randomized controlled trials, are necessary to confirm their protective effects and guide clinical recommendations.
Study Purpose
The researchers of this study aimed to assess the association between statin use and the risk of hepatocellular carcinoma (HCC) and hepatic decompensation, with a particular focus on liver fibrosis progression in adults with chronic liver disease (CLD).
Study Methodology
This cohort study analysed data from the Research Patient Data Registry (2000–2023) on individuals aged 40 years or older with chronic liver disease (CLD) and a baseline Fibrosis-4 (FIB-4) score of ≥1.3.
Participants were classified as statin users or nonusers. Statin use was defined as exposure to a cumulative defined daily dose (cDDD) of 30
Outcomes included 10-year cumulative incidence of HCC and hepatic decompensation as well as transitions in liver fibrosis risk categories based on FIB-4 scores.
Statin use was defined as exposure to a cumulative defined daily dose (cDDD) of 30 or more. Fibrosis progression was assessed through FIB-4 group transitions (low, intermediate, and high) over time.
Editors Note
The Fibrosis-4 score helps to estimate the amount of scarring in the liver.
- A FIB-4 score below 1.45 has a 90% negative predictive value for ruling out advanced fibrosis.
- A FIB-4 score above 3.25 has a specificity of 97% and a positive predictive value of 65% for detecting advanced fibrosis. 3
Findings
The cohort included 16,501 participants with CLD: 3610 were statin users, and 12,891 were nonusers.
The mean age was 59.7, and 40.9% (6750) were female,
The following were recorded:
Lipophilic statins and longer treatment duration (≥600 cDDDs) were linked to even greater risk reductions.
Among 7,038 patients with serial FIB-4 data, 14.7% of statin users with intermediate baseline FIB-4 scores progressed to the high-risk category, compared to 20.0% of nonusers.
Among patients with high baseline FIB-4 scores, statin users were more likely to show improvement. Specifically, 31.8% moved to the intermediate-risk category, while 7.0% transitioned to the low-risk group. In contrast, 18.8% of nonusers shifted to the intermediate category, and 4.3% moved to the low-risk group.
This study supports findings from previous studies and highlights a clear effect of statins on fibrosis.
Clinicians often avoid prescribing statins due to concerns about liver injury in people with chronic liver disease. However, this study suggests that when there is a clear need for statins, they should not be withheld. That said, the study had some limitations, including the broad dosing categories used, the inability to account for all possible confounding factors, and a lack of data on treatments after the study period.
Conclusion
These findings suggest that statin use, especially lipophilic statins, and longer durations of exposure may reduce the risks of HCC and hepatic decompensation in patients with chronic liver disease. The results align with previous studies, highlighting the potential of statins in preventing HCC and slowing liver disease progression. Further research, including randomized controlled trials, is needed to confirm the benefits and guide clinical recommendations.
Importance of this study for South Africa
Primary liver cancer (LC) is the seventh leading cause of death in South Africa, with rising incidence in middle-aged black African women. LC risk is highest in black African men in their early 30s, with poor survival rates due to late diagnosis, often post-mortem. 4,5
Hepatocellular carcinoma (HCC) is the predominant type, with risk factors linked to rural birthplace, male sex, urban residence <14 years, high HBV DNA levels, and HCV positivity. Interestingly, lifestyle factors and HIV alone are not significant risks. 4
Given the high public burden of this disease and the poor outcomes, alternative treatment strategies are needed to improve patient outcomes. This study indicates that statins may offer such a treatment, although more research would be required.
4. Mak, D. W. (2019). Liver cancer epidemiology and risk factors in South Africa (Doctoral dissertation, University of the Witwatersrand). https://hdl.handle.net/10539/29762
5 . Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 68(6), 394–424. https://doi.org/10.3322/caac.21492
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