Carolin Victoria Schneider

Study Links Regular Statin Use to Significant Decrease in Liver Diseases

MedicalResearch.com Interview with:
Carolin Victoria Schneider, MD
Physician-Scientist at RWTH Aachen
Former Postdoctoral Fellow at UPenn, Rader Lab

MedicalResearch.com: What is the background for this study?

Response: Our study was prompted by the ongoing global health crisis related to liver disease, which claims over 2 million lives annually. We noted the emerging literature suggesting the hepatoprotective properties of statins, which include anti-inflammatory, antiproliferative, antiangiogenic, and immunomodulatory effects.

However, we noticed a significant gap in understanding these effects in the context of the general population, especially among individuals without a history of known liver disease. Together with our excellent first author Mara Vell, I embarked on a journey aimed to fill this significant knowledge gap.

MedicalResearch.com: Were patients at higher risk of liver cancer included in the study?

Response: Yes, absolutely. We examined a diverse range of individuals in our study, encompassing over 1.7 million participants from three different cohorts, namely the UK Biobank, the Penn Medicine Biobank, and the TriNetX cohort. Utilizing propensity score matching, we maintained a balanced distribution of various key parameters such as age, sex, BMI, ethnicity, comorbidities, and medication use.

Hence, our study population is indeed representative of the general populace, inclusive of those at elevated risk for liver cancer, such as individuals with diabetes, a high FIB-4 index at baseline, genetic predispositions to liver disease, as well as those with specific comorbidities or lifestyle choices that increase the risk of liver disease. Initially, our analysis considered the entire population, but in a subsequent step, we focused on those individuals with the aforementioned higher risk factors for liver disease development.

MedicalResearch.com: What are the main findings?

Response:  Our findings indicate that regularly taking statins is linked to a noticeable decrease in the chances of developing liver diseases and dying from liver-related deaths. We also found that statins substantially decrease the risk of developing hepatocellular carcinoma, a common type of liver cancer. We found these associations in most of the groups we studied, and the benefits appeared to increase with duration and dose of statins.

In one of our studied biobanks, the UK Biobank, people who hadn’t been diagnosed with liver disease before and took statins regularly had a 15% reduced chance of getting a new liver disease and a 28% lower chance of dying from liver-related causes. The chance of getting hepatocellular carcinoma was also reduced by 42% among statin users. This effect was even stronger in the TriNetX cohort, where the chance of getting hepatocellular carcinoma was reduced by 74% among those taking statins.

We also found that in individuals from the Penn Medicine Biobank, taking statins was linked to a significant decrease in liver diseases after just one year of use. Statin use seemed to be particularly helpful in men, people with diabetes, and individuals with a high FIB-4 index at baseline, which is a score that helps predict liver disease. Individuals carrying a genetic variant (the heterozygous minor allele of PNPLA3 rs738409) that puts them at higher risk for Non-Alcoholic Fatty Liver Disease had a 69% lower chance of getting hepatocellular carcinoma when using statins.

In short, our results strongly suggest that statins could play a significant role in preventing liver disease and liver cancer.The positive effects seem to depend on how long the drug is used and what concentrations are reached in the organism. This is a significant finding that could potentially influence how we approach the prevention of these conditions in the future.

MedicalResearch.com: What should readers take away from your report?

Response: The key takeaway from our research is that statins, drugs widely used to control cholesterol levels, could also serve a crucial role in preventing liver disease. It’s important to understand that these are not simply minor reductions but significant decreases in the onset of new liver disease, deaths related to liver conditions, and notably, hepatocellular carcinoma, a common type of liver cancer.

One particular highlight is the observation that these effects seem to be dose- and duration-dependent, implying that the longer and more regularly statins are used, the more pronounced their hepatoprotective benefits might be.

Additionally, certain high-risk groups, such as those with diabetes, a high FIB-4 index, or those carrying a genetic risk factor for Non-Alcoholic Fatty Liver Disease, could potentially gain substantial benefits from regular statin use.

Our findings open up new possibilities in primary prevention strategies against liver diseases. So, it’s not just about managing cholesterol levels anymore; statin use could be a game-changer in combating liver diseases and improving overall liver health. These results call for a shift in the way we view and utilize statins in the healthcare arena, emphasizing the potential broader application of these drugs beyond their traditional use in managing cholesterol.

While our findings are compelling, it’s important to note that they reflect associations, not cause-and-effect relationships. In other words, while we observed a strong link between regular statin use and a lower risk of liver disease and related deaths, our study does not definitively prove that statins directly cause these beneficial outcomes. The effect could also be driven by other factors that are highly associated with statin intake. Moreover, the design of our study, a retrospective cohort study, is inherently subject to certain limitations, such as potential confounding factors that may influence the observed associations.

Therefore, our results should be seen as a stepping stone for future research. We need further studies, ideally randomized controlled trials, which are the gold standard in determining cause-effect relationships, to confirm our findings and understand the mechanisms involved. These future studies should also explore the optimal dosage and duration of statin use for liver disease prevention, and assess potential risks or side effects that could be associated with long-term statin use in different populations. Only then can we be fully confident in recommending statins as a primary preventive strategy for liver disease in the general population.

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: Our study points to several directions for future research. While we demonstrated a beneficial association, more investigation is needed to fully understand the mechanisms behind these hepatoprotective effects of statins. Randomized controlled trials may further confirm our observational findings. Additionally, research to identify which patient subgroups derive the most benefit from statin therapy in this context would also be valuable

MedicalResearch.com: Is there anything else you would like to add? Any disclosures?

Response:  Definitely, I would like to emphasize that our study, while suggestive of a potential protective role of statins against liver disease, does not mean that everyone should start taking statins immediately. The decision to initiate statin therapy should always be based on a comprehensive evaluation of the individual patient’s overall health, potential risks, and potential benefits. It’s a personalized decision that should be made in consultation with a healthcare provider.

Additionally, I would like to express my heartfelt gratitude to all the individuals who participated in the study. Their contribution is invaluable in advancing our understanding of liver disease prevention. I would also like to extend my appreciation to all co-authors and members of the research team for their diligent work and dedication throughout the study.  I’d particularly like to single out our first author, Mara Vell. Her exceptional contributions and meticulous work greatly shaped this study. Mara’s dedication and tenacity have been truly extraordinary, and her work on drug repurposing, especially in relation to  liver disease prevention, is making a significant impact in the field. I have no doubt we’ll continue to hear more groundbreaking insights from her in the future.

Finally, it is important to remember that our findings are a step forward, not the end goal. We’ve begun to unravel a new role for statins beyond their traditional use, and we hope our research will inspire more studies in this direction. Ultimately, we want to refine strategies to prevent liver disease, and we’re optimistic about the future.

No disclosures

Citation:

Vell MS, Loomba R, Krishnan A, Wangensteen KJ, Trebicka J, Creasy KT, Trautwein C, Scorletti E, Seeling KS, Hehl L, Rendel MD, Zandvakili I, Li T, Chen J, Vujkovic M, Alqahtani S, Rader DJ, Schneider KM, Schneider CV. Association of Statin Use With Risk of Liver Disease, Hepatocellular Carcinoma, and Liver-Related Mortality. JAMA Netw Open. 2023 Jun 1;6(6):e2320222. doi: 10.1001/jamanetworkopen.2023.20222. PMID: 37358849; PMCID: PMC10293910.

 

 

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