- In terms of death risk, liver cancer is one of the leading types of cancer linked to high mortality.
- Experts have been trying to find ways to help people who are most at risk for liver cancer.
- One study explored the use of statins, a class of medications typically used to lower LDL cholesterol levels to reduce the risk of stroke and heart disease.
- Researchers found that statin use decreased the risk for hepatocellular carcinoma and hepatic decompensation, which is an advanced stage of liver disease.
According to the National Cancer Institute, liver cancer ranks
The authors found that statin use appeared to decrease the “10-year-cumulative incidence” of liver cancer and hepatic decompensation, or decompensated cirrhosis. Hepatic decompensation is when a person may be reaching end stage liver failure and experiences complications such as ascites and jaundice as liver function continues to decrease.
Participants in this study who used lipophilic (fat-soluble) statins like atorvastatin and simvastatin had the greatest outcomes for liver cancer, and participants with longer exposure to statins had the best outcomes for liver cancer and hepatic decompensation.
Participants on statins also had better outcomes for liver fibrosis, which is a buildup of scar tissue that can make it hard for the liver to function.
Researchers examined how statin use affected hepatocellular carcinoma and liver decompensation.
This historical cohort study included 16,501 participants. Of this, 3,610 were statin users. Data was from hospitals that were part of the Mass General Brigham health care system.
The average age of participants was just under age 60. All participants were over 40 years of age and had chronic liver disease. Participants had received their chronic liver disease diagnoses between July 2000 and June 2023. They excluded participants based on factors like previous liver transplant or hepatocellular carcinoma. Regarding fibrosis, they excluded participants with a Fibrosis-4 score lower than 1.3. This blood test indicates the degree of fibrosis in the liver, with a higher number indicating worse fibrosis.
Participants were not taking statins for the first 180 days after diagnosis of chronic liver disease. Five statins participants took were lipophilic statins, and two were hydrophilic statins. Participants were considered nonstatin users if their cumulative defined daily dose was less than thirty.
During the study, there were 755 incident cases of hepatocellular carcinoma and 2,011 cases of hepatic decompensation.
The results of the study showed better outcomes for participants who used statins.
The 10-year cumulative incidence of hepatocellular carcinoma was lower for statin users. While 8% of nonusers developed hepatocellular carcinoma, only 3.8% of statin users did.
After the multivariable adjustment, researchers found that statin users’ risk for hepatocellular carcinoma was 33% lower than for participants who did not use statins.
The 10-year cumulative incidence of hepatic decompensation was also better for statin users. While 19.5% of nonusers developed hepatic decompensation, only 10.6% of statin users did. After the multivariable adjustment, statin users had a 22% lower risk for hepatic decompensation.
When looking at the duration of use, those with the longest duration saw the most minimal 10-year cumulative incidence rate of hepatocellular carcinoma and hepatic decompensation. However, those with less time of statin use still had better outcomes in these areas compared to nonusers.
Researchers also analyzed if statin type impacted the outcomes.
The lipophilic statin group had slightly better outcomes than the hydrophilic statin group for hepatocellular carcinoma. For the hydrophilic statin group, the 10-year cumulative incidence was 4.1%, while it was 3.7% for the lipophilic statin group.
In contrast, the hydrophilic statin group had better outcomes for hepatic decompensation. The hydrophilic statin group had a 7.9% 10-year cumulative incidence, while the lipophilic statin group was 11.2%.
Subgroup analyses also showed the benefits of statin use. For example, among participants with dyslipidemia, i.e. those who had blood lipid levels that were too high or low, using statins helped to decrease the risk for hepatocellular carcinoma by 57%.
Statin-using participants with cirrhosis saw a lower 10-year incidence of hepatocellular carcinoma and hepatic decompensation. Statin-using participants with metabolic dysfunction-associated steatotic liver disease and those without, with other causes of chronic liver disease, and participants taking metformin and aspirin also saw risk reduction for hepatocellular carcinoma.
Additionally, researchers examined a subset of about 7,000 participants to see if statin use affected the transition to various stages of liver fibrosis.
The authors note that people with low liver fibrosis also have low incidences of hepatocellular carcinoma. Fewer statin participants transitioned from an intermediate to a high fibrosis score. More statin users moved from the high fibrosis score group to the intermediate group than non-statin users. More statin users also moved from the intermediate group to the low group.
With participants who developed hepatocellular carcinoma, there were worse fibrosis outcomes than for participants who did not develop hepatocellular carcinoma.
Researchers note that the findings “underscore the potential of statins as chemopreventive agents against HCC [hepatocellular carcinoma] through their role in mitigating fibrosis progression.”
The research does have certain limitations. First, it focused on one region and users of one particular healthcare system; about 79% of participants were white. It also focused on hospital-based participants who met inclusion criteria. Thus, the results cannot be generalized to everyone.
Second, researchers were able to adjust for several confounders, but others, like socioeconomic status or Healthcare access, could have influenced the findings. Third, researchers could not account for possible treatments participants received postindex and had to assume that all participants received the standard of care appropriate for their type of chronic liver disease.
Finally, they only used the Fibrosis-4 score method to look at fibrosis indirectly, and liver biopsies would have been more direct.
Patrick Kee, MD, PhD, cardiologist, Vital Heart & VeinKee, who was not involved in the study, noted the following regarding the study’s limitations as well:
“This study is retrospective and did not involve randomized controlled trials to assess the efficacy of statin therapy in preventing the development of HCC and hepatic decompensation among individuals with CLD [chronic liver disease]. Most subjects who received statin treatment had other compelling reasons for its use, such as coronary artery disease, peripheral artery disease, cerebrovascular disease, hyperlipidemia, and type 2 diabetes. Consequently, the number of statin nonusers was approximately four times higher than that of statin users, which may potentially influence the observed treatment effects.”
More research is likely needed to look at the effects of different types of statins as well.
Kee noted the following:
“The apparent lower incidence of HCC and hepatic decompensation among subjects exposed to lipophilic statins compared to hydrophilic statins is minimal, with a difference of only 0.4% over a 10-year period. Consequently, its clinical significance remains uncertain.”
More research is also required to understand the particular benefits of lipophilic statins, including how they act on the body to decrease the risk of liver cancer. Continuing to examine the effects of hydrophilic statins may also be beneficial, as well as longer studies.
Wael Harb, MD, board-certified hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast and Saddleback Medical Centers in Orange County, CA, who was also not involved in the study, noted that statins may have other benefits but that more research is needed.
“While these findings cannot prove causation on their own (as this was an observational study), they contribute to a growing body of research hinting that statins might have benefits well beyond cholesterol management. Of course, further research—ideally prospective or randomized trials—would help clarify which patient subgroups benefit most, how large that benefit is, and whether specific statins or doses have the strongest effect.”
— Wael Harb, MD
This study notes the potential benefit of statin use in people who have chronic liver disease.
Harb noted the following:
“[The study] supports the hypothesis that the chemopreventive effects of statins extend to liver cancer prevention and fibrosis progression, reinforcing a potentially significant benefit for patients with chronic liver disease. The findings should prompt more focused research to understand which groups would benefit most and whether these benefits can be replicated in prospective clinical trials.”
It may be a while before there are direct clinical applications.
“Statin therapy is not intended to prevent hepatocellular carcinoma (HCC) or hepatic decompensation, but it may be considered as an additional potential benefit in patients at risk of developing these liver conditions.”
— Patrick Kee, MD, PhD
There should be caution with use as well, accompanied by expert guidance that weighs potential risks and benefits.
“In patients with dyslipidemia and elevated liver enzymes, physicians often express concerns about the safety of initiating statin therapy for treating hyperlipidemia. While rare, statins can cause liver injury, manifesting as elevated liver enzymes (AST, ALT),” Kee noted.
