medwireNews: Statins cut the risk for hepatocellular carcinoma (HCC) and hepatic decompensation in patients with chronic liver disease (CLD), a study indicates.
Specifically, there was a lower 10-year incidence of HCC in statin users than in nonusers with corresponding rates of 3.8% and 8.0%, and a significant subhazard ratio (aSHR) of 0.67 after adjusting for inverse probability of treatment weighting, and competing risks for death and liver transplant.
The researchers also found that hepatic decompensation was less likely to occur among statin users than nonusers with respective 10-year incidence rates of 10.6% versus 19.5%, and a significant aSHR of 0.78.
“These findings underscore the potential of statins as chemopreventive agents against HCC through their role in mitigating fibrosis progression,” write Jonggi Choi (University of Ulsan College of Medicine, Seoul, Republic of Korea) and colleagues in JAMA Internal Medicine.
While previous studies have suggested statins can prevent CLD progression and HCC via anti-inflammatory, antifibrotic, and antioxidant mechanisms, the research has been limited to specific CLD causes and has not explored the effects of statins on liver fibrosis progression over time, the authors say.
To address this issue, the historical cohort study took healthcare data from 16,501 patients with CLD aged 40 years and older who were included in the Research Patient Data Registry in Boston, Massachusetts, USA, between 2000 and 2023.
Eligible patients had a baseline Fibrosis (FIB)-4 score of 1.3 points or above, indicating an intermediate or high (>2.67 points) level of fibrosis. Statin users (n=3610) counted as those taking a cumulative defined daily dose (cDDD) of 30 or higher with 180 days between the statin initiation date and CLD diagnosis. Nonusers (n=12,891) had an equivalent 180-day period without any statin prescriptions.
The investigators screened the patients for incident HCC as the study’s primary outcome, and hepatic decompensation, consisting of variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome, as the secondary outcome
The patients were a mean of 59.7 years old, 59.1% were men, and 78.9% were White. Before balancing the baseline characteristics using inverse probability of treatment weighting, statin users were significantly older on average than nonusers (63.7 vs 58.5 years), and had more comorbidities, including diabetes (42.4 vs 16.9%), hypertension (79.4 vs 43.4%), coronary artery disease (40.5 vs 14.5%), and dyslipidemia (72.7 vs 24.2%).
After 4.6 years of follow-up for statin users and 2.8 years for nonusers, there were 755 incident cases of HCC and 2011 cases of hepatic decompensation.
Choi et al observe that taking statins consistently protected against HCC across all prespecified subgroups, including among patients with and without cirrhosis, and those with and without dyslipidemia.
The investigators note that users of lipophilic statins (rosuvastatin and pravastatin) had a stronger protection against 10-year cumulative incidence of HCC than users of hydrophilic statins (atorvastatin, fluvastatin, lovastatin, pitavastatin, and simvastatin), with respective rates of 3.7% and 4.1%, and significant aSHRs of 0.64 and 0.79 relative to nonusers. This finding “highlights their broader potential benefits in HCC prevention, warranting further investigation into their mechanisms of action and clinical applications,” the authors write.
On the other hand, users of hydrophilic statins had greater protection against 10-year cumulative incidence of hepatic decompensation than users of lipophilic statins, with corresponding rates of 7.9% and 11.2%, and significant aSHRs of 0.58 and 0.82 relative to nonusers.
Choi and colleagues also found that patients taking a cDDD of 600 or higher had a significantly lower 10-year HCC cumulative incidence than those taking a cDDD of 30 to 599, with respective rates of 3.5% versus 3.8%, and aSHRs of 0.60 and 0.79 relative to nonusers. They also had lower rates of hepatic decompensation than nonusers, at 9.1% versus 12.3%, and corresponding aSHRs of 0.64 and 0.87, albeit the latter did not reach significance.
The researchers say that this result “supports a duration-response relationship, highlighting the potential importance of prolonged statin use in reducing the risks of HCC and hepatic decompensation.”
In addition, among propensity score-matched patients starting with intermediate FIB-4 scores, significantly fewer statin users transitioned to high scores after 3 years than did nonusers, with corresponding rates of 13.7%% and 18.2%. Among patients starting with a high FIB-4 score, significantly more of those taking than not taking statins transitioned to a lower score, with 32.1% versus 22.7% transitioning to an intermediate score, and 7.5% versus 4.0% transitioning to a low score (<1.3 points).
The authors highlight potential limitations to the study including unmeasured factors such as socioeconomic status, healthcare access, and health literacy that “may have influenced the observed associations.” They also point out that randomized clinical trials to evaluate statins in HCC prevention are “ideal” but hard to conduct due to the need for large-scale enrollment and long-term follow-up.
“Well-designed historical cohort studies such as ours provide valuable insights into the intermediate pathways through which statins reduce HCC risk and fibrosis progression,” Choi and co-workers conclude.
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