Statin Use Reduces the Risk of Hepatocellular Carcinoma: An Updated Meta-Analysis and Systematic Review

Abstract

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver resulting in approximately 800,000 deaths annually. A growing body of research investigating statin use and HCC risk has shown conflicting results. We aim to evaluate the current evidence of statin impact on HCC risk.We performed a comprehensive literature search in PubMed, PubMed Central, Embase, and ScienceDirect databases from inception through May 2019 to identify all studies that evaluated the association between statin use and HCC. We included studies that presented an odds ratio (OR) with a 95% confidence interval (CI) or presented data sufficient to calculate the OR with a 95% CI. Statistical analysis was performed using the Comprehensive Meta-Analysis (CMA), Version 3 software, and a Forrest plot was generated. We assessed for publication bias using conventional techniques.Twenty studies (three randomized controlled trials, six cohorts, and 11 case-controls) with 2,668,497 patients including 24,341 cases of HCC were included in the meta-analysis. Our findings indicate a significant risk reduction of HCC among all statin users with a pooled odds ratio of 0.573 (95% CI: 0.491-0.668, I2= 86.57%) compared to non-users. No publication bias was found using Egger's regression test or on visual inspection of the generated Funnel plot.The results indicate that statin use was associated with a 43% lower risk of HCC compared to statin nonusers. Further prospective randomized research is needed to confirm the association. Categories: Preventive Medicine, GastroenterologyKeywords: viral hepatitis b and c, cirrhosis, cancer prevention, hepatocellular carcinoma (hcc), statin use their role in cardiovascular disease treatment and prophylaxis is essential [15]. Besides the effect of cholesterol formation, statins are known to have proapoptotic, antiangiogenic, antiproliferative, and immunomodulatory effects. For these reasons, many researchers have aimed to assess whether statins can decrease the risk for multiple malignancies, including HCC [11][12][13][14].The results of observational and randomized controlled trials (RCTs) have not been consistent. While most observational studies showed statistically reduced risk for HCC in patients who were using statins, the data from the RCTs did not. Hence, we conducted this study to examine the association between statin use and HCC utilizing all available published high-quality literature.

Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma

“…Intriguingly but somehow disappointingly, indications from prospective interventional trials and studies remain inconclusive, although association of statin use with a decreased risk of HCC carcinogenesis and recurrence has been described ( Table 2 ) ( Chiu et al, 2011 ; Tsan et al, 2012 ; Butt et al, 2015 ; Kawaguchi et al, 2017 ; Khazaaleh et al, 2022 ). In virus-independent liver lesions, atorvastatin use (10 mg/day) in NASH patients indicated an improvement in liver functions by 74%, along with a rise in serum protein and lipid metabolism regulator adiponectin ( Hyogo et al, 2008 ; Athyros et al, 2017 ).…”

New Mechanisms for Anti-Cancer Drugs

“…Intriguingly but somehow disappointingly, indications from prospective interventional trials and studies remain inconclusive, although association of statin use with a decreased risk of HCC carcinogenesis and recurrence has been described (Table 2) (Chiu et al, 2011;Tsan et al, 2012;Butt et al, 2015;Kawaguchi et al, 2017;Khazaaleh et al, 2022). In virus-independent liver lesions, atorvastatin use (10 mg/day) in NASH patients indicated an improvement in liver functions by 74%, along with a rise in serum protein and lipid metabolism regulator adiponectin (Hyogo et al, 2008;Athyros et al, 2017).…”

Don’t Judge a Book by Its Cover: The Role of Statins in Liver Cancer

“…A meta-analysis of 20 studies and a total of 2,668,497 patients [100] evaluated the beneficial role of statins for HCC prevention (OR: 0.573; 95% CI: 0.491-0.668, I2 = 86.57%); the study included six cohort studies, four of which found a positive association between statin use and a significantly lower risk of HCC development. Eleven case-control studies have also established that statin use is beneficial in reducing the risk of HCC.…”