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 non-users. Further prospective randomized research is needed to confirm the association.

Keywords: cancer prevention; cirrhosis; hepatocellular carcinoma (hcc); statin use; viral hepatitis b and c.

Figure 1. PRISMA flowchart illustrating the selection process.

Figure 2. Summary of odd ratios assessing the incident hepatocellular carcinoma with statin use

CI: Confidence interval Tsan et al. [11], Chiu et al. [20], Friis et al. [21], Marelli et al. [22], Friedman et al. [23], Khurana et al. [24], McGlynn et al. [25], Bergman et al. [26], Lai et al. [27], El-Serag et al. [28], Hsiang et al. [30], Kim et al. [31], Simon et al. [32], Chen et al. (1) [33], Chen et al. (2) [34], Tran et al./PCCIU [35], Tran et al./UK Biobank [35], Matsushita et al. [36], CTT [37], Sato et al. [38].

Figure 3. Summary of odd ratios assessing the incident of hepatocellular carcinoma based on DDD of statin use.

DDD: Defined Daily Dose Tsan et al. [11], Chiu et al. [20], Hsiang et al. [30], Kim et al. [31], Simon et al. [32], Chen et al. [33].

Figure 4. A random-effects model showing regression of log odd ratio on score, and proportion of variance explained by model.