Efficacy and Safety of Statin for Hepatocellular Carcinoma Prevention Among Chronic Liver Disease Patients

Abstract

Introduction and Aim: Hepatocellular carcinoma (HCC) is a deadly complication among patients with chronic liver disease (CLD). Controversies on the efficacy and safety of statin to prevent HCC among patients with CLD remain despite the growing evidences. We aim to investigate the efficacy and safety of using statin for HCC prevention among adult with CLD. Methods: We performed a systematic search of 4 electronic databases (PubMed/MEDLINE, EMBASE, Cochrane library, and ClinicalTrial.gov) up to April 15, 2020. We selected all types of studies evaluating the statin use and the risk of HCC among CLD patients, regardless of language, region, publication date, or status. The primary endpoint was the pooled risk of HCC. The secondary endpoint was the risk of statin-associated myopathy. Result: From 583 citations, we included a total of 13 studies (1,742,260 subjects, 7 types of statins), fulfilling the inclusion criteria, evaluating efficacy and safety of statin in CLD patients for HCC prevention. All studies were observational (2 nested case-control studies, 11 cohort studies), and no randomised trial was identified. We found that statin user has a lower pooled risk of HCC development (hazard ratio=0.57, 95% confidence interval: 0.52-0.62, I 2=42%). HCC reduction was consistent among statin users in cirrhosis, hepatitis B virus, and hepatitis C virus infections. The risk of statin-associated myopathy was similar between statin user and nonuser (hazard ratio=1.07, 95% confidence interval=0.91-1.27). Conclusion: Statin use was safe and associated with a lower pooled risk of HCC development among adults with CLD. Given the bias with observation studies, prospective randomised trial is needed to confirm this finding.

Chemopreventive Effects of Concomitant or Individual Use of Statins, Aspirin, Metformin, and Angiotensin Drugs: A Study Using Claims Data of 23 Million Individuals

“…Consistent with this study, the negative association between statin use and the liver cancer risk has been identified in previous observational studies [ 45 ]. Meanwhile, we observed an elevated risk of liver cancer in metformin users, a finding that conflicts with results of previous studies [ 46 , 47 ].…”

Reply: CHESS‐ALARM score: Can it raise the alarm accurately?

“…5,6 Similarly, statin use in retrospective studies was subjected to indication bias and immortal time bias, which was discussed in our prior study. 7 We agree with the author that the presence of T2DM, smoking, and statin use could influence the risk of cardiovascular death (which is a competing event for liver decompensation). While interesting, this is beyond the scope of our current study and should be specifically addressed in future study.…”

Lipid alterations in chronic liver disease and liver cancer

“…Several studies have demonstrated that a high-fat, high-cholesterol diet can trigger HCC in mice, 122 , 134 , 140 , 141 via a neoplastic transformation of hepatocytes caused by broad transcriptional deregulation of genes involved in metabolic pathways (`metabolism in cancer´ hallmark) and calcium signalling. 140 It has been shown that statins, which block hepatic cholesterol synthesis, protect against HCC 142 and CCA 143 development, as well as resulting in decreased risk of mortality. 144 On the other hand, a higher serum cholesterol level was shown to be reflective of conserved liver function and decreased mortality.…”