Chemopreventive Effect of Statin on Hepatocellular Carcinoma in Patients With Nonalcoholic Steatohepatitis Cirrhosis

Abstract

INTRODUCTION: To estimate the annual incidence of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis (NASH) with advanced liver fibrosis, to determine the risk factors for the development of HCC, and to evaluate the chemoprotective effect of statin use stratified by fibrosis stage. METHODS: We conducted a retrospective study at 2 US tertiary academic centers, including patients with NASH-related advanced liver fibrosis (bridging fibrosis [F3] and cirrhosis [F4]) followed between July 2002 and June 2016. Patients were followed from the date of diagnosis to the time of last abdominal imaging, liver transplantation, or HCC diagnosis. Multivariable Cox regression analysis was performed to evaluate the risk factors associated with HCC development, stratified by fibrosis stage. RESULTS: A total of 1,072 patients were included: 122 patients with F3 fibrosis and 950 patients with cirrhosis. No HCC was observed during 602 person-year follow-up among F3 patients. Among patients with cirrhosis, HCC developed in 82 patients with the annual incidence rate of 1.90 per 100 person-years (95% confidence interval [CI], 1.53–2.35). Multivariable analysis in patients with cirrhosis demonstrated that HCC development was associated with male sex (hazard ratio [HR] 4.06, 95% CI, 2.54–6.51, P < 0.001), older age (HR, 1.05, 95% CI, 1.03–1.08, P < 0.001), and CTP score (HR, 1.38, 95% CI, 1.18–1.60, P < 0.001). Statin use was associated with a lower risk of developing HCC (HR, 0.40, 95% CI, 0.24–0.67, P = 0.001). Each 365 increment in cumulative defined daily dose of statin use reduced HCC risk by 23.6%. DISCUSSION: Our findings suggest that patients with NASH and bridging fibrosis have a low risk of HCC. Dose-dependent statin use reduced HCC risk significantly in patients with NASH cirrhosis.

Statins Reduce Hepatocellular Carcinoma Risk in Patients with Chronic Kidney Disease and End-Stage Renal Disease: A 17-Year Longitudinal Study

“…Our findings not only add information on patients with CKD and ESRD but also extend previous meta-analyses findings linking statin therapy to a reduced risk of HCC [20][21][22], in patients with diabetes, cirrhosis or antiviral therapy [20] and patients with non-alcoholic steatohepatitis (NASH) [23]. An earlier case-control research reported that the prolonged use of statins was associated with increased risk of colorectal cancer, bladder cancer and lung cancer [24].…”

“…An earlier review study also failed to find clinical benefits of statin therapy for cancer patients [17]. However, prolific clinical studies and basic laboratory studies have reported evidence supporting the anti-cancer effects of statins [13,18,20,23,25].…”

Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease

“…5B). The second example is use of lipophilic statins such as atorvastatin and simvastatin, which is associated with reduced HCC incidence in NAFLD patient cohorts (HR, 0.36) ( 44 ). Prevalence of high-risk PLS-NAFLD in lipophilic statin users was threefold lower compared to nonstatin users (conditional OR, 0.33; 95% CI, 0.16 to 0.68) in severely obese patients, which is again comparable to the magnitude of reduction in HCC incidence (Fig.…”

Tumor immune microenvironment modulation by cholesterol in hepatocellular carcinoma

“…It has been demonstrated the reduction of HCC in NASH patients with advanced liver fibrosis and cirrhosis. The relevance of this retrospective study was found to be an association statin and a lower risk of developing HCC (23.6%) [87]. As the most interesting data for this review, it is important to mention that statin use also decreased the risk of NAFLD and liver fibrosis [88].…”