Can statins reduce the risk of hepatocellular carcinoma in chronic liver disease?

The incidence of hepatocellular carcinoma (HCC) has been steadily increasing worldwide. With the advent of effective antiviral therapies for chronic viral hepatitis, metabolic- and alcohol-related steatotic liver diseases are now the major cause of HCC. The rising prevalence of HCC and its associated mortality highlights the urgent need for effective HCC prevention strategies.Experimental studies suggest that statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) may prevent chronic liver disease progression and hepatocarcinogenesis through anti-inflammatory, antifibrotic and antioxidant mechanisms. Observational studies suggest that statins reduce the risk of liverdisease progression and HCC.To further examine this issue, Boston researchers evaluated the association between statin use and the risk of incident HCC and hepatic decompensation, with an emphasis on liver fibrosis progression, among adults with chronic liver disease. The cohort study used a largescale hospital registry encompassing data from 10 hospitals, reflecting evidence from routine clinical practice. Patients ≥ 40 years of age with chronic liver disease and a baseline Fibrosis-4 (FIB-4) score of 1.3 or higher were included. Participants were grouped into statin users and nonusers. Seven statins were evaluated, including five lipophilic statins (atorvastatin, fluvastatin, lovastatin, pitavastatin [not marketed in Canada] and simvastatin) and two hydrophilic statins (rosuvastatin and pravastatin). Statin use was defined as a cumulative defined daily dose (cDDD) of ≥ 30, calculated by summing monthly defined daily dose, consistent with previous studies. Cumulative statin exposure was categorized as < 30 (reference), 30–599 and ≥ 600 cDDD.Outcomes included 10-year cumulative incidence of HCC and hepatic decompensation, as well as transitions in liver fibrosis risk categories (low, intermediate, high) based on FIB-4 scores. Outcomes were analyzed using adjusted subhazard ratio and trends in serial FIB-4 scores.Results showed the following:The study included 16,501 participants (mean age, 59.7 years; 59.1% males) with chronic liver disease; 3,610 were statin users and 12,891 were nonusers.Statin users exhibited a significantly lower 10-year cumulative incidence of HCC (3.8% vs 8.0.%; risk difference, −4.2%; 95%CI, −5.3 to −3.1%) and hepatic decompensation (10.6%vs 19.5%; risk difference, −9.0%; 95%CI, −10.6 to −7.3) compared with nonusers.The adjusted subhazard ratio was 0.67 (95%CI, 0.59–0.76) for HCC and 0.78 (95%CI, 0.67–0.91) for hepatic decompensation.Exposure to lipophilic statins and duration of statin use (≥ 600 cDDDs) were associated with further reductions in HCC and hepatic decompensation risks.Serial FIB-4 data were available for 7,038 patients.For patients with intermediate baseline FIB-4 scores, 14.7% (95%CI, 13.0%–16.6%) of statin users transitioned to the high group compared with 20.0% (95%CI, 18.6%–21.5%) of nonusers.For patients with high baseline FIB-4 scores, 31.8% (95%CI, 28.0%–35.9%) of statin users transitioned to the intermediate group and 7.0% (95%CI, 5.2%–9.6%) transitioned to the low-risk group, compared to 18.8% (95%CI, 17.2%–20.6%) and 4.3% (95%CI, 3.5%–5.2%) of nonusers, respectively (p < 0.001).The researchers conclude that this hospital-based cohort study shows that statin use— particularly lipophilic statin use and longer duration of statin exposure—reduces the risks of HCC and hepatic decompensation in patients with chronic liver disease, and slows fibrosis progression. These findings provide support for the potential role of statins in prevention of HCC and liver disease progression. Reference:Choi J, Nguyen VH, Przybyszewski E, et al. Statin use and risk of hepatocellular carcinoma and liver fibrosis in chronic liver disease. JAMA Intern Med 2025. Published online March 17, 2025. (accessed March 25, 2025).

Can statins reduce the risk of hepatocellular carcinoma in chronic liver disease?

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