Statin Initiation Reduces Risk for Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

Statin Drug-Drug Interactions
Statin Drug-Drug Interactions
Researchers examined the association between initiating statin therapy and the risk for HCC in patients with NAFLD.

Beginning statin therapy was found to reduce the risk for hepatocellular carcinoma (HCC) among patients with nonalcoholic fatty liver disease (NAFLD), according to study results published in Clinical Gastroenterology and Hepatology.

For the study, researchers at Stanford University Medical Center sourced data from the Optum ClinformaticsÒ Data Mart database. Adults (N=272,431) who were diagnosed with NAFLD between 2003 and 2019 were assessed for HCC on the basis of statin initiation. To correct for cohort imbalances, an inverse probability of treatment weighting approach was used.

Patients who received statins (n=73,385) and those who did not receive statins (n=199,046) had a mean age of 58.0±12.4 and 50.0±14.9 years; 47.1% and 46.3% were men; 65.1% and 66.4% were White; 39.4% and 32.5% had overweight or obesity; 51.3% and 21.0% had diabetes; and 22.1% and 6.2% used metformin, respectively.

The incidence rate of HCC was 6.1 per 10,000 person-years (py) among statin recipients and 10.1 per 10,000 py for nonrecipients. In addition, statin treatment was associated with improved 10-year survival (P <.001).

After adjusting for cohort differences, statin initiation was associated with decreased risk for HCC (adjusted hazard ratio [aHR], 0.47; 95% CI, 0.36-0.60; P <.001).

Compared with no statin treatment, patients who had 30-299 (aHR, 0.57; 95% CI, 0.40-0.82) and 300-599 cumulative defined daily doses (cDDDs; aHR, 0.56; 95% CI, 0.35-0.90) of statins had a similar level of decreased HCC risk. Patients who received 600 cDDDs of statins or more were associated with the lowest risk (aHR, 0.30; 95% CI, 0.20-0.43).

Among the subset of patients who had liver fibrosis data, statin initiation remained associated with decreased HCC risk (aHR, 0.44; 95% CI, 0.30-0.65; P <.001). Similarly, among individuals who had advanced fibrosis there was a 55% lower risk for HCC with statin initiation.

In a sensitivity analysis among patients with abdominal imaging data 6 months prior to NAFLD diagnosis, HCC risk was reduced by 52% with statin initiation.

The study may have been limited by assessing statin dispensation and not treatment.

“Given that no NAFLD medication has been approved yet and statin is more accessible and with well-established safety profile, statin should be considered for chemoprevention of HCC among NAFLD, at least in NAFLD patients with other indications for statins such as hyperlipidemia or CVD, both of which are common comorbidities among patients with NAFLD,” the study authors wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Zou B, Odden MC, Nguyen MH. Statin use and reduced hepatocellular carcinoma risk in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. Published February 10, 2022. doi:10.1016/j.cgh.2022.01.057