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Lipophilic statins linked to lower HCC risk with viral hepatitis

August 19, 2019

By Marilynn Larkin

NEW YORK (Reuters Health) - Lipophilic, but not hydrophilic, statins were associated with a reduced risk of hepatocellular carcinoma (HCC) in an observational study of viral hepatitis patients in Sweden.

"Our study grew from observations in animal models and preliminary human studies suggesting that lipophilic statins - like atorvastatin and simvastatin - may offer unique benefits against HCC," Dr. Tracey Simon of Massachusetts General Hospital in Boston told Reuters Health by email.

"Based on those prior data," she said, "we decided to compare the relative impact of lipophilic statins or hydrophilic statins on the risk for HCC and death from chronic liver disease in adults with well-defined liver disease."

"In this population, lipophilic statins predicted significantly lower risk of HCC, but in contrast, hydrophilic statins were not associated with HCC risk reduction," she said. "This is very important because the burden of and mortality from HCC in the U.S. and Europe is growing, and right now we lack any effective medications to prevent HCC."

Dr. Simon and colleagues studied data from 6,554 adults with hepatitis B or C who took lipophilic statins and 1,780 who took hydrophilic statins, plus equal numbers of matched controls with viral hepatitis who didn't take statins. Participants' mean age at infection diagnosis was 47, and about 34% were women. Statin use was defined as 30 or more cumulative daily doses from filled prescriptions.

The 10-year HCC risk was significantly lower among lipophilic statin users: 3.3% versus 8.1% in matched nonusers (adjusted subdistribution hazard ratio, 0.56), the authors reported online August 19 in Annals of Internal Medicine.

By contrast, hydrophilic statin users were not at significantly reduced risk: 6.8% versus 8.0%.

The inverse association between lipophilic statins and HCC risk seemed to be dose-dependent. The 10-year HCC risk was lowest - at 2.5% - with 600 or more lipophilic statin cumulative daily doses, versus 8.4% among nonusers (aHR, 0.41).

Further, 10-year mortality was significantly lower among both lipophilic (7.3% versus 15.2%) and hydrophilic (11.5% versus 16.0%) statin users compared to nonusers.

Dr. Simon noted, "This was an observational study; therefore, more prospective data are needed before lipophilic statins could be incorporated into HCC prevention guidelines. We are excited for more prospective studies in this field - including well-designed randomized controlled trials - so that we might define the optimal type and dose of statin for HCC prevention."

Dr. Robert Rosenson, Director of Cardiometabolics at The Mount Sinai Hospital and Professor of Medicine (Cardiology) at the Icahn School of Medicine at Mount Sinai in New York City, commented by email, "Previous studies suggest that the use of statins in patients with viral hepatitis may increase viral replication by fostering hepatic uptake of the virus via the LDL receptor. Thus, these findings contrast with prior concerns and suggest a potential benefit."

Like Dr. Simon, he told Reuters Health that the observational study "requires confirmation with a randomized clinical trial. The strength of the observational data supports that such a clinical trial is warranted."

"Lipophilic statins have more drug-drug interactions than hydrophilic statins," he added, "so a change in prescribing is not warranted based on these observational data."


Ann Intern Med 2019.

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