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  Conference on Retroviruses
and Opportunistic Infections (CROI)
February 22-25, 2016, Boston MA
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Statin Dose and Type Tied to Lower Fibrosis
Progression and Liver Cancer Incidence
  Conference on Retroviruses and Opportunistic
Infections (CROI), February 22-25, 2016, Boston
Mark Mascolini
Higher statin doses cut the risk of liver fibrosis progression and new hepatocellular carcinoma (HCC), according to results of a study involving 9135 US veterans with HCV infection [1]. Atorvastatin and fluvastatin had the biggest impact on fibrosis. The investigators believe their findings support a potential role for statins in preventing progression of chronic liver disease.
Research has linked statin use to delayed development of fibrosis and HCC, but studies have not identified the optimal dose or specific statins associated with prevention. To address those questions, a US team studied all veterans who had a positive HCV antibody test from 2001 through 2014 and got treated for HCV infection for at least 14 days. The analysis excluded veterans coinfected with HIV or HBV and those with cirrhosis or HCC at their baseline visit.
For each statin used, the investigators calculated the cumulative defined daily dose (cDDD), defined by the World Health Organization as (total amount of drug prescribed on a daily basis) divided by (amount of drug per daily dose) times (total number of days that the drug has been prescribed). The researchers defined statin use as more than 28 cDDDs prescribed during the study period.
The analysis included 4165 veterans who used statins and 4970 who did not; 96% in both groups were men, two thirds were white, about 20% black and about 5% Hispanic. Both groups had been infected for an average of about 28 years. Variables significantly more prevalent in the statin group were diabetes, smoking history, metformin use, ACE inhibitor use, other antilipid use, completed HCV treatment course, and achieved sustained virologic response. Variables significantly less prevalent in the statin group were alcohol history and proportion with HCV genotype 1. The statin group had a significantly lower HCV load, ALT, AST, and FIB-4 score (average 1.6 versus 1.7, P < 0.0001) but significantly higher total cholesterol, low-density lipoprotein cholesterol (average 110 versus 98 mg/dL, P < 0.0001), triglycerides, and platelets.
Average FIB-4 score rose by 0.26 in veterans who did not take statins and dropped most with atorvastatin (-0.17, n = 944) or fluvastatin (-0.13, n = 34) (P = 0.006). Average FIB-4 score dropped less in people who took rosuvastatin (-0.07, n = 187) or pravastatin (-0.03, n = 609), while rising in those taking lovastatin (0.4, n = 86) or simvastatin (0.11, n = 2305).
In an analysis adjusted for baseline FIB-4 score, risk of progression to cirrhosis proved successively lower with each higher statin dose (cDDD), when compared with no statin use, as indicated by the following adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI):
-- 28-89 cDDDs: aHR 0.74 (95% CI 0.59 to 0.93)
-- 89-180 cDDDs: aHR 0.71 (95% CI 0.59 to 0.88)
-- Above 180 cDDDs: aHR 0.6 (95% CI 0.53 to 0.68)
That means a statin cDDD above 180 cut the risk of progression to cirrhosis by 40%.
In another analysis adjusted for baseline FIB-4 score, a statin dose above 180 cDDD halved the risk of progression to hepatocellular carcinoma compared with no statin use (aHR 0.51, 95% CI 0.36 to 0.72)
The researchers concluded that "statin use is associated with a clear, dose-dependent reduction in hepatic fibrosis progression as well as a dose-dependent reduction in incident HCC” and that atorvastatin and fluvastatin have significantly greater antifibrotic impact than other statins. They proposed that their findings "support the possible role for statins in the prevention of chronic liver disease progression."
1. Simon T, Bonilla H, Chung RT, Butt AA. Statin type and dose reduce the risk of cirrhosis and HCC in HCV infected patients. Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston. Abstract 551.