November 23, 2016
Every 30% increase of time taking a statin yielded a one-third lower risk of cirrhosis in HIV/hepatitis C (HCV)-coinfected male veterans who did not already have advanced liver disease. Diabetes and low high-density lipoprotein (HDL) cholesterol boosted cirrhosis risk in this 5985-veteran analysis.
HCV coinfection affects nearly 30% of the HIV population in parts of the United States and Europe and is associated with faster fibrosis progression, noted the Veterans Affairs (VA) researchers who conducted this study. Because statins have anti-inflammatory, immunomodulatory and antineoplastic traits, the VA team proposed that they might be useful adjunctive therapy to reduce liver disease progression in HIV/HCV-coinfected people.
The analysis included veterans in the VA HIV and HCV Clinical Case Registries between January 1999 and December 2010. The investigators defined cirrhosis by ICD-9 code or by aspartate aminotransferase to platelet ratio index (APRI) >2. They measured statin use as percent of time with an active prescription, and they time-updated that measure through follow-up. After stratifying participants by alanine aminotransferase (ALT) above or below 40 IU/L, the VA team used Cox proportional hazards regression to calculate the impact of statin use and other variables to time to cirrhosis.
Through an average follow-up of 6.2 years, cirrhosis developed in 2,265 veterans for a crude incidence of 6.1 per 100 person-years. Veterans in whom cirrhosis developed were less likely to ever receive antiretroviral therapy (79.5% versus 85.7%, P < .0001) and less likely to have a CD4 count above 350 cells/mm3 (48.9% versus 59.2%, P < .0001).
Statins were prescribed for a significantly lower proportion of veterans with than without cirrhosis (12.5% versus 21.2%, P = .0001). Multivariate analysis determined that in veterans with ALT ≤40 IU/L, every 30% increase in time on statins conferred a 32% lower risk of progression to cirrhosis (adjusted hazard ratio [aHR] 0.68, 95% confidence interval [CI] 0.47 to 0.98). This association did not hold in veterans with ALT >40 IU/L (aHR 0.95, 95% CI 0.83 to 1.01). But in veterans with ALT >40 IU/L, diabetes raised cirrhosis risk 15% (aHR 1.15, 95% CI 1.01 to 1.31, P = .04), low HDL cholesterol (<40 mg/dL) raised the risk 30% (aHR 1.3, 95% CI 1.2 to 1.44, P < .0001) and alcohol use boosted the risk 15% (aHR 1.15, 95% CI 1.04 to 1.26, P = .004).
Regardless of ALT, a CD4 count <200 cells/mm3 independently raised the risk of cirrhosis (for ALT ≤40 IU/L, aHR 2.4, 95% CI 1.80 to 3.19, P < .0001; for ALT >40 IU/L, aHR 1.9, 95% CI 1.71 to 2.12, P < .0001). Veterans spending more than 80% of time with an undetectable HIV load had almost a 30% lower risk of cirrhosis (for ALT ≤40 IU/L, aHR 0.72, 95% CI 0.51 to 1.0, P = .05; for ALT >40 IU/L, aHR 0.72, 95% CI 0.64 to 0.8, P < .0001). Age over 50 raised the risk of cirrhosis in both groups (for ALT ≤40 IU/L, aHR 2.54, 95% CI 1.54 to 4.18, P = .0002; for ALT >40 IU/L, aHR 1.28, 95% CI 1.09 to 1.50, P = .002), as did a Deyo comorbidity score ≥2 (for ALT ≤40 IU/L, aHR 3.23, 95% CI 2.31 to 4.5, P < .0001; for ALT >40, aHR 1.5, 95% CI 1.28 to 1.93, P < .0001).
The researchers suggested that low statin use in these veterans might reflect "hesitation in prescribing medications with potential hepatotoxicity." But they argued that statins are generally safe in patients with liver disease or liver enzyme elevation and proposed that, "if followed closely, patients with slightly elevated ALT should be able to receive statins." Statins may not be needed as adjunctive therapy for liver disease in patients whose HCV infection can be cured by direct-acting antivirals.
A study of HCV-monoinfected veterans found a statin dose-dependent reduction in fibrosis progression and incident hepatocellular carcinoma, particularly with atorvastatin and fluvastatin.
Mark Mascolini writes about HIV infection.
Copyright © 2016 Remedy Health Media, LLC. All rights reserved.
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