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Faster Fatty Liver Progression With Statin Than Placebo in SATURN HIV Trial
  IDWeek2017/IDSA, October 4-8, 2017, San Diego
Mark Mascolini
HIV-positive people randomized to rosuvastatin in the SATURN trial had faster progression to steatosis than people randomized to placebo [1]. The finding runs counter to the belief that statins may show merit in treating nonalcoholic fatty liver disease (NAFLD) in the general population.
NAFLD may affect as many as one third of people with HIV infection but free of HBV or HCV [2]. Researchers from Cleveland's Case Western Reserve University noted limited evidence that statins may fill a therapeutic void for this condition, including a 7-person analysis in people with HIV and NAFLD [3].
To learn how a statin may affect NAFLD in a larger HIV population, the Case Western group analyzed people in the SATURN HIV trial, which randomized adults with fasting low-density lipoprotein (LDL) cholesterol at or below 130 mg/dL to 10 mg of rosuvastatin daily or placebo [4]. The SATURN team already reported that rosuvastatin (1) lessens monocyte and lymphocyte activation and lowers levels of several inflammation markers, (2) increases insulin and insulin resistance, and (3) does not change peripheral or central fat.
The NAFLD analysis involved 72 people randomized to rosuvastatin and 75 randomized to placebo. Age averaged 45 in both study groups, about 80% of participants were men and two thirds black. Three quarters of the study group had a viral load below 50 copies. Average body mass index (28 kg/m2) and waist-to-hip ratio (0.94) were the same in the two study arms.
Through 96 weeks liver fat score rose significantly in both the rosuvastatin arm (P < 0.01) and the placebo arm (P = 0.01), with hardly any difference between the two groups (P = 0.49). An analysis adjusted for baseline liver fat score, trunk fat, body mass index, "bad" LDL cholesterol, and some inflammation and activation markers discerned a trend toward a greater increase in liver fat score in the rosuvastatin arm (P = 0.06). Viral load below 48 copies was associated with decreasing liver fat score (-0.250, P = 0.03).
The researchers then looked at 10 people in the rosuvastatin arm and 3 in the placebo arm who did not have pretreatment hepatic steatosis (liver fat score at or above 1.267) but had steatosis by week 96. People in the statin group proved almost 3 times more likely to acquire steatosis by week 96 (odds ratio [OR] 2.8). That association held true in analyses adjusted for (1) age, sex, race, and body mass index (OR 2.6), (2) those variables plus insulin resistance by HOMA-IR (OR 3.1), (3) HCV status (OR 2.8), and (4) 4 or more alcoholic drinks per day (OR 3). The association attenuated somewhat with adjustment for 96-week change in HOMA-IR (OR 1.5), a finding suggesting that insulin resistance had the biggest impact on progression to steatosis in people taking rosuvastatin.
The SATURN team cautioned that their findings may not apply to everyone with HIV because most of their participants were African American, had LDL cholesterol below 130 mg/dL, and had elevated markers of inflammation. "Despite its effective role in reducing cardiovascular disease risk and inflammation," the researchers concluded, "statin therapy does not appear effective in hepatic steatosis."
1. El Kamari V, Hileman CO, McComsey G. Fatty liver disease in HIV: predictors and response to statin therapy. IDWeek2017/IDSA. October 4-8, 2017. San Diego. Abstract 1813.
2. Maurice JB, Patel A, Scott AJ, Patel K, Thursz M, Lemoine M. Prevalence and risk factors of nonalcoholic fatty liver disease in HIV-monoinfection. AIDS. 2017;31:1621-1632.
3. Lo J, Lu MT, Kim EA, et al. Statin effects to reduce hepatosteatosis as measured by computed tomography in patients with human immunodeficiency virus. Open Forum Infect Dis. 2016;3(2):ofw062. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4943550/
4. Longenecker CT, Sattar A, Gilkeson R, McComsey GA. Rosuvastatin slows progression of subclinical atherosclerosis in patients with treated HIV infection. AIDS. 2016;30:2195-2203.