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Abstract Objective The nonalcoholic fatty liver disease fibrosis score (NFS) is comprised of unique metabolic risk indicators that may accurately predict residual cardiovascular (CV) risk in patients with established coronary disease and metabolic dysfunction. Methods We applied the NFS prospectively to 14,819 post-ACS patients randomized to ezetimibe/simvastatin (E/S) or placebo/simvastatin (P/S), in the IMPROVE-IT trial, using validated NFS cutoffs. The primary endpoint included CV death, myocardial infarction, unstable angina, revascularization or stroke. Outcomes were compared between NFS categories and treatment arms using frequency of events, KM rates and adjusted Cox proportional hazard models. The ability of the NFS to predict recurrent CV events was independently validated in 5395 placebo-treated patients enrolled in the SOLID-TIMI 52 trial. Results Among 14,819 patients enrolled in IMPROVE-IT, 14.2% (N = 2106) were high-risk (NFS > 0.67). The high-risk group had a 30% increased risk of recurrent major CV events, compared to the low-risk NFS group (HR 1.30 [1.19–1.43]; p < 0.001). Among high-risk patients, ezetimibe/simvastatin conferred a 3.7% absolute reduction in risk of recurrent CV events, compared to placebo/simvastatin (HR 0.85 [0.74–0.98]), translating to a number-needed-to-treat of 27. Similar benefit was not found in the low-risk group (HR ezetimibe/simvastatin vs. placebo/simvastatin, 1.01 [0.91–1.12]; p-interaction = 0.053). The relationship between NFS category and recurrent CV events was independently validated in patients enrolled in SOLID-TIMI 52 (HR for NFS > 0.67 vs. NFS < −1.455 = 1.55 [1.32–1.81]; p < 0.001). Conclusion Stratification of cardiovascular risk by NFS identifies an independent population of patients who are at highest risk of recurrent events, and most likely to benefit from dual lipid-lowering therapy. Clinical trials.gov : NCT00202878. Highlights • The NFS is a novel tool for predicting residual CV risk in established CAD. • A high-risk NFS group had 30% higher risk of CV events, compared to low-risk NFS. • A high-risk NFS group was significantly more likely to benefit from early ezetimibe. • The positive association between high-risk NFS and CV risk was externally validated. [ABSTRACT FROM AUTHOR]

Background: Coinfection with human immunodeficiency virus (HIV) accelerates hepatitis C virus (HCV)-related liver fibrosis. Macrophages are triggered during both viral infections and are critical in liver inflammation/fibrogenesis. Liver fibrosis strongly associates with serum soluble CD163 (sCD163, a macrophage activation marker); comprehensive evaluation in HIV/HCV coinfection is lacking.Methods: We retrospectively analyzed sCD163 (enzyme-linked immunosorbent assay) and hepatic CD163 (immunofluorescent CD163/CD68 costaining) in patients infected with HIV/HCV, HCV, or HIV, pre- and post-antiviral therapy.Results: sCD163 was significantly higher in HIV/HCV compared to either monoinfection, and decreased following successful antiviral therapy, although did not fully normalize. In HIV/HCV, sCD163 was associated with necroinflammation, Ishak fibrosis scores, and noninvasive fibrosis scores. We observed a novel trend whereby sCD163 levels progressively increase with increasing Ishak fibrosis score, peaking at stage 4, above which levels plateaued. Periportal CD163+ macrophage frequency was also higher with increasing fibrosis score. When stratified by fibrosis stage, sCD163 levels were higher in HIV/HCV than HCV but only in individuals with mild to moderate fibrosis.Conclusions: In HIV/HCV, increasing sCD163 levels accompanied periportal CD163+ macrophage enrichment in mild to moderate fibrosis, but not in established cirrhosis, suggesting that sCD163 is a dynamic biomarker of fibrogenesis rather than accumulated fibrosis. Our findings implicate HIV-related macrophage activation in accelerated fibrosis progression in HIV/HCV coinfection. [ABSTRACT FROM AUTHOR]

Purpose of Review: Here, we review the epidemiology, diagnosis, and management of non-alcoholic fatty liver disease (NAFLD) in the general population, discuss HIV-specific differences in NAFLD pathogenesis, and summarize what is known regarding differences in NAFLD by race/ethnicity and sex.Recent Findings: The reported prevalence of NAFLD among people living with HIV varies by age, body mass index, comorbidity, and method of NAFLD diagnosis, but is generally thought to be greater among HIV-infected compared to HIV-uninfected populations. Minorities and women tend to experience poorer HIV treatment outcomes (Meditz et al. J Infect Dis. 203(4):442-51, 2011; Beer et al. Medicine (Baltimore). 95(13):e 3171, 2016; Gant et al. MMWR Morb Mortal Wkly Rep. 66(40):1065-72, 2017; Millett et al. Lancet. 380(9839):341-8, 2012; Wejnert et al. J Infect Dis. 213(5):776-83, 2016), and are at the greatest risk for significant weight gain with HIV treatment (Erlandson et al. Medicine (Baltimore). 95(46):e 5399, 2016). Thus, women and minorities living with HIV may be at a higher risk of developing NAFLD and progressive liver disease.Summary: Disparities in the diagnosis, progression, and prognosis of NAFLD and HIV-associated NAFLD may be, in part, explained by genetic and sex differences; however, data is limited. [ABSTRACT FROM AUTHOR]