In univariable analysis, the presence of significant fibrosis (METAVIR stage >1) was not associated with BMI [prevalence ratio 1.01; 95% confidence interval (CI) 0.97, 1.06, P = 0.7], extremity fat (prevalence ratio 0.99, 95% CI 0.94, 1.05, P = 0.79), trunk fat (prevalence ratio 1.00; 95% CI 0.96, 1.04, P = 0.97), or trunk/lower extremity FMR (prevalence ratio 1.75; 95% CI 0.90, 3.41, P = 0.10). The association between fibrosis and trunk/lower extremity FMR was not statistically significant after adjustment for other confounders including age, sex, race, PI use at DXA, steatosis, and AST (data not shown). Similar results were obtained for both models 1 and 2 when the sample was restricted to the 145 African-American participants (data not shown).
There are important physiologic differences in various adipose tissue depots. Central fat has a major role in the pathogenesis of steatosis, likely through increased insulin resistance , elaboration of free fatty acids , and adipocytokine production . In contrast, subcutaneous fat of the lower extremities may protect against metabolic derangement, including steatosis, by serving as a triglyceride storage depot . In the FRAM cohort, for example, hypertriglyceridemia and elevated alanine aminotransferase (ALT), suggestive of steatosis, were associated with both increased visceral fat and lower amounts of subcutaneous fat [19,23]. As a result, in HIV-infected patients, measures of fat distribution, such as the ratio of central fat to lower extremity fat may be particularly relevant in identifying those at increased risk of metabolic abnormalities . Similarly, we found that this DXA-derived measure of fat distribution was associated with steatosis, independent of BMI.
Our study had several limitations. First, 94% of our cohort was infected with genotype 1 and most are African-American; thus, it is unclear whether our findings are generalizable to populations with other genotypes or different racial composition. Genotype 3 virus, in particular, is thought to cause steatosis through direct viral mechanisms, and steatosis is likely a more important problem in countries, such as Spain, with higher genotype 3 HCV prevalence . Second, although well correlated with other measurement techniques, such as magnetic resonance imaging , DXA does not distinguish subcutaneous from visceral fat, which would be helpful in understanding the contributions of various fat depots to steatosis risk. It is also impossible to ascertain whether the association between unsuppressed HIV RNA and steatosis reflects HIV replication or other factors like unacknowledged alcohol use that might be associated with both steatosis and incomplete antiretroviral adherence.
In conclusion, the relative and absolute amount of central fat was correlated with hepatic steatosis. These findings underscore the potential of weight loss to improve hepatic outcomes in HIV/HCV co-infected patients. In addition, the independent association of uncontrolled HIV infection and hepatic steatosis suggests that effective HIV therapy may be an important tool to reduce the burden of liver disease in HIV-infected patients.
Financial support for this study came from K24 DA00432, DA-11602, DA-16065 and DA-13806 from the National Institute on Drug Abuse, AA016893 from the National Institute on Alcohol Abuse and Alcoholism, K23 AT002862 (TTB) from the National Center for Complementary and Alternative Medicine, grant HS 07-809 from the Agency for Healthcare Policy and Research and the Clinical Research Unit at the Johns Hopkins Medical Institutions, M01RR-02719
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