Increased fat accumulation in the liver in HIV-infected patients with antiretroviral therapy-associated lipodystrophy

Objective: To determine liver fat content in patients with highly active antiretroviral therapy (HAART)-associated lipodystrophy. Background: Lipodystrophy in several animal models is associated with fat accumulation in insulin-sensitive tissues, such as the liver. This causes hyperinsulinaemia, dyslipidaemia and other features of insulin resistance. Design: A cross-sectional study. Subjects and methods: Three age- and weight-matched groups were compared: 25 HIV-positive men with HAART-associated lipodystrophy (HAART+LD+), nine HIV-positive men receiving HAART, but without lipodystrophy (HAART+LD-), and 35 HIV-negative healthy men (HIV-). Liver fat content was measured using proton spectroscopy. Intra-abdominal and subcutaneous fat were determined using magnetic resonance imaging. Results: Liver fat content was significantly higher in the HAART+LD+ (8 ± 10%) than the HIV- (5 ± 7%; P < 0.05) or the HAART+LD- (3 ± 5%; P < 0.01) group. Liver fat content correlated with serum fasting insulin in the HAART+LD+ (r= 0.47; P < 0.05) and HIV- groups (r= 0.65; P< 0.001), but not with the amount of intra-abdominal fat. Within the HAART+LD+ group, serum insulin did not correlate with the amount of intra-abdominal fat. The HAART+LD+ group had a lower serum leptin concentration when compared to the two other groups. Features of insulin resistance, including hepatic fat accumulation, were not found in HAART+LD- group. Conclusions: The severity of the insulin resistance syndrome in patients with HAART-associated lipodystrophy is related to the extent of fat accumulation in the liver rather than in the intra-abdominal region. Fat accumulation in the liver may therefore play a causative role in the development of insulin resistance in these patients.