Abdominal Fat Accumulation, Elevated ALT, and Liver Steatosis in HIV Positive Individuals

By Liz Highleyman

A growing body of evidence shows a link between obesity, liver steatosis (fat accumulation in liver cells), and progression of liver fibrosis. Two recent studies looked at these associations in HIV positive individuals with and without hepatitis C virus (HCV) coinfection.

Study 1

In the first study, published in the June 1, 2008 Journal of Acquired Immune Deficiency Syndromes, Phyllis Tien and colleagues with the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) examined the association between body fat distribution and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations in HIV-infected individuals.

ALT and AST are liver enzymes used to monitor liver injury, including drug-related hepatotoxicity.

This cross-sectional analysis included 1119 HIV positive patients (with and without HCV) and 284 HIV negative control subjects. Magnetic resonance imaging (MRI) was performed to measure regional adipose (fat) tissue volume, both visceral (surrounding the internal organs) and subcutaneous (under the skin).

Results

• After adjustment for demographic and lifestyle factors, visceral adipose tissue (VAT) was positively associated with ALT in HIV-HCV coinfected patients (+9.8%), HIV monoinfected individuals (+8.0%), and HIV negative control subjects (+5.9%).

• By contrast, lower trunk subcutaneous adipose tissue (SAT) was negatively associated with ALT in HIV-HCV-coinfected patients (-14.3%) and HIV monoinfected individuals (-11.9%), and there was a statistical trend toward an association in control subjects (-7.1%).

• Estimated associations between regional adipose tissue and AST levels were small and did not reach statistical significance.

Based on these findings, the researchers concluded, "More VAT and less lower trunk SAT are associated with elevated ALT, which likely reflects the presence of steatosis. There was little association with AST."

"HCV infection and having more VAT or less lower trunk SAT are independently associated with elevated ALT in HIV infection," they continued. "Study regarding the association between VAT, trunk SAT, HCV, and progression of steatosis and fibrosis is needed in HIV-infected individuals."

University of California, San Francisco, CA; Department of Veterans Affairs Medical Center, San Francisco, CA; St. Luke's-Roosevelt Hospital, New York, NY; Washington University, St. Louis, MO; University of Alabama, Birmingham, AL; Department of Veterans Affairs Medical Center, Atlanta, GA; Northern California Institute for Research and Education, San Francisco, CA; Case Western Reserve University, Cleveland, OH.

Study 2

In the second study, researchers assessed the prevalence and predictors of nonalcoholic fatty liver disease (NAFLD) in antiretroviral therapy-experienced HIV positive patients, and the association of NAFLD with cardiovascular risk and subclinical atherosclerosis (hardening of the arteries).

This cross-sectional observational study enrolled 225 participants (72.4% men). NAFLD was defined by liver-spleen attenuation values of < 1.1 by computed tomography in individuals who had neither evidence of chronic viral hepatitis nor a significant history of heavy alcohol consumption.

Results

• NAFLD was diagnosed in 83 patients (36.9% of the total cohort).

• The following variables were significantly associated with NAFLD in univariate analyses:

• sex;
• waist circumference;
• body mass index;
• cumulative exposure to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs);
• visceral adipose tissue;
• insulin resistance (by HOMA-IR);
• serum ALT and AST levels;
• ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol.

• Coronary artery calcification scores and diagnosis of diabetes were not associated with NAFLD.

• In multivariable logistic regression analyses, factors associated with NAFLD were:

• higher serum ALT-to-AST ratio (odds ratio [OR] 4.59);
• male sex (OR 2.49);
• greater waist circumference (OR 1.07);
• longer duration of NRTI use (OR 1.12 per year of exposure).

"NAFLD is common among HIV-infected persons who have the traditional risk factors for NAFLD (elevations in serum [ALT] level, male sex, and increased waist circumference) apparent," the study authors concluded.

They added that, "Exposure to nucleoside reverse transcriptase inhibitors was an independent risk factor for NAFLD, with an 11% increase in the odds ratio for each year of use."

University of Modena and Reggio Emilia School of Medicine, Modena, Italy; Feinberg School of Medicine, Northwestern University, Chicago, IL.

6/24/08

References

PC Tien, DP Kotler, ET Overton, and others (Study of Fat Redistribution and Metabolic Change in HIV Infection Investigators). Regional adipose tissue and elevations in serum aminotransferases in HIV-infected individuals. Journal of Acquired Immune Deficiency Syndromes 48(2): 169-176. June 1, 2008.

G Guaraldi, N Squillace, C Stentarelli, and others. Nonalcoholic fatty liver disease in HIV-infected patients referred to a metabolic clinic: prevalence, characteristics, and predictors. Clinical Infectious Diseases. June 4, 2008 [Epub ahead of print].