Patients treated with antiretroviral therapy have a high prevalence of fatty liver disease, according to an Italian study published in the July 15th edition of the Journal of Infectious Diseases. The overall prevalence of the condition amongst individuals in the study was 37%. None of these individuals had hepatitis B or C infection, drank excessively or were drug users.
A risk factor for nonalcoholic fatty liver disease was cumulative length of treatment with nucleoside reverse transcriptase inhibitors (NRTIs), and the investigators suggest that “nonalcoholic fatty liver disease fatty liver disease is the hepatic equivalent of metabolic syndrome”.
Nonalcoholic fatty liver disease is, as the name suggests, associated with a fatty liver, often called hepatitis steatosis. It happens in patients without other risk factors for a fatty liver, which includes infection with hepatitis B or hepatitis C, or excessive alcohol consumption. Nonalcoholic fatty liver disease can not only lead to liver problems, including fibrosis (scarring of the liver), but also to changes in the body’s metabolism, such as atherosclerosis (hardening or the arteries). The presence of nonalcoholic fatty liver disease is not only a marker of the presence of cardiovascular disease, but it may also be an early cause of this.
The benchmark test for nonalcoholic fatty liver disease is a liver biopsy. But other screening tools include ultrasound, and CT and MRI scans. The presence of a fatty liver using a CT scan is detected when the attenuation of liver tissue is greater than that seen in the spleen. A liver-spleen attenuation ratio of < 1.1 can predict over 30% of cases of fatty liver disease. In addition, the condition is often accompanied by inflammation of the liver shown by increases in ALT and AST levels.
It is estimated that between 14% - 31% of the general population have nonalcoholic fatty liver disease. The condition is associated with obesity and diabetes.
A few previous studies have looked at the prevalence of nonalcoholic fatty liver disease in patients with HIV. These suggested that it was present in 30% - 40% of individuals, with one study finding that it occurred more often in antiretroviral-treated patients with lipodystrophy than in the general population.
It has been suggested that nonalcoholic fatty liver disease might be a long-term side-effect of anti-HIV treatment. Investigators in Modena therefore designed a cross-sectional (or “snap-shot”) study to find out the prevalence and risk-factors for nonalcoholic fatty liver disease in a group of 225 patients who had been taking anti-HIV treatment for at least two years.
None of the patients were coinfected with hepatitis B or hepatitis C, used recreational drugs, or had significant alcohol consumption. CT scans were used to check for the presence of the condition, and those with liver-spleen attenuation values of below 1.1 were diagnosed as having nonalcoholic fatty liver disease.
Most of the patients (72%) were men and the mean age was 48. Obesity, defined as a body mass index (BMI) above 30 was present in 5% and patients, and 14% had diabetes. Liver inflammation, shown by elevations in ALT and ASTs, was present in 28%.
On the basis of CT scans, 37% of patients were diagnosed with nonalcoholic fatty liver disease. The condition was present in significantly (p < 0.001) more men (44%) than women (28%).
Other factors significantly associated with the condition included higher total cholesterol (p = 0.04); lower “good” HDL cholesterol (p = 0.047); impaired insulin metabolism (p < 0.001); liver inflammation, as indicated by higher ALT (p < 0.001) and AST (p < 0.001) values; a higher BMI (p < 0.001); larger waist circumference (p < 0.001); higher waist-to-hip ratio (p < 0.001); and visceral adiposity (p = 0.017).
Subsequent multivariate analysis showed the following factors were significantly associated with nonalcoholic fatty liver disease:
- Elevated ALTs and ASTs (OR, 4.59; 95% CI, 2.09 – 10.08).
- Male sex (OR, 2.49; 95% CI, 1.07 – 5.81).
- Elevated waist circumference (OR, 1.07; 95% CI, 1.03 – 1.11).
- NRTI treatment (OR, 1.12; 95% CI, 1.03 – 1.22).
The investigators stress that their findings show that each year of treatment with an NRTI increased the risk of nonalcoholic fatty liver disease by 11%.
There was a non-significant association between nonalcoholic fatty liver disease and hardening of the arteries (p = 0.08).
They comment, “in our cohort, nonalcoholic fatty liver disease was an entity most commonly seen among HIV-infected, nonobese, lipoatrophic men.” They note that they found an association between the condition and abnormalities in cholesterol, as well as high blood sugars, increased waist circumference and visceral adiposity. They write, “these associations led us to believe that there are etiologic links between nonalcoholic fatty liver disease and HIV-associated body fat redistribution syndrome (i.e. lipodystrophy) and other HIV-associated metabolic abnormalities, particularly serum lipid abnormalities and decreased insulin sensitivity”.
Guaraldi G. et al. Nonalcoholic fatty liver disease in HIV-infected patients referred to a metabolic clinic: prevalence, characteristics, and predictors. J Infect Dis 47: 250 – 257, 2008.