Italian researchers focus on fatty liver
By Sean R. Hosein
Non-alcoholic fatty liver disease (NAFLD) is, as the name suggests, a condition in which the liver becomes increasingly swollen with fat. In addition to an enlarged liver, NAFLD also causes an increasing degree of liver damage. And as the liver becomes damaged and dysfunctional, complications ensue.
Fatty liver can occur because of obesity, but the following can also trigger NAFLD:
- insulin resistance
- a deficiency of the B vitamin choline
- liver damage due to hepatitis C virus (genotype 3)
In the past several years, researchers have found cases of NAFLD in HIV positive people. However, these cases have largely occurred in the absence of obesity or HCV genotype 3 infection.
To try to understand risk factors that might play a role in the development of NAFLD, a team of researchers at the University of Modena in Italy assessed physical, biochemical and other features in about 200 HIV positive participants. Their results suggest that NAFLD is indeed a problem in some HIV positive people. Risk factors associated with fatty liver included traditional risk factors and also, perhaps, treatment-related factors.
Study detailsThe study team had researchers with expertise in several fields, including infectious diseases, hormones, metabolism, cardiovascular disease, psychology and nutrition. Experts at interpreting CAT scans were also part of the team, as CAT scans of the liver and spleen were used to help form a diagnosis of NAFLD. In this condition, these organs have a somewhat different appearance than they might normally have on CAT scans.
The team recruited 225 HIV positive participants from its region between 2006 and July 2007. All participants had been taking highly active antiretroviral therapy (HAART) for at least two years before entering the study. No one had hepatitis B or C or any other disorder (such as alcoholism) that might contribute to fatty liver.
The average profile of participants was as follows:
- 28% females, 72% males
- most had normal weight
- in general, participants drank little or no alcohol
- length of HIV infection – 13 years
The study team conducted interviews and performed extensive medical tests and scans.
Results—NAFLDThe team made diagnoses of NAFLD based on CAT scans of the trunk of the body. The following proportion of participants had fatty liver:
- females – 19%
- males – 44%
This difference was statistically significant; that is, not likely due to chance alone.
It is noteworthy that only 5% of participants were obese, a condition usually associated with NAFLD.
Factors associated with having NAFLD were as follows:
- biochemical evidence of liver inflammation (higher-than-normal levels of liver enzymes ALT and AST)
- larger-than-normal waist size
- being male
- use of anti-HIV nucleoside analogues (nukes)
Note that the first three factors are traditionally found in HIV negative cases of NAFLD.
Nukes and NAFLDThe researchers noted a statistical association between NAFLD and exposure to nukes. In this study, each year of using nukes was linked to an 11% increased risk of NAFLD. There was no association between the use of certain nukes or combinations of nukes and the presence of NAFLD.
Putting it into perspectiveIt is important to bear in mind that this was a cross-sectional study. Such a study cannot conclusively prove a connection between cause (such as exposure to nukes) and effect (the development of NAFLD). Cross-sectional studies can only describe what they find at a particular moment in time. However, associations found in a cross-sectional study can later be explored in a study of a different design.
The study team suspects that NAFLD may be linked to presence of the HIV lipodystrophy syndrome. But, due to the study design, the researchers cannot be certain about the therapeutic or metabolic events that may trigger this condition.
The findings from this moderately sized Italian study suggest that traditional risk factors for NAFLD are associated with this condition in HIV positive people. Additionally, the researchers said that they “believe” that exposure to nukes over time increases the risk of NAFLD. Studies that monitor the liver health of HAART users before, during and after they take treatment containing nukes need to be conducted so we can move beyond “belief” and into the field of knowledge and evidence-based clinical practice.
REFERENCES:
1. Mohammed SS, Agdhassi E, Salit IE, et al. HIV-positive patients with nonalcoholic fatty liver disease have a lower body mass index and are more physically active than HIV-negative patients. Journal of Acquired Immune Deficiency Syndromes 2007 Aug 1;45(4):432-8.
2. Siegelman ES, Rosen MA. Imaging of hepatic steatosis. Seminars in Liver Disease. 2001;21(1):71-80.
3. Guaraldi G, Squillace N, Stentarelli C, et al. Nonalcoholic Fatty Liver Disease in HIV-Infected Patients Referred to a Metabolic Clinic: Prevalence, Characteristics, and Predictors. Clinical Infectious Diseases. 2008; in press.
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