Fatty liver may be common in non-coinfected people with HIV: small study

According to an evaluation of a small group of US patients, hepatic steatosis may be more common than supposed among HIV-positive individuals, even when hepatitis C coinfection is not present. Steatosis was reported among 42% of a small group of HIV-positive individuals without viral hepatitis in Boston, Massachusetts, in a study published in the November 1^st, 2007 edition of the Journal of Acquired Immune Deficiency Syndromes.

Hepatic steatosis – fatty infiltration of the liver tissue – has been widely reported in many specific subgroups of people with HIV, including those with hepatitis C virus (HCV) coinfection, lipodystrophy, and high liver transaminase enzymes. Antiretrovirals including d4T (stavudine, Zerit) and ddI (didanosine, Videx) have also been associated with steatosis (see aidsmap report here).

Little, however, is known about the overall prevalence of steatosis among people with HIV. Therefore, investigators from Massachusetts General Hospital and the National Institute of Allergy and Infectious Diseases (NIAID) recruited HIV-positive men and women from the greater Boston area between November 2004 and March 2006. Participants were excluded for reasons including diagnosed cirrhosis, end-stage liver disease, or current treatment for viral hepatitis; if on antiretroviral therapy, the regimen had to have been stable for the past three months.

A total of 33 participants were evaluated: 24 men and nine women, median age was 46 years, 55% were Caucasian, 33% black, 12% Hispanic and 12% of mixed race. Recruitment did not select on the basis of liver disease, coinfection, antiretroviral therapy or lipodystrophy; of the actual participants enrolled, 21% were HCV coinfected, 85% were on antiretroviral therapy, and the overall median CD4 cell count was 441 cells/mm³. Thirteen participants (39%) reported a history of alcoholism, but none within the past three years. One participant tested positive for hepatitis B (HBV) antigen.

Participants completed two days of comprehensive metabolic testing, body composition evaluation including cross-sectional computerised tomography (CT) scans, and liver examination via non-invasive 1H-magnetic resonance spectroscopy (MRS).

Of the 33 participants, 14 (42%) had hepatic steatosis, defined as a liver fat content of ≥5% by net weight, in accord with traditional definitions. In these 14, hepatic fat content ranged from 6.4% to 29%, with a mean of 14%. By univariate analysis, steatosis was more likely in those with greater body mass index (BMI), waist-to-hip ratio, visceral abdominal fat (VAT) and subcutaneous fat (SAT), and those who met criteria for metabolic syndrome (obesity, high blood pressure, high triglycerides or glucose, or low HDL cholesterol). Those with steatosis were also more likely to have high ALT, triglyceride and insulin levels and insulin resistance. The most significant factors by multivariate analysis were abdominal fat (VAT) area (p = 0.007) and insulin resistance (p= 0.0004).

No participants entered the study with a known history of diabetes, but one patient with hepatic steatosis was diagnosed with diabetes during participation due to high fasting glucose levels.

Previous studies have shown that increased fat levels within muscle cells are associated with insulin resistance; here, the researchers found that a significant association between increased liver fat (hepatic steatosis) and intramuscular fat, as measured by muscle attenuation on CT scan, suggesting that "abnormal deposition of lipid in muscle and in hepatocytes may be an important component of insulin resistance."

The researchers concluded that they "identified a high prevalence (42%) of hepatic steatosis among a sample of HIV-infected men and women not selected for specific risk factors related to steatosis… steatosis may be common among HIV-infected patients and … may play a significant role in the insulin resistance and metabolic disturbances seen in this population."