Although incredible advances in the development and dissemination of antiretroviral therapy (ART) have enabled many individuals with HIV to avoid progressing to AIDS, the efficacy of this therapy means the population may now live long enough to succumb to diseases that often plague the non- HIV–infected population. Chief among these is liver disease, specifically nonalcoholic fatty liver disease (NAFLD), which is characterized by fatty deposits in the liver and can lead to liver fibrosis (stiffness), cirrhosis, or death.
In patients who do not have HIV, the primary driver of NAFLD is metabolic syndrome. According to the National Heart, Lung, and Blood Institute, metabolic syndrome pertains to a cluster of risk factors that predispose a person to heart disease, diabetes, and stroke, and its incidence is rising worldwide. Prominent among these risk factors is obesity concentrated in the abdominal area. Additional risk factors include hypertension, a high fasting blood glucose level, and high triglyceride and low high-density lipoprotein (HDL) cholesterol levels. Now, NAFLD driven by metabolic syndrome is becoming more common in individuals with HIV as well—approximately one-third have NAFLD, according to the authors of a new study on the link between liver fibrosis and metabolic syndrome in individuals living with HIV.1
The study was conducted by a European team that analyzed 405 HIV-monoinfected adults, mostly male, who appeared in a database of patients being followed for treatment at a Paris hospital. The subjects all had been diagnosed with HIV at least 5 years prior to the study, and none had a history of excessive alcohol consumption. Their average age was 53, and 203 had metabolic syndrome. Upon enrollment, each participant had the stiffness of his or her liver measured using transient elastography, a noninvasive method similar to an ultrasound. Blood samples also were taken after a 12-hour fast.
The team found that liver stiffness, along with cirrhosis, was measurably higher in patients who had markers of metabolic syndrome, including low HDL cholesterol and high triglycerides. The higher the patient’s body mass index (BMI), the higher the risk of fibrosis and cirrhosis. Patients with a BMI of at least 30 kg/m2
were especially likely to have fibrosis, as were patients whose blood work suggested insulin resistance. Overall, 25.1% of HIV-monoinfected patients who had metabolic syndrome had significant fibrosis, with 8.4% found to have cirrhosis. Among HIV-monoinfected patients without metabolic syndrome, fewer than 8% had fibrosis. Because fibrosis is a known marker of the severity of chronic liver disease, and because it has a proven association with deaths due to liver disease in individuals with NAFLD who don’t have HIV, these findings have important implications for the HIV community.
Liver disease has long been a concern in individuals living with HIV, especially as they’ve seen their lives extended thanks to ART. “Most of the time, patients with HIV develop liver fibrosis/ cirrhosis in a background of viral hepatitis (hepatitis B virus [HBV] or hepatitis C virus [HCV]) coinfection,” Maud Lemoine, a senior clinical lecturer at Imperial College London and the lead author of the study, told Contagion®
. “But in patients without HBV or HCV coinfection, metabolic syndrome [arises] mainly due to obesity inducing fat into the liver, which can progress to inflammation and fibrosis.”
Exactly how and why NAFLD and metabolic syndrome contribute to liver fibrosis in individuals living with HIV is not well understood. Researchers are unsure of the causative biological processes, but they have confirmed that HIV-monoinfected patients with metabolic syndrome experience changes in the levels of proteins emitted by fat tissue as well as higher levels of cells that induce an immune response. “The HIV infection itself is connected to a chronic inflammatory state,” Dr. Lemoine said, but added that scientists do not know whether HIV has a direct impact on the liver. “We analyze patients that are very well suppressed, with no detectable viral load.”
What she and her team do know is that adipose tissue from obesity is the main driver of this condition. “So far, it has been a neglected problem in HIV patients,” she said, noting that there have been many studies examining the role of obesity and metabolic disease in individuals without HIV.