Metabolic concerns in aging HIV-infected persons: From serum lipid phenotype to fatty liver

Among HIV-infected persons, the assessment of nonalcoholic fatty liver disease (NAFLD) provides a window through which overall metabolic health can be evaluated. In this review, we summarize clinical data that support the roles of aging and metabolic dysregulation as factors contributing to fatty liver/NAFLD among HIV-infected persons. Age-related metabolic alterations include hepatic anatomic and functional changes, altered homeostasis of gastrointestinal microbiota and anthropometric changes (such as a shift of body fat depots from the subcutaneous to the visceral compartment) that are often associated with the development of insulin resistance and increased cardiovascular risk. Fatty changes in the liver occur not only with metabolic disruption but also with virus-induced injury. Chronic hepatitis C virus infection is commonly associated with fatty liver, and can be related to both hepatitis C virus genotype and host metabolic features. Similarly, HIV infection is associated with fatty liver as a result of multiple viral and host factors. Clearly, lipodystrophy, dysregulation of the gut-liver axis and HIV infection itself may each contribute simultaneously to NAFLD pathogenesis. Although lifestyle changes are the mainstay of treatment, to date no drug has specifically been approved for use in persons with NAFLD. Moreover, current guidelines provide no specific therapeutic recommendations for persons with NAFLD older than 65 years. Well-designed studies characterizing the epidemiology, pathogenesis, clinical outcomes and potential therapeutic interventions for liver disease and associated metabolic comorbidities in older HIV-infected patients are urgently needed.