Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in HIV infection: a metabolic approach of an infectious disease

ABSTRACT

Introduction: With the successes of antiretroviral therapy, patients infected with human immunodeficiency virus (HIV) living longer. Regarding this, the common diseases of HIV population (i.e., opportunistic infections) are now losing ground in front of metabolic alterations. This phenomenon is related to the delay in progression to acquired immune deficiency syndrome (AIDS), making it so that patients live in a chronic inflammatory state which, combined with other mechanisms such infectious ones, cause metabolic diseases.

Areas covered: Considering a high prevalence of metabolic alterations, the relationship between metabolic syndrome (MetS) with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), and liver diseases as a major cause of death in the HIV-infected population, this paper aims to overview the mechanisms and prevalence of NAFLD and NASH as they relate to the developed metabolic diseases of HIV patients.

Expert opinion: The pathways underlying MetS include the effects of HIV and ART on the liver, adipose tissue, and muscle. These mechanisms result in liver damage, consequently leading to NAFLD and its more severe form NASH. These conditions have increased in HIV-infected population in recent years and since their life expectancy is improving it is important to be ready to attend their new emerging diseases.

KEYWORDS:

• HIV
• antiretroviral
• NASH
• NAFLD
• metabolic syndrome
• insulin resistance
• HCV

Article highlights

• According to the WHO in its report of 2018, 36.9 million people globally were living with HIV in 2017. However, several studies have reported significant advances against AIDS with the successful use of combined ART. Since then, the idea of the end of AIDS and HIV infection as a chronic disease has emerged.

• The new ART improves health and life expectancy of HIV population. However, with the present success, a more set of HIV-associated complications have emerged, particularly to relate to metabolic alterations and cardiovascular disease. Regarding this issue, the population with HIV infection compared to the general population presents a high risk to develop MetS. Probably secondary to the viral mechanism and the use of antiretrovirals.

• NAFLD is the manifestation of MetS in the liver, consequently is a major cause of death on the HIV population. Currently, are exploring the mechanisms by HIV infection lead to progression NAFLD. Classically, one of the main metabolic alterations in subjects with HIV infection was lipodystrophy syndrome, is highly related to PIs. Moreover, the HIV viral protein R which impairs PPARγ and PPARα, modify the expression of free fatty acids-catabolizing enzymes in the liver, therefore, a dysregulation of adipogenesis and adipocyte differentiation in fat tissues. In addition, this protein activates the LXRα inducing de novo lipogenesis and decreasing fatty acid oxidation. Another major viral mechanism is the effect of HIV envelope protein gp120 over the hepatic cells, this phenomenon promotes the expression of proinflammatory cytokines which activate Kupffer cells and hepatic stellate cells inducing liver fibrosis.

• On the other hand, despite the progress against HCV infection, the HIV-HCV coinfection is still common. HCV infection is also related to metabolic alterations such as insulin resistance, mainly genotype 3 HCV induced hepatic steatosis.

• Another important matter is the case of overweight and obesity, especially in women infected with HIV. There is information that the prevalence of overweight and obesity is increasing in HIV-infected patients due to several factors, such as ART, age, gender, and lifestyle.

• Finally, therapy with antiretrovirals is not harmless. Several studies showed a strong association with some components of MetS. The most common side effects are insulin resistance and dyslipidemia. Furthermore, it has been described recently the possible effects of antiretrovirals against endothelial injury and hepatocytes mediated through oxidative stress, and the decreasing of nitric oxide production. Fortunately, new ARVs are improving by showing fewer side effects.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosure

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was in part supported by the Medica Sur Clinic & Foundation.