Abstract
While the interactions between HIV and various liver cell populations have been explored, the relevance of these interactions when patients are well-controlled on ART is less clear. Therefore, we focus this perspective on HIV-related alterations that may drive hepatic inflammation and fibrosis in aviremic patients, with a focus on Kupffer cells and Hepatic Stellate Cells. Persistent CD4+ T cell depletion in the gut resulting in increased gut permeability has been postulated to play a role in systemic immune activation in HIV patients. The liver, with its unique location, remains the gatekeeper between the gut and the systemic circulation. The resident liver macrophage, Kupffer cell, is responsible for clearing and responding to these products. We propose that changes in Kupffer cell biology, in the context of HIV infection, creates a mileu that drives hepatic inflammation and fibrosis in response to microbial translocation. Targeting these pathways may be helpful in improving liver-related outcomes in HIV patients.
Highlights
End-stage liver disease is a major cause of non-AIDS related mortality in HIV+ patients even with effective anti-retroviral therapy, accounting for almost 15% of deaths [1,2,3,4,5,6,7]
While many may have an unrecognized chronic liver injury, a higher frequency of liver fibrosis was demonstrated in HIV-1–monoinfected patients compared with uninfected patients even without coinfection of hepatitis viruses and alcohol abuse, suggesting a correlation between HIV-1 infection and advanced liver fibrosis [14,15,16,17,18,19]
Immunostaining on liver tissue derived from aviremic HIV+ patients demonstrated an increased expression of IL-1β compared to normal liver with a high degree of colocalization in CD68+ macrophages [54]
Summary
End-stage liver disease is a major cause of non-AIDS related mortality in HIV+ patients even with effective anti-retroviral therapy, accounting for almost 15% of deaths [1,2,3,4,5,6,7]. Most data regarding fibrosis progression rates is derived from those with coinfection These patients have a higher relative risk (RR) of cirrhosis, increased development of decompensated cirrhosis and accelerated fibrosis progression rates compared with those who are only infected with HCV or HBV [10, 11]. Alcohol consumption is associated with increased relative risk of fibrosis progression in HIV mono-infected patients [12] while NASH is emerging as a major cause of liver disease, with half of mono-infected patients with unexplained liver enzyme elevations having NASH [13]. Persistent HIV-1 infection and viral associated liver immune dysfunction may independently contribute to the progression of liver diseases [20] In those on ART, drug-induced liver injury and increased rates of NASH due to both medications and metabolic derangements common in HIV. While hepatic stellate cells are the downstream effector of liver fibrosis, this perspective focuses on the role Kupffer cells play in promoting a mileu conducive to fibrosis progression in patients with HIV infection, in aviremic patients
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