Review
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2018; 24(42): 4728-4737
Published online Nov 14, 2018. doi: 10.3748/wjg.v24.i42.4728
Liver as a target of human immunodeficiency virus infection
Murali Ganesan, Larisa Y Poluektova, Kusum K Kharbanda, Natalia A Osna
Murali Ganesan, Kusum K Kharbanda, Natalia A Osna, Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
Murali Ganesan, Kusum K Kharbanda, Natalia A Osna, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, United States
Larisa Y Poluektova, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, United States
Author contributions: All authors equally contributed to this review with conception and design, literature review, drafting and critical revision, editing, and approval of the final version.
Supported by the Nebraska Research Initiative Grant.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Natalia A Osna, MD, PhD, Associate Professor, Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE 68105, United States. nosna@unmc.edu
Telephone: +1-402-9953735 Fax: +1-402-4490604
Received: August 28, 2018
Peer-review started: August 28, 2018
First decision: October 9, 2018
Revised: October 10, 2018
Accepted: October 21, 2018
Article in press: October 21, 2018
Published online: November 14, 2018
Processing time: 77 Days and 15.3 Hours
Abstract

Liver injury is a characteristic feature of human immunodeficiency virus (HIV) infection, which is the second most common cause of mortality in HIV-infected patients. Now it is recognized that liver plays a key role in HIV infection pathogenesis. Antiretroviral therapy (ART), which suppresses HIV infection in permissive immune cells, is less effective in hepatocytes, thereby making these cells a silent reservoir of HIV infection. In addition to direct hepatotoxic effects of HIV, certain ART treatment modalities provide hepatotoxic effects. The exact mechanisms of HIV-triggered chronic hepatitis progression are not elucidated, but the liver is adversely affected by HIV-infection and liver cells are prominently involved in HIV-elicited injury. These effects are potentiated by second hits like alcohol. Here, we will focus on the incidence of HIV, clinical evidence of HIV-related liver damage, interactions between HIV and liver cells and the role of alcohol and co-infection with hepatotropic viruses in liver inflammation and fibrosis progression.

Keywords: Liver cells; Antiretroviral therapy; Apoptosis; Inflammation; Fibrosis; Immunodeficiency virus; Alcohol

Core tip: Here, we summarized the literature and our recent findings on human immunodeficiency virus (HIV)-related liver damage. Liver injury is the second and most frequent cause of HIV patients’ death after acquired immune deficiency syndrome. The results of clinical studies support close association between HIV severity and liver disease progression. It is clear now that both liver parenchymal and non-parenchymal cells play a significant role in HIV-triggered liver inflammation and fibrosis pathogenesis and might serve as reservoirs of HIV-infection. Hepatotoxicity comes from the direct interactions between HIV and liver cells as well as from harmful effects of anti-retroviral therapy potentiated by second insults, like alcohol.