Abstract
Chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV). Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV.
Highlights
Hepatitis C virus (HCV) infection is prevalent among human immunodeficiency virus (HIV)-infected populations, with about 7 million people worldwide being coinfected [1]
It can be caused by toxic, metabolic, or viral insult, and occurs when there is an imbalance in extracellular matrix (ECM) protein turnover, i.e., enhanced synthesis and reduced degradation
hepatic stellate cells (HSCs) are generally quiescent in the hepatic perisinusoidal space [14], but become active in response to chemical stimuli produced by hepatocytes or Kupffer cells following cell injury; these stimuli include reactive oxygen species (ROS), lipid peroxides, growth factors and inflammatory cytokines [10]
Summary
Hepatitis C virus (HCV) infection is prevalent among human immunodeficiency virus (HIV)-infected populations, with about 7 million people worldwide being coinfected [1]. Liver-related mortality remains still higher among coinfected individuals compared with those with only HIV or HCV monoinfection [2]. Natural history studies have shown that HIV coinfection promotes accelerated. HCV-related hepatic fibrosis progression, even with HIV replication under full control by ART [3]. HIV alters the natural history of HCV-related liver disease through mechanisms that are independent of its effects on T cell-mediated immunity [5]. The most relevant mechanisms involved include direct viral effects, immune/cytokine dys-regulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. We discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV. Pathophysiology of Liver Fibrosis in Chronic Hepatitis C Virus (HCV) Infection
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