2018, Number 6
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Ann Hepatol 2018; 17 (6)
Immunometabolic Effect of Cholesterol in Hepatitis C Infection: Implications in Clinical Management and Antiviral Therapy
González-Aldaco K, Torres-Reyes LA, Ojeda-Granados C, José-Ábrego A, Fierro NA, Román S
Language: English
References: 125
Page: 908-919
PDF size: 640.81 Kb.
ABSTRACT
Hepatitis C virus (HCV) is a lipid-enveloped virion particle that causes infection to the liver, and as part of its life cycle, it disrupts
the host lipid metabolic machinery, particularly the cholesterol synthesis pathway. The innate immune response generated by liver
resident immune cells is responsible for successful viral eradication. Unfortunately, most patients fail to eliminate HCV and progress
to chronic infection. Chronic infection is associated with hepatic fat accumulation and inflammation that triggers fibrosis, cirrhosis,
and eventually hepatocellular carcinoma. Despite that the current direct-acting antiviral agents have increased the cure rate of HCV
infection, viral genotype and the host genetic background influence both the immune response and lipid metabolism. In this context,
recent evidence has shown that cholesterol and its derivatives such as oxysterols might modulate and potentialize the hepatic innate
immune response generated against HCV. The impairment of the HCV life cycle modulated by serum cholesterol could be relevant
for the clinical management of HCV-infected patients before and after treatment. Alongside, cholesterol levels are modulated either
by genetic variations in
IL28B, ApoE, and LDLR or by dietary components. Indeed, some nutrients such as unsaturated fatty acids
have demonstrated to be effective against HCV replication. Thus, cholesterol modifications may be considered as a new adjuvant
strategy for HCV infection therapy by providing a biochemical tool that guides treatment decisions, an improved treatment response
and favoring viral clearance. Herein, the mechanisms by which cholesterol contributes to the immune response against HCV infection
and how genetic and environmental factors may affect this role are reviewed.
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