Review
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World J Hepatol. Oct 27, 2013; 5(10): 528-540
Published online Oct 27, 2013. doi: 10.4254/wjh.v5.i10.528
Chronic HCV infection and inflammation: Clinical impact on hepatic and extra-hepatic manifestations
Rosa Zampino, Aldo Marrone, Luciano Restivo, Barbara Guerrera, Ausilia Sellitto, Luca Rinaldi, Ciro Romano, Luigi E Adinolfi
Rosa Zampino, Aldo Marrone, Division of Internal Medicine and Hepatology, Second University of Naples Polyclinic Hospital, 80100 Naples, Italy
Luciano Restivo, Barbara Guerrera, Ausilia Sellitto, Luca Rinaldi, Luigi E Adinolfi, Division of Internal Medicine, Second University of Naples, Clinical Hospital of Marcianise, Caserta Local Health Unit, 81100 Marcianise, Italy
Ciro Romano, Division of Internal Medicine, Allergy and Clinical Immunology, Second University of Naples Polyclinic Hospital, 80100 Naples, Italy
Author contributions: Zampino R contributed to conception, drafting of the article and literature review; Marrone A contributed to drafting of the article and literature review; Restivo L, Guerrera B, Sellitto A, Rinaldi L and Romano C reviewed the literature and approved the final version of this article; Adinolfi LE contributed to conception, drafted the article, critically reviewed the manuscript and approved the final version of this article.
Supported by A grant from Regione Campania
Correspondence to: Luigi E Adinolfi, MD, Professor, Head of Internal Medicine, Second University of Naples, Clinical Hospital of Marcianise, Caserta Local Health Unit, Corso Umberto I, 179, 81100 Marcianise, Italy. luigielio.adinolfi@unina2.it
Telephone: +39-82-3690642 Fax: +39-82-3690642
Received: June 26, 2013
Revised: September 5, 2013
Accepted: September 13, 2013
Published online: October 27, 2013
Abstract

The liver has a central role in regulating inflammation by its capacity to secrete a number of proteins that control both local and systemic inflammatory responses. Chronic inflammation or an exaggerated inflammatory response can produce detrimental effects on target organs. Chronic hepatitis C virus (HCV) infection causes liver inflammation by complex and not yet well-understood molecular pathways, including direct viral effects and indirect mechanisms involving cytokine pathways, oxidative stress and steatosis induction. An increasing body of evidence recognizes the inflammatory response in chronic hepatitis C as pathogenically linked to the development of both liver-limited injury (fibrosis, cirrhosis and hepatocellular carcinoma) and extrahepatic HCV-related diseases (lymphoproliferative disease, atherosclerosis, cardiovascular and brain disease). Defining the complex mechanisms of HCV-induced inflammation could be crucial to determine the global impact of infection, to estimate progression of the disease, and to explore novel therapeutic approaches to avert HCV-related diseases. This review focuses on HCV-related clinical conditions as a result of chronic liver and systemic inflammatory states.

Keywords: Hepatitis C virus, Inflammation, Cytokines, Oxidative stress, Hepatic disease, Extra-hepatic diseases

Core tip: Chronic hepatitis C virus (HCV) infection causes liver inflammation by complex and not yet well-understood molecular pathways. HCV-induced inflammation has a significant clinical impact on development of both hepatic disease and HCV-associated extrahepatic manifestations. Knowledge of the complex mechanisms underlying HCV-related inflammation and development of disease as well as individuation of relevant markers of inflammation could be of importance for understanding disease progression, predicting prognosis and, possibly, conceiving new therapeutic approaches targeting the different steps of the inflammatory response.