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Inflammation and Repair in Viral Hepatitis C

  • Manuela G. Neuman
  • Kevin Sha
  • Rustan Esguerra
  • Sam Zakhari
  • Robert E. Winkler
  • Nir Hilzenrat
  • Jonathan Wyse
  • Curtis L. Cooper
  • Devanshi Seth
  • Mark D. Gorrell
  • Paul S. Haber
  • Geoffrey W. McCaughan
  • Maria A. Leo
  • Charles S. Lieber
  • Mihai Voiculescu
  • Eugenia Buzatu
  • Camelia Ionescu
  • Jozsef Dudas
  • Bernhard Saile
  • Giuliano Ramadori
Review Paper

Abstract

Hepatitis C viral infection (HCV) results in liver damage leading to inflammation and fibrosis of the liver and increasing rates of hepatic decompensation and hepatocellular carcinoma (HCC). However, the host’s immune response and viral determinants of liver disease progression are poorly understood. This review will address the determinants of liver injury in chronic HCV infection and the risk factors leading to rapid disease progression. We aim to better understand the factors that distinguish a relatively benign course of HCV from one with progression to cirrhosis. We will accomplish this task by discussion of three topics: (1) the role of cytokines in the adaptive immune response against the HCV infection; (2) the progression of fibrosis; and (3) the risk factors of co-morbidity with alcohol and human immunodeficiency virus (HIV) in HCV-infected individuals. Despite recent improvements in treating HCV infection using pegylated interferon alpha (PEGIFN-α) and ribavirin, about half of individuals infected with some genotypes, for example genotypes 1 and 4, will not respond to treatment or cannot be treated because of contraindications. This review will also aim to describe the importance of IFN-α-based therapies in HCV infection, ways of monitoring them, and associated complications.

Keywords

Hepatitis C Inflammation Fibrosis Cytokines Chemokines HIV 

Abbreviations

ABC

Abacavir

AIDS

Acquired immunodeficiency syndrome

ADH

Alcohol dehydrogenase

ALD

Alcohol liver disease

ALDH

Acetaldehyde dehydrogenase

APCs

Antigen presenting cells

APV

Amprenavir

ART

antiretroviral therapy

ARV

Antiretroviral

AZT

Zidovudine

BMP-6

Bone morphogenetic protein-6

CC

Chemokines with two N-terminal cysteines

CCR/CXCR

CC/CXC Receptor

CD

Cluster of differentiation

CIFN

Consensus IFN

C

Core protein

CXC

Chemokines presenting an amino acid between the two N-terminal cysteine residues

EFZ

Efevirez

ECM

Extracellular matrix

ELISA

Enzyme-linked immunosorbent assay

GTP

Guanisine 5′-triphosphate

HAART

Highly active antiretroviral therapy

HCV

Hepatitis C virus

HIV

Human immunodeficiency virus

HCC

Hepatocellular carcinoma

HSC

Hepatic stellate cells

IDU

Injection drug users

IDV

Indinavir

IGF

Interferon growth factor

IFN

Interferon

IL

Interleukin

IMPDH

Inosine monophosphate dehydrogenase

IRF

Interferon response factor

JAK

Janus kinases

LPV

Lopinavir

MCP-1

Monocyte chemo-attractant protein 1

MFB

Myofibroblast

MHC

Major histocompatible complex

MIP-1

Macrophage inflammatory protein 1

MMP

Matrix metalloproteinases

NFV

Nelfinavir

NNRTI

Non-nucleoside reverse transcriptase inhibitor

NRTI

Nucleoside reverse transcriptase inhibitor

NARTI

Nucleoside analogue reverse transcriptase inhibitor

NVP

Nevirapine

PDGF

Platelet-derived growth factor

PEG

Polyethylene glycol

PEGIFN

Pegylated interferon

PI

Protease inhibitor

RANTES

Regulated upon activation, normal T-cell expressed, and presumably secreted

Smad

Signal mothers against decapentaplegic

SNPs

Single nucleotide polymorphisms

SOCS

Suppressor of cytokine signaling

STAT

Signal transducer and activator of transcription

TIMP

Tissue inhibitor of metalloproteinases

Th

T helper

TLRs

Toll-like receptors

Treg

T regulatory

TGF-β

Transforming growth factor beta

TGF-βR

Transforming growth factor beta receptor

TDF

Tenofovir disoproxil fumarate

TNF-α

Tumor necrosis factor-alpha

TNFRS

Tumor necrosis factor receptor signaling

ZDV

Zidovudine

Notes

Acknowledgements

This paper was presented at the “7th International Symposium on Cytokines and Chemokines” (Montreal, Canada, 7–9 September, 2006). Dr Manuela G. Neuman, scientific organizer of the symposium is grateful for the financial support given by the Institute of Infection and Immunity of Canadian Institutes of Health Research and by the National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, USA.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Manuela G. Neuman
    • 1
    • 2
  • Kevin Sha
    • 1
    • 2
  • Rustan Esguerra
    • 1
    • 2
  • Sam Zakhari
    • 3
  • Robert E. Winkler
    • 4
  • Nir Hilzenrat
    • 5
  • Jonathan Wyse
    • 5
  • Curtis L. Cooper
    • 6
  • Devanshi Seth
    • 7
    • 8
  • Mark D. Gorrell
    • 8
    • 9
  • Paul S. Haber
    • 7
    • 8
    • 9
  • Geoffrey W. McCaughan
    • 8
    • 9
  • Maria A. Leo
    • 10
  • Charles S. Lieber
    • 10
  • Mihai Voiculescu
    • 11
  • Eugenia Buzatu
    • 11
  • Camelia Ionescu
    • 11
  • Jozsef Dudas
    • 12
  • Bernhard Saile
    • 12
  • Giuliano Ramadori
    • 12
  1. 1.In Vitro Drug Safety and Biotechnology, Department of Pharmacology, Biophysics and Global Health, Institute of Drug Research, and Centre for International HealthUniversity of TorontoTorontoCanada
  2. 2.In Vitro Drug Safety and Biotechnology, Toxicology and Biotechnology, South Tower of the MaRS Discovery CentreTorontoCanada
  3. 3.Division of Metabolism and Health EffectsNational Institute on Alcohol Abuse and Alcoholism, NIHBethesdaUSA
  4. 4.HepatologySchering-Plough CorporationKenilworthUSA
  5. 5.Division of Gastroenterology, Department of MedicineSMBD-Jewish General Hospital, McGill UniversityMontrealCanada
  6. 6.Division of Infectious Diseases, The Ottawa Hospital-General CampusUniversity of Ottawa HospitalOttawaCanada
  7. 7.Drug Health Services & A.W. Morrow Gastroenterology and Liver Centre Royal Prince Alfred HospitalCamperdownAustralia
  8. 8.Centenary Institute & Discipline of Medicine, The University of SydneySydneyAustralia
  9. 9.Discipline of MedicineThe University of SydneySydneyAustralia
  10. 10.Alcohol Research CenterJ. J. Peters Veteran Administration Hospital and Mount Sinai HospitalRdBronxUSA
  11. 11.Centre of Internal Medicine—Fundeni Clinical InstituteBucharestRomania
  12. 12.Department of Internal Medicine, Section of Gastroenterology and EndocrinologyGeorg-August-University GoettingenGoettingenGermany

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