Inflammation and repair in viral hepatitis C.
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-alpha) 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-alpha-based therapies in HCV infection, ways of monitoring them, and associated complications.
Neuman
Manuela G
MG
In Vitro Drug Safety and Biotechnology, Department of Pharmacology, Biophysics and Global Health, Institute of Drug Research, University of Toronto, Toronto, ON, Canada. m_neuman@rogers.com
Sha
Kevin
K
Esguerra
Rustan
R
Zakhari
Sam
S
Winkler
Robert E
RE
Hilzenrat
Nir
N
Wyse
Jonathan
J
Cooper
Curtis L
CL
Seth
Devanshi
D
Gorrell
Mark D
MD
Haber
Paul S
PS
McCaughan
Geoffrey W
GW
Leo
Maria A
MA
Lieber
Charles S
CS
Voiculescu
Mihai
M
Buzatu
Eugenia
E
Ionescu
Camelia
C
Dudas
Jozsef
J
Saile
Bernhard
B
Ramadori
Giuliano
G
D000437:Alcoholism / Q000150:complications; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000276:immunology*; D018450:Disease Progression; D005838:Genotype; D015658:HIV Infections / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007249:Inflammation; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000276:immunology / Q000821:virology*; D008113:Liver Neoplasms / Q000276:immunology / Q000821:virology; D012254:Ribavirin / Q000627:therapeutic use; D012307:Risk Factors
D000998:Antiviral Agents; D016207:Cytokines; D016898:Interferon-alpha; D012254:Ribavirin