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Interferon
Natural Interferons
Interferon Basics
Interferons play an important role in the first line of defense against viral infections
Interferons are part of the non-specific immune system Interferons are made by cells in response to an appropriate stimulus
Types on Interferon
alpha (leukocyte interferon)
produced by virus infected leukocytes
Mechanisms of Action
IFN alpha and beta
induction of inhibitory protein synthesis
IFN gamma
inc class II MHC molecules of APC Inc ability of macrophages to resist viral infx and kill other cells if infected
All IFN
inc class I MHC molecules inc activity of NK cells
beta
Multiple Sclerosis, (Ulcerative colitis)
HCV Epidemiology
HCV is leading cause of liver disease 4 million Americans have been exposed
approx 3 million are infected
HCV infection leads to decompensated cirrhosis and hepatocellular carcinoma HCV-related cirrhosis is the most common reason for OLT in the US
NIH Consensus Development Conference Statement 2002
Distribution of HCV
Management of Hepatitis C
Consensus Statement in 2002
treatment eligible patients
IVD users, consume alcohol, comorbidities (depression, HIV coinfections)
pegylated interferon with ribiviran better than peginterferon monotherapy or standard interferon-ribivarin
HCV Infection
Interferon in Hepatitis C
Monotherapy
standard interferon 3 Million units inj tiw (Low Sustained virologic response)
Combination therapy
standard interferon with ribivarin pegylated interferon with ribivarin
Interferon in HCV
Limitations
monotherapy not very effective cumbersome dosing (TIW) multiple side effects
Flu-like symptoms Headache Nausea, vomiting, diarrhea Depression, irritability, anxiety Injection site reactions, partial alopecia Hematologic abnormalities Autoimmune disorders
Hematologic abnormalities
neutropenia and thrombocytopenia
treatment options include decreasing dose or giving hematopoietic growth factors
Pegylated Interferon
HCV is an ideal setting for peginterferon
polyethylene glycol (PEG):interferon
P=<0.001
Differences in PEG
peginterferon alfa-2b
linear molecule weight 12 kDa
peginterferon alfa-2a
larger, branched molecule weight 40 kDa
Peginterferon
Peg alfa-2a 8L 50 80
20 L 4.6 40
alfa 2a
fixed dose at 180 mcg/week low volume of distribution
Conclusions
Interferons are important in the nonspecific immune response Interferons are effective in the treatment of patients with chronic hepatitis Pegylated interferons are superior therapies for patients with HCV Side effects should be monitored closely