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Hepatitis C (HCV) (Pathogenesis (T-Cell Response (Suggests these people…
Hepatitis C (HCV)
General
Discovered 1989
Flavivirus
+ssRNA
Most common cause of Non-A-non-B Hep
Risk Factors
Alcohol Consumption
Sex
Being male has an increased progression
For end stage liver disease
Age at infection
40yrs
Transmission
IV Drug use (60%)
Sexual (15%)
Transfusion, pre screening (10%)
Virus discovery lead to screening and diagnostics
Haemophilia
Had greatest prevelance of HCV
Next IV drug users
Clinical Features
Incubation Period
Average 6-7 weeks
Range 2-26 weeks
Acute Illness (Jaundice)
Mild <20%
Acute case fatality rate
Low
Chronic Infection
60-85%
CLD Mortality
1-5%
Serological Time Course
Recovery
Symptoms correspond with peak viremia and ALT
Anti-HCV antibodies are enough to clear infection and persist
Chronic
Anti-HCV
Doesn't clear infection
Persisting ALT at fluctuating low levels
Bouts of viremia
Control
UK
Mostly increasing awreness
Increase testing of risk groups
Heavily underdiagnosed
Risk avoidance
Therapies
PEG-IFNa and Ribavirin
48 weeks
Aim - reduce viral load
Look for Sustained Virologic Load (SVR)
No detectable viremia after 24 weeks then 'cure'
Not used anymore
Bad side effects
Antivirals
Targets are virus enzymes
Telaprevir/Boceprevir
Target NS3/4A protease
VERY effective
Can be very expensive for a treatment course
Given if no change in 6 months after acute diagnosis
Given as combination therapy
Mir-122
Essential for replication
miRNA
Why HCV has to replicate in liver cells
Though involved in
normal
liver function
Hard to target
Main problems are
resistance
Geneotypes/Epidemiology
Highest prevalence of infection
Africa
SE Asia
Genotype
Though Africa Type IV majority
Majority infected with type I
130-150mill Persons with chronic infection
It's a growing problem
Increase in CLD
Pathogenesis
Immune disruption of liver cells
Routinely establishes chronic infection
T-Cell Response
Patients selected with HLA-A2 so only responsive to specific peptide
T-cell response stronger in those who cleared the infection than chronic
Suggests these people better adapted
Didn't find why
Shows that even acute stage of infection is different
Same Isolate Variability
Cohort of (-)Rh women
Same isolate as got from same infected blood
Older
Even though same isolate got a wide variety of outcomes
e.g. HCV -ve, Chronic infection and HCV +ve no infection
Therefore must be some host genetic factor
HLA
Some HLA are predictive of clearance
A*03 antigen
Some are predictive of chronic infection
B*27 antigen
Human Leukocyte Antigen
Has a high mortality rate :smiley:
Therapy and Host Genotype
rs12979860
SNIP(s)
Look at sequence variation
At this NT position can have T/C, T/T & C/C
In all ethnic groups C/C was most responsive to therapy and more likely to spontaneously cure infection
Lies in between two IFN genes
Not causeative
T/T has greater IFN expression levels
Also most common in africa
C/C most common in SE Asia
May be brought about by selective pressures