Download Hepatitis C in Pregnancy

Hepatitis C
What’s New
Alan Kilby, M.D.
Portland Gastroenterology Center
Maine Medical Center VTC
Sept 27, 2013
Disclosures
Maine Medical Ctr VTC Funding
Schering, Merck, Vertex
Experimental Drugs Discussed
Sofosbuvir, Simeprevir, Ledipasvir
This talk is not FDA approved
Hepatitis C
What’s New
1. Test baby boomers (1945-65)
2. Exciting new treatments
2014? Sofosbuvir, Simeprevir
2015? One pill a day possible
3. Fibroscan-liver fibrosis test
4. ECHO-Telemedicine Project
Test Baby Boomers
Birth Cohort 1945-1965:
Prevalence of hep C=3.5%
Infected in 1960’s thru 1980’s
75% of hep C cases, 2-3 million
Only 45% report a risk factor
At least 45% unaware; often think
they are tested with routine labs
Even with risk factors, test rate low
Antiviral treatment rates are very low
Test Baby Boomers
75% Hep C Deaths: Baby Boomers
Liver Failure and Liver Cancer
Median Age of Death is 57 years
After 20 years of infection:
20% Cirrhosis, 5% Liver mortality
Cirrhosis, Liver cancers, deaths
increase with each decade
Test Baby Boomers
CDC has Patient Information Sheet
Recommended testing:
1. HCV antibody
2. Positive HCV antibody triggers
HCV RNA testing.
3. I strongly encourage reflex HCV
RNA testing on same sample
Test Baby Boomers
HCV RNA positive patients
Alcohol counseling
Hepatitis A and B vaccination
I recommend CBC, CMP, INR,
Ultrasound of Abdomen, HCV
Genotype, HBsAg, HIV Ab
Evaluation for HCV treatment
Test Baby Boomers
Benefits of Rx with SVR(Cure)
1. Liver decompensation greatly
reduced
2. Liver Cancer risk reduced
3. Study of 16,000 US Veterans
demonstrated 55% reduction in all
cause mortality
Hepatitis C
What’s New
2. Exciting new treatments
2014? Sofosbuvir, Simeprevir
2015? One pill a day possible
Genotype and Viral Load in US
Patients
Genotype 4,5,6
High Viral Load 2.7%
Genotype 4,5,6
1.3% Low Viral Load
Genotype 2,3
Low Viral Load 7.3%
14.7%
Genotype
2,3 HVL
Genotype 1
LVL
24.5%
Alter et al. N Engl J Med. 1999;341;556-562.
Blatt et al. J Viral Hepatitis. 2000;7:196-202.
Genotype 1
HVL
49.5%
Sustained Viral Response:
Before 2011
• Peg-Interferon Weekly + Ribavirin Daily
Genotype 1
SVR=40%
48 week treatment
Wt-based ribavirin
Genotypes 2,3
24 week treatment
Low dose ribavirin (800 mg)
SVR=80%
Side Effects of Interferon
• Flu-like symptoms
–
–
–
–
Headache
Fatigue or asthenia
Myalgia, arthralgia
Fever, chills
• Neuropsychiatric
disorders
– Depression
– Mood lability
•
•
•
•
•
•
Alopecia
Thyroiditis
Nausea
Diarrhea
Injection-site reaction
Lab alterations
– Neutropenia
– Anemia
– Thrombocytopenia
Side Effects of Ribavirin
• Hemolytic anemia
• Teratogenicity
• Cough and dyspnea
• Rash and pruritus
• Insomnia
• Anorexia
COPEGUS™ (ribavirin, USP) [package insert]. Nutley, NJ: Hoffmann-La Roche; 2002.
Hepatitis C
Treatment Since 2011
Direct-Acting Antivirals
Protease Inhibitors
Boceprevir (Victrelis)
Telaprevir (Incivek)
Triple TherapyPEG-Interferon/Ribavirin/Protease
Inhibitor for genotype 1, 24-48
weeks
SVR for Genotype 1: 65-75%
Hepatitis C
Treatment Since 2011
Problems with Telaprevir/Boceprevir
1. New side effects-Rash
(Telaprevir), diarrhea,
nausea; increased
anemia
2. Poor tolerance in cirrhotics
3. Drug Interactions
(Cytochrome system):
Hormonal contraceptives,
Hepatitis C
Treatment Since 2011
Problems with Telaprevir/Boceprevir
triple therapy
Limited to genotype 1
3x per day dosing, 6-12 pills
Low barrier to drug resistance
Poor efficacy: Cirrhotics, prior
non-responders, genotype 1a,
IL28B genotype CT and TT
Hepatitis C
Treatment: The Future
HCV Life Cycle Video
Hepatitis C
Treatment: The Future
Sofosbuvir-Nucleotide HCV
polymerase (NS5B) inhibitor
Once a day dosing
All genotypes treated
Minimal side effects/drug
interactions
Drug resistance not observed
Hepatitis C
Treatment: 2014
Likely FDA Approvals
Sofosbuvir + Ribavirin: 1st
Interferon-free treatment available
Geno 2, 12 weeks, SVR 97%
Geno 3, 12 weeks, SVR 56%
G3 does better with 16 weeks
Cirrhosis-better with 16 weeks
Hepatitis C
Treatment: 2014
Likely FDA Approvals
12 wks Sofosbuvir/Riba/PEG-IFN
Geno 1, 4, 5, 6 SVR 90%
Cirrhosis 80%
Hepatitis C
Treatment: 2014
Likely FDA Approvals
Simeprevir-once-a-day protease
inhibitor
Simeprevir given for 1st 12 weeks
PEG-IFN/Ribavirin started with
simeprevir and given for 24 or 48
wks
Genotype 1 SVR 83-85%
Hepatitis C
Treatment: 2015
Drugs from 2+ classes, as in HIV
Increases efficacy and minimizes
resistance
One Example (Many under study)
NS5b and NS5a inhibitor
Sofosbuvir + Ledipasvir; one pill a
day; ?available 2015
Hepatitis C
What’s New
Fibroscan- A non-invasive liver
fibrosis test
FDA approved
FibroScan-Non-invasive test
of liver fibrosis
The probe induces an
elastic wave through
the liver
The velocity of the ultrasonic shear wave is
a measure of elasticity (fibrosis)
2.5 cm
Explored volume
1 cm 
4 cm
FibroScan-Non-invasive
test of liver fibrosis
Good accuracy in detecting cirrhosis
Combined with clinical, lab, imaging
results: Will likely replace liver
biopsy in detection of cirrhosis
Cirrhotics require additional
monitoring
Cirrhosis: Preventive
Measures
No Alcohol
Vaccines: Pneumonia, Flu,
Hepatitis A and B
Screen for Esophageal Varices
Screen for Liver Cancer
Hepatitis C
What’s New
ECHO-Telemedicine Project
ECHO-Telemedicine Project
Central site: Education/support
Remote sites: Treat patients
Come online together: Didactic
session + Case Presentations
Goal: Increase treatment at the local
level, especially in remote areas
Coming to Maine!
Dr. Kilby wants
One pill a day treatment for PCP.
Treats all patients regardless of
genotype, severity of liver disease,
presence of co-morbidities.
Requires minimal monitoring and
has few side effects, drug
interactions or drug resistance.
Non-invasive testing for cirrhosis