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Hepatitis C Update
September 2015
Amy C. Smith, FNP
Hepatitis C
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Identified 1989
Testing available 1992
Non-A, Non-B
Blood-borne infection
No vaccine available
Leading cause of liver transplant
Hepatitis C
• According to CDC
– New infections: 21,870/ year
– Chronic infections: 2.7 – 3.9 M
• Does not include prisoners, homeless, institutionalized
– Annual deaths: 15,000
• In 2007, HCV deaths > HIV deaths
• Prevalence
– US:
3-5 M
– Worldwide: 170 M
Epidemiology
• VERY high rate with IV illicit drug use
– 60% all new infections
– Single largest risk category
• High rate in correctional institutions
– 31% + (2000)
• Incarceration + IV drug use EXTREMELY high
– Up to 91% in one state facility tested
– General assumption is ~ 80%
Epidemiology
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ther risks:
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Blood products and transplants before 1992
Multiple sexual partners (? 4+)
Intranasal drug use
“Unclean” body piercing or tattoos
O
ccupational exposure
Dialysis
Tattooing/piercings
Low socioeconomic level
ETOH
??? Many unknown source
Epidemiology
• VERY low risk:
– Mother to fetus
– Non-sexual household contact
• Razors, toothbrushes, clippers
– Sexual transmission in monogamous relationship
Epidemiology
• NOT SPREAD BY:
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Sneezing
Coughing
Food/water
Sharing utensils or drink
Handshake or holding hands
Hugging
Kissing
Playing
Donating blood
O
verview
• HCV
– Acute
• Self-limited
• Rare hepatic failure
• Typically leads to chronic infection
– 20% clear spontaneously: + HVC Ab, - HCV RNA (PCR)
– Chronic
• Progressive course over many years
• Can result in cirrhosis and HCC
• Can result in need for transplant
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verview
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• Fibrosis seems to be more rapid with:
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Duration of infection
O
lder age at exposure
Male
Co-infection with Hep B or HIV
Heavy ETOH use
O
ngoing drug use
O
besity
Cigarette and marijuana smoking
• Fibrosis --> Cirrhosis
– Compensated: extensive scarring but liver still works fairly well
– Decompensated: very extensive scarring and liver function is
compromised
• Portal HTN, Ascites, Varices, Encephalopathy, Coagulopathy
O
verview
• Cirrhosis:
– 3% to 5% will develop Hepatocellular Carcinoma
(HCC)
– Incidence of HCV decreasing, but number of
cirrhotics and ESLD increasing
– Expected to peak 2020 - 2030
– Many will need transplant
• Cost of transplant: $577,100
• Cost of annual anti-rejection meds: $30,000
Symptoms
• Many have NOsymptoms
• Non-specific, mild, intermittent
– Fatigue
– Headache
– Insomnia
– Dark Urine
– Joint pain
– Pruritus
– Jaundice
Evaluation
• Who to test:
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USPSTF: everyone born 1945 – 1965
Received blood products or organ before 1992
IV drug use (evenONCE)
Chronic liver disease
HIV
Abnormal LFTs
Exposure to known HCV + blood
Hemodialysis
Mother with HCV
Diagnosis
• Check HCV Ab
– If positive, confirm with HCV RNA (PCR)
• Genotype:
– 7 different genotypes
– In US, 70% are genotype 1
• 29% genotype 2 or 3
• Subtypes
• Immigrants
• Liver biopsy
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Gold standard for assessing fibrosis
>Stage 3, easier to get treatment
Risks
O
ptions of noninvasive “biopsy”
• Fibroscan, Fibrosure, Fibrospect, Hepascore
• Limitations
Diagnosis
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CBC
CMP
TSH
Hep A and B panel
– Acute panel does not tell immunity status
– HAV IgM Ab, HBV sAg, HBV core IgM, HCV Ab
– Must add HAV IgG, HBV sAb, HBV core Ab total
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HIV
AFP
PT/INR
Iron, ferritin
US
Diagnosis
• O
nce confirmed, then check HCV RNA
Quantitative and Genotype
– Gives specific genotype and viral load to direct
treatment
Management
• AASLD and IDSA joint guidelines (2014)
• www.hcvguidelines.org
• Treatment:
– Direct Antiviral therapy (cornerstone)
– Psychological counseling
– Symptom management
– Dose adjustment of medications
– Assessment of fibrosis
– Screening for cirrhosis/complications
Management
• If no antibodies for Hep A and B, should get
vaccinated
• Screening for depression at diagnosis and
subsequent visits
• Support group
• Fatigue
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Cause uncertain
? From liver disease vs depression/other
Improves with SVR
?? Zofran
Management
• Counseling
– Routes of HCV transmission
– Risk of infecting household contacts
– Lifestyle factors that promote hepatic fibrosis
Management
• Dose Adjustment of Medications
– Try to avoid NSAIDs in advanced liver disease
– Do not need to avoid acetaminophen, but do not
exceed 2g/24 hours
– Available data FAILS to show an increased risk of
adverse effects with compensated chronic liver
disease and statins
• Safe in stable HCV
• Associated reduction in portal pressure with cirrhotics
Management
• Screening
– Cirrhotic:
• Esophageal varices
– EGD
• Hepatocellular Carcinoma
– U/S, AFP tumor marker
Goal of Antiviral Therpay
• Eradicate HCV RNA (SVR)
• SVR = cure of the HCV infection
• Decrease:
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All-cause mortality
Liver-related death
Need for liver transplant
HCC rates
Liver-related complications
• Including those with advanced liver fibrosis
– Reduce transmission
• ULTIMATE GOAL: achieve undetectalbe HCV RNA level
– SVR at 12 or 24 weeks post-treatment completeion
– Longterm clearance 99%
– SVR: virologic cure
Antiviral Therapy
• Direct acting antivirals has changed the face of
treatment and who we should treat
– Vast majority of patients are candidates
– Special consideration:
• Chronic kidney disease
• Liver transplant
• HCC
• Highly effective (98-100% SVR)
• All-oral regimens
– Interferon-free
– Also Ribavirin-free in some cases
Antiviral Therapy
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$$$$
Media attention in the US
$95,000 (8 weeks) to $145,000 (12 weeks)
Even at high introductory cost, they are costeffective
• Superior efficacy: 98-100%
• Does limit access for some
Antiviral Therapy
• Treatment selection based on GENOTYPE
– Genotype 1
– Genotype 2 and 3
– Genotype 4, 5, 6, 7
Antiviral Therapy
• Two main new drugs for Genotype 1
– Harvoni (Sofosbuvir/Ledipasvir)
– Viekira Pak (Ombitasvir/paritaprevir/ritonavir +
dasabuvir)
• In combination with Ribavirin
Harvoni
• Adverse Events
– > 10%: headache, fatigue
– > 5%: nausea, diarrhea, insomnia
• Drug Interactions
– Contraindication: Rifampin, St. John’s Wort
– PPI, H2-blockers, antacids: can alter absorption
(dose separately)
Harvoni
• Treatment-naïve, no cirrhosis, viral load < 6M:
8 weeks (97% clearance)
• Treatment-naïve, with or without cirhosis,
viral load > 6 M: 12 weeks (99% clearance)
• Treatment-experienced, without cirrhosis: 12
weeks (99% clearance)
• Treatment-experienced, with cirrhosis: 24
weeks (100% clearance)
Harvoni
• Price
– 8 weeks:
– 12 weeks:
$63,000
$94,500
• Highlights:
–O
ne pill once daily
– With or without food
– No Indication for ESRD
– ? Genotype 4
Viekira Pak
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Competition for Harvoni
As effective as Harvoni
A little cheaper: 12 weeks for $88,000
3 pills in AM, 1 pill in PM PLUS weight-based
Ribavirin (usually 2 pills twice daily)
• Must be taken with food
• Ribavirin has increased drug interactions and
must monitor labs closely (every 2-4 weeks)
– CBC, CMP, TSH, INR
Viekira Pak
• Genotype 1a:
– Without cirrhosis: 12 weeks
– With cirrhosis: 24 weeks
• Genotype 1b:
– Without cirrhosis: (NO RIBA) 12 weeks
– With cirrhosis: 24 weeks
Who Should Be Treated?
• My theory: almost everyone
– Exceptions: ESRD, ongoing drug and/or ETOH abuse
• Insurance company’s theory: almost noone
– Want stage F3-F4 fibrosis (cirrhosis) before approval
– Exclusion clauses
– Numerous appeals and denials
• AASLD highest priority:
– Advanced fibrosis, compensated cirrhosis, pre- and
post-transplant, Severe extra-hepatic complications
Who Should Be Treated?
• If 2 appeal failures with insurance, Gilead
(Harvoni) will pay for treatment
• Similar program for Viekira
• GREAT options for uninsured through the
pharm companies
Resources
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AASLD Guidelines
Hcvguidelines.org
UptoDate
CDC