Alan Franciscus

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HCV Training Workshop

• Alan Franciscus
• Executive Director, Hepatitis C Support Project
• Join us on Twitter Facebook HCVAdvocate
• BLOG hcvadvocate.blogspot.com/

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People Who Make a Difference

• Irina Gavrilova
• Christine M. Kukka
• Clara Maltras
• Kate Frye
• Patrick Daniel

• C.D. Mazoff
• Lucinda Porter
• Rose Christensen
• Liz Highleyman
• Leslie Hoex

www.hcvadvocate.org
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www.hcvadvocate.org
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Numbers

• Website average
• Average 550,000 hits/week
• Educational Materials 600,000 pieces
• Not counting website downloads
• Fact Sheets 400-500 downloads weekly

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Legend Completed
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Legend Completed Planned
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Effect on HCV Community

• HCSP Educators more than 11,000
• 50 people
• In one year outcome is 550,000 people
• Ultimate goal
• Improved education, support and services

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The Liver
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THE LIVER

• About 3 lbs (men) size of a football
• Located in the upper right side beneath the rib
  cage
• 1.5 quarts of blood flow through it every minute
• Chemical factory gt 500 functions
• Bile regulates hormones immune system cells

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Liver Functions - continued

• Sugar fat metabolism Nutrient storage
• Stores some vitamins minerals
• Fat soluble vitamins A, D, E, K
• Minerals copper iron
• Clotting factors makes proteins to help the
  blood clot
• Filters breathed in the air, absorbed through
  the skin and taken by mouth
• Regeneratesgrows or shrinks

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Healthy People

• Healthy peopleno more than
• 2 alcoholic drinks a day for men 1 alcoholic
  drink a day for women
• HCV NO ALCOHOL
• Be cautious about mixing drugs especially with
  alcohol
• Acetaminophen (Tylenol) 600 products
• Over 56,000 emergency room visits 500 deaths a
  year
• NSAIDs
• 16,500 annual deaths
• Eat a healthy, balanced diet
• www.choosemyplate.gov

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HEPATITIS

• Means
• Inflammation of the liver
• Causes
• Viruses, toxins, genetic disorders, bacteria and
  parasites

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Hepatitis A (HAV)

• USNew infections 17,000 (US 2012)
• 180, 000 in 1997
• Vaccine available since 1995 2 doses (0 6
  months)
• Estimated 33 have been infected with HAV
• Resolves (not chronic)
• Transmission fecal/oral

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HEPATITIS B (HBV)

• US 38,000 new infections (CDC 2012)
• Vaccine available since 1982 3 doses (0, 1, 6
  months)
• US chronic 1.2 Million
• Worldwide 350-400 million
• US 3,000 deaths a year
• Worldwide 660,000 annual deaths

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HBV Transmission

• Blood borne can live outside the body for at
  least 7 days
• Highly infectious in semen and vaginal secretions
  50 - sexual transmission
• Sharing needles to inject drugs
• Needle stick and blood exposure accidents
• Sharing personal items
• Mother-to-child transmission

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HBV Prevention

• Get vaccinated
• Do not share needles or works
• Safer sex
• Standard safety precautions
• Do not share personal items
• HBV-infected mother-to-child intervention

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Chronic HBV
Chronic 5-6 Adults 90 Infants
These drugs are recommended as first line of
treatment
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HCV Transmission / Prevention
Hepatitis C is Spread by Blood-to-Blood Contact
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HCV Survival

• The hepatitis C virus lives for at least 16 hours
  but no longer than 4 days outside the body
• In syringes up to 63 days
• Commercially available Disinfects Kill HCV
• Collected shared Swabs 83 tested positive
  for HCV
• HCV detected in used water for greater than 3
  weeks
• In bottles HCV RNA detected even after rinsing
  out plastic and aluminum retained HCV RNA
  longer
• 10 of filters wrapped in foil had HCV RNA after
  24 and 48 hours

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Transmission/Prevention

• Sharing needles and drug preparation tools
• Blood products solid organ transplantation
  before 1992
• Clotting factors before inactivation in 1987
• Sexual transmission (0-3)
• Mother-to-child (4-5)
• Healthcare workers (2)
• Hemodialysis

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Possible Transmission Routes

• Tattoo piercing
• Personal care salons
• Shared household (hygiene) items
• Coke/crank straws crack pipes
• 10 of routes can not be identified
• Higher in unsafe non-commercial settings
  prisons/mental institutions/on the streets/home
  grown

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Safer Tattoos www.hepatitistattoos.org
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Little or no data.

• Dental and other procedures before universal
  precautions
• Jet gun injections
• Transgender people
• Sharing needles and re-assignment surgeries

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HCV is Not Spread by

• Breast feeding
• Food or water
• Sharing eating utensils or drinking glasses
• Sneezing
• Hugging
• Not spread by casual contact

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Prevention

• Do not share anything Needles, cookers, cotton,
  tourniquets, water, water containers, etc. Wash
  hands

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Prevention - more

• Do not share non-injection drug equipment
• Coke/crank straws
• Crack pipes
• Tattoo / Piercing
• Sterilization, autoclave, separate ink pot, new
  needles

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Prevention - more

• Sexual 0-3 monogamous partners counsel
• Safer sex additional risk through sex
• Multiple partners
• Coinfection with HIV or HBV
• Having herpes, lesions, sores, open cuts, wounds
• Sexually transmitted diseases
• Mother-to-child

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More Prevention

• Health care workers
• blood borne pathogen protection
• Razors / toothbrushes covered
• Cover all wounds
• Transfusions estimated that less than one per 2
  million transfused units of blood tainted with
  HCV
• People with HCV Do not donate blood, sperm,
  eggs or organs EXCEPTIONS..

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HCV Diagnostic Tools

• Hcv Identified in 1989

Important Interpretation of test results and
decisions about healthcare are a collaboration
between a medical provider and a patient
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HCV Diagnostic Tools

• Hcv Identified in 1989

Important Interpretation of test results and
decisions about healthcare are a collaboration
between a medical provider and a patient
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Lifecycle

• Single stranded RNA virus
• Mainly infects liver cellsbut also found in
  other cells of the body
• Cell Culture discovered and available

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Baby Boomers Account for the Majority of HCV
Cases in United States
Estimated Prevalence by Age Group
1.6
Number With Chronic HCV Infection (millions)
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
1990
1980s
lt1920
1970s
1920s
1950s
1940s
1960s
1930s
Birth Year Group
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Increased Diagnosis and Treatment
The Tipping Point?
OraQuick HCV Antibody Test
New Antivirals
Aged-Based Testing
Templates

• Finger Prick
• Whole Blood Draw
• Oral Swab
• Results available within 20 minutes
• More testing within clinics and mobile sites can
  lead to increased consultations about care,
  management and treatment

• New HCV Treatments
• New Therapies 80
• Higher cure rates will mean more treatment naïve
  and prior non-responders will seek treatment
• Interferon-free therapies will mean more people
  will be treated in the future

• The Centers for Disease Control has recommended a
  one-time test for persons born between 1945 and
  1965

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HCV Antibody Tests

• HCV Elisa III (EIA), CIA Detects antibodies
• Signal to cut off ratio 95 chance true
  antibody positive
• Home Access test kit
• Window period 2-26 weeks

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OraQuick HCV Rapid Antibody Test

• FingerPrick whole blood
• FDA and CLIA Waiver approved 2011
• Oral swab Pending fda and clia approval 2013?

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HCV RNA Viral Load

• PCR (polymerase chain reaction) lowest range
• TMA (transcription mediated amplification)
  lowest range
• DNA (bDNA) assay highest range
• Amount of virus per milliliter of blood
• International units
• Low less than 800,000 IU/mL
• High more than 800,000 IU/mL

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How is Viral Load Used?

• Confirm active infection
• Soft predictor of treatment response
• Confirm HCV medications are working and dictate
  treatment duration
• Does Not Correlate with Disease Progression

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Genotype Quasi-species

• Six major genotypes (plus sub-types)
• Genotypes numbered 1, 2, 3, 4, 5, 6, (1a, 1b,
  etc.)
• Genotype 1 70 of US population with HCV
• Genotypes 2, 3 30 of US population with HCV
• Quasi-species
• High error prone virus mutates quickly

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Liver Tests

• ALT a non-specific marker of liver inflammation
• Not a good test to monitor people with HCV
• AST, AP, GGT, bilirubin, platelet, prothrombin
  time (PT)

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Liver Biopsy

• Measures liver health
• Treatment decisions
• Benchmark

Metavir Scoring System 0, 1, 2, 3, 4 No
activity Severe activity
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HCV Symptoms, Disease Progression Management

• Living with hcv is often easy, often difficult
  and sometimes impossible
• Peter Mare Latham

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Future Disease Burden

• Institute of Medicine (IOM) Report 2010
• Milliman Report Annual cost of advanced liver
  disease to 85 billion in the next two decades
  and Medicare costs will increase 500, from 5
  billion to 30 billion
• Aging of the Hepatitis C Virus-Infected
  Persons in the United States A Multiple Cohort
  Model of HCV Prevalence and Disease Progression
  Progression to cirrhosis will peak at 1.0 million
  in 2020
• http//www.iom.edu/Reports/2010/Hepatitis-and-Liv
  er-Cancer-A-National-Strategy-for-Prevention-and-C
  ontrol-of-Hepatitis-B-and-C.aspx
• http//www.milliman.com/expertise/healthcare/pub
  lications/rr/pdfs/consequences-hepatitis-c-virus-R
  R05-18-09.pdf
• GL Davis and colleagues PMID 19861128
  PubMed - as supplied by publisher

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Drug Based Therapies
Social Stigma
Health Policies
Housing
Support
HCV Positive
Health Access
Mental Health
Addiction
HAV HBV Vaccine
What may be needed even before considering
treatment
CAM
Ann Shindo
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Liver Specialists

• GASTROENTEROLOGIST
• HEPATOLOGIST
• THE FUTURE?
• Primary care, infectious disease specialists and
  others

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Acute HCV

• Initial or acute infection
• Many people have no symptoms
• Flu-likefatigue, nausea, fever, indigestion,
  loss of appetite, night sweats, jaundice
• Lasts up to 6 months
• Spontaneous (natural) clearing by gender
• Women 40
• Men 19
• Treatment of acute HCVthe majority of people
  with acute HCV can clear the virus with
  interferon monotherapy

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Chronic Infection

• Longer than 6 months
• Does not mean severe disease progression
• CDC 7585 of cases become chronic
• Studies 55 to 85 become chronic
• 10 to 25 have serious disease progression over a
  10 to 40 year period disease progression is not
  linear
• Fibrosis / Cirrhosis / Steatosis

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Chronic Symptoms

• Fatigue mild to severe
• Brain Fog
• Flu-like symptoms
• Depression

• Liver pain
• Loss of appetite
• Headaches
• Gastro problems
• And more.

Symptoms dont necessarily correlate with disease
progression with the exception of end-stage liver
disease
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HCV Infection Extrahepatic Manifestations

• Hematologic
• Mixed cryoglobulinemia
• Aplastic anemia
• Thrombocytopenia
• Non-Hodgkins b-cell lymphoma

• Salivary
• Sialadenitis

• Ocular
• Corneal ulcer
• Uveitis

• Dermatologic
• Porphyria cutanea tarda
• Lichen planus
• Cutaneous necrotizing vasculitis

• Vascular
• Necrotizing vasculitis
• Polyarteritis nodosa

• Neuromuscular
• Weakness/myalgia
• Peripheral neuropathy
• Arthritis/arthralgia

• Renal
• Glomerulonephritis
• Nephrotic syndrome

• Endocrine
• Anti-thyroid antibodies
• Diabetes mellitus

• Autoimmune
• Phenomena
• CREST syndrome

Hadziyannis SJ. J Eur Acad Dermatol Venereol.
19981012-21.
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U. S. Statistics CDC

• New (acute) infections 17,000
• Total chronic infections UP TO 3.2 million
• 15,000 deaths annually
• Not factored into above Prisoners, homeless,
  people in mental institutions

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Disease Progression

• Compensatedextensive scarring, but liver is
  still working fairly well
• Decompensatedvery extensive scarring and liver
  function has become severely compromised
• Conditions
• Portal Hypertension / Ascites Edema / Varices /
  Encephalopathy
• Liver Cancer
• 3 to 5 of people with chronic HCV will develop
  liver cancer after severe fibrosis or cirrhosis
• Transplantation 250,000 to 314,000 up to
  500,000 Annual costs of medications 21,900

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Disease Management Lifestyle Changes

• Avoid alcohol
• Lowers immune response HCV treatment response
• Helps HCV to replicate and mutate
• Increases levels of iron and fat in the liver
• Avoid or reduce
• Cigarette smoking, drugs or any substance that
  can harm the liver
• Eat a healthy well balanced diet
• www.choosemyplate.gov

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Disease Management

• Hepatitis A hepatitis B vaccine
• Avoid raw undercooked shellfish
• HAV / Vibrio vulnificus
• Exercise
• Moderationbalance activity with rest

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SUPPLEMENTS

• Avoid high doses of vitamins and supplements
• General recommendations
• Vitamin supplement (daily requirements with no
  iron)
• Always check-in with a medical provider

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Discrimination Stigma

• Americans with Disabilities Actallows for
  certain protections
• Call the ADA (800-949-4232)
• Social Security Disability
• The effect of stigma

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Support Groups

• Informational emotional
• One of the few places where people with HCV can
  connect, advocate, support and learn from peers
• HCSP support group in a bag
• Support group manual on web site

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HCV Medical Treatment
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General Treatment Guidelines

• Overall health is stable
• Active hcv infection
• Compensated liver disease
• Decompensated generally only in transplant
  centers
• Some case studies with DAA combinations successful

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Pre-Treatment Predictors of Treatment Response

• Younger Age under 40 yo
• Little or no steatosis, insulin resistance
• Race
• Asian
• Caucasians
• African Americans
• Low HCV RNA (viral load)
• Little or no scarring of the liver

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Pre-Treatment Predictors of Treatment Response

• variation of Il28b Genotype 1

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Treatment Goals Success

• GOALS of treatment
• Clear virus out of the body
• Improve inflammation scarring
• Slow disease progression,
• Improve symptoms and quality of life
• To put HCV behind and move on with life
• Sustained virological response (SVR)
• HCV is undetectable during and 6 months following
  HCV medical therapy
• 5 year follow-up gt99 still HCV RNA undetectable

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Response to Therapy

• Adherence Important for overall treatment
  successmore important with new HCV protease
  inhibitors
• Rapid Virological Response (RVR) 4 week HCV RNA
  negative
• Complete Early Virologic Response (cEVR)12 week
  RNA negative
• Extended RVR (eRVR) HCV RNAnegative at week 4
  and week 12

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Treatment of Chronic HCV Genotype 2, 3

• Treatment duration 24 weeks
• Ribavirin fixed dose 800 mg/daily
• Taken with high fat food
• Currently HCV protease inhibitors are not
  approved to treat genotypes 2 and 3

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Treatment Genotypes 2 and 3Pegylated and
Ribavirin (FDA Package Insert)

• Merck /Schering PEG-Intron Rebetol
  (800-1400mg)
• Genotypes 2 thru 6 75 (48 weeks)
• One large multi-international study
• Genentech/Roche Pegasys Copegus (1000-1200
  mg)
• Genotypes 2 3 82 SVR (24 weeks)
• Genotypes 2 thru 6 70 SVR (48 weeks)
• Two large multi-international studies
• Also approved to treat compensated
  cirrhosis, HIV/HCV Coinfection, Renal (mono) and
  HBV (mono)

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Treatment of HCV Genotype 1

• Protease combination therapy is only FDA approved
  for treatment of chronic HCV genotype 1
• Treatment with an HCV protease inhibitor is only
  used in combination with pegylated interferon and
  ribavirin
• Ribavirin taken with food
• The HCV protease inhibitors are taken every 7 to
  9 hours with food
• Boceprevir light meal / Telaprevir not low fat

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Victrelis (Boceprevir)4-week lead in PEG/RBV

• treatment naïve Genotype 1
• Up to 66 SVR
• African Americans up to 53 vs. 23 SVR
• Treatment duration either 28 or 48 weeks
• Treatment Experienced Genotype 1
• Prior non-respondersup to 66 SVR (null
  responders not studied)
• Treatment duration 36 or 48 weeks

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Incivek (Telaprevir)Incivek, pegylated
interferon, ribavirin taken for 12 weeks
onlyfollowed by pegylated interferon/ribavirin

• Treatment naïve Genotype 1
• Up to 79 SVR
• African American patients 62 vs. 25 SVR
• People with cirrhosis 62 vs. 33 SVR
• Treatment Experienced genotype 1
• Up to 86 SVR depending on type of non-response
  (relapsers, non-responders, null responders)
• Treatment duration 24 or 48 weeks
• Warning on skin reactions

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Standard Protocol

• Pegylated (injected once a week)
• Ribavirin (pill or capsule oral twice a day)
  with food
• Victrelis / Incivek (pill every 7 to 9 hours)
  for genotype 1 only with food
• Treatment is guided by type of on-treatment
  response (week 4 and 12)

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Side-effects

• Interferon

• Ribavirin

• Anemia, rash, dry cough
• Black box warning
• Women of childbearing age, their partners and
  female partners of male patients taking ribavirin
  must practice two forms of contraception during
  to 6 months post-treatment
• Low red blood cells

• Physical
• fatigue, muscle/joint pain, headaches, dry skin,
  insomnia,
• Anxiety, depression, mania
• Low white blood cells
• Low platelets

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Side-effects

• Victrelis

• Incivek

• Up to 50 anemia
• Taste changes, especially metal taste

• Body rash
• Up to 36 anemia
• Anal itching
• Diarrhea

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Managing Side Effects

• Time injection
• Drink lots of water
• Low doses of ibuprofen or acetaminophen
• Pain/sleep medications
• Light exercise

• Daily moisturizing
• Vary injection sites
• Anti-depressants
• Plenty of rest
• Small frequent healthy meals

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Programs

• Patient Assistance Programs
• Partnership for Prescription Assistance
• www.pparx.org
• Needy Meds www.needymeds.org
• Genentech www.genentechaccesssolutions.com
• Merck www.merck-cares.com
• Vertex www.vrtx.com
• Kadmon http//kadmon.com/

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Drugs in Development

• Phase III StudiesDAA with PEG/RBV
• DAA combinations with and without ribavirin
  interferon-free
• BI 201335 (Faldaprevir) (protease inhibitor)
• BMS-790052 (Daclatasvir) (NS5A Inhibitor),
• GS-7977 (Sofosbuvir) (polymerase inhibitor)
• Phase II StudiesDAA Combination with RBV
• Many DAA drugs in combination with other DAAs
  and with ribavirin (no pegylated interferon)
• HCV Advocate Drug Pipeline

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Clinical Trials
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Complementary Therapies

• Herbs Herbs can interact with other medications
  and have a potential to be unsafe
• Always check-in with medical provider and use a
  reputable herbalist
• Milk Thistle the most common herb used by
  people with HCV
• May interact and increase blood levels of some
  substances
• St. Johns Wort Must avoid with Protease
  Inhibitors (PIs) (lowers PI drug levels)
• Caution
• Bupleurum should not be used by someone taking
  interferon

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Complementary Practices

• Acupuncture
• Thin needles are inserted into acupuncture points
  to stimulate the flow and balance of qi (the flow
  of vital energy)
• Acupressure
• Finger pressure stimulated flow of qi
• Traditional Chinese Medicine
• Whole body concept to restore qi balance
• Acupuncture, acupressure, tai chi, moxibustion,
  massage

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Turn In

• Participant checklist
• Plan of action
• Evaluation
• Demographic information
• Order by fax form

www.hcvadvocate.org
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NeedyMeds Drug Discount Card
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What is the NeedyMeds Drug Discount Card?

• A FREE drug discount card that can save users up
  to 80 off the cost of
• Prescription medications
• Over-the-counter medications and medical supplies
  written as a prescription
• Pet prescriptions purchased at a pharmacy

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How Does it Work?

• No activation or registration needed
• Never expires
• No residency, income or insurance guidelines.
• Accepted at over 62,000 pharmacies including all
  the major and local chains.
• Bring the card into the pharmacy along with a
  valid prescription from your doctor and save!

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Are There Insurance Guidelines?

• No insurance guidelines
• The card cannot be combined with insurance
• Those who are uninsured can use the card.
• Those that have a public (such as Medicare or
  Medicaid) or private insurance plan can use the
  card instead of their insurance if for example
• They have a medication not covered
• They are in a coverage gap, like the donut hole
• They have a high copay or deductible

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Where Do I Get One?

• You can send a self-addressed stamped envelope
  to
• NeedyMeds Drug Discount Card
• PO Box 219
• Gloucester, MA 01931
• Or go online and print a card by visiting
  http//www.needymeds.org/drugcard/drugcard.pdf

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Help for Card Users

• Visit http//drugdiscountcard.org
• Or call [phone]
• Additional Services
• Information about patient assistance programs
• List of low cost medical clinics
• Webinars to explain services

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