The Liver

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The Liver

• Largest internal organ
• Approximately 3 lbs (men)
• Size of a football
• 1.5 quarts of blood flow through it every minute

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Liver Functions

• Bile
• Immune System
• Chemical Factory-
• gt500 chemical functions

• Detoxifies
• Clotting Factors
• Hormones

Regenerates Itself!
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Keep Your Liver Healthy (Healthy People)

• No more than 2 alcoholic drinks daily
• Be cautious about mixing drugs especially with
  alcohol
• Healthy, balanced diet
• Get HAV HBV vaccinations
• Avoid toxic substances / fumes

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Some Statistics

• 3 of world has HCV (150-200 million)
• 4 Million in U.S. infected with HCV
• 10,000 in U.S. die of complications from HCV in
  10 years will triple
• HCV is the leading cause for liver transplants
• 55-80 of HCV infected become chronic

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More Statistics

• U.S. Population
• 1.8 overall
• 2.1 Mexican-Americans
• 3.4 African Americans

• California
• 500,000 infected with HCV
• 85-95 - IDUs
• Prisons 63,500 inmates infected or (41)

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What Does It Mean?

• Only 10-30 progress on to serious liver disease
• Treatment options do work for some

• Better treatment options within 5 years
• Lifestyle changes can make a big difference

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Some HCV History

• 1948 blood samples stored since 1948
  contain HCV antibodies, earliest
  known
• 1970s many cases reported called non-A,
  non-B hepatitis
• 1988 hepatitis C virus identified
• 1990 antibody screening tests available
• 1992 better tests to insure safety of blood
  supply

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Lifecycle

• Incubation period
• 2-25 weeks - average 7-9 weeks
• Virus enter the body
• Binds enters cell (usually liver receptor)
• Virus loses lipid coat and polyprotein envelop
  freeing RNA
• Enzymes in the cell make large viral protein to
  help make new viral RNA
• Virus releases new virus into blood and
  eventually kills host cell
• Replication - gt 1 trillion per day

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Lifecycle (cont)

• 20-45 of acute case resolve
• 55-80 of acute cases become chronic
• Chronic cases may progress on to serious liver
  disease or remain stable

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Dialogistic Tools

• Elisa II / Riba Test for anti-body
• Hepatitis C RNA by PCR - gt50 particles
• Hep C RNA by branched DNA Assay gt200,000
  particles
• Genotype (six major subtypes 72 of U.S.
  population have genotype 1)
• Liver Biopsy

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Transmission / Prevention
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Harm Reduction

• Prevention
• Needle exchange clean needles and drug
  preparation tools cookers cottons
• Bleach Does it work?
• 101
• Cover wounds

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HCV CAN NOT BE SPREAD BY

• BREAST FEEDING
• SNEEZING
• HUGGING
• COUGHING

• FOOD OR WATER
• SHARINING EATING UTENSILS OR DRINKING GLASSES
• CASUAL CONTACT

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Symptoms

• Acute vs. Chronic
• Fatigue mild to severe
• Flu-like symptoms (muscle/joint/fever)
• Brain Fog

• Liver Pain
• Loss of appetite
• Headaches
• Gastro Problems

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Conditions Linked to HCV

• Arthritis
• Autoimmune hepatitis
• Sjogrens Syndrome
• Cryoglobulinemia
• Kidney disease
• Liver Cancer

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QUALITY OF LIFE

• Patients with chronic hepatitis C have a
  significantly reduced quality of life compared to
  those with HIV.
• Patients with HIV/HCV co-infection quality of
  life is not worse than patients with HCV alone
• Edmund J Bini, New York AASLD 2000

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Treatment Medications

• Interferon by injection - first FDA approved
  treatment (3 mu, thrice weekly for 48 weeks)
• Genotype 1 - 9 SVR
• Genotype other than 1 30 SVR

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Interferon and Ribavirin

• Interferon and ribavirin(capsule)- combo
  therapy
• INF 3 mu units, thrice weekly - Ribavirin
  800-1200 mg daily
• Overall SVR up to 45
• Genotype 1 12 mos 29 SVR
• Genotype Non 1 6 mos - 62 SVR

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Pegylated Interferon

• Schering- PEG-Intron
• Approved by FDA 1-2001
• 24 sustained response rate
• ROCHE Pegasys FDA approval expected 4-2001
• 39 sustained response rate

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Pegylated and Ribavirin

• Schering PEG-Intron plus ribavirin
• Phase III clinical data 54 sustained response
  rates
• Roche Pegasys plus ribavirin
• Phase II clinical data 70 end of treatment
  response rate
• 4-2001 report sustained response rates

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Treatment Decisions

• General Treatment Guidelines
• Healthy
• Active HCV
• Elevated ALTs
• Compensated liver disease

• Optimal Response
• Younger
• Female
• Low viral load
• Minimal liver damage
• Genotype other than 1

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Pre-Treatment Tests

• Complete Blood Count
• Liver panel
• Thyroid function test (TSH,T4)
• Pregnancy Tests
• Autoimmune tests
• Rule out heart, lung, eye or any serious
  disease

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Side-effects

• Interferon
• Fatigue
• Muscle/Joint pain
• Nausea
• Headaches
• Anxiety
• Depression
• Dry Skin/rashes

• Ribavirin
• seems to make interferon side effects worse
  especially fatigue-Anemia
• (both men women must use birth control)

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Managing Side-Effects

• Inject before bedtime
• Drink lots of water
• Low doses of ibuprofen or acetaminophen
• Pain medications

• Light exercise
• Daily moisturizing
• Vary injection sites
• Anti-Depressants
• Plenty of rest
• Frequent small meals

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Monitoring Therapy Potential Problems

• Neutropenia (low white blood cells)
• Thrombocytopenia (low platelets)
• Neumega approved for chemotherapy
• Anemia
• Procrit

• Thyroid disease
• Depression / anxiety
• Treat with anti-depressants / anti-anxiety drugs
• General Health

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Response to Therapy

• Decrease (2 log drop) or elimination of virus at
  week 12 is predictive of sustained virologic
  response
• Histological response
• Stop Therapy?

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Experimental Therapies

• Amantadine - pill
• Maxamine by injection (phase II studies)
• Ribozymes
• Helicase Inhibitors
• Protease Inhibitors
• Interleukin-10

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Clinical Trials

• Phase I safety tolerability in (healthy
  subjects)
• Phase II- measures drug efficiency /
  effectiveness
• Phase III comparing the new drug to standard
  treatment
• Phase IV refine the treatment for maximum
  effectiveness

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Benefits of Clinical Trials

• Pharmaceutical may pick up some or all costs of
  medications, visits, tests
• Opportunities to try new medications
• Usually support is good monitoring and access
  to clinical nurse

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Disadvantages of Clinical Trials

• Guinea pig
• May not get optimal medication or dose
• May withhold information medicine or test
  results
• Important know your rights!
• Can never be forced to stay in study

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Complementary Medicine

• Herbs milk thistle
• Always check with your doctor and herbalist
  some herbs are TOXIC
• Acupuncture / Acupressure
• Traditional Chinese Medicine

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Lifestyle Changes That Help!

• Alcohol - Avoid
• Get vaccinated Hep A Hep B
• Healthy balanced diet

• Exercise
• Stress Reduction
• Support Groups

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Advocate for Yourself!

• Educate yourself
• Establish a good relationship with your doctor
• Bring an advocate for doctors visits

• Ask questions
• Keep copies of all medical tests
• Keep a diary
• Keep an open mind