Viral Hepatitis A to C

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Viral HepatitisA to C
Patrick Lynch, MD Gastroenterology Elmhurst
Clinic Clinical Affiliate Hepatology Northwestern
University
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Viral Hepatitis - Overview

Type of Hepatitis
A
B
C
D
E
Source of
feces
blood/
blood/
blood/
feces
virus
blood-derived
blood-derived
blood-derived
body fluids
body fluids
body fluids
Route of
fecal-oral
percutaneous
percutaneous
percutaneous
fecal-oral
transmission
permucosal
permucosal
permucosal
Chronic
no
yes
yes
yes
no
infection
Prevention
pre/post-
pre/post-
blood donor
pre/post-
ensure safe
exposure
exposure
screening
exposure
drinking
immunization
immunization
risk behavior
immunization
water
modification
risk behavior
modification
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Acute Viral Hepatitis by Type, United States,
1982-1993
34
47
16
Hepatitis A
Hepatitis B
Hepatitis C
3
Hepatitis Non-ABC
Source CDC Sentinel Counties Study on Viral
Hepatitis
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Hepatitis A - Clinical Features

• Incubation period Average 30 days
• Range 15-50 days
• Jaundice by lt6 yrs, lt10age
  group 6-14 yrs, 40-50 gt14 yrs,
  70-80
• Complications Fulminant hepatitis Chole
  static hepatitis Relapsing hepatitis
• Chronic sequelae None

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Hepatitis A Virus Infection
Typical Serologic Course
Symptoms
Total anti-HAV
ALT
Titer
Fecal HAV
IgM anti-HAV
0
1
2
3
4
5
6
12
24
Months after Exposure
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Hepatitis A Virus Transmission

• Close personal contact(e.g., household contact,
  sex contact, child day care centers)
• Contaminated food, water(e.g., infected food
  handlers, raw shellfish)
• Blood exposure (rare)(e.g., injecting drug use,
  transfusion)

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Hepatitis A Vaccination Strategies Epidemiologic
Considerations

• Many cases occur in community-wide outbreaks
• no risk factor identified for most cases
• highest attack rates in 5-14 year olds
• children serve as reservoir of infection
• Persons at increased risk of infection
• travelers
• homosexual men
• injecting drug users

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Recommendations - Hepatitis A Vaccine

• Persons at increased risk for infection
• travelers to intermediate and high HAV-endemic
  countries
• homosexual and bisexual men
• drug users
• persons with chronic liver disease
• Communities with high rates of hepatitis A(e.g.,
  Alaska Natives, American Indians)
• routine childhood vaccination

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Hepatitis A Prevention - Immune Globulin

• Preexposure
• travelers to intermediate and high HAV-endemic
  regions
• Postexposure (within 14 days)
• Routine
• household and other intimate contacts
• Selected situations
• institutions (e.g., day care centers)
• common source exposure (e.g., food prepared by
  infected food handler)

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Hepatitis B - Clinical Features

• Incubation period Average 60-90 days
• Range 45-180 days
• Clinical illness (jaundice) lt5 yrs,
  lt10 ³5 yrs, 30-50
• Acute case-fatality rate 0.5-1
• Chronic infection lt5 yrs, 30-90 ³5
  yrs, 2-10
• Premature mortality fromchronic liver disease
  15-25

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Hepatitis B Infection
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Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
Acute (6 months)
Chronic (Years)
HBeAg
anti-HBe
HBsAg
Total anti-HBc
Titer
IgM anti-HBc
Years
0
4
8
12
16
20
24
28
32
36
52
Weeks after Exposure
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Elimination of Hepatitis B Virus Transmission
United States
Strategy

• Prevent perinatal HBV transmission
• Routine vaccination of all infants
• Vaccination of children in high-risk groups
• Vaccination of adolescents
• all unvaccinated children at 11-12 years of age
• high-risk adolescents at all ages
• Vaccination of adults in high-risk groups

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Hepatitis C Virus

capsid
envelope protein
protease/helicase
RNA-dependent
RNA polymerase
c22
c-100
33c
3
5
core
E1
E2
NS2
NS3
NS4
NS5
hypervariable region
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HCV Background

• 1-2 US population infected 4 million
• 4-5 more times more prevalent than HIV
• Incidence 180,000. Decreased to 30,000
• Men gt Women
• Inversely proportional to socioeconomic status

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Hepatitis C - Clinical Features

Incubation period Average 6-7
wks Range 2-26 wks Clinical illness
(jaundice) 30-40 (20-30) Chronic
hepatitis 70 Persistent infection 85-100
Immunity No protective antibody
response identified
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Risk Factors Associated with Transmission of HCV

• Transfusion or transplant from infected donor
• Injecting drug use
• Hemodialysis (yrs on treatment)
• Accidental injuries with needles/sharps
• Sexual/household exposure to anti-HCV-positive
  contact
• Multiple sex partners
• Birth to HCV-infected mother

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Estimates of Disease Burden
HCV related deaths/year
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HCV Diagnosis

• Most patients asymptomatic
• Abnormal liver function tests AST/ALT
• Hepatitis C antibody (EIA)
• RIBA
• Hepatitis C RNA levels
• Liver biopsy grade and stage damage

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Interferon

• Family of cellular proteins with similar
  intracellular actions.
• Described originally in the 1957.
• High toxicity, cost, must be given iv or
  subcutaneously.
• Difficult to test new therapies.

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HIV Patients Sustained Virologic Response
IFN alfa-2a RBV
PEGASYS(40 kDa) Placebo
PEGASYS(40 kDa) COPEGUS
Defined as lt50 IU/mL HCV RNA at week 72 ITT
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Patient Selection the difficult balance
Low level HCV RNA Non-type 1 genotype Short
duration of infection Mild histological
disease
High level HCV RNA Genotype 1 Advanced
histological disease
Most in need of treatment May have increased
risk of disease progression
Most likely to respond
Viral hepatitis epidemic in the making. ADHF
1998
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Patient Selection

• Not all hepatitis C patients should be treated.
• Patient selection
• Degree of liver damage
• Psychological factors
• Other medical issues

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VA Multicenter HCV Eligibility Study

• Over 4000 pts evaluated after referral for
  hepatitis C dx. Over 1 yr period.
• 24 VA medical centers
• Collected data on hepatitis C treatment selection
• ONLY 32 considered candidates for therapy.

The American Journal of GastroenterologyVolume
100 Page 1772  - August 2005
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VA Multicenter HCV Eligibility Study

• Ongoing Substance abuse
• Medical disease
• Psychiatric conditions
• Approximately 30 refused therapy once offered.

The American Journal of GastroenterologyVolume
100 Page 1772  - August 2005
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European HCV Eligibility Study

• Belgium Study that examined eligibility of 1700
  hepatitis C pts.
• Files of 299 pts reviewed
• 60 NOT treated
• Exclusion-
• Medical contraindication 34
• Most Psychiatric
• Noncompliance 25
• Normal liver function 24
• Refused therapy

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Depression and Anxiety in HCV patients

• DSM-IV Criteria used to assess pts with HCV
  undergoing evaluation.
• 90 subjects
• 28 Depression dx 72 undiagnosed
• 24 Anxiety dx- 86 undiagnosed
• Methadone therapy strongly correlated with
  depression

General Hospital Psychiatry Volume 27 Issue 6
Nov-Dec 2005, Pages 431-438
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Patient Selection Criteria

• Medically indicated and no co-morbid medical
  illness
• Psychiatric evaluation
• No substance abuse/ Etoh for 6 months
• Chemical dependence input
• Demonstration of medical compliance
• Multidisciplinary approach

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Patient Selection Criteria

• Concerned about Depression
• Psychiatric Input
• Antidepressant pretreatment
• SSRI
• Anxiety benzo
• Monitor Closely- Beck Dep Inv
• Social support at home
• Available

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SSRI and Interferon

• Scattered data emerging regarding use of SSRI in
  HCV treatment
• MS study in NEJM
• Case control series regarding use of SSRI in pts
  with depression on IFN
• Prophylaxis vs symptomatic therapy

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Future Therapy HCV

• New oral medications expected by 2011
• Most new drugs will be combined with Pegylated
  interferon and ribavirin
• Future drug regimens will be comprised of
  multidrug cocktails to prevent hepatitis C
  progression.

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Protease Inhibitors

• Telaprevir- in phase 3 trials with early data
  demonstrating up to 68 SVR.
• Resistance issues
• Boceprevir- in phase 2 trials
• Resistance issues
• TMC435350- phase 2 trials
• Once daily dosing

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Polymerase Inhibitors

• R7128- nucleoside anologs, promising drug now
  being studied with pegylated interferon and
  ribavirin
• VCH759 and GS 9190

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Interferons

• Long term interferon- HALT C trial
• Concensus Interferon
• Albinterferon- once to twice a week interferon

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HCV Treatment
Summary

• Psychiatric diagnosis are common in HCV pts
• Patient Selection is critical
• Education
• Input from Psychiatry and Chemical Dep
• Pretreatment /SSRI

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Coinfection HCV and HIV

• Hepatitis C is considered an opportunistic
  infection (OI). Over 330,000 coinfected US.
• Overall coinfection rate 33
• Sexual 8-10
• Hemophilia 40-60
• IVDA 80-90
• Liver disease accounts for 43 of deaths in HIV
  infected patients (hospitalized).

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Declining morbidity and mortality among patients
with advanced HIV. HIV Outpatient Study
Investigators
Percentage of Patient-days on HAART
Deaths per 100 Person-Years
Palell. Palella, N Engl J Med, 1998. 338(13) p.
853
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HIV-HCV Treatment

• APRICOT is the largest and the only international
  registration study in HIV/HCV co-infection
• HCV therapy did not negatively impact control of
  HIV
• 40 SVR is the highest of any reported study in
  HIV/HCV co-infection

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IFN in HCV HIV

• Depends upon a number of factors including
• Virus Genotype, HCV RNA
• HIV status
• Host Race, age, weight
• Drug Adherence, ribavirin dosing

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Therapy Liver Transplantation

• Pre-HAART era contra-indication to Tx
• Pittsburgh data- overall outcomes comparable to
  non HIV infected transplant recipients.
• Hepatitis C coinfected transplant recipients have
  more aggressive hepatitis C recurrance.

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Conclusions

• Current therapy produces response rates of 50 to
  80.
• There are many predictors for need for therapy
  and response to therapy.
• New drugs will be combined with standard of care
  to boost response rates.

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To Get CMEs

• Log on to website stdptc.uc.edu
• Look for e-learning seminar title
• Log onto the CME link
• Questions or Comments
• 1-513-558-3197