hepatitis b l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
HEPATITIS B PowerPoint Presentation
Download Presentation
HEPATITIS B

Loading in 2 Seconds...

play fullscreen
1 / 48

HEPATITIS B - PowerPoint PPT Presentation


  • 681 Views
  • Uploaded on

HEPATITIS B Anna S. F. Lok, MD University of Michigan Ann Arbor, MI What is Hepatitis B? Hepatitis B is an infection of the liver caused by the hepatitis B virus How common is hepatitis B? Worldwide 400 million people are chronic carriers About 75% of HBV carriers live in Asia

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'HEPATITIS B' - Audrey


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
hepatitis b

HEPATITIS B

Anna S. F. Lok, MD

University of Michigan

Ann Arbor, MI

what is hepatitis b
What is Hepatitis B?
  • Hepatitis B is an infection of the liver caused by the hepatitis B virus
how common is hepatitis b
How common is hepatitis B?

Worldwide

  • 400 million people are chronic carriers
  • About 75% of HBV carriers live in Asia
  • 0.5-1 million deaths per year due to HBV

Asia

  • Liver cancer is the 2nd cancer killer among Asian men and the 5th cancer killer among Asian women
  • Roughly 40% of Asian men and 15% of Asian women with chronic hepatitis B die of a liver-related illness
slide4

Geographic Distribution of

Chronic HBV Infection

HBsAg Prevalence

8% - High

2-7% - Intermediate

<2% - Low

hepatitis b and asian americans
Hepatitis B and Asian Americans
  • Less than 0.5% (1 in 200) Americans have chronic hepatitis B
  • About 10-15% (1 in 8 to 10) Asian Americans have chronic hepatitis B
  • About 50% (1 in 2) of the people in the US with chronic hepatitis B are Asian Americans
  • A much higher percent of Asian Americans compared to Americans of other races have hepatitis B
why is hepatitis b so common among asian americans
Why is Hepatitis B so common among Asian Americans?
  • Hepatitis B is very common in Asia
  • Many Asian Americans were infected with hepatitis B before they came to the US
  • Asian Americans born in the US may be infected through their mother or other family members, who are HBV carriers
hepatitis b and asian americans7
Hepatitis B and Asian Americans

National Health and Nutrition Examination Survey (NHANES)

  • Survey on prevalence of various diseases in the US
  • Sampled cohorts representative of US population
  • African Americans and Hispanics over sampled to ensure sufficient number studied to permit conclusions on prevalence of diseases among those racial/ethnic groups
  • Reliable data not available for Asian Americans because Asians not over sampled, number studied too small to be conclusive, and Asians lumped as “other racial/ethnic groups”
hepatitis b and asian americans8
Hepatitis B and Asian Americans
  • NHANES III – 1988-1994
    • Current and past HBV infection: 4.9%
    • Chronic HBV infection: 0.4%
      • Highest prevalence among blacks
      • 5%-15% among immigrants from Central and Southeast Asia, Middle East and Africa
      • Prevalence data for Asians not available
why is it that hepatitis b gets so little attention in the us
Why is it that hepatitis B gets so little attention in the US?

Federal and state governments – public health

  • Overall prevalence is low: not a very common problem here
  • Most of those affected by HBV are Asians – who are politically silent (squeaky wheel gets the oil)

NIH, CDC, Scientific organizations – research and education

  • Not a common problem
  • With an effective vaccine, hepatitis B will be eradicated in the next generation.. we predicted that in the 1980s
  • Competition for $$ and attention from other more trendy diseases: HIV, HCV, SARS, avian ‘flu, cancers….
how is hbv spread
How is HBV spread?
  • HBV is more easily spread than HIV (virus that causes AIDS) and HCV
  • HBV can live outside the human body for up to 7 days
  • People with chronic hepatitis B can have very large amounts of virus in their blood – serum HBV DNA up to 11 log10 copies/mL (100 billion)
how is hbv spread11
How is HBV spread?

Mainly through blood and bodily secretions

  • Infected mother to babies at birth
  • Contact with blood from carriers through wounds, contaminated household articles such as razors, toothbrushes, or contaminated needles used for tattoos and injecting drugs
  • Sexual contact with carriers
how is hbv spread12
How is HBV spread?

HBV is not spread by:

  • Hugging or kissing
  • Coughing or sneezing
  • Sharing eating utensils
outcome of acute hbv infection
Outcome of Acute HBV Infection

Recovery

Acute Hepatitis

SubclinicalHepatitis

FulminantHepatitis

Death

Acute Infection

Chronic Infection

what is hepatitis b14
What is Hepatitis B?

Hepatitis B may be ACUTE

  • Recent infection
  • May have no symptoms, especially in children
  • Common symptoms: easily tired, poor appetite, nausea, abdominal discomfort, jaundice
  • Roughly 95% recover, usually in 2-3 months
  • About 1% severe hepatitis with acute liver failure
  • About 5% go on to chronic infection, lasts longer than 6 months
risk of chronic hbv infection

100

80

60

%

Risk

40

20

0

Neonates

Infants

Children

Adults

Age at Infection

Risk of Chronic HBV Infection
outcome of chronic hbv infection
Outcome of Chronic HBV Infection

Chronic HBV Infection

Inactive Carrier State

Chronic Hepatitis

Cirrhosis

HCC

what is hepatitis b17
What is Hepatitis B?

Hepatitis B may be CHRONIC

  • Long-lasting infection, persists for more than 6 months
  • Most people have no symptoms
  • Common symptoms: easily tired, poor appetite, nausea, abdominal discomfort
  • Can go on to cirrhosis, liver failure, liver cancer, and death
how can hepatitis b be diagnosed
How can hepatitis B be diagnosed?
  • The only way to know is to have a blood test
  • Most people with hepatitis B have no symptoms until late stages of liver disease
  • Tests for hepatitis B or liver enzymes are not included in most routine check-ups
  • Hepatitis B may be present even if liver enzymes were tested and were normal
serological markers of hbv infection

Serological Markers of HBV Infection

HBsAg Acute/Chronic infection

Anti-HBc IgM Recent infection

HBeAg High infectivity

Anti-HBe Low infectivity

Anti-HBs Immunity

Anti-HBc IgG + HBsAg Chronic infection

Anti-HBc IgG + anti-HBs Resolved infection

slide20

Acute HBV Infection

HBV DNA

HBeAg

Anti-HBe

Anti-HBe

Anti-HBs

Anti-HBc

HBsAg

Anti-HBc IgM

0 2 4 6

Months Years

slide21

HBV DNA

HBeAg

Anti-HBe

HBsAg

Anti-HBc

Anti-HBc IgM

Months

Years

Chronic HBV Infection

serum hbv dna is the most reliable marker of hbv replication and infectivity
Serum HBV DNA is the most reliable marker of HBV replication and infectivity
  • Fluctuating levels, serial tests important for clinical assessment
  • Virus persists at low levels even after recovery
  • Reactivation can occur spontaneously and more often when immune system is suppressed
  • HBV DNA levels do not always correlate with ALT levels or histologic activity of liver disease
  • Persistently high serum HBV DNA levels are associated with increased risk of cirrhosis and HCC
hepatitis b vaccines
Hepatitis B Vaccines
  • Genetically engineered hepatitis B surface antigen only
  • 3 doses: month 0, 1, 6
  • Immune response: 50% after 1 dose 95% after 3 doses
  • Duration of protection: >15 years, dependent on initial antibody response
  • Factors associated with poor response: older age, chronic medical illness (cirrhosis, kidney failure, diabetes), decreased immune response, smoking, obesity, genetics
indications for hbv vaccines
Indications for HBV Vaccines
  • Hepatitis B immune globulin and HB vaccine to infants of HBsAg+ mothers
  • All infants
  • All children and adolescents who were not vaccinated at birth
  • Vaccination of adults at risk of infection
    • Occupational
    • Sexual / household contacts
    • Injection drug users
    • Long-term residence in high prevalence areas
hbv vaccine safety

HBV Vaccine: Safety

Worldwide, more than 500 million individuals have received HB vaccine over the past 20 years

Most common adverse event – soreness and erythema at the injection site

Systemic symptoms – transient low-grade fever, headache, malaise and myalgia in ~10%

slide26

Impact of HBV vaccination on HBV infection rates in Taiwanese children

30

HBsAg+

Anti-HBc+

20

%

10

0

1984

1994

1999

Vaccination of infants born to HBsAg+ mother

Universal vaccination of infant/preschool children

Ni YH, Ann Intern Med 2001;135:796

slide27

Impact of HBV Vaccination on Incidence

of HCC in Taiwanese Children

Universal Vaccination of Newborns

Chang MH, NEJM 1997;336:1855

hepatitis b factors affecting disease activity and progression
Hepatitis BFactors affecting disease activity and progression

VIRUS

Genotype

Molecular Variants

HOST

Gender

Age

Immune Response

Genetics

ENVIRONMENT

Alcohol

HCV, HDV, HIV

Carcinogens

slide29

Stages of chronic HBV infection

Immune

Immune

Low replicative

Reactivation

tolerance

clearance

phase

phase

HBeAg - / anti-HBe + (PC/CP variants)

HBeAg + (wild)

>

<

<

>

>105 cp/ml

HBV-DNA

<105 cp/ml

109-1010 cp/ml

107-108 cp/ml

ALT

Normal /

mild CH

moderate/severe CH

Normal/mild CH

moderate/severe CH

cirrhosis

Inactive cirrhosis

cirrhosis

HBeAg +

Chronic hepatitis

Inactive-carrier state

HBeAg –

Chronic hepatitis

slide30

Unique Aspects of Hepatitis B among Asians

Clinical Manifestations/Natural history

  • Immune tolerant phase
  • Frequent exacerbations and reactivations
  • Increased risks of HCC
slide31

Immune Tolerant Phase

  • First 10-30 years of perinatally acquired HBV infection
  • Asymptomatic
  • High HBV DNA levels but normal ALT
  • Very low rates of spontaneous/treatment-induced HBeAg seroconversion
slide32

Immune Clearance Phase

HBeAg → anti-HBe seroconversion

Predictors : ALT, age, gender, HBV genotype

Annual rate = 5-15%

Hepatitis Flares

⅔ HBeAg seroconversion preceded by flares

¼ flares followed by HBeAg seroconversion

More common in men

Increased risk of cirrhosis

slide33

Stages of chronic HBV infection

Immune

Immune

Low replicative

Reactivation

tolerance

clearance

phase

phase

HBeAg - / anti-HBe + (PC/CP variants)

HBeAg + (wild)

>

<

<

>

>105 cp/ml

HBV-DNA

<105 cp/ml

109-1010 cp/ml

107-108 cp/ml

ALT

Normal /

mild CH

moderate/severe CH

Normal/mild CH

moderate/severe CH

cirrhosis

Inactive cirrhosis

cirrhosis

HBeAg +

Chronic hepatitis

Inactive-carrier state

HBeAg –

Chronic hepatitis

inactive hbsag carrier state

Inactive HBsAg Carrier State

HBsAg+ > 6 months

HBeAg- , anti-HBe+

Serum HBV DNA < 103 copies/ml

Persistently normal ALT

Outcome dependent on liver damage accrued prior to entering inactive carrier state and any subsequent reactivation

slide35

HBeAg – Chronic Hepatitis B

  • HBsAg +
  • HBeAg –
  • Serum HBV DNA > 104-5 copies/ml
  • Elevated ALT / moderate-severe inflammation on biopsy
  • Frequently associated with precore or core promoter mutations that prevent or decrease HBeAg production
slide36

Risk factors for progression to cirrhosis

Viral factors Host Factors External Factors

  • Persistently high HBV DNA levels
  • HBV precore/CP variant?
  • HBV genotype (C > B)
  • Older age
  • Male gender
  • Advanced fibrosis
  • Persistent ALT elevation
  • Recurrent hepatitis flares
  • HDV, HCV coinfections
  • HIV coinfection
  • Alcohol
slide37

Risk factors for progression to HCC

Viral factors Host Factors External Factors

  • Persistently high HBV DNA levels
  • HBV CP variant
  • HBV genotype (C > B)
  • Older age
  • Male gender
  • Asians??
  • Advanced fibrosis
  • Persistent ALT elevation
  • Recurrent hepatitis flares
  • HDV, HCV coinfections
  • HIV coinfection
  • Family history of HCC
  • Alcohol
  • Aflatoxin
  • Smoking
what can patients do to protect their liver
What can patients do to protect their liver?
  • Do not drink alcohol
  • Do not take any herbal medicine that might hurt the liver
  • Eat a balanced diet, exercise regularly, avoid getting overweight

Hepatitis B is a chronic health problem, HBV levels and severity of liver damage can change with time, see their doctor and get tested at least once a year even if they have no symptoms

slide39

Treatment of Chronic Hepatitis B

Goals

  • Suppression of HBV replication
  • Decrease hepatic necroinflammation and fibrosis
  • Prevent progression to cirrhosis, liver failure and HCC
treatment of chronic hepatitis b definition of response
Treatment of Chronic Hepatitis BDefinition of Response

HBeAg+ patients

  • Serum HBV DNA decrease to <100,000 copies/ml
  • Loss of HBeAg ± anti-HBe seroconversion
  • Normalization of ALT level

HBeAg- patients

  • Serum HBV DNA decrease to undetectable by PCR
  • Normalization of ALT level

On-treatment response – initial / maintained

Off-treatment sustained response – FU mo 6 or 12

Lok A et al., Gastro 2001;120:1828

slide41

Randomized controlled trial of lamivudine in patients with advanced liver disease

HBeAg+ and/or serum HBV DNA >700,000 gEq/mL

% with disease progression

21%

Placebo

P=0.001

9%

Lamivudine

Time to disease progression (months)

Placebo (n=215) ITT population

Lamivudine (n=436) p=0.001

Liaw YF, NEJM 2004; 351:1521

who should be treated
Who Should be Treated?
  • Not a question of who to treat but when – treat now or monitor and treat when indicated
  • All HBV carriers are potential treatment candidates
  • A patient who is not a treatment candidate now can be a treatment candidate in the future
    • Changes in HBV replication status and/or activity/stage of liver disease
    • Availability of new and better treatments
when to start treatment
When to start treatment?

Benefits

Risks

Likelihood of

sustained response

cirrhosis and HCC

Side effects

Drug resistance

Patient’s age

Co-morbid illness

Costs

Likelihood of cirrhosis / HCC in the next 10-20 yrs

Likelihood of sustained viral suppression after a defined course of treatment

what should be the primary treatment
What should be the primary treatment?

Long-term Benefits

Long-term Risks

Antiviral potency

Durability of response

Side effects

Drug resistance

Contraindications

Ease of administration

Duration of Rx

Costs of Rx & monitoring

Patient and provider preference

when can treatment be stopped
When can treatment be stopped?
  • IFN treatment: finite duration, 12 mos
  • Nucleoside/tide analogues
    • HBeAg+ patients: 6-12 mos after HBeAg seroconversion (~50% after 5 yr Rx)
    • HBeAg- patients: endpoint not defined, ?until HBsAg loss (~5% after 5 yr)
    • Cirrhosis patients: endpoint not defined, ?life-long