HealthCamp – BarCampX Yangon 2012 MICT Park, Hlaing, Yangon 5th August 2012

Hepatitis B Virus (HBV) Infection: A Silent Epidemic

Aung Zayar Paing M.B.,B.S.

  BC 2000 - Some ancient records showed epidemic of hepatitis.

  1883 - Lurman found that people vaccinated for small pox with lymph from other people suffered from hepatitis (known as serum hepatitis at that time).

•  Many similar outbreaks happened when treating syphilis with reused needles in 1909.

•  Most probably due to Hepatitis B.

  1965 - Baruch Blumberg discovered ‘Australian antigen (now known as HBs Antigen)

  1970 - D.S. Dane and others discovered the virus particle with electron microscope.

 1980-81 – HBV vaccine derived from serum was developed by Hilleman and collegues, proved effective and licensed for use.

 1983-86 - William Rutter and colleagues developed HBV vaccine derived from yeast using recombinant DNA technology.

 2010 – Clément Gilbert and Cédric Feschotte found the fragments of HBV genes in the 19-millions-old fossils of songbirds.

 2012 - Korean and Islraeli scientists can map the entire genome of HBV found in the preserved liver of 16th century Korean mummified child.

 About 2 billion people have been infected with HBV infection around the world.

 > 2 million people have chronic HBV infection.

 About 600 000 die every year due to the acute and chronic consequences of HBV. (WHO 2012)

 About 25% (20-30%) of chronic infection results in cirrhosis or liver cancer.

Prevalence of HBs Antigen, 2006 (CDC)

 Myanmar is one of the countries with high HBV burden.

 HBV prevalence rate in Myanmar varies from study to study.

o  It varies from 8 – 12%. (Healthy people)

 Based on the population of Myanmar, disease burden can be calculated as follows:

o  Population: 48,000,000 (48 million)(World Bank 2011)

o  Disease burden: 3,840,000 to 5,760,000

 HBV is a member of smallest virus family Hepadnaviridae

 It measures 42 nm.

 It can survive for 15 years at -20ºC, for 24 months at -80ºC, for 6 months at room tempature, and 7 days at 44ºC.

•  Some said that it can be inactivated in 10 minutes when heated at 80ºC.

 HBV is 100 times more infectious than HIV. (Very minute amount of blood can be infectious.)

Name Abbreviation Definition/Comment

Hepatitis B Surface Antigen HBsAg Antigen indicating infection

HBV Deoxyribonucleic Acid HBV DNA Indicates active viral replication

Alanine Aminotransferase ALT An enzyme produced in the liver. Increases in ALT levels are often associated with liver cell inflammation or liver cell injury

Hepatitis B Core Antibody anti-HBc Appears at the onset of symptoms in acute hepatitis B and persists for life. It indicates previous or ongoing infection with hepatitis B virus (HBV)

Hepatitis B Surface Antibody anti-HBs Usually indicates immunity

Hepatitis B e Antigen HBeAg Antigen correlating with HBV replication and infectivity, but low or undetectable in patients with precore or core mutation

Hepatitis B e Antibody anti-HBe Usually appear in early recovery stage before anti-HBs

HBeAg negative chronic Hepatitis B

-variant of HBV which has mutation in precore region. HBV DNA is high with HBeAg negative.

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Picture source: CCO Hepatology inPractice

  Transmitted by blood, semen and vaginal fluid of an infected person.

o  Unprotected sexual contact with infected person

o  Infectious blood and blood related instruments

•  Blood transfusion

•  Unsterilized/under-sterilized needles and syringes

•  Needle stick injury

•  Toothbrush and razor

o  From mother to child (esp. during childbirth) (Common in South-East Asia)

 Grammatically it’s just a simple ‘Yes or No’ question.

 However medically or scientifically, it cannot be answered simply with ‘Yes’ or ‘No’.

Transmission through saliva

•  CDC factsheet about HBV doesn’t include saliva as an infectious source. (Hepatitis B General information, Hepatitis B Are you at risk?: CDC June 2010)

•  WHO HBV factsheet mentions only blood, semen and vaginal fluid as infectious. (Hepatitis Fact sheet N°204, July 2012)

•  Let’s explore more …

 Generally speaking risk of infection increases if the donor has high HBV DNA load and replication.

 For transmission through saliva, the chance of getting infection increases in following conditions:

o  Infected saliva mixed with blood

o  Non-intact skin or mucosa (inflammation, cut, etc)

o  High HBV DNA load in saliva

Acute Hepatitis B   It refers to the conditions following transmission of HBV.

  Usually lasts for 4-8 weeks.

  Two third (2/3) of patients are asymptomatic. (don’t suffer from anything)

  Chance of progression to chronic HBV depends on age of acquiring HBV.

Chronic Hepatitis B •  HBsAg-positive >6 months

•  Serum HBV DNA >20,000 IU/mL (105copies/mL), lower values 2,000-20,000 IU/mL (104-105 copies/mL) are often seen in HBeAg-negative chronic hepatitis B

•  Persistent or intermittent elevation in ALT/AST levels

•  Liver biopsy showing chronic hepatitis with moderate or severenecroinflammation (AASLD: Chronic Hepatitis B: Update 2009)

Chronic Hepatitis B

•  Chronic HBV patients (chronic carrier) may feel healthy without having any illness for long time.

•  To know the disease progression and need for treatment

•  ALT, Ultrasound should be checked every 3-6 months.

•  If available and affordable, better to check HBV DNA.

•  Should avoid risk factors (alcohol, smoking, liver toxic agents) and should be vaccinated against Hepatitis A & E.)

•  If HBV DNA is high enough to start treatment, decreasing HBV DNA with drugs is needed to prevent further liver damage from HBV.

Common in SEA

Risks of Chronic Hepatitis B •  Progress of chronic hepatitis B to cirrhosis and Liver cancer

can be as high as 20-30%.

•  Factors influencing disease progress are:

•  High HBV DNA in blood

•  Precore mutant HBV (HBe Ag negative chronic HBV)

•  Male patients

•  Alcohol and other hepatotoxic agents/drugs use

•  Smoking

•  Coinfection with HIV and/or HCV

•  Genotype of HBV (e.g., genotype C)

•  Immune status of the patient

Tests

•  Anyone should get tested for HBsAg.

•  If HBsAg is positive for first time, recheck HBsAg after 6 months.

•  If HBsAg is negative, check anti-HBs Antibody.

•  If anti-HBs Ab is ≥ 10 IU/L, vaccination is not needed.

•  If anti-HBs Ab is negative or ≤ 10 IU/L, vaccination should be started.

 Avoidance of risk factors

 Vaccination

 Anti-viral drugs administration to mother and immunoprophylaxis (HBIG) to baby (for HBs Ag + mother)

 Prevention of occupational and non-occupational exposures

Vaccination

•  Actually HBV vaccine is the introduction of HBsAg to the body to illicit immune response to HBV infection.

•  It has to be administered 3-4 doses to make our immune system to remember the incoming enemy.

•  After 3 doses, anti-HBs antibody level needs to be checked to assess if you have enough protection.

Vaccine schedule for Babies

Vaccination schedule for children, adolescents and adults

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Prevention of mother-to-child transmission

•  Antiviral drugs are not usually needed to prevent transmission to baby from infected mother.

•  Nucleos(t)ide analogues are recommended to start at last 3 months of pregnancy only if maternal HBV DNA is high and HBeAg (+).

•  Every baby born to HBsAg has to be vaccinated with both Hepatitis B Immunoglobulin (HBIG) and Hepatiti B vaccine.

•  Babies who had prophylaxis and vaccine are unlikely to get HBV from breastfeeding.

 Acute HBV infection is not usually treated with anti-virals

 Indications for treatment depends on:

o  Serum HBV DNA levels. (HBV DNA level to treat varies from guideline to guideline) (≥ 2000 - > 20,000 IU/mL)

o  Serum ALT levels.

o  Severity of liver fibrosis (scarring)

2 types of treatment regimens can be chosen

Interferon therapy Nucleos(t)ide analogues (NAs)

Advantages Finite duration Potent anti-viral effect

Absence of resistance Fewer side effects

Higher rates of anti-HBe & anti-HBs seroconversion with 12 mo of therapy

Oral administration

Better to choose for patient coinfected with HCV

TDF is also active against HIV.

Disadvantages Moderate anti-viral effect Infinite duration

Substantial side effects Risk of resistance

Sub-cutaneous injection Lower rate of HBeAg & HBs Ag loss

Cannot be used in cirrhosis and liver failure

Available drugs for HBV treatment

•  Interferons o  Interferon alfa (IFN-a)

o  Pegylated interferon alfa 2a (Peg-IFN-a 2a)

•  Nucleos(t)ide analogues (NA) o  Tenofovir (also useful in patients resistant to other NAs)

o  Entecavir

o  Lamivudine

o  Adefovir

o  Telbivudine

These are not recommended for initial monotherapy

Conclusion •  Myanmar is one of the countries with high HBV

prevalence. (8-12%) •  HBV Genotype C (common in Myanmar) has high

risk of bad outcomes. •  Anyone should be tested for HBsAg. (Most chronic

hepatitis B infected patients don’t know that they carries the virus.)

•  Vaccination is the best prevention. (including immuoprophylaxis for babies)

•  Chance of progressing to chronic hepatitis B increases when acquiring HBV in young age. (It’s commonest in South-East Asia.)

Conclusion (2) •  Chronic carriers (Chronic Hepatitis B) should be routinely

checked for disease progress and need to be treated.

o  They should avoid alcohol, smoking and get vaccinated for other hepatitis viruses. (Hepatitis A and E.)

o  20-30% of chronic carrier can progress to cirrhosis and liver cancer.

o  Identification of chronic hepatitis B patients is important to prevent bad outcomes.

•  Anyone who are exposed to HBV infection are at risk of HBV reactivation when immune system is compromised. (esp. with steroid therapy and anti-cancer drugs)

July 28 is World Hepatitis Day.

Let’s get tested, vaccinated and treated!!!

Email: azayarp@googlemail.com