Viral Hepatitis B, D


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Viral Hepatitis B, D


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What Is Hepatitis? The word " hepatitis " means inflammation of the Liver Toxins, certain drugs, some diseases, heavy alcohol use, bacterial and viral infections can all cause hepatitis. Hepatitis is also the name of a family of viral infections that affect the liver; the most common types in the United States are hepatitis A, hepatitis B, and hepatitis C. Dr.T.V.Rao MD 2


Hepatitis Hepatitis (plural hepatitides ) implies injury to the liver characterized by the presence of inflammatory cells in the tissue of the organ. The name is from ancient Greek hepar or hepato , meaning liver , and suffix -itis , meaning "inflammation" (c. 1727) Dr.T.V.Rao MD 3

What Is Hepatitis?:

Viral Hepatitis A group of viruses known as the hepatitis viruses cause most cases of liver damage worldwide. Hepatitis can also be due to toxins (notably alcohol), other infections. Common viruses cause hepatitis include A,B,C,D,E. G ………. Dr.T.V.Rao MD 4


A “ Infectious” “ Serum” Viral hepatitis Enterically transmitted Parenteraly transmitted F, G, TTV ? other E NANB B D C Viral Hepatitis - Historical Perspectives Dr.T.V.Rao MD 5

Viral Hepatitis:

Source of virus feces blood/ blood-derived body fluids blood/ blood-derived body fluids blood/ blood-derived body fluids feces Route of transmission fecal-oral percutaneous permucosal percutaneous permucosal percutaneous permucosal fecal-oral Chronic infection no yes yes yes no Prevention pre/post- exposure immunization pre/post- exposure immunization blood donor screening; risk behavior modification pre/post- exposure immunization; risk behavior modification ensure safe drinking water Type of Hepatitis A B C D E Dr.T.V.Rao MD 6

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Hepatitis B Infection Dr.T.V.Rao MD 7


Hepatitis B Hepatitis B is a liver disease caused by the hepatitis B virus (HBV). It ranges in severity from a mild illness, lasting a few weeks (acute), to a serious long-term (chronic) illness that can lead to liver disease or liver cancer. Dr.T.V.Rao MD 8

Hepatitis B Infection:

Hepatitis B Virus Blumberg in 1965 discovers, names as Australia antigen. 1968 identified with association in serum hepatitis. Surface component of HBV called as surface antigen. Dr.T.V.Rao MD 9

Hepatitis B:

Hepatitis B In the World 2 billion people have been infected (1 out of 3 people). 400 million people are chronically infected. 10-30 million will become infected each year. An estimated 1 million people die each year from hepatitis B and its complications. Approximately 2 people die each minute from hepatitis B. Dr.T.V.Rao MD 10

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Hepatitis B is Serious – Global Impact It’s a common disease! Over 350 million people in the world have chronic hepatitis B 1 1 Centers for Disease Control and Prevention. Hepatitis B FAQs for Health Professionals. Available at: Accessed January 28, 2010. 2 World Health Organization. Hepatitis B. Available at: Accessed June 1, 2004. Dr.T.V.Rao MD 11

Hepatitis B In the World :

Hepatitis B Virus - Virology Double stranded DNA virus, the + strand not complete Replication involves a reverse transcriptase. Complete Dane particle 42 nm, 28 nm electron dense core, containing HBcAg and HBeAg. The coat and the 22 nm free particles contain HBsAg At least 4 phenotypes of HBsAg are recognized; adw, adr, ayw and ayr. The HBcAg is of a single serotype Dr.T.V.Rao MD 12

Hepatitis B is Serious – Global Impact :

Typing of HBV Hepatitis B virus (HBV) has been classified into 8 genotypes (A-H). Genotypes A and C predominate in the US. However, genotypes B and D are also present in the US. Genotype F predominates in South America and in Alaska, while A, D and E predominate in Africa. Genotype D predominates in Russia and in all its prior dominions, while in Asia, genotypes B and C predominate. Dr.T.V.Rao MD 13

Hepatitis B Virus - Virology:

HBV Virology Under Electron Microscope Spherical particles 22 nm in diameter Filamentous or tubular 22 nm with varying length Called as HBs Ag surface components which are produced in excess. Third type double walled spherical structure 42 nm diameter called HBV Called as Dane particle Dr.T.V.Rao MD 14

Typing of HBV:

HBV – Surface antigens Enveloped proteins on surface of virions and surplus 22 nm diameter spherical and filamentous particles constitute the B surface antigens HBs Ag consists two major polypeptides and is glycolated Dr.T.V.Rao MD 15

HBV Virology Under Electron Microscope:

Antigenic Diversity of HBV HBV shows antigenic diversity, two different antigenic components and common group reactive antigen a Two contain specific antigens d y w r Only one member of each pair being present at a time Divided into four Major antigenic subtypes adw,adr, ayw, and ayr Dr.T.V.Rao MD 16

HBV – Surface antigens:

Hepatitis B Virus Dr.T.V.Rao MD 17

Antigenic Diversity of HBV:

HBV : Structure Dr.T.V.Rao MD 18

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There are 4 open reading frames derived from the same strand (the incomplete + strand) S - the 3 polypeptides of the surface antigen ( preS1, preS2 and S - produced from alternative translation start sites. C - the core protein P - the polymerase X - a trans activator of viral transcription (and cellular genes?). HBx is conserved in all mammalian (but not avian) hepadnaviruses. Though not essential in transfected cells, it is required for infection in vivo. Open Reading Frames Dr.T.V.Rao MD 20


Prevalence of Divergent Strains ayw – common in Europe,Australia,and America. adr - Prevalent in south, East India and Far east, ayr - very rare Core antigen HB c ag Be HBe is a soluble non particle nucelocapsid protien Both Hbc and Hbe are coded by same genes Dr.T.V.Rao MD 21

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Hepatitis B Perinatal Transmission If mother positive for HBsAg and HBeAg 70%-90% of infants infected 90% of infected infants become chronically infected If positive for HBsAg only 5%-20% of infants infected 90% of infected infants become chronically infected *in the absence of postexposure prophylaxis Dr.T.V.Rao MD 22

Prevalence of Divergent Strains :

How the HBV is transmitted Dr.T.V.Rao MD 23

Hepatitis B Perinatal Transmission:

Risk Factors for Hepatitis B MMWR 2006;55(RR-16):6-7 Dr.T.V.Rao MD 24

How the HBV is transmitted:

Hepatitis B Virus Infection by Duration of High-Risk Behavior Years at Risk 0 3 6 9 12 15 0 20 40 60 80 100 Percent infected IV drug user Homosexual men HCWs Heterosexual Dr.T.V.Rao MD 25

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Pathogenesis of HBV i nfectio n Disease is Immune mediated Hepatocytes carry viral antigen Immune response subject to antibody dependent. N K cell and cytotoxic T cell attack In the absence of adequate immune response HBV infection may not cause hepatitis. But lead to carrier state. Infection – Immunodeficient person are likely to because asymptomatic carrier followed infection Dr.T.V.Rao MD 26

Hepatitis B Virus Infection by Duration of High-Risk Behavior:

Dr.T.V.Rao MD 27

Pathogenesis of HBV infection:

Incubation period: Average 60-90 days Range 45-180 days Clinical illness (jaundice): <5 yrs, <10% 5 yrs, 30%-50% Acute case-fatality rate: 0.5%-1% Chronic infection: <5 yrs, 30%-90% 5 yrs, 2%-10% Premature mortality from chronic liver disease: 15%-25% Hepatitis B - Clinical Feature s Dr.T.V.Rao MD 28

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Spectrum of Chronic Hepatitis B Diseases Chronic Persistent Hepatitis - asymptomatic Chronic Active Hepatitis - symptomatic exacerbations of hepatitis Cirrhosis of Liver Hepatocellular Carcinoma Dr.T.V.Rao MD 29

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Risk of Chronic HBV Carriage by Age of Infection Dr.T.V.Rao MD 30

Spectrum of Chronic Hepatitis B Diseases:

High (>8%): 45% of global population lifetime risk of infection >60% early childhood infections common Intermediate (2%-7%): 43% of global population lifetime risk of infection 20%-60% infections occur in all age groups Low (<2%): 12% of global population lifetime risk of infection <20% most infections occur in adult risk groups Global Patterns of Chronic HBV Infection Dr.T.V.Rao MD 31

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Dr.T.V.Rao MD 32

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High Moderate Low/Not Detectable blood semen urine serum vaginal fluid feces wound exudates saliva sweat tears breastmilk Concentration of Hepatitis B Virus in Various Body Fluids Dr.T.V.Rao MD 33

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How Hepatitis B is transmitted Contact with infectious blood, semen, and other body fluids from having sex with an infected person, sharing contaminated needles to inject drugs, or from an infected mother to her newborn. Dr.T.V.Rao MD 34

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Sexual - sex workers and homosexuals are particular at risk. Parenteral - IVDA, Health Workers are at increased risk. Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations. Hepatitis B Virus Modes of Transmission Dr.T.V.Rao MD 35

How Hepatitis B is transmitted:

Pathology Both Hepatitis B and C are cytopathogenic Cellular damage is immune mediated Both HBV and HBC have significant roles in in the development of Hepatocellular carcinoma Carcinoma may appear 15 – 60 years after the beginning of infection. 36 Dr.T.V.Rao MD

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、 Pathogenesis & Immunity Virus enters hepatocytes via blood Immune response (cytotoxic T cell) to viral antigens expressed on hepatocyte cell surface responsible for clinical syndrome 5 % become chronic carriers (HBsAg> 6 months) Higher rate of hepatocellular ca in chronic carriers, especially those who are “e” antigen positive Hepatitis B surface antibody likely confers lifelong immunity (IgG anti-HBs) Hepatitis B e Ab indicates low transmissibility Dr.T.V.Rao MD 37


High-risk groups for HBV infection People from endemic regions Babies of mothers with chronic HBV Intravenous drug abusers People with multiple sex partners Hemophiliacs and other patients requiting blood and blood product treatments Health care personnel who have contact with blood Residents and staff members of institutions for the mentally retarded Dr.T.V.Rao MD 38

、Pathogenesis & Immunity:

Hepatitis B Complications Fulminant hepatitis Hospitalization Cirrhosis Hepatocellular carcinoma Death Dr.T.V.Rao MD 39

High-risk groups for HBV infection:

Diagnosis A battery of serological tests are used for the diagnosis of acute and chronic hepatitis B infection. HBsAg - used as a general marker of infection. HBsAb - used to document recovery and/or immunity to HBV infection. anti-HBc IgM - marker of acute infection. anti-HBcIgG - past or chronic infection. HBeAg - indicates active replication of virus and therefore infectiveness. Anti-Hbe - virus no longer replicating. However, the patient can still be positive for HBsAg which is made by integrated HBV. HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy. Dr.T.V.Rao MD 40

Hepatitis B Complications:

Treatment Interferon - for HBeAg +ve carriers with chronic active hepatitis. Response rate is 30 to 40%. alpha-interferon 2b (original) alpha-interferon 2a (newer, claims to be more efficacious and efficient) Lamivudine - a nucleoside analogue reverse transcriptase inhibitor. Well tolerated, most patients will respond favorably. However, tendency to relapse on cessation of treatment. Another problem is the rapid emergence of drug resistance. Dr.T.V.Rao MD 41


Treatment Adefovir – less likely to develop resistance than Lamivudine and may be used to treat Lamivudine resistance HBV. However more expensive and toxic Entecavir – most powerful antiviral known, similar to Adefovir Successful response to treatment will result in the disappearance of HBsAg, HBV-DNA, and seroconversion to HBeAg. Dr.T.V.Rao MD 42


Statistics on HBV Most healthy adults (90%) who are infected will recover and develop protective antibodies against future hepatitis B infections 90% of infants and up to 50% of young children infected with hepatitis B will develop chronic infections. Dr.T.V.Rao MD 43


Protect Yourself And Your Family! Hepatitis B can infect EVERYONE, regardless of age By getting tested and vaccinated , you can protect your family If you test positive, ask your doctor about your treatment /management options Prevention is the best approach to hepatitis B. Dr.T.V.Rao MD 44

Statistics on HBV:

Prevention Vaccination - highly effective recombinant vaccines are now available. Vaccine can be given to those who are at increased risk of HBV infection such as health care workers. It is also given routinely to neonates as universal vaccination in many countries. Dr.T.V.Rao MD 45

Protect Yourself And Your Family!:

Post vaccination Serologic Testing Healthcare personnel who have contact with patients or blood should be tested for anti-HBs (antibody to hepatitis B surface antigen) 1 to 2 months after completion of the 3-dose series Dr.T.V.Rao MD 46


Hepatitis B Vaccine Composition Recombinant HBsAg Efficacy 95% (Range, 80%-100%) Duration of Immunity 20 years or more Schedule 3 Doses Booster doses not routinely recommended Dr.T.V.Rao MD 47

Post vaccination Serologic Testing:

Management of Nonresponse to Hepatitis B Vaccine Complete a second series of three doses Should be given on the usual schedule of 0, 1 and 6 months Retest 1-2 months after completing the second series Dr.T.V.Rao MD 48

Hepatitis B Vaccine:

Prevention Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positive. Other measures - screening of blood donors, blood and body fluid precautions. Dr.T.V.Rao MD 49

Management of Nonresponse to Hepatitis B Vaccine:

Prognostic Tests Genotyping – genotype 1 and 4 have a worse prognosis overall and respond poorly to interferon therapy. A number of commercial and in-house assays are available. Genotypic methods – DNA sequencing, PCR-hybridization e.g. INNO-LIPA. Serotyping – particularly useful when the patient does not have detectable RNA. Viral Load – patients with high viral load are thought to have a poorer prognosis. Viral load is also used for monitoring response to IFN therapy. A number of commercial and in-house tests are available. Dr.T.V.Rao MD 50


Treatment Interferon - may be considered for patients with chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment. Ribavirin - there is less experience with ribavirin than interferon. However, recent studies suggest that a combination of interferon and ribavirin is more effective than interferon alone. Dr.T.V.Rao MD 51

Prognostic Tests:

Hepatitis D Infection Dr.T.V.Rao MD 52


Delta antigen In 1977, a previously unrecognized nuclear antigen was detected in hepatocytes of patients with chronic hepatitis B. The antigen resembled hepatitis B core antigen (HBcAg) in its subcellular localization. Its presence was always associated with hepatitis B virus (HBV) infection, but it rarely coexisted with HBcAg. It was termed "delta antigen". Patients with delta antigen develop anti-delta antibodies. Dr.T.V.Rao MD 53

Hepatitis D Infection:

Hepatitis D virus (HDV) Hepatitis D virus (HDV) is found only in people who carry the hepatitis B virus. HDV may make a recent (acute) hepatitis B infection or an existing long-term (chronic) hepatitis B liver disease worse. It can even cause symptoms in people who carry hepatitis B virus but who never had symptoms. Dr.T.V.Rao MD 54

Delta antigen:

HBsAg RNA  antigen Hepatitis D (Delta) Virus Dr.T.V.Rao MD 55

Hepatitis D virus (HDV) :

Hepatitis D Virus The delta agent is a defective virus which shows similarities with the viroids in plants. The agent consists of a particle 35 nm in diameter consisting of the delta antigen surrounded by an outer coat of HBsAg. The genome of the virus is very small and consists of a single-stranded RNA Dr.T.V.Rao MD 56

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Risk factors include: Abusing intravenous (IV) or injection drugs Being infected while pregnant (the mother can pass the virus to the baby) Carrying the hepatitis B virus Men having sexual intercourse with other men, Receiving many blood transfusions Dr.T.V.Rao MD 57

Hepatitis D Virus:

Percutaneous exposures injecting drug use Per mucosal exposures sex contact Hepatitis D Virus Modes of Transmission Dr.T.V.Rao MD 58

Risk factors include::

Coinfection severe acute disease. low risk of chronic infection. Superinfection usually develop chronic HDV infection. high risk of severe chronic liver disease. may present as an acute hepatitis. Hepatitis D - Clinical Features Dr.T.V.Rao MD 59

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HDV can lead to fulminant Hepatitis HDV infection of chronically infected HBV-carriers may lead to fulminant acute hepatitis or severe chronic active hepatitis, often progressing to cirrhosis. Chronic hepatitis D may also lead to the development of hepatocellular carcinoma. Dr.T.V.Rao MD 60

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Consequences of HDV Infection Infection with both HBV and HDV is associated with more severe liver injury than HBV infection alone. HDV infection of chronically infected HBV carries may lead to fulminant acute hepatitis or chronic active hepatitis, often progressing to cirrhosis. Chronic HDV infection may also lead to the development of hepatocellular carcinoma. Dr.T.V.Rao MD 61

HDV can lead to fulminant Hepatitis :

Prevention Prompt diagnosis and treatment of hepatitis B infection can help prevent hepatitis D. Avoid intravenous drug abuse. If you use IV drugs, avoid sharing needles. A vaccine is available to prevent hepatitis B. Adults who are at high risk for hepatitis B infection, and all children should consider getting this vaccine. Dr.T.V.Rao MD 62

Consequences of HDV Infection :

Best Way to Prevent HDV Infection Control of HDV infection can be achieved by targeting and limiting HBV infections. HBV vaccination is therefore recommended to avoid HBV-HDV confection. Dr.T.V.Rao MD 63

Prevention :

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