Hepatitis B

Hepatitis B

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2. DEPARTMENT OF PUBLIC HEALTH DENTISTRY SEMINAR HEPATITIS B Presented by:- Dr. Amrita Rastogi 2

3. contents HISTORY INTRODUCTION PREVALENCE OF HEPATITIS B HEPATITIS B VIRUS STRUCTURE OF HEPATITIS B VIRUS REPLICATION OF HEPATITIS B VIRUS MODES OF TRANSMISSION HIGH-RISK GROUPS FOR HBV INFECTION STAGES OF THE DISEASE 3

4. PATHOLOGY & PATHOGENISIS SIGNS AND SYMPTOMPS CLINICAL FEATURES CLINICAL OUTCOME OF THE DISEASE DIAGNOSIS LEVELS OF PREVENTION CONCLUSION REFERENCES 4

5. History (1) Its an ancient disease first described in 5 th century B.C. Earliest recognized blood-borne outbreak of hepatitis was in Germany in 1883 after receiving smallpox vaccine. In 1947 MacCalum and Bauer introduce the term Hepatitis A for infectious and Hepatitis B for serum hepatitis This terminology was adopted by WHO in 1973 5

6. INTRODUCTION (1)(2) The term hepatitis describes inflammation of the liver. Hepatitis may be caused by alcohols, drugs, autoimmune diseases, metabolic diseases, and viruses. Viral infections accounts for more than half the cases of acute hepatitis. Viral hepatitis is a systemic infection affecting the liver predominately with primary inflammation of the liver by any one of a heterogeneous group of hepatotropic viruses 6

7. Different types of Hepatitis viruses are:- Hepatitis A (HAV) (1973) Hepatitis B (HBV) (1970) Hepatitis C (HCV) (1988) Hepatitis D (HDV) (1977) Hepatitis E (HEV) (1983) Hepatitis F – Not separate entity – Mutant of B Virus. Hepatitis G (HGV) (1995) 7

8. All of these are RNA viruses except HBV which is a DNA viruses. The viral hepatitis is classified as: Acute hepatitis (self-limited liver injury of less than 6 months) Chronic hepatitis ( hepatic inflammation more than 6 months) 8

9. Hepatitis B is a serious and common infectious diseases of the liver, affecting millions of people throughout the world. The severe pathological consequences of persistent HBV infections include the development of chronic hepatic insufficiency, cirrhosis and hepato cellular carcinoma (HCC). In addition, HBV carriers can transmit the disease for many years. 9

10. PREVALENCE OF HEPATITIS B (4)(5) More than 2,000 million people alive today have been infected with HBV at some time in their lives. Of these, about 350 million remain infected chronically and become carriers of virtues. Three quarters of the world’s population live where there are high levels of infection. Every year there are over 4 million acute causes of HBV, and about 25% of carriers, 1 million people a year, die from chronic active hepatitis, cirrhosis or primary liver cancer. 10

11. 11 . Worldwide prevalence of hepatitis B carriers and primary hepatocellular carcinoma. (Courtesy Centers for Disease Control and Prevention, Atlanta.)

12. 12 The world can be divided into 3 areas where the prevalence of chronic hepatitis infection is high (>8%), intermediate(2-8%), and low (<2%). High endemicity areas include south-east Asia and Pacific Basin, sub-Saharan Africa, parts of middle east, some countries in eastern Europe. In these areas about 70-90% of population becomes HBV infected before the age of 40, and 8 to 20% of people are HBV carriers.

13. Low endemicity areas include North America, Western and Northern Europe, Australia. The carrier rate here 2% and less than 20% of the population infected with HBV The rest of the world falls into intermediate range of HBV prevalence, with 2 to 8% of a given population being HBV carriers. 13

14. HEPATITIS B VIRUS (5)(6) Hepatitis B is caused by the hepatitis B virus (HBV), an enveloped virus containing a partially double stranded, circular DNA genome, and classified within the family of hepadnavirus . 14

15. The virus interferes with the functions of liver while replicating in hepatocytes . The immune system is then activated to produce a specific reaction to combat and possibly eradicate the infectious agents. As a consequence of pathological damage, the liver becomes inflamed. HBV may be the cause of upto 80% of all cases of hepatocellular carcinoma world wide. 15

16. STRUCTURE OF HEPATITIS B VIRUS (5)(6)(7) Hepatitis virus is a DNA virus with a remarkably compact genomic structure. It have circular partially double-stranded DNA viruses. Replication occurs by reverse transcriptase. It is small, circular, 3200 base- pair size, HBV DNA codes for four sets of viral products and has a complex, multi particle structure. 16

17. The hepatitis B virus is 42nm in diameter and composed of 27 nm nucleocapsid core ( HBcAG ), surrounded by outer lipo protein coat (also called envelope) containing the surface antigen ( HBsAG ) Virion also referred to as Dane particle ( ds-tranded DNA) Core antigens located in the center ( nucleocapsid ) * Core antigen ( HBcAg ) * e antigen ( HBeAg 17

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19. HBsAg = surface (coat) protein HBcAg = inner core protein HBeAg = secreted protein 19

20. REPLICATION OF HEPATITIS B VIRUS (7)(8) 20 The HBV virion binds to a receptor at the surface of the hepatocyte . Viral nucleocaspids enter the cell and reach the nucleus, where the viral genome is delivered.

21. 21 Reverse transcription: one of the mRNAs is replicated with a reverse transcriptase making the DNA that will eventually be the core of the progeny virion RNA intermediate: HBV replicates through an RNA intermediate and produces and release antigenic decoy particles. Integration: Some DNA integrates into host genome causing carrier state

22. HOW THE VIRUS REPRODUCES ? 1.First the virus attached to a liver cell membrane 22

23. 2. The virus is then transported into the liver cell. 23

24. 3. The core particle then releases it’s contents of DNA and DNA polymerase into the liver cell nucleus. 24

25. 4.Once within the cell nucleus the hepatitis B DNA causes the liver cell to produce, via messenger RNA ; HBs protein , HBc protein , DNA polymerase, the HBe protein , and other undetected protein and enzymes. 5. DNA polymerase causes the liver cell to make copies of hepatitis B DNA from messenger RNA. 25

26. 6. The cell then assembles “live” copies of virus. 26

27. 7.However because of the excess numbers of surface proteins produced many of these stick together to form small spheres and chains. These can give a characteristic “ ground glass” appearance to blood samples seen under microscope . 27

28. 8. The copies of the virus and excess surface antigen are released from the liver cell membrane into blood stream and from there can infect other liver cells 28

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30. MODES OF TRANSMISSION (9) 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. 30

31. 31 Perinatal transmission Horizontal transmission Mother Infant Host Perinatal 90% of infected infants become chronically infected 6% of people infected over the age of 5 become chronically infected Recipient Child-to-child Contaminated needles Sexual contacts Healthcare worker Blood transfusion

32. 32 Heterosexual* (41%) Homosexual Activity (9%) Household Contact (2%) Health Care Employment (1%) Others (1%) Unknown (31%) Injecting Drug Use (15%)

33. High-risk groups for HBV infection (9) People from endemic regions Babies of mothers with chronic HBV Intravenous drug abusers People with multiple sex partners Hemo dialysis patients Health care personnel who have contact with blood Residents and staff members of institutions for the mentally retarded 33

34. STAGES OF THE DISEASES (10)(11) FIRST STAGE The duration of this stage for healthy adults is approximately 2-4 weeks and coincide with the incubation period . For newborns, the duration of this period often is decades. Active viral replication is known to continue despite little or no elevation in the aminotransferase levels and no symptoms of illness. 34

35. SECOND STAGE In the second stage, an inflammatory reaction with a cytopathic effect occurs. HBeAg can be identified in the sera and a decline of the levels of HBV DNA is seen. The duration of this stage for patients with acute infection is approximately 3-4 weeks (symptomatic period). For patients with chronic infection, 10 years or more may elapse before cirrhosis develops . 35

36. THIRD STAGE In the third stage, the host can target the infected hepatocytes and the HBV Viral replication no longer occurs. HBeAb can be detected. The HBV DNA levels are lower or undetectable, and aminotransferase levels are within the reference range. In this stage, an integration of the viral genome into the host's hepatocyte genome takes place. HBsAg still is present. 36

37. FOURTH STAGE In the fourth stage, the virus cannot be detected and antibodies to various viral antigens have been produced. Different factors have been postulated to influence the evolution of these stages, including age, sex, immunosuppression , and co-infection with other viruses. 37

38. PATHOLOGY (11)(12) Three antigen-antibody system 1) HBsAg -- anti-HBs system: HBsAg appears 1-2 weeks (late up to 11-12 weeks) after exposure, persists for 1-6 weeks( even 5 months) in acute hepatitis B. In chronic patients or carrier, HBsAg persist many years HBsAg is the marker of infectivity 38

39. HBsAg can be found in blood and secretions: saliva, urine, semen, tears, sweat and breast milk Anti-HBs appear after HBsAg disappear several weeks (or months) anti-HBs is protective antibody, can persist for many years 39

40. 2) HBcAg —anti- HBc system HBcAg can be found in the nuclei of liver cells, no free HBcAg in serum HBcAg is the marker of replication of HBV The stage called window phase Anti- HBc IgM is a marker of acute infection and acute attack of chronic infection of HBV. Anti- HBc IgG is the marker of past infection, high titer means low level replication of HBV 40

41. 3) HBeAg —anti- HBe system HBeAg is a soluable antigen HBeAg is a reliable indicator of active replication of HBV Anti- HBe is a marker of reduced infectivity. If exist long may be a marker of integration of HBV into liver cell 41

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44. PATHOGENISIS (11) HBV invades into the human body by skin and mucosa, Via blood flow enters the liver and other organs such as pancreas, bile ducts, vessels, WBC, bone marrow, glomerular basement membrane. HBcAg,HBsAg,HBeAg and HLA- Ⅰappear on the liver cells infected with are recognized by CTL simultaneously and lead to the cytolysis of liver cells. 44

45. Helper T cell are activated by the receptor of HLA- on its surface combing with HBsAg , HBcAg and HLA- antigen on the B cells promote B cell to release anti-HBs and clear HBV The representation of HBcAg on the liver cells may cause cytopathy 45

46. SIGNS AND SYMPTOMS (12) Fever Fatigue Loss of appetite Nausea Vomiting Abdominal pain Dark urine Clay-colored bowel movements Joint pain Jaundice Hepatomegaly 46

47. Symptoms begin an average of 3 months (range: 2–5months) after exposure to HBV. Symptoms typically last for several weeks but can persist for up to 6 months. 47

48. CLINICAL FEATURES (12)(13) 48 Incubation period Average 60-90 days Range 45-180 days Clinical illness (jaundice) <5 yrs- <10% >5yrs- 30-50% Acute case-fatality rate 0.5%-1% Chronic infection <5 yrs- 30-90% >5yrs- 2-10% Premature mortality from chronic liver disease 15%-25%

49. CLINICAL FEATURES ACUTE HEPATITIS B Incubation period- 45to 120 days average 60 to 90 days. Phases of disease Preicteric Icteric Convalescent 49

50. Preicteric Tiredness Anorexia Vague abdominal discomfort Nausea & Vomiting Sometime arthralgias & rash 50

51. Icteric Within 10days of initial symptoms Dark urine Pale stool Yellowish discoloration of mucous membranes. Total bilirubin - exceeds 20 to 40 mg/l Hepatosplenomegaly After disappearance of jundice -Anti HBs. 51

52. Convalescent Anti HBc IgM to IgG type Transient presence of HBsAg , HBeAg and viral DNA (<6 months) Seroconversion to anti HBsAg and anti HBeAg 52

53. Chronic Hepatitis B After acute infection virus remain in 5 to 10% cases of adult, even more higher among children upto 70 to 90%. 350 million of person worldwide are chronic carriers. Among them 100 million in China. Among the persistent carrier 70% will develop Chronic persistent hepatitis and remaining 30% will develop Chronic active hepatitis. 53

54. Clinical outcomes of Hepatitis B infections (14)(15) 54

55. Hepatocellular carcinoma Only 5% patient with cirrhosis develop HCC. HCC is responsible for 90% of primary malignant tumor of liver. Worldwide 7 th most common cancer in male while 9 th in female. Causes >500000 deaths annually with male & female ratio 4:1. 55

56. Appears after a mean duration of about 35 years of HBV infection. 56

57. Fulminant Hepatitis Rare condition, develop in about 1% cases. It is due to massive necrosis of liver substance. Usually fatal Survival in adult is uncommon. Genetic heterogeneity, co-infection, host immunological factors are responsible. 57

58. Extra-hepatic manifestations (15) Mediated by circulating immune complexes Both acute hepatitis & chronic hepatitis Acute hepatitis –10-20% Serum sickness like illness, Fever, rash, artralgia . Gainotti - Crosti syndrome Papular acrodermatits (children) Glomerular disease 58

59. DIAGNOSIS (16)(17) 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. 59

60. 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. 60

61. Concentration of Hepatitis B Virus in Various Body Fluids (16) High Moderate Low/Not Detectable blood serum wound exudates Semen Vaginal fluid Saliva Urine Feces Sweat Tears Breast Milk 61

62. LEVELS OF PREVENTION FOR HEPATITIS B (17)(18) Primary Prevention Advocacy and raising awareness of all types of viral hepatitis infections help to reduce transmission in the community. Safe and effective vaccines are widely available for the prevention of HAV and HBV infections and an HEV vaccine has recently been licensed in China. Implementation of blood safety strategies, including blood supplies based on voluntary non-remunerated blood donations, effective public education on blood donation, donor selection, and quality-assured screening of all donated blood and blood components used for transfusion can prevent transmission of HBV and HCV. 62

63. Infection control precautions in health care and community settings can prevent transmission of viral hepatitis as well as many other diseases. Safe injection practices can protect against HBV and HCV transmission. Safer sex practices. Harm reduction practices for injecting drug users prevent HAV, HBV and HCV transmission. Occupational safety measures prevent transmission of viral hepatitis to health care workers. Safe food and water provide protection against HAV and HEV infection . 63

64. HEPATITIS B VACCINATION (19) 1965 Discovery of Australian antigen 1973 Successful HBV infection of chimpanzees 1981 Licensure of plasma-derived vaccine 1986 Licensure of recombinant vaccine 1991 Universal infant vaccination 1996 Universal adolescent vaccination 64

65. Vaccines against hepatitis B were introduced in the early, 1980s. More than 110 countries have adopted a national policy of immunizing all infants with hepatitis B vaccine. HB vaccine is the most effective tool in preventing the transmission of HBV and HVD. Vaccine are composed of the surface antigen of HBV( HBsAg ), and are produced by two different methods: plasma derived or recombinant DNA. 65

66. PLASMA DERIVED VACCINE These vaccines, derived from the plasma of HBsAg - positive donors, consist of highly purified, formalin-inactivated and/or heat-inactivated, alum-absorbed, hepatitis B sub virion particles (22nm) of HBsAg that are free to detectable nucleic acid and therefore, noninfectious. The first plasma derived vaccines were manufactured in USA and France in 1981-1982. 66

67. Recommendation for pre exposure immunization with Hepatitis B Infants (Universal immunization) Infants and adolescents not vaccinated previously (catch-up vaccination) Person with occupational risk Haemodialysis patients Recipients of blood and blood products Susceptible drug abusers. Sexually active men or women Susceptible inmates who have a history of high risk behavior 67

68. Household contacts and sex partners of HBV carriers Population with a high incidence of disease International traveler to area of high HBV endemicity Transplant candidates. 68

69. COMBINATION VACCINES The HBsAg vaccines can be combined with other vaccines such as Calmetta -Guerin Bacillus(BCG), measles, mumps, and rubella, Haemophilus influenzae b, diptheria , tetanus and petussis combined with polio. Neonates born to mother who are HBsAg positive should be given a combination of passive and active immunization to provide immediate protection in the first 6 hours after delivery, followed by long term immunity with the vaccine. 69

70. The vaccine is administered by intramuscular injection in the antrolateral aspect of the thigh of the new born and infants or deltoid (arm) muscle of children and adults in order to achieve optimal protection. It is particular effective 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. Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. 70

71. Hepatitis B Vaccine Adolescent and Adult Schedule 71 Dose Primary 1 Primary 2 Primary 3 Minimum Interval - - - 4 weeks 8 weeks* Usual Interval --- 1 month 5 months *third dose must be separated from first dose by at least 16 weeks

72. Recommended Dose of Hepatitis B Vaccine 72 Infants and children <11 years of age Adolescents 11-19 years Adults > 20 years Recombivax HB Dose (mcg) 0.5 mL (5) 0.5 mL (5) 1.0 mL (10) Engerix -B Dose (mcg) 0.5 mL (10) 0.5 mL (10) 1.0 mL (20)

73. Factors for decreased vaccine response: - Smoking - Obesity - HIV infection - Imunocompromised patients - Haemodialysis - Prematurity - Genetic factors - Chronic disease. - Subcutaneous injection - Freezing of vaccine - Accelerated schedule 73

74. DENTAL CONSIDERATION For dentists : Hepatitis B & Hepatitis C virus are important as they can be transmitted by various methods as it is most common blood borne infection. Its is associated with many clinical features which are encountered by dentist like: Sjorgren’s syndrome lichen planus glossitis and/or angular cheilosis Mucosal Ecchymosis 74

75. Management for dentists: Pre – Exposure vaccination : Engerix . Which is available commonly. Maintaining proper sterilization and infection control measures. More use of disposable products like disposable gloves, mouth mask, syringes, etc. Proper disposal of used needles. 75

76. ROLE OF A PUBLIC HEALTH DENTIST A public health dentist can play an important role in preventing the hepatitis B by: Educating people about ways of mode of transmission of diseases. By telling the real facts and myths related to disease. To encourage people for vaccination Telling about healthy lifestyle and habits to prevent any kind of liver related diseases. 76

77. SECONDARY PREVENTION (20) Early diagnosis provides the best opportunity for effective medical support and prevention of further spread. It also allows the infected persons to take steps to prevent transmission of the disease to others. Early diagnosis of those with chronic infection also allows people to take precautions to protect the liver from additional harm, specifically by abstaining from alcohol and tobacco consumption and avoiding certain drugs that are known to be toxic to the liver. 77

78. Treatment of acute HBV infection is primarily supportive. Good nutrition and bed rest should be reinforced. Abstinence from alcohol and the use of hepatotoxic drugs is also necessary. Conversely, chronic HBV infection may be progressive and, therefore, requires management. The goals of therapy include minimization of hepatocellular damage and viral clearance. 78

79. Possible adverse effects to interferon include fever and chills, headache, depression, malaise, tachycardia, bone marrow suppression, alopecia and, on rare occasion ,cardiac or renal failure. 79

80. In acute hepatitis B the treatment is basically symptomatic Rest Ant emetics to control vomiting Plenty of fluids and carbohydrates Hepatotropic agents 80

81. Chronic Hepatitis B (20)(21) Interferon - for HBeAg + ve carriers with chronic active hepatitis. Response rate is 30 to 40%. 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. Successful response to treatment will result in the disappearance of HBsAg , HBV-DNA, and seroconversion to HBeAg . 81

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83. TERTIARY PREVENTION There is no surgical treatment for hepatitis B. In case of advanced liver damage because of hepatitis and condition becomes life-threatening, their is need a liver transplant. In rare cases, acute hepatitis B progresses rapidly to liver failure, a deadly condition called fulminant hepatitis. For people who develop this condition, a liver transplant is the only treatment choice. 83

84. CONCLUSION Hepatitis B is the most common serious liver infection in the world. It is caused by the hepatitis B virus (HBV) that attacks liver cells and can lead to liver failure, cirrhosis scarring) or cancer of the liver. The virus is transmitted through contact with blood and bodily fluids that contain blood. 84

85. The hepatitis B virus is 100 times more infectious than the AIDS virus. Yet, hepatitis B can be prevented with a safe and effective vaccine. For the 400 million people worldwide who are chronically infected with hepatitis B the vaccine is of no use. However, there are promising new treatments for those who live with chronic hepatitisB . 85

86. REFERENCES 1. Hepatitis B Epidemiology and Prevention of Vaccine-Preventable Diseases The Pink Book: Course Textbook - 12th Edition Second Printing (May 2012) Center Of Diseases Control 2. Fauci , Braunwald , Isselbacher Harrison’s Principle of internal mediciene vol-2 14 th edition. 3. Haslett, Chivers , Boon Davidson’s Principles and Practice of Mediciene . 2004 19 th edition. 4. Churchill’s Illustrated Medical Dictionary, New York , Churchill Livingstone, 1989. 5. Harmanjit Singh Hira Text book of General Medicine for Dental Students. 6. Manual of Clinical Microbiology, Patrick R Murray 9 th edition. 7. Topely and Wilson’s, Virology volume-1 ,9 th edition. 86

87. 8. Mandell’s , Principle and Practice of Infectious Diseases, 5 th edition 9. Documents on Hepatitis A-E published by WHO, Department of Communicable Diseases Surveillance and Response 10. Textbook of Microbiology, Ananthanarayan and Paniker,7 th edition 11. European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 2009;50:227–242. 87

88. 12. Ganem D, Schneider RJ. Hepadnaviridae : The Viruses and Their Replication. In : Knipe DM et al., eds. Fields Virology, 4 th edition, Philadelphia, Lippincott Willams & Wikins , 2001:2923-2969. 13. Ganem D, Prince AM. Hepatitis B virus infection – natural history and clinical consequences. N Engl J Med 2004;350:1118–1129. 14. Hepatitis B ; World Health Organization, Department of Communicable Diseases Surveillance and Response; WHO/CDC/LYO/2002.2: Hepatitis B. 15. Center for Disease Control and prevention. Hepatitis B vaccine. 1998 ( http://www.cdc.gov/ncidod/diseases/b/hebqafn.htm ) 16. Gitlin N. Hepatitis B: diagnosis, prevention, and treatment. Clinical Chemistry, 1997, 43:1500-1506. 17. Prevention and Control of Viral Hepatitis; Frame Work for global action;WHO/HSP/PED/HIP/GHP/2012.1 88

89. 18. Jacobsen KH, Wiersma ST. Hepatitis A virus seroprevalence by age and world region, 1990 and 2005 Vaccine, 2010, 28: 6653–6657. 19. Perz JF et al. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. Journal of Hepatology , 2006,45: 529–538. 20. World Health Organization. Hepatitis B vaccines. Weekly Epidemiological Record, 2004.79:255-263. 21.Hepatitis B Department of Health and Human Services Center Of disease conrol and prevention ; Division of viral hepatitis.June 2010 (WWW.CDC.gov/hepatitis) 89

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