EPIDEMIOLOGY OF HEPATITIS B AND C

1. EPIDEMIOLOGY OF HEPATITIS B AND C Dr. Soumya Swaroop Sahoo JR,Dept . of Community Medicine PGIMS Rohtak

2. CONTENTS Introduction Global burden Problem statement in India Virus and transmission Clinical manifestations Treatment Prevention and control Vaccination

3. INTRODUTION Hepatitis B initially called as serum hepatitis is an acute systemic illness with major pathology in liver. HBV infection is the 10th leading cause of death and HBV related hepatocellular carcinoma(HCC ) is the 5th most frequent cancer worldwide.

4. HEPATITIS- Historical Perspective A “ Serum” Viral hepatitis Enterically transmitted G E NANB B D C Parenterally transmitted

5. PROBLEM STATEMENT : WORLD 2 billion people have been infected (1 out of 3 people). 350 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. Source-(WHO, hepb.org)

6. Prevalence of Chronic HBV Infection, Worldwide, 2006 Source: CDC and Prevention. MMWR 2008;57(RR-8):1-20. HBsAg Prevalence > 8% = High 2-7% = Intermediate < 2% = Low

7. PROBLEM STATEMENT : INDIA India has over 40 million HBV carriers and accounts for 10–15% of the entire pool of HBV carriers of the world. Estimated 43-45 million new cases per year. 100,000 death annually by disease related to HBV infection. Of 25 million newborn annually, 1 million run lifetime risk of HBV infection. Source-1) API 2)World Health Organization (2012)

8. STUDIES IN HARYANA In Sirsa an outbreak of hepatitis B occured in 1997. 54 cases of jaundice occurred in Dhottar village (population 3096) 8 (33·3%) of them died Virtually all fatal cases were adults and tested positive for HBsAg . The results linked the outbreak to the use of unnecessary therapeutic injections Source-Journal of epidemiology and infection,2000(125) ,693-99

9. STUDIES IN HARYANA In a Study titled To Assess Trend In Seroprevalence Of Hepatitis B Virus Infection Among Blood Donors Of Southern Haryana, 11,340 blood donors screened The overall seroprevalence of HBsAg was observed to be 1.32%. According to the WHO classification, this southern part of Haryana qualifies as a low prevalence area.  The Internet Journal of Pathology . 2012 Vol 13 (2)

10. Acute hepatitis B: Case Definition A clinical case of acute viral hepatitis is an acute illness that includes discrete onset of symptoms and jaundice or elevated serum aminotransferase levels (>2.5 times the upper limit of normal) A confirmed case of hepatitis B is a suspected case that is laboratory confirmed: HBsAg positive or Anti- HBc - IgM positive and Anti-HAV- IgM negative.

11. AGENT AGENT Hepatitis B virus belongs to hepadnavirdae family. Complex 42 nm. Double stranded Enveloped DNA virus (DNA polymerase with reverse transcriptase activity) Known as “Dane” particle. Has affinity for liver and hepatocytes

12. AGENT FACTORS Reservoir of infection Human beings are the only reservoir Infection spread by cases or carriers Carrier state defined as persistence of HBsAg > 6 months Resistance of virus: Quite stable, can survive for days in environmental conditions . Can be destroyed by sodium hypochlorite Also by autoclaving for 30 to 60 minutes Period of communicability: From incubation period upto disappearance of HBsAg and appearance of antibody.

13. HOST FACTORS AGE: Acute Hepatitis B occurs in 1% perinatal, 10% early childhood (1-5 yrs) and 30% in older children (>5 yrs age) HBV infections. Outcome age dependent Development of chronic infection inversely related to age. Young children who become infected are most likely to develop chronic infections: 90% of infants infected during the first year of life develop chronic infections; 30–50% of children infected between one to four years of age develop chronic infections.

14. HOST FACTORS 25% of adults who become chronically infected during childhood die from hepatitis B-related liver cancer or cirrhosis; 90% of healthy adults infected with HBV recover and get completely rid of the virus within six months. Globally, HBV causes 60 - 80% of the world’s primary liver cancers. Motality from fulminant Hepatitis B -70%

15. High Risk groups Health care workers and laboratory personnel High risk sexual behaviour (homosexuals, prostitutes) Frequent blood transfusion recepient I.v . drug users Immunocompromised individuals Infants of HBV carrier mothers Recipients of solid organ transplants

16. ROUTES OF TRANSMISSION 1) Vertical transmission 2) Sexual transmission 3) Parenteral transmission Needle stick injury Household contacts

17. Virus and Transmission In developing countries, common routes of transmission are: perinatal (from mother to baby at birth) early childhood infections (inapparent infection through close interpersonal contact with infected household contacts) unsafe injection practices unsafe blood transfusions unprotected sexual contact I.V. drug use

18. Virus and Transmission In developed countries patterns of transmission are different from those in developing countries. Majority of infections in developed countries are transmitted during young adulthood by unsafe sexual practices I .V. drug use. The virus is not spread by contaminated food or water, and cannot be spread casually in the workplace.

19. jaundice fever Abdominal pain and joint pain Symptoms of acute infection

20. Symptoms HBeAg anti- HBe Total anti- HBc IgM anti-HBc anti-HBs HBsAg 4 8 12 16 20 24 28 32 36 52 100 Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Weeks after Exposure Titre

21. IgM anti-HBc Total anti-HBc HBsAg Acute (6 months) HBeAg Chronic (Years) anti-HBe 4 8 12 16 20 24 28 32 36 52 Years Weeks after Exposure Titre Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course

22. DIAGNOSIS 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 HBV-DNA - indicates active replication of virus, more accurate than HBeAg . Used mainly for monitoring response to therapy.

23. EXPOSURE Acute hepatitis B infection Asymptomatic Or Subclinical infection(33%) Clinical infection -jaundice -flu like symptom(66%) Fulminant hepatitis (0.5%) Death Chronic Carrier (5-10%) Recovery Immunity (85-90%) Minimal liver Disease (70-90%) Chronic Hepatitis (10-30%) Primary hepatocellular carcinoma cirrhosis DEATH Reactivation

24. Hepatitis B and HIV Around 10 percent of 40 million people infected with HIV are coinfected with Hep B. HBV infection has minimal effect on progression of HIV. But HIV markedly increases the risk of developing cirrhosis and hepatocellular CA . HIV treatment can be used safely and effectively if coinfected with hepatitis B .

25. Hepatitis B in Pregnancy Risk of transmission ranges from 10% in 1 st trimester to about 90% in 3 rd trimester. If a pregnant woman tests positive for hepatitis B, the newborn must be given - the 1st dose of hepatitis B vaccine and one dose of hepatitis B immune globulin (HBIG). Given within 12 hours of life, a newborn has 95% chance of being protected against a lifelong hepatitis B infection. If not given in time - > 90% possibility that the baby will become chronically infected. According to WHO, it is safe for an infected woman to breastfeed her child since the benefits of breastfeeding outweigh the potential risk of transmitting the virus through breast milk.

26. Treatment Acute : No medication available; best addressed through supportive treatment Chronic hepatitis B: Antivirals : interferon- α- 2a , interferon- α-2 b, Lamivudine, Adefovir , Entecavir Immune-modulators: prednisone, interleukin, thymosin , levamisole Liver cirrhosis and Hepatocellular CA: Liver transplant

27. PREVENTION AND CONTROL Goals of prevention : To decrease prevalence of chronic carrier and chronic liver disease Prevention of acute hepatitis B infection Strategies: Hepatitis B vaccination. Screening of blood, plasma and organ donor. Universal precautions.

28. HEPATITIS B VACCINATION Active immunization Passive immunization ACTIVE IMMUNIZATION Two types of vaccine available 1. Plasma derived vaccine 2. Recombinant DNA vaccine PLASMA DERIVED VACCINE: Based on HBsAg derived from plasma of human carrier. Formalin inactivated Costlier

29. Recombinant DNA Vaccine Introduced in 1986 in USA. Has replaced plasma derived vaccine. Cost effective Available as monovalent or combined vaccine Active substance: - HBsAg derived from culture of yeast or mammalian cells Adjuvant: - Alum or thiomersal Storage: -2 to 8°C - Freezing avoided HEPATITIS B VACCINATION

30. Age : Ideal first dose at birth ( within 24 hours) Next 2 or 3 dose according to immunization schedule No. of doses: 3 or 4 First at birth , second and third with DPT1 and DPT3. First at birth, second, third and fourth with DPT A dults 3 doses at 0, 1 month, 6 month HEPATITIS B VACCINATION

31. Neither pregnancy nor lactation is a contraindication for its use. Usually provides life long immunity Adverse reactions: Infrequent and rare transient fever(1-5%) , local reaction(5%), soreness, myalgia Very rarely anaphylactic reaction . HEPATITIS B VACCINATION

32. PASSIVE IMMUNIZATION Hepatitis B immunoglobulin used for temporary post-exposure prophylaxis. Combined active and passive vaccination is advised in following cases: - Newborn of HBsAg + ve mother - Percutaneous exposure - Sexual exposure - After liver transplant in case of recurrent HBV infection Time : within 6 hours of exposure and maximum upto 48 hours. Dose: 0.05 to 0.07 ml. / kg. body weight. Provides short term passive immunity for 3 months. HEPATITIS B VACCINATION

33. HEPATITIS B VACCINATION As of July 2011, 179 countries have included hepatitis B as part of their vaccination schedules – a major increase compared with 31 countries in 1992. Hep B3 coverage- 34% (WHO and UNICEF immunization coverage 2011) Catch up campaign for older age groups is important in intermediate and low endemicity area. Catch up campaign for infants and young children is important in high endemicity area. Source - WHO

34. PREVENTION AND CONTROL For quality, safety and efficacy of blood transfusion, the National Blood Policy, 2002 was formulated by the government. According to it each blood unit shall be tested to be free from Hepatitis B surface antigen and HCV antibody with the results recorded on the label of the container.

35. SURVEILLANCE Hepatitis B and C are included in the IDSP reporting format. Hepatitis B disease surveillance procedures should include Monitoring disease incidence Determination of sources of infection and modes of transmission by epidemiological investigation Detection of outbreaks Spread containment Identification of contacts of cases for postexposure prophylaxis

36. HEPATITIS C

37. INTRODUCTION By the late 1970s it was apparent that HBV was not the only cause of "serum" hepatitis, and that other "non-A-non-B" hepatitis viruses existed. Houghton and colleagues cloned and expressed portions of a RNA virus from the plasma of an infected chimpanzee in 1989. This virus, designated hepatitis C virus (HCV), is now known to be a major cause of both transfusion-associated and sporadic non-A-non-B hepatitis

38. INTRODUCTION

39. PROBLEM STATEMENT: WORLD According to WHO estimates 3% of world population infected with HCV 170 million are chronic carriers 3–4 million new infections per year more than 350 000 people die every year from hepatitis C-related liver diseases Highest – Egypt(15%) Most common cause of chronic liver disease in the United States and the most common indication for liver transplantation

40. PROBLEM STATEMENT:INDIA HCV prevalence-1.5% About 12 million chronic carriers HCV antibodies found in 2% of voluntary blood donors. 42% of patients with hepatocellular CA had markers of HCV infectio n. Source-WHO, http://www.epidemic.org

41. HIGH RISK GROUPS Current or former i.v . drug users Recipients of clotting factor concentrates Recipients of blood transfusions or donated organs before July 1992 Persons with known exposures to HCV (e.g., healthcare workers after needlestick injuries) Infants born to infected mothers Long-term haemodialysis patients

42. ACUTE HEPATITIS C: Case Definition Acute illness typically including acute jaundice, dark urine, anorexia, malaise, extreme fatigue, and right upper quadrant tenderness. Biological signs include increased urine urobilinogen and >2.5 times the upper limit of serum alanine aminotransferase . Laboratory criteria for diagnosis: Hepatitis C: Positive for anti-HCV Confirmed Case: a suspected case that is laboratory confirmed.

43. Agent HCV is a Small(55-65nm) enveloped, single-stranded, RNA virus Flaviviridae family Classified into 6 genotypes No resemblance to HBV or HDV.

44. Clinical Course Incubation period- mean 6-7 wks 85% of individuals, the clinical course of the acute infection is asymptomatic and easily missed Persistent infection and chronic hepatitis are the hallmarks of HCV infection, despite the generally asymptomatic nature of the acute illness.(75% to 85% of cases) Immunity- no protective antibody response

45. ROUTES OF TRANSMISSION Intravenous drug use: sharing of needles and syringes Reuse of contaminated needles 2) Sexual transmission 3) Blood transfusion 4) Vertical transmission 5) Needlestick injury

46. fever Nausea & vomiting fatigue Muscle & joint aches Clay colored Stools & Dark urine jaundice SYMPTOMS OF ACUTE INFECTION

47. Symptoms anti-HCV ALT Normal 1 2 3 4 5 6 1 2 3 4 Hepatitis C Virus Infection Typical Serologic Course Titre Months Years Time after Exposure

48. DIAGNOSIS Diagnosis of acute infection is often missed because a majority of infected people have no symptoms. Common methods of antibody detection cannot differentiate between acute and chronic infection. The presence of antibodies against HCV indicates infection. Recombinant immunoblot assay (RIBA) and hepatitis C virus RNA testing are used to confirm the diagnosis. Chronic Hepatitis C- anti HCV> 6 months

49. Natural history of HCV infection Exposure (Acute Phase) Chronic Cirrhosis HCC Transplant Death Resolved Stable Slowly Progressive 85%(85) 80%(68) 20%(17) 25%(4) 75%(13) 15%( 15) HIV and Alcohol

50. Progression of HCV Infection

51. TREATMENT Acute : Antiviral ( Ribavirin ) and supportive treatment Chronic Regular monitoring for signs of liver disease progression; antiviral drugs – peginterferon Cirrhosis, liver cancer patients- liver transplant

52. PREVENTION Primary prevention There is no vaccine for hepatitis C. The risk of infection can be reduced by avoiding: unnecessary and unsafe injections; unsafe blood products; unsafe sharps waste collection and disposal; use of illicit drugs and sharing of injection equipment; unprotected sex with hepatitis C-infected people; sharing of sharp personal items that may be contaminated with infected blood; tattoos, piercings and acupuncture performed with contaminated equipment.

53. PREVENTION Secondary prevention: For people infected with the hepatitis C virus, WHO recommends: education and counselling on options for care and treatment; immunization with the hepatitis A and B vaccines to prevent coinfection ; early and appropriate medical management including antiviral therapy ; and regular monitoring for early diagnosis of chronic liver disease.

54. Difference between Hepatitis B& C Viral Hepatitis Type B Viral Hepatitis Type C Incubation period 50-180 days ( avg 60-90) 40-120 days Principal age of distribution 15-29 years Adults Seasonal incidence Throughout the year Throughout the year Route of infection Predominantly parenteral Predominantly parenteral Occurrence of virus Blood Months to years Months to years Stool Absent Probably absent Urine Absent Probably absent Saliva ,semen Frequently present Unknown Clinical &lab features Onset Insidious Insidious Fever >38 o c (100.4 F) Less common Less common

55. Viral Hepatitis Type B Viral Hepatitis Type C Duration of aminotransferase elevation 1-6+ months 1-6+ months Immunoglobulins ( Ig M) Normal to slightly elevated Normal to slightly elevated Complications Chronicity in 5-10% cases Chronicity in >50% cases Mortality rate 1-2% 0.5-1% HBs Ag Present Absent Immunity Homologous Yes ? heterologous No No Duration Probably lifetime ? Immunoglobulins Prevents jaundice only if immunoglobulin is of sufficient potency against HBV

56. 500 million people worldwide infected with either Hepatitis C or Hepatitis B. Hepatitis B and C kill 1.5 million people a year. ONE in every 3 people in our planet exposed to either or both virus. Most of the 500 million infected do not know. ONE in every 12 people worldwide are living with either chronic Hepatitis B or Hepatitis C.

57. REFERENCES Park’s Textbook of preventive and social medicine, 21 st edition World Health Organisation (WHO) www.who.org Hepatitis B foundation, www.hepb.org Robbins Textbook of Pathology, 8 th edition Centre for Disease Control and Prevention(CDC) www.cdc.gov_hepatitis_hbv_pdfs_hepbgeneralfactsheet Virology Journal, An overview of molecular epidemiology of hepatitis B virus (HBV) in India Association of Physicians of India: Indian Guidelines and Protocols: Hepatitis B

58. WORLD HEPATITS DAY- 2012