1. An Overview

2. Hepatitis = 'inflammation of the liver'. five medically important viruses are commonly described as “hepatitis viruses”: HAV,HBV,HCV,HDV,HEV. Other reasons: Sporadic hepatitis (viruses): yellowfever/CMV/EBV/HSV/Rubella/enteroviruses Hepatitis may occasionally occur as a complication of leptospirosis, syphilis, tuberculosis, toxoplasmosis, and amebiasis, Noninfectious causes included: Wilson disease, drug toxicity, and drug hypersensitivity reactions. General Concepts

3. Acute: Short term and/or severe. Chronic: Lingering or lasting - may or may not be severe Fulminant: Developing quickly and lasting a short time, high mortality rate. Cirrhosis: Hardening: may be the result of infection or toxins (e.g. alcohol) Jaundice: Yellowing of the skin, eyes, levels of bilirubin in the blood due to liver damage. Hepatocellular carcinoma ： is closely associated with hepatitis B, and at least in some regions of the world with hepatitis C virus. Definitions for Hepatitises

5. Hepatitis A Definition: Etiologic agent of infectious hepatitis Prototype of genus Hepatovirus Only one serotype is known Stable to acid, pH (1 for 2 hrs) and heat Transmission: fecal-oral, prevalence : high Fulminant: rare, chronic disease: never pathologically similar to HBV

6. Hepatitis A HAV is widespread throughout the world. Outbreaks of type A hepatitis are common in families and institutions, summer camps, day care centers, neonatal intensive care units, and among military troops. Most cases of hepatitis type A occur without jaundice during childhood

7. HAV is seldom transmitted by the use of contaminated needles and syringes or through the administration of blood The onset of disease tends to occur abruptly with HAV (within 24 hours), in contrast to a more insidious onset with HBV and HCV. The disease is more severe in adults than in children. Relapses of HAV infection can occur 1–4 months after initial symptoms have resolved.

8. Fecal HAV Symptoms 0123 4561224 Hepatitis A Infection Total anti-HAV TitreALT IgM anti-HAV Months after exposure Typical Serological Course Hepatitis A virus appears early in the disease and disappears within 2 weeks following the onset of jaundice.

9. Acute infection is diagnosed by the detection of HAV-IgM in serum by EIA. Past Infection i.e. immunity is determined by the detection of HAV-IgG by EIA. Cell culture – difficult and take up to 4 weeks, not routinely performed Direct Detection – EM, RT-PCR of faeces. Can detect illness earlier than serology but rarely performed. Laboratory Diagnosis

11. Formalin-inactivated HAV vaccines: The vaccines are safe, effective, and recommended for use in persons over 1 year of age. Immune globulin (IG) is prepared from large pools of normal adult plasma and confers passive protection in about 90% of those exposed when given within 1–2 weeks after exposure to hepatitis A.. Preventaion

13. Hepatitis Type B HBV is classified as a hepadnavirus Etiologic agent of Serum hepatitis HBV establishes chronic infections, especially in those infected as infants. it is a major factor in the eventual development of liver disease and hepatocellular carcinoma in those individuals.

15. 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. Statistics on HBV

16. 42nm, Dane particle * Surface Ag (HBS-Ag), * Core antigen (HBcAg), Core antigens located in the center (nucleocapsid) * e antigen (HBeAg)- an indicator of transmissibility 22nm, spheres and filaments (decoy particles), other forms- no DNA in these forms so they are not infectious (result from overproduction of HBsAg), they are immunogenic, HBV : Structure

17. Electron micrograph showing three distinct HBsAg-bearing forms: 20-nm pleomorphic spherical particles (A), filamentous forms (B), and 42-nm spherical Dane particles, the infectious form of HBV (C).

18. Hepatitis B HBV is worldwide in distribution. Hepatitis B infections are common among patients and staff of hemodialysis units. The incubation period of hepatitis B is 50–180 days, with a mean between 60 and 90 days.

19. Spectrum of Hepatitis B Diseases 1Acute hepatitis 2Chronic Persistent Hepatitis - asymptomatic 2.Chronic Active Hepatitis - symptomatic exacerbations of hepatitis 3. Cirrhosis of Liver 4. Hepatocellular Carcinoma Both HBV and HCV have significant roles in the development of hepatocellular carcinoma that may appear many (15–60) years after establishment of chronic infection.

20.  Parenteral - IV drug abusers, health workers are at increased risk.  Sexual - sex workers and homosexuals are particular at risk.  Perinatal (Vertical) - mother(HBeAg+) → infant. Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. HBV: Modes of Transmission

21. HighModerate Low/Not Detectable bloodsemenurine serumvaginal fluidfeces wound exudatessalivasweat tears breastmilk Concentration of Hepatitis B Virus in Various Body Fluids

22. 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.

23. Symptoms HBeAg anti-HBe Total anti-HBc IgM anti-HBc anti-HBs HBsAg 0481216 20 242832 36 52100 Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Weeks after Exposure Titr e

24. IgM anti-HBc Total anti-HBc HBsAg Acute (6 months) HBeAg Chronic (Years) anti-HBe 048 12 16202428 32 36 52 Years Weeks after Exposure Titre Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course

28. Interferon Alfa (Response rate is 30 to 40%). for HBeAg +ve carriers with chronic active hepatitis Lamivudine (relapse,drug resistance, a nucleoside analogue reverse transcriptase inhibitor ) Adefovir dipivoxil Entecavir : similar to Adefovir Current Treatment Options

29. Prevention Vaccination – P reparing by purifying HBsAg associated with the 22- nm particles from healthy HBsAg-positive carriers 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.

30. HBsAg RNA  antigen Hepatitis D (Delta) Virus

31. Hepatitis D Virus It is classified in the Deltavirus genus, which is not assigned to any virus family The delta agent is a defective virus which shows similarities with the viroids in plants. The genome of the virus is single-stranded, circular, negative-sense RNA, 1.7 kb in size It acquires an HBsAg coat for transmission.

32. Hepatitis D (Delta Agent ) HDV is found throughout the world Its highest prevalence has been reported in Italy, the Middle East, central Asia, West Africa, and South America. HDV infects all age groups. Persons who have received multiple transfusions, intravenous drug abusers, and their close contacts are at high risk.

33.  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

35. HBV-HDV Coinfection Pre or postexposure prophylaxis to prevent HBV infection. Delta hepatitis can be prevented by vaccinating HBV- susceptible persons with hepatitis B vaccine. HBV-HDV Superinfection Education to reduce risk behaviors among persons with chronic HBV infection. However, vaccination does not protect hepatitis B carriers from superinfection by HDV. Hepatitis D - Prevention

36. Hepatitis C:

37. Hepatitis C Definition: Acommon etiologic agent of posttransfusion HCV is classified as flaviviridae Genus Hepacivirus HCV is a positive-stranded RNA Most cases of posttransfusion NANB hepatitis were caused by HCV

38.  HCV has been classified into a total of six genotypes (type 1 to 6) on the basis of phylogenetic analysis  Most primary infections are asymptomatic or clinically mild (20– 30% have jaundice, 10–20% have only nonspecific symptoms such as anorexia, malaise, and abdominal pain)  Acute infection: 15%  Chronic infection: 70%  Developing cirrhosis: 15%

39.  Transfusion or transplant from infected donor  Injecting drug use  Hemodialysis (yrs on treatment)  Accidental injuries with needles/sharps  Sexual/household exposure to anti-HCV-positive contact  Multiple sex partners  Birth to HCV-infected mother (3% to 10%). Risk Factors Associated with Transmission of HCV

40. 3%

41. HCV antibody - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears. HCV-RNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. HCV-antigen - an EIA for HCV antigen is available. It is used in the same capacity as HCV-RNA tests but is much easier to carry out. Laboratory Diagnosis

42. 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. Treatment

43. Prevalence No vaccine Control measures focus on prevention activities that reduce risks for contracting HCV. These include screening and testing blood, plasma, organ, tissue, and semen donors; virus inactivation of plasma-derived products; counseling of persons with high-risk drug or sexual practices;

44. Hepatitis Type E

45. Hepeviridae unenveloped RNA virus, 32-34nm in diameter +ve stranded RNA genome, 7.6 kb in size. Can only be cultured recently Hepatitis E Virus

46. Hepatitis Type E There is evidence of HEV or HEV-like infections in rodents, pigs, sheep, and cattle in the United States. There is the possibility of spread of virus from animals to humans.

47. Most outbreaks associated with faecally contaminated drinking water. Minimal person-to-person transmission. Mortality 10 times more than HAV (1-2%) Fulminant: in pregnancy woman (mortality : 20%) Hepatitis E - Epidemiologic Features

48. Symptoms IgG anti-HEV Hepatitis E Virus Infection Typical Serologic Course Symptoms ALT IgG anti-HEV IgM anti-HEV Virus in stool 012345678910101 1212 1313 Titer Weeks after Exposure

49. More in Pakistan, nepal, north africa and Mexican