14/2/2011Dr. Salwa Tayel1

14/2/2011Dr. Salwa Tayel221/2/20102 Viral Hepatitis Associate Professor Family and Community Medicine Department King Saud University

14/2/2011Dr. Salwa Tayel3 A “Infectious” “Serum” Viral hepatitis EntericallytransmittedParenterallytransmitted other other E “NANB” BD C Viral Hepatitis – Historical Perspective

14/2/2011Dr. Salwa Tayel4 A, B, Cs of Viral Hepatitis A –fecal-oral spread: hygiene, drug use, men having sex with men, travelers, day care, food –vaccine-preventable B –sexually transmitted – 100x more infectious than HIV –blood-borne (sex, injection drug use, mother- child, and health care) –vaccine-preventable C –blood borne (injection drug use primarily) – 4-5 times more common than HIV –NOT vaccine-preventable!

14/2/2011Dr. Salwa Tayel5 Acute Hepatitis – Clinical Symptoms Asymptomatic > Symptomatic > Fulminant Liver Failure > Death Symptoms (if present) are the same, regardless of cause (e.g., A, B, C, other viruses, toxins) Nausea, vomiting Abdominal pain Loss of appetite Fever Diarrhea Light (clay) colored stools Dark urine Jaundice (yellowing of eyes, skin)

Dr. Salwa Tayel6 Infectious hepatitis, epidemic hepatitis, epidemic jaundice. Children are usually asymptomatic, adults symptomaticChildren are usually asymptomatic, adults symptomatic Onset is usually sudden with fever followed within few days by jaundice.Onset is usually sudden with fever followed within few days by jaundice. Complete recovery is the rule (no chronicity).Complete recovery is the rule (no chronicity). The case-fatality rate among persons of all ages is approximately 0.3%The case-fatality rate among persons of all ages is approximately 0.3% but is approximately 2% among persons > 40 years.but is approximately 2% among persons > 40 years.

Dr. Salwa Tayel7 It is worldwide In developing countries, it occurs in endemic and epidemic forms due to: Poor environmental sanitation Overcrowding Lack of personal hygiene.

Dr. Salwa Tayel8 Geographic Distribution of HAV Infection

Dr. Salwa Tayel9 Endemicity Disease Rate Peak Age of Infection Transmission Patterns Early childhood Late childhood/ young adults Young adults High Moderate Low Very low Low to high High Low Very lowAdults Person to person; outbreaks uncommon Person to person; food and waterborne outbreaks Person to person; food and waterborne outbreaks Travelers; outbreaks uncommon Global Patterns of Hepatitis A Virus Transmission

Dr. Salwa Tayel10 Agent Susceptible Host Reservoir Mode of transmission Cycle of infection Portal of Exit Portal of Inlet IP PC

Dr. Salwa Tayel11 Hepatitis A Virus Picornavirus (RNA) Stable at low pH Inactivated by high temperature, formalin, chlorine

Dr. Salwa Tayel12 Human  clinical  sub-clinical cases  incubating carriers Through anal orifice with faeces.

Dr. Salwa Tayel13 1. Fecal-oral route. Close personal contact; house hold contact,, sex contact, day care centers. 2.Common vehicle; contaminated water and food; raw shellfish food handlers. 3. Rarely through blood transfusion and contaminated syringes.

Dr. Salwa Tayel14 Through the mouth. Susceptibility is general. Post infection immunity after the attack probably lasts for life.

Dr. Salwa Tayel15 Incubation period 28 days (range days) The maximum infectivity is during the latter half of the incubation period (2 weeks before and 1 week after onset of jaundice).

Dr. Salwa Tayel16 Prevention of Hepatitis A Vaccination Immune globulin Good hygiene (hand washing) Clean water systems; avoidance of food contamination Food sanitation especially shell fish and raw eaten food.

Dr. Salwa Tayel17 Pre-exposure – travelers to intermediate and high HAV-endemic regions Post-exposure (within 14 days) Routine – household and other intimate contacts Selected situations – institutions (e.g., day care centers) – common source exposure (e.g., food prepared by infected food handler) Hepatitis A Prevention – Immune Globulin

Dr. Salwa Tayel18 Hepatitis A Vaccine Inactivated whole virus vaccine. Licensed for persons 1 year of age and older. Schedule 2 doses First dose then booster dose 6-18 months after first. Gives protection after 4 weeks of the fist dose. The vaccine should be administered intramuscularly. Site: deltoid muscle.

Dr. Salwa Tayel19 Persons at increased risk for infection: – travelers to intermediate and high HAV-endemic countries (Individuals who will travel to high ‑ risk areas <4 weeks after the initial dose of vaccine should also be given IG) – MSM (Men who have sex with men) – illegal drug users – Persons who have clotting factor disorders – persons with chronic liver disease For communities with historically high rates of hepatitis A: -routine childhood vaccination Indications of Hepatitis A Vaccine

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14/2/2011Dr. Salwa Tayel2121/2/ Viral Hepatitis B (HBV)

14/2/2011Dr. Salwa Tayel22 Serum hepatitis, serum jaundice.  Clinical signs & symptoms occur more in adults.  At least 50% of infections are asymptomatic  Onset is usually gradual with anorexia, nausea and vomiting, often progressing to jaundice.

14/2/2011Dr. Salwa Tayel23 Incubation period: Average days Range days Clinical illness age 5 yrs, 30%-50% Acute case-fatality rate: 0.5%-1% Chronic infection: 5 yrs, 2%-10% Premature mortality from chronic liver disease: 15%-25% Hepatitis B – Clinical Features

14/2/2011Dr. Salwa Tayel24 Symptomatic Infection (%) 100 Symptomatic Infection Birth 1-6 mos 7-12 mos 1-4 yrs Older Children and Adults Symptomatic Infection of Hepatitis B Virus by Age at Infection

14/2/2011Dr. Salwa Tayel25 Risk of Chronic HBV Carriage by Age of Infection

14/2/2011Dr. Salwa Tayel26 Chronic Infection (%) Symptomatic Infection (%) 100 Symptomatic Infection Chronic Infection Birth 1-6 mos 7-12 mos 1-4 yrs Older Children and Adults Outcome of Hepatitis B Virus Infection by Age at Infection

14/2/2011Dr. Salwa Tayel27 Gow, P. J et al. BMJ 2001;323: Outcome of HBV Infection

14/2/2011Dr. Salwa Tayel28 CHRONIC Hepatitis B Virus Infection Overall risk: 10% of all acute infections. About 15%-25% of persons with chronic HBV infection might die from either cirrhosis or liver cancer Chronic infection occurs in: ~ 90% of infants infected with HBV at birth ~ 30% of children infected at age 1- 5 years 2- 6% of people infected after age 5 years

14/2/2011Dr. Salwa Tayel29 HBsAg Prevalence  8% - High 2-7% - Intermediate <2% - Low Geographic Distribution of Chronic HBV Infection

14/2/2011Dr. Salwa Tayel30 High (>8%): High (>8%): –45% of global population – early childhood infections common Intermediate (2%-7%): Intermediate (2%-7%): –43% of global population – infections occur in all age groups Low (<2%): Low (<2%): –12% of global population – most infections occur in adult risk groups Global Patterns of Chronic HBV Infection

14/2/2011Dr. Salwa Tayel31 Dr. Salwa Tayel 31 Agent Susceptible Host Reservoir Mode of transmission Cycle of infection Portal of Exit Portal of Inlet IP PC

14/2/2011Dr. Salwa Tayel32 HBsAg Double-Stranded DNA HBsAg HBcAg HBeAg Hepatitis B Virus  The presence of HBsAg indicates active infection or chronic carrier.  Antibody to HBsAg, from either disease or vaccine, indicates immunity.

14/2/2011Dr. Salwa Tayel33 Human (cases and carriers).  Human blood and blood products can transmit infection if not screened for HBs Ag.  Other body Fluids have the virus with varying concentrations.

14/2/2011Dr. Salwa Tayel34 Low/Not HighModerateDetectable semen serumvaginal fluid blood wound exudatessaliva urine feces sweat tears breast milk Concentration of HBV in Various Body Fluids

14/2/2011Dr. Salwa Tayel35 1.Parenteral: Unsafe injections and transfusions, organ transplants, sharing needles, haemodialysis, needle sticks, tattooing, razors and toothbrushes. 2.Perinatal exposure, especially when HBs Ag carrier mothers are also HBe Ag positive. 3.Sexual exposure.

14/2/2011Dr. Salwa Tayel36 From days, average days. 1-2 months before the onset of symptoms during acute clinical course during the chronic carrier state which may persist for life.

14/2/2011Dr. Salwa Tayel37  Prevent perinatal HBV transmission  Routine vaccination of all infants  Vaccination of children in high-risk groups  Vaccination of adolescents & all children up through age 18  Vaccination of adults in high-risk groups Strategy Elimination of HBV Transmission

14/2/2011Dr. Salwa Tayel38 Currently, subunit recombinant HBs Ag given IM in the deltoid region.given IM in the deltoid region. 3 dose series, typical schedule 0, 1-2, 4-6 months - no maximum time between doses (no need to repeat missed doses or restart)3 dose series, typical schedule 0, 1-2, 4-6 months - no maximum time between doses (no need to repeat missed doses or restart) ProtectionProtection ~30-50% dose 1~30-50% dose 1 75% - dose 275% - dose 2 96% - dose 396% - dose 3 lower protection in older, immunosuppressive illnesses (e.g., HIV, chronic liver diseases, diabetes), obese, smokerslower protection in older, immunosuppressive illnesses (e.g., HIV, chronic liver diseases, diabetes), obese, smokers Hepatitis B Vaccine

14/2/2011Dr. Salwa Tayel39 Routine for infants. Routine for infants. Ages “ catch up ”, and through age 18 years Ages “ catch up ”, and through age 18 years Over 18 – high risk Over 18 – high risk –Occupational risk health care workers (HCWs) –Hemodialysis patients –All clinic clients of sexually transmitted diseases (STD) –Multiple sex partners or prior STD –MSM (Men having sex with men) –IDU (injecting drug users) –Institution for developmental disability (Staff & clients) Indication of Hepatitis B Vaccination

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14/2/2011Dr. Salwa Tayel41 Prevention of perinatal HBV transmission Prevent perinatal HBV transmission by: screening all pregnant women for hepatitis B surface antigen (HBsAg) &screening all pregnant women for hepatitis B surface antigen (HBsAg) & providing hepatitis B immune globulin (HBIG) in combination with hepatitis B vaccine to infants of HBsAg ‑ positive mothersproviding hepatitis B immune globulin (HBIG) in combination with hepatitis B vaccine to infants of HBsAg ‑ positive mothers

14/2/2011Dr. Salwa Tayel42 Immunoglobulins (HBIG): (HBIG) is indicated in combination with the vaccine in:  accidental needle stick injury  sure sexual exposure  perinatal exposure In blood banks:  screening of blood donors  And avoid donors from risky group.

14/2/2011Dr. Salwa Tayel43  Use of adequately sterilized syringes and needles or preferably use disposal equipment.  Discourage risky behaviors e.g. tattooing, drug abuse and extramarital relations.  Avoid transmission from persons with (e antigen), especially medical and dental personnel who routinely perform invasive procedures.  Health care personnel should follow the universal precautions.

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14/2/2011Dr. Salwa Tayel45 HBsAg RNA  antigen Hepatitis D (Delta) Virus HDV is a defective single ‑ stranded RNA virus (delta Ag) It requires HBV for synthesis of envelope protein composed of HBsAg.

14/2/2011Dr. Salwa Tayel46 Low HDV Prevalence High Intermediate Very Low No Data Geographic Distribution of HDV Infection

14/2/2011Dr. Salwa Tayel47 Coinfection with HBV – severe acute disease – low risk of chronic infection Superinfection on top of chronic HBV – usually develop chronic HDV infection – high risk of severe chronic liver disease Hepatitis D - Clinical Features

14/2/2011Dr. Salwa Tayel48 Percutanous exposuresPercutanous exposures  injecting drug use Permucosal exposuresPermucosal exposures  sex contact Hepatitis D Virus Modes of Transmission

14/2/2011Dr. Salwa Tayel49 HBV-HDV Coinfection – Pre or postexposure prophylaxis to prevent HBV infection (HBIG and/or Hepatitis B vaccine) HBV-HDV Superinfection – Education to reduce risk behaviors among persons with chronic HBV infection Prevention of Hepatitis D

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14/2/2011Dr. Salwa Tayel51 Prevalence of HCV Infection Among Blood Donors

14/2/2011Dr. Salwa Tayel52 Incubation period: Average wks Range 2 – 26 wks Acute illness (jaundice) Mild (≤20%) Case fatality rate Low Chronic infection 60%-85% Chronic hepatitis 70% Cirrhosis 5%-20% Mortality from CLD : 3% Hepatitis C – Clinical Features

14/2/2011Dr. Salwa Tayel53 Natural History of HCV Infection 100 People Resolve (15) 15% Chronic (85) 85% Cirrhosis (17) Stable (68) 80% 75% Stable (13) Mortality (4) 25% Time 20% Leading Indication for Liver Transplant

14/2/2011Dr. Salwa Tayel54 Chronic Hepatitis C Factors Promoting Progression or Severity Increased alcohol intakeIncreased alcohol intake Age > 40 years at time of infectionAge > 40 years at time of infection HIV co-infectionHIV co-infection Others:Others: Male genderMale gender Chronic HBV co-infectionChronic HBV co-infection

14/2/2011Dr. Salwa Tayel55 Illegal injection drug use Transfusion or transplant from infected donor Occupational exposure to blood – Mostly needle sticks Iatrogenic (unsafe injections) Birth to HCV-infected mother Sexual/household exposure to anti-HCV positive contact Multiple sex partners Risk Factors Associated with Transmission of HCV

14/2/2011Dr. Salwa Tayel56 Sources of Infection for Persons With Hepatitis C Sexual 15% Other 1%* Unknown 10% Injecting drug use 60% Transfusion 10% (before screening) * Nosocomial; iatrogenic; perinatal Source: Centers for Disease Control and Prevention Occupational 4%

14/2/2011Dr. Salwa Tayel57 Other modes of transmission:  percutaneous procedures using inadequately sterilized equipment (e.g. ear and body piercing, circumcision, tattooing)  HCV do not spread by sneezing, hugging, coughing, food or water, sharing eating utensils, or casual contact

14/2/2011Dr. Salwa Tayel58 Prevention of HCV transmission - Reduce or Eliminate Risks for Acquiring HCV Infection - Preventing HCV Transmission from patients to Others - HCV testing/ screening

14/2/2011Dr. Salwa Tayel59 Screening and testing donors of blood, organs, and tissues Screening and testing donors of blood, organs, and tissues Virus inactivation of plasma-derived products Virus inactivation of plasma-derived products Risk-reduction counseling and services Risk-reduction counseling and services –Obtain history of high-risk drug and sex behaviors –Provide information on minimizing risky behavior, including referral to other services Infection control practices Infection control practices Blood and body fluid precautions Blood and body fluid precautions Prevention of HCV transmission

14/2/2011Dr. Salwa Tayel60 Anti-HCV-positive persons should: Be considered potentially infectious Be considered potentially infectious Keep cuts and skin lesions covered Keep cuts and skin lesions covered Be informed of the potential for sexual transmission Be informed of the potential for sexual transmission Be informed of the potential for perinatal transmission Be informed of the potential for perinatal transmission – no evidence to advise against pregnancy or breastfeeding Anti-HCV-positive persons should not: Donate blood, organs, tissue, or semen Donate blood, organs, tissue, or semen Share household articles (e.g., toothbrushes, razors) Share household articles (e.g., toothbrushes, razors) Public Health Service Guidelines for Anti-HCV-Positive Persons

14/2/2011Dr. Salwa Tayel61 The End Thank You Website