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HEPATITIS AND THE NEWBORN INFANT

HEPATITIS AND THE NEWBORN INFANT. Niraj Patel, MD, MS Department of Pediatrics Section of Infectious Disease Levine Children’s Hospital. Objectives. Know routes of transmission Be able to interpret hepatitis serologies

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HEPATITIS AND THE NEWBORN INFANT

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  1. HEPATITIS AND THE NEWBORN INFANT Niraj Patel, MD, MS Department of Pediatrics Section of Infectious Disease Levine Children’s Hospital

  2. Objectives • Know routes of transmission • Be able to interpret hepatitis serologies • Know post exposure prophylaxis methods

  3. Total Hepatitis A Hepatitis B Hepatitis C Acute Viral Hepatitis A, B and C by Year, United States, 1952-2000

  4. Acute Viral Hepatitis by Type, 1982-95 2007 53%X 34% X 35% 48% X 9% 15% Hepatitis A Hepatitis B Hepatitis C 3% Hepatitis Non-ABC Source: CDC Sentinel Counties Study on Viral Hepatitis

  5. Reported Cases of Selected Notifiable Diseases Preventable by Vaccination, United States, 2001 2007 Varicella 22,536 Hepatitis A 10,609 Hepatitis B 7,843 Pertussis 7,580 Meningococcal disease 2,326 H. influenzae, invasive 1,597 Mumps 266 Measles (total) 116 Rubella 23 2,979 4,519

  6. ROUTE OF TRANSMISSION: FECAL - ORAL •Hepatitis E•Hepatitis A

  7. DISEASE BURDEN FROM HEPATITIS AUNITED STATES, 2007 Prevalence of chronic infection: None

  8. GLOBAL DISTRIBUTION OF HAV INFECTION

  9. HAV in U.S.A.

  10. HAV-Clinical features • Acute self limited illness • fever, malaise, jaundice, anorexia, nausea • Symptoms in 30% children < 6 years • Usually symptomatic in older children/adults (70% jaundiced) • Fecal-oral route: person-to-person, ingestion of contaminated food or water • Incubation period: 15-50 days • Fulminant hepatitis rare but more frequent in those with underlying liver disease

  11. HAV ACUTE INFECTION

  12. HAV Diagnosis and Management • HAV total and IgM antibody • Treatment supportive • Post-exposure prophylaxis (household/close contacts)

  13. www.cdc.gov/vaccines/recs/schedules/child-schedule.htm

  14. Post Exposure Prophylaxis for HAV Future Weeks exposure? Age Action§______  2 No All IG* Yes 1yr IG* HAV vaccine  2 No All None Yes 1yr HAV vaccine § AAP Recommended childhood and adolescent immunization schedule – United States ,2007. Pediatrics. 2007;119:207-8 #IG dose = 0.02ml/kg IM

  15. Newborn Infants of HAV infected mothers • Risk of perinatal transmission rare • IG 0.02ml/kg IM if mother symptomatic within 2 weeks before and one week after delivery; efficacy not established • Severe disease rare in healthy infants

  16. HEV: Epidemiology • Transmitted by fecal-oral route • Contaminated water • Symptoms more common in adults • Sporadic outbreaks Asia, Africa, Mexico • Fecal viral shedding and viremia for 2 weeks after acute infection

  17. Hepatitis E – Clinical Features Incubation period:Average 40 days Range 15-60 days Case-fatality rate:Overall, 1%-3%Pregnant women, 25%-30% Illness severity:Increased with age Chronic sequelae:None

  18. HEV Diagnosis and Treatment • IgM to HEV • HEV RNA by PCR in serum/feces • Supportive Care • Contact precautions • Avoiding potential contaminants • Passive immunoprophylaxis with US prepared immune globulin has not been effective

  19. HCV Epidemiology • Single stranded RNA virus • Multiple genotypes exist • fail to elicit cross neutralizing antibodies in animal models • Incubation period 6-7 weeks (2weeks–6months) • 170 million infected world-wide • Prevalence of 1-2% in women of child-bearing age (CDC)

  20. Hep C

  21. Risk factors for infection • IV Drug Use • Percutaneous exposure to blood/blood products • hemophilia • haemodialysis patients (10-20%) • risk is 1 in 1 million units of blood transfused • IV and IM immunoglobulin products safe • Sexual transmission (monogamous couples - 1.5%) • Household contacts / HCWs • Perinatal transmission 5-6% • Coinfection with HIV increases risk 17%

  22. HCV Infection, U.S. New infections (cases)/year, 2007 849 Deaths from acute liver failure Rare Persons ever infected (1.8%) 3.9 mill. (3.1-4.8)* Persons with chronic infection 2.7 mill. (2.4-3.0)* Of chronic liver disease - HCV-related 40% - 60% Deaths from chronic disease/year 8,000-10,000 . *95% Confidence Interval

  23. HCV- Clinical features • Acute disease • Indistinguishable from hepatitis • mild and insidious in onset • asymptomatic in most children • Only 25% are jaundiced • fewer abnormalities in LFTs than with HBV

  24. Persistent infection in at least 85% even with normal LFTs Most children with chronic disease are asymptomatic Complications chronic hepatitis cirrhosis Primary hepatocellular carcinoma 40-60% cases of liver transplantation annually HCV (cont)

  25. HCV CHRONIC INFECTION anti-HCV Symptoms +/- HCV RNA Titer ALT Normal 6 1 2 3 4 0 1 2 3 4 5 Years Months Time after Exposure

  26. HCV Diagnosis • Antibody assays • Screening enzyme immunoassay (EIA) • 80% positive within 5 - 6 weeks of infection(false negative early in infection) • HCV PCR • HCV RNA (highly sensitive) • may be detected intermittently, a single negative is inconclusive • Can detect RNA within 1-2 weeks after exposure

  27. HCV Management • Monitor liver function • Vaccination against Hepatitis A & B (all patients) • Interferon   ribavirin in adults • IFN monotherapy sustained response in 10-40% • Combined therapy sustained response in 30-80% • Lower sustained responses in genotype 1 • Interferon-2b + ribavirin in children 3-17 yrs • Referral to specialist in management of HCV

  28. HCV Perinatal transmission • Antenatal screening if risk factors • Transmission occurs in 5-6% (0-25%) • Factors possibly associated with transmission • Maternal HIV co-infection • Maternal viral load during pregnancy unclear • No evidence to date that breast-feeding increases the risk • Mode of delivery not a risk factor

  29. HCV - Perinatally Exposed Infant • PCR testing may identify infected infants earlier but defer until after one month of age* • Maternal passively acquired antibody persists for 18 months - defer antibody testing • Immune globulin for post exposure prophylaxis is not recommended • HBV vaccination (all infants) + HAV vaccination (if infected) • Referral to specialist if infected *Dunn et al. Pediatr Infect Dis J. 2001;20(7):715-6

  30. HEPATITIS B • DNA virus • Circular genome encoding: • 3 envelope proteins (HBsAg) • nucleocapsid proteins • HBeAg - secreted from the infected hepatocyte • HBcAg- translated from the core sequence / not found in serum

  31. GLOBAL DISTRIBUTION OF HBV INFECTION

  32. Modes of transmission include: • Homosexual/heterosexual activity • Sharing or re-using needles or syringes • Percutaneous/mucous membrane exposure to blood/body fluids • Person to person e.g. household, sharing toothbrushes, razors, skin lesions etc. • Transfusion • Occupational risk • HCW/needlestick • Mother to infant

  33. HBV Clinical Features • Wide spectrum of illness • asymptomatic • subacute illness • non-specific, abnormal LFTs • Clinical hepatitis • 10% immune complex mediated illness • polyarthritis, angiodema • urticaria and jaundice • maculopapular eruptions & glomerular involvement • Clinical hepatitis with jaundice • Fatal fulminant hepatitis

  34. HBV Clinical Features • Incubation period 45-180 days (90 days) • Age at acquisition most important factor in determining chronic infection • 90% perinatally infected infants • 25-50% children infected age 1-5 years • 6-10% older children, adolescents, adults

  35. HBV Chronic Infection • Increased risk of chronic liver disease, cirrhosis, hepatocellular carcinoma • Risk of death is 25% in those acquiring chronic infection in childhood

  36. Outcome of HBV Infection by Age

  37. HBV RESOLVED INFECTION

  38. HBV CHRONIC INFECTION

  39. HBsAganti-HBsTotal anti-HBcInterpretation 1)— + + Resolved infection — 2)+ + Chronic infection 3) — + — Hep B vaccination

  40. HBV Diagnosis and Treatment • Serology • Hybridization and gene amplification assays to measure HBV-DNA  correlates with HBeAg and infectivity • TreatmentAdults IFN-2a: remission in 25-40% Lamivudine, adefovir, entecavir Children INF-2a: remission in 35% Lamivudine (2 years and older) • Monitor LFTs, serum  fetoprotein, abd US

  41. Perinatal transmission • 70-90% risk of transmission if mother HBsAg and HBeAg+ (a reportable disease) • 90% infants become chronic carriers • 95% of neonatal infections preventable by • HBV vaccination in the neonatal period • Hepatitis B immune globulin • Vaccinate within 12 hours after birth • Breast feeding poses no additional risk to infant

  42. HBV Infection by Year, United States 1982-2005 HBsAg screening of pregnant women recommended HBV Vaccine licensed Infant Immunization recommended Adolescent Immunization recommended Modified from Long et al: Principles and Practice of Pediatric Infectious Diseases, 3ed

  43. Preventing Neonatal Infection • Antenatal screening • early in pregnancy for all women • near delivery for women at high risk

  44. Algorithm for Preventing Neonatal Infection • If term infant (>2kg) and mother HBsAg+ • Then: • HBV vaccine + HBIG within 12 hours at different sites • 2nd, 3rd vaccine doses at 1-2 mo and 6 mo • Test at 9-15 mo for HBsAg and anti-HBs • If negative, reimmunize with 3 doses at 2 mo intervals and retest

  45. Algorithm for Preventing Neonatal Infection • If preterm infant (<2kg) and mother HBsAg+ • Then: • HBV vaccine + HBIG within 12 hours • 1st vaccine dose not counted in series, so infants need 4 doses in total (0, 1, 2-3, 6-7mo)

  46. If term infant and mother HBsAg unknown Then: Test mom ASAP Vaccinate infant within 12h of birth HBIG if mom HBsAg+ within 7 days at birth Algorithm for Preventing Neonatal Infection

  47. Algorithm for Preventing Neonatal Infection • If preterm infants <2kg and mother HBsAg unknown • Then • Test mom ASAP • Vaccinate infant and give HBIG within 12h if mom’s status still unknown • *95% of neonatal transmission can be prevented by following the above guidelines

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