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Hepatitis A: Time course of infection
Atypical manifestations of hepatitis A virus infection
Cholestatic Hepatitis Occasional get prolonged cholestasis. Get raised bili (<170)- peaks at 8 wks, ALP, cholesterol and small ALT rise Jaundice can last >12 weeks but completely resolves Treatment is usually supportive. Relapsing Hepatitis 10 % Occurs 1-4 m post full recovery. Usually milder. Can get multiple relapses Patients remain infectious ALT can be >1000 IU/L during relapse;IgM anti-HAV typically persist throughout the course of the disease. A cholestatic form can also be seen. Extrahepatic Mnifestations Rash 11%; Arthralgia14 % Immune complex disease and vasculitis assoc. diseases eg: Leukocytoclastic vasculitis ( legs and buttocks; IgM anti-HAV and complement in blood vessel walls)Glomerulonephritis; Arthritis; Cryoglobulinemia;Toxic epidermal necrolysis;Myocarditis;Optic neuritis; Transverse myelitis; Thrombocy - topenia; Aplastic anemia; Red cell aplasia; Autoimmune hepatitis More common in protracted disease,eg relapsing or cholestatic hepatitis Live attenuated vaccines Well tolerated and highly immunogenic but use is limited Inactivated HAV vaccines HAVRIX-inactivated- need booster 6m after 1st dose VAQTA inactivated- poor- need booster 12m after 1st dose Immunogenicity Antibody titres peak at 7m then decline slowly Lasts 20-30 yrs so no boosters may be unnecessary. Child-Pugh class B or C predictive of a lower vaccination response rate. Simultaneous administration with other vaccines Can be given with most other vaccines Indications for Vaccination: -Clotting-factor disorders. -Chronic liver disease- esp in Hep C (high mortality with Hep A superinfection) but response will be less. -Homosexual men or users of illegal drugs. -Hep A researchers. -Travellers to countries with high or intermediate endemicity. -Children. -HIV infection-recommended but decreased efficacy. Give single antigen vaccine or IG ASAP post-exposure Close personal contact Prev. unvaccinated household +sexual contacts Hep A contact get IG. Shared drugs, get IG and vaccine Child care centers Vaccine or IG to all staff and attendees if: 1) 1+ hepatitis A in kids/ employees or 2)in 2+ households of center attendees. If centre has children without any nappie wearers,Hep A vaccine or IG should be given to classroom contacts of an index patient only, rather than to all staff and attendees. IF outbreak happens, give vaccination or IG to household contacts of nappie wearing kids Common-source exposure Vaccine or IG to all food handlers at index establishment No vaccination for patrons unless 1)Whilst in infectious period, food handler directly handled uncooked foods or foods after cooking and had diarrhea or poor hygienic practices and 2) patrons can be identified and treated >2 weeks after exposure. If exposure occurred over time, more reason to use of hepatitis A vaccine or IG is warranted. Schools, hospitals and work settings Hepatitis A PEP not needed for a single case in adult environment and source is outside of work Do vaccinate if transmission documented between close contacts
Treatment and Prognosis Treatment is supportive. Mortality is 0.1 % in infants and children, 0.4% in15-39 yrs. Handwashing is v. effective- HAV can survive for 4 hrs on fingertips. Chlorination and disinfectants (household bleach 1:100 dilution) can inactivate virus.
Epidemiology Spread is by the faeco-oral route. 10% is from sexual/ household contact with hep A case. 9% is from homosexual activity in men. 7% is from food or waterborne outbreaks. 4% is from child or employee in a daycare centre. 3% is from IVDU. Community outbreaks from water/food (often shellfish or green onions) (can survive up to 6 months in well water) can occur. Hepatitis A can occur sporadically or in an epidemic form.
Remains detectable for decades
Gold standard for acute illness= Serum IgM anti-HAV But raised IgM can be due to prolonged presence of IgM anti-HAV, a false-positive result, or asymptomatic infection (which is much more common in children < six) Remains positive for 4-6m Incubation average 30 days Prodrome (1-2 weeks) Fatigue, malaise,N+V, anorexia, fever, +RUQ pain. Dark urine, acholic stool, jaundice (70%), and pruritus and hepatomegaly (80%). Prodrome disappears at jaundice onset Rarely: splenomegaly, cervical LN, evanescent rash, arthritis, and, rarely, a leukocytoclastic vasculitis. High ALT (>1000), ALP, Bilirubin (can be>170) Can also get raised ESR, CRP and IG’s
Usually acute, self-limited; Fulminant hepatic failure v rare. Kids: Usually silent or subclinical. Adults: Mild flu-like illness to fulminant hepatitis (more likely if liver disease esp Hep C) NK cells
CD8+ T lymphocytes
Destroy infected cells- example excessive host response causing the hepatitis Hep A itself is non cytopathic Assembled virus particles are shed into the biliary tree and excreted in the feces
85 % make full recovery by 3m, and 99% by 6m Recovery in ALT faster than bilirubin.
Hepatitis A
Genomic Organiza - tion It is a heparnavirus genus of the Picornaviridae. It is a nonenveloped, icosahedral,+ve- stranded RNA virus. There are 4 distinct genotypes. Complications
Pathogenesis
Vaccination Types
Postvaccination testing Postvaccination testing is not required because of the high rate of vaccine response among adults and children. Postexposure Prophylaxis : 1.1% if >40 (especially in chronic hep C) Prevention
Written by Dr Sebastian Zeki
