Hepatitis a. (2)

pathogenesis , clinical management , vaccination , pre-and post exposure prophylaxsis

1. Hepatitis A Dr.Mohamed .A Ahmed( marwan)

2. Overview Hepatitis A (formerly known as infectious hepatitis ) is an acute infectious disease of the liver caused by the hepatitis A virus (HAV). Hepatitis A virus (HAV) is a Picornavirus ; and contains a single- stranded RNA .

3. Transmission HAV is spread via the fecal-oral route. The majority of patients who acquire the illness have had personal contact with an infected person . Tens of millions of individuals worldwide are estimated to become infected with HAV each year . Worldwide , geographic area can characterized by high , intermediate , low level of endemicity. . HAV is highly contagious .

4. Reservoir : human rarely chimpanzees . Mode of transmission : person to person by fecal – oral rout. Incubation period : average 15-50 days(28) . Highest Period of communicability : is 1 st week before and after the onset of symptoms HAV RNA can be detected in stools at least one week before the onset of histologic and biochemical evidence of hepatitis , and it can be detected for at least 33 days after the onset of disease . In neonates and younger children, HAV RNA can be detected in stools for several months

5. Risk factors Poor sanitation. Lack of safe water. Injecting drugs. Living in a household with an infected person. Travelling to areas of high endemicity without being immunized. Working in a health care, food, or sewage. nursing home center. Being a sexual partner of someone with acute hepatitis A infection

6. Clinical manifestations HAV infection produces a self-limited disease that does not result in chronic infection or chronic liver disease.. Acute liver failure from Hepatitis A is rare (overall case-fatality rate: 0.1%- 0.3% ). Most (70%) of infections in children younger than age 6 are not accompanied by symptoms .

7. pathogenesis The degree of hepatic injury during HAV infection depends upon the host's immune response . HAV infection is transmitted via the fecal-oral route, and viral replication occurs in the liver, leading to hepatic injury. The entire liver exhibits necrosis, which is most marked in the centrilobular areas, as well as increased cellularity in the portal areas. The regional lymph nodes and spleen may become enlarged . Liver injury is represented in 3 ways: Direct cellular injury that elevates serum liver enzyme levels Cholestasis  that causes jaundice and hyperbilirubinemia Inadequate liver function that lowers serum albumin levels and prolongs the prothrombin time (PT) CD8+ T cells are responsible for the destruction of the infected liver cells . Interferon gamma appears to have a central role in promoting clearance of infected hepatocytes .

8. Clinical manifestations The illness is much more likely to be symptomatic in older adolescents or adults, in patients with underlying liver disorders, and in those who are immunocompromised. It is characteristically an acute febrile illness with an abrupt onset of anorexia, nausea, malaise, vomiting, and jaundice. The typical duration of illness is 7-14 days . the other organ systems can be affected during acute HAV infection. Regional lymph nodes and the spleen may be enlarged. the most common extrahepatic manifestations of HAV infection include an evanescent maculopapular rash (11 %) and arthralgias (14 % ) . Much less common extrahepatic manifestations include vasculitis, arthritis, optic neuritis, transverse myelitis, encephalitis, and bone marrow suppression .

9. DIAGNOSIS HAV infection should be suspected in a patient presenting with nonspecific symptoms (fever, malaise, anorexia, vomiting, nausea, abdominal pain or discomfort, and diarrhea), sometimes followed by development of jaundice and mild hepatomegaly approximately one week later, with marked elevations in serum aminotransferases and bilirubin. Many individuals, especially young children, have few or no symptoms . The diagnosis of acute HAV infection is confirmed by the detection of anti-HAV immunoglobulin M (IgM), which is the gold standard for the detection of acute illness. This antibody is positive at the onset of symptoms, peaks during the acute or early convalescent phase of the disease, and remains positive for approximately four to six months after the acute infection . Anti-HAV immunoglobulin G (IgG) becomes detectable shortly after the IgM titer appears and usually increases as the IgM level decreases. IgG persists for life and provides ongoing immunity against reinfection.

10. Anti-HAV (IgG) confers long-term protection. Rises in serum levels of ALT, AST, bilirubin, alkaline phosphatase, 5′-nucleotidase, and γ- glutamyl trans- peptidase are almost universally found and do not help to differentiate the cause of hepatitis. Complications < 0.5% ALF , endemic area ALF due HAV constitutes up to 40% of all cases of pediatric ALF . HAV can also progress to a prolonged cholestatic syndrome that waxes and wanes over several months. Pruritus and fat malabsorption are problematic

11. Treatment There is no specific treatment for hepatitis A. Supportive treatment consists of intravenous hydration as needed and antipruritic agents and fat-soluble vitamins for the prolonged cholestatic form of disease. Serial monitoring for signs of ALF and, if ALF is diagnosed, a prompt referral to a transplantation center can be lifesaving.

12. PREVENTION AND PROPHYLAXIS General measures  —Patients infected with HAV are contagious for 2 wk before and approximately 7 days after the onset of jaundice .  Since HAV is transmitted predominantly by the fecal-oral route, prevention can be aided by improved sanitary conditions ,and adherence to sanitary practices ( eg , handwashing). enforcing good hygiene in child care centers heating foods appropriately avoidance of water and foods from endemic areas. Handwashing is highly effective in preventing the transmission of the virus since HAV may survive for up to four hours on the fingertips.

13. Routine childhood vaccination The availability of 2 inactivated, highly immunogenic, and safe HAV vaccines has had a major impact on the prevention of HAV infection. Both vaccines are approved for children older than 12 mo. They are administered intramuscularly in a 2-dose schedule, with the 2nd dose given 6-12 mo after the 1st dose. Seroconversion rates in children exceed 90% after an initial dose and approach 100% after the 2nd dose; protective antibody titer persists for longer than 10 yr in the vast majority of patients.  HAV vaccine may be administered simultaneously with other vaccines. There are two very similar hepatitis A vaccines : Havrix , VAQTA All children aged 12–23 months Unvaccinated children and adolescents aged 2–18 years

14. Vaccination of high-risk groups  — In addition to the routine childhood vaccination described above, vaccination is recommended for all nonimmune members of high-risk groups, including : ●Arriving international adoptees from endemic areas (≥1 year of age) and their close contacts ● International travelers to endemic areas (including infants ≥6 months of age) . ●People with HIV (≥1 year of age) ●People with chronic liver disease (≥1 year of age) If the vaccine is given to infants 6 to <12 months (ie, because of travel), this does not count towards the routine two-dose vaccination series 

15. References https://www.uptodate.com/contents/overview-of-hepatitis-a-virus-infection-in-children?search=hepatitis%20a&topicRef Medscape Nelson textbook of pediatrics 20e .

16. THANKS