Etiology HAV is a small, RNA-containing picornavirus and the only hepatitis virus that has been successfully grown in culture (Fig. 1, A). The structure is a simple nonenveloped virus with a nucleocapsid designated as the hepatitis A (HA) anti gen (HA Ag). Inside the capsid is a single molecule of single stranded ribonucleic acid (RNA). The RNA has a positive polarity and proteins are translated directly from the RNA. Replication of HAV appears to be limited to the cytoplasm of the hepatocyte.

Fig1. Electron micrographs of hepatitis viruses. A, Hepatitis A virus (HAV). B, Hepatitis B virus (HBV). Note Dane particles. (From Katz SL, Gershon AA, Wilfert CM, Krugman S, editors: Infectious diseases of children, ed 9, St Louis, 1992, Mosby.)

The highest titers of HAV are detected in acute-phase stool samples. Human infectivity of saliva and urine from patients with acute hepatitis A does not pose a significant risk. Sexual contact has been suggested as a possible mode of transmission.

Epidemiology

Hepatitis A virus was formerly called infectious hepatitis or short-incubation hepatitis. In developing countries, hepatitis A is primarily a disease of young children; the prevalence of infection, as measured by the presence of antibody (immunoglobulin G [IgG] anti-HAV), approaches 100% at or shortly after 5 years of age. The national rate of hepatitis A has declined steadily since the last peak in 1995 (Fig. 2). After asymptomatic infection and underreporting were taken into account, an estimated 21,000 new infections occurred in 2009 (the last year for which statistics were available at the time of publication).

Fig2. Incidence of hepatitis A, by year, 1980-2009. (Courtesy National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta.)

The incidence of hepatitis A varies by age. Historically, the highest rates were observed among children and young adults. Effective vaccines have been available since 1995. Since the issuance in 1999 of recommendations for routine childhood vaccination, rates of hepatitis A have declined. In 2005, the licensing of hepatitis A vaccines was revised to allow vaccination of children aged 12 to 23 months. Nationwide, hepatitis A vaccination of children is likely to result in lower overall rates of infection.

Susceptibility to infection is independent of gender and race. Crowded unsanitary conditions are a definite risk factor. HAV is transmitted almost exclusively by a fecal-oral route during the early phase of acute illness; the virus is shed in feces for up to 4 weeks after infection. Large outbreaks are usually traceable to a common source, such as an infected food handler, contaminated water supply, or consumption of raw shellfish. Institutions and day care centers are known to be favorable sources for transmission as well.

Hepatitis A infection is noted for occurring in isolated out breaks or as an epidemic, but it also may occur sporadically. Although rarely a transfusion-acquired hepatitis because of its transient nature, an outbreak of HAV infection that occurred in 52 patients with hemophilia in Italy was documented to have been acquired through infusion of contaminated factor VIII concentrate. This concentrate had been treated by a virucidal method (solvent detergent) that ineffectively inactivates nonenveloped viruses.

Improvements in socioeconomic and sanitary conditions and declining family size may be responsible for a decreasing frequency of infection. The incidence of HAV infection is not increasing among health care workers or in dialysis patients. Maternal-neonatal transmission of HAV is not recognized as an epidemiologic entity. Person to person contact, usually among children and young adults, remains the major route of HAV infection.

The most frequently identified risk factor for hepatitis A has been international travel, reported at 15% of patients overall. Most travel-related cases have been associated with travel to Mexico and Central or South America (70%). As HAV trans mission in the United States has decreased, cases among travelers to countries where hepatitis is endemic have accounted for an increased proportion of all cases.

Sexual and household contact with another person with hepatitis A have been among the most frequently identified risk factors, reported for 10% of cases in 2006. In 2006, the proportion of HAV-infected persons who reported injection of street drugs was 2.1%.

Signs and Symptoms

Nonimmune adult patients infected with HAV can develop clinical symptoms within 2 to 6 weeks after exposure (average, ≈4 weeks). However, hepatitis A is often a subclinical disease, with many patients being anicteric. Clinically apparent cases show elevated serum liver function enzyme and bilirubin levels, with jaundice developing several days later. Viremia and fecal shedding of virus disappear at the onset of jaundice. Atypical presentations include prolonged intrahepatic cholestasis, relapsing course, and extrahepatic immune complex deposition, all of which resolve spontaneously.

Complete clinical recovery is anticipated in almost all patients. Hepatitis A rarely causes fulminant hepatitis and does not progress to chronic liver disease. Unusual clinical variants of hepatitis A include cholestatic, relapsing, and protracted hepatitis. In cholestatic hepatitis, serum bilirubin levels may be dramatically elevated (>20 mg/dL) and jaundice persists for weeks to months before resolution. In relapsing hepatitis and protracted hepatitis, complete resolution is anticipated.

A chronic carrier state (persistent infection) and chronic hepatitis (chronic liver disease) do not occur as long-term sequelae of hepatitis A. Rarely, injection with HAV may cause fulminant hepatitis, with about 0.1% mortality. Fulminant hepatitis is the most likely complication of coinfection with other hepatitis viruses.

Immunologic Manifestations

 Shortly after the onset of fecal shedding, an IgM antibody is detectable in serum, followed within a few days by the appearance of an IgG antibody. IgM anti-HA is almost always detectable in patients with acute HAV. IgG anti-HAV, a manifestation of immunity, peaks after the acute illness and remains detect able indefinitely, perhaps lifelong.

The finding of IgM anti-HAV in a patient with acute viral hepatitis is highly diagnostic of acute HAV. Demonstration of IgG anti-HAV indicates previous infection. The presence of IgG anti-HAV protects against subsequent infection with HAV but is not protective against hepatitis B or other viruses.

Diagnostic Evaluation

 Testing methods for HAV include the following:

 • Hepatitis A antibodies (total)—enzyme immunoassay (EIA)

• Hepatitis A antibody, IgM antibody

The short period of viremia makes detection difficult. Specific IgM antibody usually appears about 4 weeks after infection and may persist for up to 4 months after onset of clinical symptoms. The presence of IgG or total (IgM and IgG) anti body indicates past infection or immunization and associated immunity. The total assay detects IgM and IgG antibodies but does not differentiate between them. The hepatitis A antibody IgM assay is appropriate when acute HAV infection is suspected. Specific IgG antibody apparently protects an individual from symptomatic infection, but specific IgM may increase with reinfection. In the acute phase of HAV, liver function levels (e.g., serum liver enzyme levels) will be elevated and may aid in establishing the diagnosis.

Prevention and Treatment

The first effective control measures to prevent enterically trans mitted viral hepatitis resulted from World War II research. In 1945, the following were demonstrated: (1) infectious virus could be transmitted by contaminated drinking water; (2) treatment of the water by filtration and chlorination made it safe to drink; and (3) gamma globulin derived from convalescent-phase serum from patients with hepatitis could protect adults from clinical hepatitis. For 50 years, refining food and water preparation and establishing standards for immune globulin constituted the methods of HAV prevention. An individual who has had close contact with an HAV-infected person should receive passive immunization with immune globulin intramuscularly.

A safe, highly immunogenic, formalin-inactivated, single dose vaccine is available to prevent HAV infection. HAV vaccine should be targeted at high-risk groups (e.g., staff in child care centers; food handlers; international travelers, including military personnel; homosexual men; institutionalized patients).

Universal childhood vaccination may prove to be the most cost-effective method of protecting large populations, both nationally and globally. Routine childhood hepatitis A vaccination is recommended.

In May 2001, the U.S. Food and Drug Administration (FDA) approved a new combination vaccine that protects individuals 18 years of age and older against diseases caused by HAV and HBV. The vaccine, called Twinrix (GlaxoSmithKline Beecham, Philadelphia), combines two already approved vac cines, Havrix (hepatitis A vaccine, inactivated) and Engerix-B (hepatitis B vaccine, recombinant) so that those at high risk for exposure to both viruses can be immunized against both at the same time. Areas with a high rate of both HAV and HBV include Africa, parts of South America, most of the Middle East, and South and Southeast Asia. Clinical trials of Twinrix, given in a three-dose series at ages 0, 1, and 6 months, have shown that the combination vaccine is as safe and effective as the already licensed, separate HAV and HBV vaccines.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم شؤون المعارف ينظم دورة متقدمة في تحقيق المخطوطات لملاكاته

قسم الشؤون الفكرية يصدر العدد العشرين من مجلة دراسات إفريقية

المجمَع العلمي يكرم الأساتذة المشاركين في مشروع الدورات القرآنية الصيفية في كربلاء

العتبة العباسية المقدسة تختتم فعاليات البرنامج المركزي الأسبوعي لمنتسبيها

المزيد

الآخبار الصحية

تحذير من "عدوى بكتيرية" تسبب نوبات قلبية

ماذا يحصل لجسمك عند التوقف عن استخدام الزيت في الطهي؟

الأمل في كبسولة.. "فيتامين شهير" يبطئ التقدم في العمر

اشتهاء أطعمة بشكل مفاجئ.. ناقوس خطر للسرطان ؟!

المزيد

الآخبار التكنلوجية

زلزال أفغانستان يحصد أكثر من ألف قتيل.. ويدمر آلاف المنازل !

ناجٍٍ وحيد من انزلاق أرضي.. دمّر قرية سودانية بأكملها !

نهر الفرات.. مورد مائي بين الندرة والتقاسم

ما السر وراء مشية إيلون ماسك الغريبة والسريعة ؟

المزيد

مواضيع ذات صلة

Pathogenesis and clinical significance of HIV

Transmission of HIV

HIV replication

Hepatitis D

Prevention and Treatment of hepatitis B

Differentiating Acute and Chronic Hepatitis and the Chronic Carrier State

Flaviviridae

Togaviridae

Caliciviridae

Picornaviridae

Laboratory Assays of Hepatitis B

Epidemiology of Hepatitis B