HEPATITIS B Type B hepatitis serum hepatitis Homologous
HEPATITIS B (Type B hepatitis, serum hepatitis, Homologous serum jaundice, Australia antigen hepatitis, HB)
Introduction • Hepatitis B is caused by hepatitis B virus, a hepadnavirus, with ds. DNA. • The virus is inactivated by heat at 60 o. C for 10 hours and by hypochlorite (10, 000 ppm available in chlorine), or 2% glutaraldehyde for 10 minutes. • Generally, HBV is much more resistant to destruction than other hepatitis viruses. • HBV is the major cause of chronic liver disease and hepatocellular carcinoma.
Introduction contd. • Three particles seen in blood in HBV infection: i. Hepatitis B surface antigen (HBs. Ag): spherical and filamentous particles of about 22 nm composed of lipid, protein and carbohydrate, which are not infectious and consist solely of surplus virion envelope. ii. Hepatitis B core antigen (HBc. Ag): Dane particle (42 nm) containing DNA and polymerase. iii. Hepatitis B e antigen (HBe. Ag): soluble antigen, whose sequences are a subset of those in the core antigen but without cross-reactivity.
Introduction contd. • There are 8 genotypes (A-H) of HBV. • Some genotypes are distributed world-wide, whereas others have a more restricted geographical distribution. • Genotype E is found predominantly in Sub. Saharan Africa, B and C in the Far East, F and H in Central and South America.
Introduction contd. • HBs. Ag contains a common ‘a’ antigen and two sets of mutually exclusive determinants’ ‘d’ or ‘y’ and ‘w’ or ‘r’, giving the four main types- adw, adr, ayw and ayr. • Associated with different HBV genotypes is ayr. • Fortunately, the invariant ‘a’ determinant is the main target of the protective antibody response to infection, and immunity induced by infection or immunization with one HBV genotype cross protects against infection with others.
Occurrence of HB • Worldwide, but endemic in some countries (especially South -East Asia) with little seasonal variation. • Widespread infection may occur in infancy and childhood, but common in young adults. • HBV infection is common in certain high risk groupsparenteral drug users, heterosexuals with multiple partners, homosexual men, client and staff of institutions for the retarded, patients and employees in certain health care and public safety occupations- hemodialysis centers.
Occurrence of HB • Frequent and routine exposure to blood and serous fluids is the common denominator of health care occupational exposure; - Surgeons - Laboratory Scientists - Dentists - Pathologists - Operating room and emergency room staff - Clinical laboratory workers who handle blood and blood products are at highest risk.
Occurrence of HB • Hepatitis B infections result in 500, 000 to 1, 200, 000 deaths per year worldwide due to the complications of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. • Chronic hepatitis develops in the 15% of adults who are unable to eliminate the virus after an initial infection.
Reservoirs of HBV • Primates -Man - Chimpanzee, etc.
Mode of transmission of HBV • The source of HBV infection in some cases cannot be determined. However, transmission is usually via contact with HBV contaminated: - blood (blood transfusion, sharing of syringes in intravenous drug use, sharing of shaving and tattoo accessories such as razor blades, or touching of wounds on infected persons) - Saliva - Semen and Vaginal fluids.
Mode of transmission of HBV contd. • Transplacental transmission is also possible, though with minimal evidence. • Transmission via breast feeding.
Incubation period of HB • The incubation period is usually 45 -180 days, but could be as short as 2 weeks and rarely as long as 6 -9 months. On the average, the symptoms manifest within 60 -90 days. • Factors that determine the incubation period are: - The amount of virus in the inoculum, - The mode of transmission, and - Host factors.
Pathogenesis of HB • On entry into the host, the viruses are carried to hepatocytes through the blood stream. Attachment, penetration, coating and replication occur within the cytoplasm and nucleus of the hepatocytes respectively. • The presence of viral particle incites both B and T cell responses. Damage to the hepatocyte result from antibody-dependent, natural killer (NK) and cytotoxic T cell action.
Pathogenesis of HB contd. • Expression of major histocompatibility complex (MHC) class I antigens is poor in hepatocytes but can be enhanced as interferon is produced in response to the infection leading to increased antigen recognition and lysis of the infected hepatocytes. • HBV is non-cytocidal without the assistance of the host’s immune system.
Pathogenesis of HB contd. • Chronic carriers of HBs. Ag may not have demonstrable evidence of liver disease. • Persistent viral hepatitis, with mild benign disease may occur in adult patients. • Cirrhosis and hepatocellular carcinoma can arise after the loss of Hbe. Ag (a variant of HBV) and the clearance of HBs. Ag from the blood, although viral DNA may still be present. • Progression to cirrhosis and carcinoma depends on the stage of infection, the state of the patient’s immune system, geographic and genetic factors.
Pathogenesis of HB contd. • Hepatocellular carcinoma is one of the ten most common tumours in the world. It can take 30 -40 years between infection and tumour development • The disease is usually milder in the immunocompromised. A similar sequence of events occurs in the silent case except that the liver damage is less severe.
Signs and symptoms • Jaundice, anorexia and malaise • In acute stage, - There are signs of inflammation in the portal triads; the infiltrate is mainly lymphocytic. - Single cells in liver parenchyma show ballooning and form acidophilic (councilman) bodies as they die.
Signs and symptoms • In healthy carriers, - The inflammatory response is mild, and the affected hepatocytes are pale staining and glassy. • In chronic case, - Damage extends out from the portal tracts, giving the piecemeal necrosis appearance. - Some lobular inflammation is also seen. - As the disease progresses, fibrosis develops and eventually, cirrhosis.
Immunity • Patients with chronic hepatitis B have antibodies against hepatitis B, but these antibodies are not enough to clear the infection of the affected liver cells. • The continued production of virus combined with antibodies is a likely cause of the immune complex disease seen in these patients. • Anti-HB develops and HBs. Ag is negative.
Laboratory diagnosis • Specimen - Blood, liver biopsy, bile, stool, semen, urine, vaginal fluid, breast milk and other body fluids • Tests - Liver function tests show raised serum alanine amino transaminase and bilirubin values. - Detection of HBV particles in specimens by immune electron microscopy, immunoassays, immunohistochemistry, nucleic acid hybridization assays, or polymerase chain reaction are presumptive.
Laboratory diagnosis contd. - High levels of Ig. M-specific anti-HBc are frequently detected at the onset of clinical illness 2 -3 weeks after HBs. Ag reactivity appears. - Antibody to HBs. Ag is first detected after the disappearance of HBs. Ag. - Before HBs. Ag disappears, HBe. Ag is replaced by anti-HBe, signaling the start of resolution of the disease. - Anti-Hbe levels often are no longer detectable after 6 months. Therefore, the presence of Anti-HBe and absence of HBV DNA in serum indicate a relative lack of infectivity.
Laboratory diagnosis contd. • HBV chronic carriers are those in whom HBs. Ag persists for more than 6 months in the presence of HBe. Ag or anti-HBe. Hbs. Ag may persist for years after loss of HBe. Ag. • In contrast to high titer of Ig. M anti-HBc observed in acute disease, low titers of Ig. M anti-HBc are found in sera of most chronic HBs. Ag carriers.
Prevention and control • Two types of inactivated vaccines are available - Plasma derived vaccine, prepared from a plasma from HBs. Ag-positive carriers and - subunit HBs. Ag-containing vaccine made by recombinant DNA (r. DNA) technology. • Combined passive-active immunoprophylaxis with hepatitis B immunoglobin (HBIG) and vaccine is effective and capable of preventing infection from hepatitis B for life.
Prevention and control contd. • Patients with hepatitis C are susceptible to severe hepatitis if they contract either hepatitis A or B. This makes it imperative for all persons with hepatitis C to be immunized against hepatitis A and hepatitis B if they are not already immune. • Since alcohol exacerbates hepatitis, its avoidance should be emphasized.
Prevention and control contd. • Screening of all pregnant women for the presence of HBs. Ag and if positive, management of their infants is of extreme importance. • Enforcement of strict discipline in blood banks have contributed immensely in protecting susceptible individuals and controlling the infection through; – screening of all donated blood, – Rejection as donors all individuals who have history of viral hepatitis or show evidence of drug addiction, or those who have received a blood transfusion or tattoo within the preceeding 6 months
Prevention and control contd. • Unscreened blood should not be transfused and there should be post transfusion hepatitis surveillance. • Re-usable surgical materials should be adequately sterilized, while the use of disposable syringes and needles should be emphasized. • Control of patients, contacts and the immediate environment is of utmost importance.
Treatment • There are six treatment options approved by the U. S Food and Drug Administration (FDA) available for persons with a chronic hepatitis B infection. These include; alpha-interferon, pegylated interferon adefovir, entecavir, telbivudine, and lamivudine. • About 65% of persons on treatment achieve a sustained response. • Some authors indicated no specific antiviral treatment.
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