HEPATITIS B VIRUS
A nucleocapsid core protein (HBcAg) and a longer polypeptide transcript with a pre-core and core region, designated (HBeAg)
Envelope glycoprotein (HBsAg) Infected hepatocytes are capable of synthesizing and secreting massive quantities of non-infective surface protein (HBsAg).
A DNA polymerase that exhibits reverse transcriptase activity and genome replication occurs through an intermediate RNA template.
A protein from the X region (HBX), which is necessary for virus replication and acts as a transcriptional transactivation of the viral genes and a wide variety of host gene promoters. HBX is also thought to play a key role in the causation of hepatocellular carcinoma.
Epidemiology
The hepatitis B virus is present worldwide with estimated 300million carriers. The UK and the USA have a low carrier rate (0.5), but it rises to 10 15 in parts of Africa, the Middle and Far East (Kumar Clark, 2008).
HBV is a blood-borne virus, being present in all the human body fluids. It is usually transmitted by blood blood contact (parenteral transmission). Although blood and body fluids are the primary modes of transmission, the virus may also be transmitted by contact with other body secretions such as sweat, saliva, tears, semen, breast milk, and other pathologic effusions. Vertical transmission (spread from an infected mother to a neonate) is common in some regions such as Africa and Southeast Asia. Neonatal infections such as this usually lead to a carrier state for life. The virus has been detected in some insects, particularly mosquitoes and bed bugs, but there is no evidence of the virus replication in these insect vectors. Transfusion, blood products, dialysis, needle-stick accidents among health workers, intravenous drug abuse, and homosexual activity constitute the primary risk categories for HBV infection (Kumar et al, 2008).
Pathogenesis
HBV, the cause of serum hepatitis, can also produce
Acute hepatitis,
Non-progressive chronic hepatitis,
Progressive chronic hepatitis ending in early cirrhosis,
Fulminant hepatitis with massive liver necrosis,
An asymptomatic carrier state, with or without progressive subclinical disease, and
The backdrop for hepatitis D virus (HDV) (Kumar et al, 2008).
HBV infection occurs in phases proliferative and integrative phases. In the proliferative phase, the DNA of the virus is present in episomal form along with the production of complete virions and all associated antigens. Still in this phase, there is activation of cytotoxic CD8 T lypmhocytes by the cell surface expression of viral HBsAg and HBcAg in association with the major histocompatibility complex (MHC) class I molecules. The activated cytotoxic CD8 lymphocytes then attack and destroy infected cells bearing the viral antigens. During the integrative phase, the viral DNA is inserted and incorporated into the host genome. This phase usually occurs in liver cells that have not been destroyed by the immune response by rampaging T lymphocytes. Infectivity occurs when viral replication ceases and antiviral antibodies appear in the blood.
Also, immune complexes of antigens (HBsAg) and antibodies can deposit in tissues and activate the immune system, resulting in arthritis, as well as skin and glomerular (kidney) damage.
Clinical features
Most of the clinical features of HBV infection arise as a result of the cell-mediated immune system attack on infected cells. The initial viremia causes the patient to feel unwell (malaise) along with the non-specific symptoms such as anorexia, nausea and distaste for cigarettes. Most patients recover at this stage and remain anicteric.
After one to two weeks, some patients become jaundiced and the symptoms will improve at this point. As the jaundice deepens, the urine becomes dark and the stools pale owing to intrahepatic cholestasis. Usually, the liver is moderately enlarged and the spleen can be palpated in about 10 of patients. Occasionally, tender lymphadenopathy is seen, with a transient rash in some cases. Later, the jaundice reduces and in most cases, the illness is over within three to six weeks. Rarely, the disease becomes severe with fulminant hepatitis, liver coma and death.
In patients who have immunocompromised states, such as malnutrition, AIDS, and chronic illnesses, they are more likely to be asymptomatic carriers because their immune system may not attack the invading virus.
Complications
Primary hepatocellular carcinoma is a major complication of HBV. With chronic infection, the HBV DNA becomes incorporated into the hepatocyte DNA and triggers malignant growth. There is a 200 times increase in the risk of developing primary hepatocellular carcinoma in HBC carriers as compared to non-carriers. Infections with HBV can also result in primary liver scarring and loss of hepatocytes, referred to as liver cirrhosis.
Investigations
Serology Serologic tests help establish HBV infection. The extent of the infection can be determined using different markers, especially levels of antigens and antibodies in the serum. These include
HBsAg Its presence always means that there is a live virus and infection, either acute or chronic, or carrier. It appears in the blood from about 1 months (6 weeks) to 3 months after an acute infection, then disappear.
Anti-HBsAg It appears late and signifies immunity, cure or no active disease.
HBeAg It appears in the serum soon after HBsAg and it signifies active viral replication. It also signifies high infectivity.
Anti-HBeAg It appears after anti-HBcAg. Its appearance also signifies low and decreased infectivity.
HBV DNA it suggests active viral DNA replication. It can be found in the serum and in the liver.
Anti-HBcAg It is usually the first antibody to appear in. IgM anti-HBcAg signifies an acute and continuous infection while IgG anti-HBcAg does not appear until the acute disease is over and is usually not detectable for a few weeks to several months after the disappearance of HBsAg. IgG anti-HBcAg signifies an old infection.
Liver Biochemistry In the acute stage, the hepatocytes produce enzymes that are released during cell death. These are liver function enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase. Elevated blood levels of these liver enzymes help in establishing the diagnosis of hepatitis. In the icteric stage, the serum bilirubin reflects the level of jaundice (Kumar Clark). Serum AST reaches a maximum in 1 2 days after the appearance of jaundice, and may rise above 500IUL. Serum ALP is usually less than 300IUL.
Treatment
There is no specific treatment apart from symptomatic therapy. Antiviral agents for treatment of chronic active or persistent HBV infection includes
Prevention and prophylaxis
Prevention involves avoiding risk factors such as multiple sexual partners, multiple homosexual partners (male), and sharing needles. Also, standard safety precautions should be enforced in health care centers, laboratories and hospitals in order to avoid needle-stick injuries and contact with infected body fluids.
Prophylaxis can be given in the form of passive or active immunization. Passive immunization is induced by the administration of antibodies against virus. Adults are administered with 500IU of specific hepatitis B immunoglobulin (HBIG) and newborns with 200IU of HBIG intramuscularly. Active immunization is induced with the use of a recombinant yeast vaccine produced by cloning the gene coding for HBsAg in yeasts. There is no risk of developing disease from the vaccine because it contains only the surface envelope and proteins (HBsAg). It is now given to all infants at birth, 2, 4, and 15 months. It is also given as three injections to adolescents and high-risk adults (e.g. health workers, IV drug users, etc).
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