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Hepatitis B infection is a global health problem. According to World Health Organization, an estimated 600,000 people die every year due to the acute or chronic consequences of Hepatitis B infection (WHO fact sheet, 2008).
For the year 2000, a mathematical model to estimate global hepatitis B burden and vaccination impact estimated that, 620â€‰000 persons died worldwide from HBV-related causes. Thus, 580â€‰000 (94%) from chronic infection-related cirrhosis and hepatocellular carcinonoma and 40â€‰000 (6%) from acute hepatitis B (Goldstein et al., 2005). In the surviving birth cohort for the year 2000, the model estimated that without vaccination, 64.8 million would become HBV-infected and 1.4 million would die from HBV-related disease (Goldstein et al., 2005).
HBV infection accounts annually for 4000 to 5500 deaths in the United States and 1 million deaths worldwide from cirrhosis, liver failure, and hepatocellular carcinoma (Lee, 1997, Ganem et al, 2004).
HBV also plays an important role in the development of liver cirrhosis in Ghana. Studies done on 70 patient with liver cirrhosis, 30 (42.86%) were positive for HbsAg. (Blankson et al, 2005). It is therefore vital to effectively screen the general public for Hepatitis B to help reduce the transmission of the infection.
There are approximately 50 million chronic carriers of hepatitis B virus (HBV) in Africa, with a 25% mortality risk (Kiire C F, 1996).
Blood transfusion services is a vital part of modern health care system, with a every unit of blood there is 1% chance of transfusion associated problems including transfusion transmitted diseases (Garg S, et al., 2001). Transfusion infected blood to patients is considered a crime. It is therefore mandatory to test each and every unit of blood for antibodies to HIV-1 and 2, syphilis, hepatitis C and Hepatitis B surface antigen (Nanu A, et al., 1997)
The surface antigen of HBV (HBsAg) may be detected in serum 30-60 days following infection and may persist for widely variable periods of time. An important proportion (7-40%) of individuals who are HBsAg-positive may also carry the hepatitis B 'e'antigen (HBeAg), which is associated with high infectivity. Unless vaccinated at birth, the majority of children born to mothers who are HBeAg-positive will become chronically infected. (Beasly et al., 1983)
All patients with acute hepatitis B are HBeAg positive and therefore highly infectious and contact with their blood or body fluids can lead to HBV infection (Hollinger, 2001).
HBeAg-positive specimens contain high concentrations of infectious virions and HBV DNA, in contrast to anti-HBe positive samples, in which the number of hepatitis B virions is substantially reduced ( Hollinger FB, 2001).
Chronic hepatitis is characterized by either the presence or absence of HBeAg. (Fattovich, 2003) A study conducted in Italy on HBsAg positive samples had 86.4% being HBeAg-negative and the Mediterranean, Asia and in the Far East had a population of 30-80% also being HBeAg-negative. The proportion of HBeAg-negative is rising worldwide, with patients with HBeAg-negative chronic hepatitis developing more active, advanced, and progressive liver disease. (Laras et al., 1998)
The screening test for hepatitis B infection is detection of HBsAg which does not rule out the risk of transmission of hepatitis B as the donor may be in the 'window period'. During this period, detection of the antibody to the hepatitis B core antigen (anti-HBc) IgM type serves as a useful serological marker. (Kumar H et al., 2009)
Antibody to hepatitis B core antigen is the first to develop, following acute hepatitis B infection, which appears predominantly as IgM anti-HBc at about 6 weeks after infection. The antibody typically persists for life except resolution of acute hepatitis B virus infection occurs (Hollinger, et al., 2001)
Some chronically-infected patients will resolve their HBV infection, either naturally or occasionally following interferon-based therapy. These patients typically show clearance of HBsAg but are anti-HBc positive and usually develop anti-HBs, along with anti-HBc (Perrilo RP, 2001)Â
Sheik et al reported a seroprevalence of 10% of IgM anti-HBcore in Pakistan (Sheikh et al., 2011). A 4% seroprevalence of IgM anti-HBcore was reported in Italy amongst HBsAg positive donors who were chronically infected but 85% of the same patients tested positive to IgM anti-HBcore when they were acutely infected (Lavarini et al., 1983).A total prevalence of anti HBcore (consisting of both IgG anti-HBcore and IgM anti-HBcore) of 16.2% was reported in Yemen and 13.5% in Korea amongst blood donors. (Bawazir et al., 2011, Seo, et al., 2011). This present study also seeks to determine the prevalence of anti-core antibody among blood donors in Ghana.
HBV DNA has been detected in the serum of patients with anti-HBc hepatitis. (Antar et al.2010)
Antar et al reported a 6.25% detectable serum HBV DNA amongst Egyptian blood donors. (Antar, et al, 2010) The issue of isolated hepatitis brings to forefront the ineffectiveness of HBsAg screening (which is what is used in Ghana) in protecting blood recipients from hepatitis B infection. It has been suggested that anti-HBc testing should be combined with HBsAg screening of blood donors to reduce the risk of HBV infection (Findik et al., 2007).
The serological markers of Hepatitis B virus are HBsAg, anti-HBs, HBcAg, anti-HBc (IgM and IgG), HBeAg, anti-HBe, and HBV DNA; these are important as they can be used in the diagnosis of the infection and to determine the severity of the infection (Gitlin Norman, 1996).
One of the most sensitive and specific methods for diagnosing HBV infections is enzyme-linked immunosorbent assay (ELISA) and early detection of HBsAg may be helpful for simplifying the treatment of HBV-associated diseases. (Fontirrochi et al., 1993)
The prevalence of hepatitis B virus (HBV) chronic carriage in sub-Saharan Africa ranges between 3% and 22% in blood donors (Allain et al., 2003, Nkrumah et al., 2011, Dongdem et al., 2012, Sarkodie et al., 2001).
Studies from different parts of Ghana have reported varying prevalence rates among blood donors. Studies conducted in one rural area have reported HBsAg prevalence of 13.8 %. (Nkrumah et al., 2011) Another research done in the Northern part of Ghana reported a prevalence rate of 10.79% for voluntary donors and 11.59% for replacement donors (Dongdem et al., 2012).
A seroprevalence rate of 19.5% was also found in blood donors in the Upper West Region of Ghana (Adu-Sarkodie et al., 1997).
A study done in three densely populated communities in Kumasi, Ghana had an overall sero-prevalence rate of hepatitis B surface (HBsAg) antigen of 8.68% (Amidu N et al., 2012).
This study will therefore provide information on additional viral markers which will be used for assessing the state and risk of blood donors.
The HBeAg will determine the infectivity state of the individuals while the anti-core IgM and IgG will distinguish individual who are acutely infected from those who have recovered from HBV infection. Therefore this study will inform us about the Hepatitis B status of Blood Donors and also estimate the total prevalence of the infection.
Although there are some data on the seroprevalence of HBsAg in some parts of Ghana, there is no established data on HBsAg prevalence in Techiman in the Brong Ahafo. This present study will determine the prevalence of Hepatitis B infection in Techiman and also provide information on additional viral markers which could be used in establishing the risk factors of the viral hepatitis infection. Knowledge of this will be important in determining policies and intervention, which will curb the spread of viral hepatitis.
This research seeks to address the prevalence of HBV infected individuals and to identify the proportion with high infectivity among the pool of chronic carriers in the Techiman area.
1.2 Objectives of the study
To determine the prevalence of Hepatitis B infection among blood donors in the Techiman municipality of Ghana.
To estimate the proportion of HBV infected individuals with the following viral serological markers; HBeAg, HBsAg and anti-hepatitis B core Antibody.
To determine the risk factors associated with exposure to HBsAg, HBeAg and anti-hepatitis B core Antibody.
2.0 Hepatitis B virus (HBV)
Hepatitis B is an infectious inflammatory illness of the liver and is most commonly caused by the hepatitis B virus (HBV). It was originally known as "serum hepatitis (Barker et al., 1996). The liver is the primary site of HBV replication (Krugman et al., 1994).
Hippocrates described episodes of jaundice, which were likely to have been viral hepatitis caused by various viruses. In 1883 hepatitis transmitted through blood or blood products was first documented in Germany during a smallpox immunization campaign. McCallum proposed the term hepatitis B for 'serum' hepatitis in 1947. The Australia antigen, now called the hepatitis B surface antigen (HBsAg), was first identified in 1967 and the discovery of this antigen facilitated the isolation and characterization of the viral particles. It is also the basis for the current recombinant vaccines (Alter, et al 1993, Blumberg et al., 1965).
There are five main hepatitis viruses, referred to as types A, B, C, D and E. (WHO factsheet, 2012) Types B and C lead to chronic disease in hundreds of millions of people and, together, are the most common cause of liver cirrhosis and cancer. (WHO factsheet, 2012)
The prevalence of chronic hepatitis B virus (HBV) infection varies greatly in different parts of the world and this could be categorized as high, intermediate and low endemicity. (Margolis et al., 1991) (Figure 1)
Hepatitis B is highly endemic in developing regions with large population such as South East Asia, China, sub-Saharan Africa and the Amazon Basin, where at least 8% of the population are HBV chronic carrier. In these areas, 70-95% of the population shows past or present serological evidence of HBV infection. Most infections occur during infancy or childhood. Since most infections in children are asymptomatic, there is little evidence of acute disease related to HBV, but the rates of chronic liver disease and liver cancer in adults are high (Alter, 2003).
Hepatitis B is moderately endemic in part of Eastern and Southern Europe, the Middle East, Japan, and part of South America. Between 10-60% of the population have evidence of infection, and 2-7% are chronic carriers (Toukan, 1990). Acute disease related to HBV is common in these areas because many infections occur in adolescents and adults; however, the high rates of chronic infection are maintained mostly by infections occurring in infants and children (Toukan, 1990).
The endemicity of HBV is low in most developed areas, such as North America, Northern and Western Europe and Australia. In these regions, HBV infects 5-7% of the population, and only 0.5-2% of the population are chronic carriers (McQuillan et al., 1989). In these areas, most HBV infections occur in adolescents and young adults in relatively well-defined high-risk groups, including injection drug user, homosexual males, and health care workers, patients who require regular blood transfusion or hemodialysis (McQuillan et al., 1989).
Figure 1: Geographical distribution of hepatitis B infection.
Source: CDC (2008) Traveler's health; yellow book.
2.2 Hepatitis B structure
The hepatitis B virus, is a 42 nm partially double stranded DNA virus, composed of a 27 nm nucleocapsid core (HBcAg), surrounded by an outer lipoprotein coat containing the surface antigen (HBsAg); ( Figure 2) (Gatlin et al., 1997).
The 42Â nm, double-shelled particle, originally called the Dane particle, consists of a 7Â nm thick outer shell and a 27Â nm inner core. The core contains a small, circular, partially double-stranded DNA molecule and an endogenous DNA polymerase. This is the prototype agent for the family Hepadnaviridae (Hollinger et al., 2001).
The viruses have enveloped virions containing 3 to 3.3 kb of relaxed circular, partially duplex DNA and virion-associated DNA-dependent polymerases and also have reverse transcriptase activities (Robinson. 1994).
The most abundant are small, spherical, noninfectious particles, containing HBsAg, that measure 17 to 25 nm in diameter. (Robinson, 1995).The Hepatitis B surface antigen are complex of antigenic determinants found on the surface of HBV. They are tubular, filamentous forms of various lengths, but with a diameter comparable to that of a small 22nm particle. They also contain HBsAg polypeptides (Hollinger et al., 2001).
The HBV core gene codes for two distinct protein products: a 21.5-kDa protein that assembles to form nucleocapsid particles designated HBcAg, which in mature virions contains the viral DNA as well as the viral polymerase and RNase H, and a precore protein, which is directed to the endoplasmic reticulum (ER), and is N- and C-terminally processed and secreted as non-particulate e-antigen (HBeAg) (Florian et al., 1993).
The core antigen (HBcAg) is present on the surface of core particles. HBcAg and core particles are not present in the blood in a free form, but are found only as internal components of virus particles (Mahoney, 1999).
Hepatitis B envelope antigen is the antigenic determinant that is closely associated with the nucleocapsid of HBV. It also circulates as a soluble protein in serum (Hollinger et al., 2001).
The core antigen shares its sequences with the e antigen (HBeAg), identified as a soluble antigen, but no cross reactivity between the two proteins is observed (Robinson et al., 1995).
Antibody to HBsAg, HBcAg, and HBeAg are specific antibodies that are produced in response to their respective antigenic determinants (Hollinger et al., 2001).
The protein coat of HBV contains HBsAg, which is highly immunogenic and induces anti-HBs (humoral immunity). Whereas the structural viral proteins induce specific T-lymphocytes, capable of eliminating HBV-infected cells through cell mediated immunity (Chisari FV et al., 1997).
Figure 2: The Dane particle.
Source: Fenner F., White D. Medical Virology. New York: Academic Press.
2.3 HBV Genome
The genome of the HBV is a circular partially double stranded DNA molecule of about 3.2 kb in length that contains four overlapping open reading frames (ORFs) named S, P, C and X (Figure 3) The ORF S contains three initiation codons and encodes three polypeptides of different sizes called large, middle, and small that form the outer envelope of the virus pre-S1, 5 pre-S2, and S (hepatitis B surface antigen or HBsAg). The ORF P encodes the viral polymerase. The ORF C has two initiation codons that encode the hepatitis core antigen (HBcAg) that forms the nucleocapsid and a soluble antigen that is secreted into the blood stream, termed hepatitis B 'e' antigen (HBeAg), The function of the protein coded for by gene X is not fully understood (Juergen, 2007).
Figure (3): Organization of Hepatitis B virus genome. ORF stands for Open Reading Source: GrahamColm
2.4 Viral Stability
The stability of HBV may depend on the concentration of the virus. Excessively high concentration of the virus may results in incomplete inactivation or destruction, if expose to ether, acid of PH of 2.4 for at least 6 hours and heat at 98Â°C for 1 min. (Hollinger et al., 2001). However, antigenicity and infectivity are destroyed after exposure of HBsAg to sodium hypochlorite for 3 min, autoclaving at 121CÂ° for 20 min or dry heat treatment at 160Â°C for 1 hour (Hollinger et al., 2001, Robinson, 1995).
HBV is also inactivated by exposure to 2% aqueous glutaraldehyde at room temperature for 5 min, Sporicidin, formaldehyde at 18.5 g/l (5% formalin in water), 70% isopropylalcohol, 80% ethyl alcohol at 11Â°C for 2 min, an iodophor disinfectant and UV irradiation (WHO., 1993).
HBV is able to retain its infectivity when stored at 30-32Â°C for at least 6 months and when frozen at 215Â°C for 15 years. HBV present in blood can withstand drying on a surface for at least a week (Robinson, 1995, Hollinger et al, 2001)
2.5 Life Cycle of Hepatitis B Virus
The HBV virion binds to a receptor at the surface of the hepatocyte (Ganem, 2001). A number of candidate receptors have been identified, including the transferrin receptor, the 35 asialoglycoprotien receptor molecule, and human liver endonexin. The mechanism of HBsAg binding to a specific receptor to enter cells has not been established yet. Viral nucleocapsids enter the cell and reach the nucleus, where the viral genome is delivered (Chisari, et al., 1997, Guidotti, et al., 1994, Mahonney, et al., 1999).
In the nucleus, second-strand DNA synthesis is completed and the gaps in both strands are repaired to yield a covalently closed circular (ccc) supercoiled DNA molecule that serves as a template for transcription of four viral RNAs that are 3.5, 2.4, 2.1, and 0.7 kb long (Chisari, et al., 1997, Guidotti, et al., 1994, Mahonney, et al., 1999) These transcripts are polyadenylated and transported to the cytoplasm, where they are translated into the viral nucleocapsid and precore antigen (C, pre-C), polymerase (P), envelope large (L), medium (M), small (S), and transcriptional transactivating proteins (X) long (Ganem 2001., Chisari et al., 1997, Guidotti et al., 1994, Mahonney et al., 1999). The envelope proteins insert themselves as integral membrane proteins into the lipid membrane of the endoplasmic reticulum (ER).
The 3.5-kb species, spanning the entire genome and termed pregenomic RNA (pgRNA), is packaged together with HBV polymerase and a protein kinase into core particles where it serves as a template for reverse transcription of negative strand DNA. The RNA to DNA conversion takes place inside the particles (Ganem, 2001, Mahonney et al., 1999). The new, mature, viral nucleocapsids can then follow two different intracellular pathways, one of which leads to the formation and secretion of new virions, whereas the other leads to amplification of the viral genome inside the cell nucleus (Ganem, 2001, Mahonney et al., 1999).
In the virion assembly pathway, the nucleocapsids reach the ER, where they associate with the envelope proteins and bud into the lumen of the ER, from which they are secreted via the Golgi apparatus out of the cell (Ganem, 2001, Mahonney et al., 1999). In the genome amplification pathway, the nucleocapsids deliver their genome to amplify the intranuclear pool of covalently closed circular DNA (cccDNA) (Ganem, 2001, Mahonney et al., 1999). The precore polypeptide is transported into the ER lumen, where its amino- and carboxy-termini are trimmed and the resultant protein is secreted as precore antigen
(eAg). The X protein contributes to the efficiency of HBV replication by interacting with different transcription factors, and is capable of stimulating both cell proliferation and cell death (Ganem, 2001, Mahonney et al., 1999). The HBV polymerase is a multifunctional enzyme. The products of the P gene are involved in multiple functions of the viral life cycle, including a priming activity to initiate minus-strand DNA synthesis, a polymerase activity, which synthesizes DNA by using either RNA or DNA templates, a nuclease activity which degrades the RNA strand of RNA-DNA hybrids, and the packaging of the RNA pregenome into nucleocapsids (Chisari et al., 1997, Ganem, 2001, Mahonney et al., 1999). Nuclear localization signals on the polymerase mediate the transport of covalently linked viral genome through the nuclear pore (Chisari et al., 1997).
2.6 HBV Transmission
The virus is transmitted by percutaneous and permucosal exposure to infected blood and other body fluids. Infectious levels of the virus are also found in feces, saliva, urine, serous fluids, vaginal secretions, and semen (Larsen et al., 1995).
Another important mode of HBV transmission is from child to child during early life resulting from blood contact (Gatlin N, 1997).
Risk factors associated with Centers for Disease Control and Prevention (CDC) reported Hepatitis B cases in the United States include 36% spread by heterosexual activity, 13% by intravenous drug use, 11% by homosexual activity, 3% by household contact, 2% healthcare employment and 33% by unknown causes (Duma, 1995).
Most hepatitis B virus (HBV) infections in sub-Saharan African infants and children are acquired through horizontal transmission. (Francis E A. Martinson et al., 1998).
In Ghana, the behaviors most strongly associated with prevalence of HBV were sharing of bath towels, sharing of chewing gum or partially eaten candies, sharing of dental cleaning materials and biting of fingernails in conjunction with scratching the backs of carriers (Francis E A. Martinson et al, 1998).
2.7 Clinical Manifestation of Hepatitis B virus Infection
After exposure to the Hepatitis B virus, the incubation period before symptoms appear ranges from 60 to 180 days (Larsen et al., 1995).
The disease can manifest in three ways acute, fulminant or chronic (Figure 4). Acute viral hepatitis begins with general ill-health, anorexia, malaise, fever, nausea, diarrhoea, abdominal tenderness and fullness in the right upper abdominal quadrant is also felt (Drew L W, 1994).
Chronic infection with hepatitis B virus either may be asymptomatic or may be associated with a chronic inflammation of the liver, leading to cirrhosis over a period of several years (Gan Si et al., 2005).
Chronic hepatitis is strongly linked to the development of hepatocellular carcinoma (HCC). Fulminant infections cause massive liver necrosis, cerebral function changes, hepatic failure and often death (Drew L W, 1994).
Acute hepatitis B occurs in approximately 1% of perinatal infections, 10% of early childhood infections (children aged 1-5 years) and 30% of late infections (people aged >5 years). Fulminant hepatitis develops in 0.1-0.6% of acute hepatitis cases; mortality from fulminant hepatitis B is approximately 70%. The development of chronic HBV infection is inversely related to the age of acquisition, occurring in approximately 80-90% of people infected perinatally, about 30% of children infected before the age of 6 years, and in <5% of infections occurring in otherwise healthy adults (Hyams KC, 1995).
Source: Murray et al, Medical Microbiology, 6th Edition
Copyright @ 2009 by Mosby an imprint of Elsevier, Inc. All rights reserved.
2.8 Pathogenesis of Hepatitis B virus infection
Initial exposure to the HBV infection may occur through injection, heterosexual and homosexual sex and birth. The virus then spreads to the liver, replicates, induces a viremia, and is transmitted in various body secretions to start the cycle (Murray et al., 2009)
The virus starts to replicate in the liver within 3 days of its acquisition, but as already noted, symptoms may not be observed for 45 days or longer, depending on the infectious dose, the route of infection, and the person. The virus replicates in hepatocytes with minimal cytopathic effect. Infection proceeds for a relatively long time without causing liver damage (i.e., elevation of liver enzyme levels) or symptoms. During this time, copies of the HBV genome integrate into the hepatocyte chromatin and remain latent. Intracellular buildup of filamentous forms of HBsAg can produce the ground-glass hepatocyte cytopathology characteristic of HBV infection. (Murray et al., 2009)
Cell- mediated immunity and inflammation are responsible for causing the symptoms and affecting resolution of the HBV infection by eliminating the infected hepatocyte. However, it has been suggested that much of the liver damage is due to secondary antigen non specific inflammatory responses that are set in motion by the response, such as TNF, free radicals and proteases. Other immune cell populations, notably natural killer T cells, probably also contribute to liver injury (Ganem et al., 2004)
2.9 Hepatocellular Carcinoma
Epidemiologic studies have demonstrated that there is a consistent and specific causal association between HBV infection and HCC (Beasly RP et al., 1981, Chen et al., 1997, Popper et al., 1982).
In patients with persistent HBV infection, the risk of HCC was 100 times higher than in non-infected individuals (Beasley et al., 1981)
The global distribution of hepatocellular carcinoma correlates with the geographic prevalence of chronic carriers of HBV, who number 400 million worldwide. The highest rates are in Southeast Asia and sub-Saharan Africa, with the HCC incidence >50/100, 000 population (Bosch et al., 1999)
Virological factors in the pathogenesis of hepatocellular carcinoma have recently been defined. Both retrospective and prospective studies strongly supported the relation between positive HBeAg and the risk of HCC (Lin et al., 1991, Yang et al., 2002). HBV DNA was identified as the most important predictor of the development of hepatocellular carcinoma in HBsAg-positive patients with different clinical conditions (Ishikawa et al., 2001, Ohata et al., 2004)
Therefore, efforts at eradicating or reducing the viral load may reduce the risk for HCC. Additionally, HBV genotype might play a role in the development of HCC. (Ikeda et al., 2003)
2.10 Occult Hepatitis B infection
A silent form of hepatitis B infection called occult hepatitis B infection (OBI) has been recognized for nearly 20 years with the improvements in sensitivity of serological and genomic amplification assay, it is defined as the presence of HBV-DNA without detectable HBsAg with or without anti-HBc or anti-HBs, outside the pre-seroconversion window period. Serum HBV level is usually less than 104 copies/ml (Xu et al., 1999).
The frequency of occult hepatitis B infection depends on the relative sensitivity of both HBsAg and DNA assays, and also depends on the prevalence of HBV infection in the population. Occult hepatitis B infection (OBI) may follow recovery from infection, displaying antibody to hepatitis B surface antigen (anti-HBs) and persistent low-level viremia, escape mutants undetected by the HBsAg assays, or healthy carriage with antibodies to hepatitis B envelope antigen (anti-HBe) and to hepatitis B core antigen (anti-HBc) (Allain, 2004)
Overall, occult HBV infection is seen in 7%-13% of anti-HBc-positive and/or anti-HBs-positive subjects, and in 0% to 17% of blood donors. Occult HBV infection represents a potential transmission source of HBV via blood transfusion or organ transplantation. The clinical significance of occult HBV infection remains unclear. (Brechot, et al., 2001)
2.11 Host Immune Response to Hepatitis B virus infection
During HBV infection, the hostÂ immune responseÂ causes both hepatocellular damage and viral clearance. Although the innate immune response does not play a significant role in these processes, the adaptive immune response, in particular virus specific cytotoxic T lymphocytes (CTLs), contributes to most of the liver injury associated with HBV infection. CTLs eliminate HBV infection by killing infected cells and producing antiviral cytokines, which are then used to remove HBV from viable hepatocytes. (Innacone et al, 2007)Â Although liver damage is initiated and mediated by the CTLs,Â antigen-nonspecificÂ inflammatory cellsÂ can worsen CTL-induced immunopathology, andÂ plateletsÂ activated at the site of infection may facilitate the accumulation of CTLs in the liver. (Innacone et al., 2005)
Primary infection leads to an IgM and IgG response to HBcAg shortly after the appearance of HBsAg in serum, at onset of hepatitis. Anti-HBs and anti-HBe appear in serum only several weeks later, when HBsAg and HBeAg are no longer detected, although in many HBsAg-positive patients, HBsAg-anti-HBs complexes can be found in serum (Robinson, 1994, Mahoney, 1991)
2.12 Diagnosis of Hepatitis B virus infection
The tests called assays used for detection of hepatitis B virus infection involve serum or blood which detects viral antigens orÂ antibodies produced by the host. (Bonino et al, 1987)
The diagnosis of HBV infection requires the evaluation of the patient's blood for HBsAg, hepatitis B surface antibody (HBsAb), and hepatitis B core antibody (HBcAb). The presence of HBsAg indicates either acute or chronic infection; the presence of HBsAb indicates recovery and immunity from HBV infection or successful immunization against HBV. HBcAb appears at the onset of acute HBV infection, but may also indicate chronic HBV infection. Whiles detection of Hepatitis E surface antigen (HBeAg) indicates that someone with a chronic infection is more contagious (Table 1).
Acute / Chronic infection
Anti-HBc IgG and HBsAg
Anti-HBc IgG and anti-HBs
Table 1: Interpretation of HBV immunologic markers.
Source: Sjogren MH. Serological diagnosis of viral hepatitis
PCRÂ tests have been developed to detect and measure the amount of HBV DNA, called theÂ viral load, in clinical specimens. These tests are used to assess a person's infection status and to monitor treatment. (Zoulim, 2006)
The enzyme-linked immunosorbent assay (ELISA) is one of the most sensitive and specific methods for diagnosing HBV infections. It is useful for early detection of HBsAg. (Fontirrochi et al., 1993)
2.13 Prevention of Hepatitis B infection
ï»¿ Hepatitis B virus infection is a preventable disease. Transmission of HBV via transfusion of blood and plasma-derived products has been eliminated in most countries through donor screening for HBsAg and viral inactivation procedures. However, transmission also occurs with inadequately sterilized needles and medical instruments, reuse of disposable needles and syringes, and contamination of multiple-dose medication vials (Alter, 2003). The use of condom is recommended to avoid infection through sexual contacts. Immune-prophylaxis with Hepatis B immune-globulin (HBIG) has shown significant protection against infection in HBV exposed individuals (Szmuness et al., 1974). Hepatitis B immune-Globulin (HBIG) is also potent to cut down HBV intrauterine infection when administered to pregnant women during late pregnancy (Li et al., 2004). However, vaccination is the most important tool in preventing the transmission of HBV. In 1992, the World Health Organization recommended that childhood hepatitis B vaccination should be included in immunization programs of all countries (World Health Assembly, 1992). High efficacy and safety have been proved for the vaccines used with protective levels of antibodies elicited in more than 90% of the recipients (Hammond et al., 1991). The implementation of vaccination has dramatically changed the epidemiology of HBV in countries where the transmission has been mostly vertical (Chang et al., 1997).
Education regarding infection prevention and transmission especially of the groups at risk of hepatitis exposure is supposed to be one of the cost- effective ways of infection control (Alavian et al., 2007). However, despite the implementation of public health interventions, such as universal immunization and harm reduction programs for HBV, HBV transmission still persists among new generations of injecting drug users (Lum et al., 2008).
2.14 Treatment of Hepatitis B virus infection
TheÂ hepatitis BÂ infection does not usually require treatment because most adults clear the infection from their body (Hollinger et al., 2006). Treatment with antiviral drugs may be required in less than 1% of people, whose infection takes on very aggressive course and in those who are in immunocompromised. Treatment lasts from six months to a year, depending on medication and genotype (Lai et al., 2007, Alberti, et al., 2011).
Available drugs for treatment of Hepatitis B infection do not necessary clear the virus, but they can stop the virus from replicating, thus minimizing liver damage. As of 2008, seven medications have been licenced for the treatment of Hepatitis B infection in the United States. These antiviral drugs are lamivudine, tenofovir, adefovir, telbivudine, entecavir and two immune system modulators interferon, alpha-2a and PEGylated interferon alpha-2a (Pegasys) (Dienstag JL, 2008). The treatment reduces viral replication in the liver, thereby reducing the amount of virus particles in the blood (viral load) (Pramoolsinsup, 2002)