CHAPTER ONE
INTRODUCTION
A virus is a small infectious agent
having a simple acellular organization with a nucleic acid and aprotein
coat.It lacks independent metabolism and replicate only within living
hosts. A virus invades living cells and uses its chemical machinery to
keep itself alive and replicate in the host. It may reproduce with
fidelity or with errors (mutations); this ability to mutate is
responsible for the ability of some viruses to change slightly in each
infected person, making treatment difficult. Viruses cause many human
infections and are also responsible for a number of rare diseases. The
human diseases they cause may affect different organs or parts of the
body. An inflammation of the liver is often referred to by a general
term called Hepatitis, which is often caused by a variety of viruses
which include hepatitis A, B, C, D and E. Of the viral causes of
hepatitis, there are few of greater global importance than hepatitis B
(Ganem et al, 2001).
The hepatitis B virus (HBV) belongs to
the family Hepadnaviridae,which consists of hepatotropic DNA viruses.
The family of Hepadnaviruses comprises members recovered from animal
species including the woodluck hepatitis virus (WHV), the ground
squirrel hepatitis virus (GSHV), and the duck HBV. Common features of
all of these viruses are enveloped virions containing 3 to 3.3 kb of
relaxed circular partially duplex DNA and have reverse transcriptase
activities. Hepadnaviruses show narrow host ranges, growing only in
species close to the natural host, like gibbons, African green monkeys,
rhesus monkeys and woolly monkeys (Gitlin,1997).The Hepatitis virus
belongs to the genus Hepadnavirus. It is a 42nm partially
double stranded DNA virus, composed of a 27nm nucleic acid core (HBcAg),
a DNA polymerase reverse transcriptase, surrounded by an outer
lipoprotein coat (called envelope) containing the surface antigen
(HBsAg)that play a major role in the diagnosis of HBV infection (Ganem et al;
2001; Gitlin,1997). The genome consists of a partially double-stranded
circular DNA molecule of about 3200 base pairs in length with known
sequence as well as genetic organization. Virion particles are identical
to the virion ‘tails’- they vary in length and have a mean diameter of
about 22nm. They sometimes display regular, non-helical transverse
striations.
The viral DNA polymerase-reverse
transcriptase is encoded by the polymerase gene [P] and is of central
importance for viral replication. Different from all known mammalian DNA
viruses, hepadnaviruses replicate via reverse transcription of a RNA
intermediate (Summerset al.,1982), the pregenomic RNA, which is
a strategy central to the life cycle of RNA retroviruses. Similarities
and differences between retroviral and hepadnaviral replication have
been defined (Nassal, 1999). Based on the unique replication cycle of
HBV, antiviral therapeutic strategies aimed at the reverse transcription
of HBV RNA or at HBV reverse transcriptase have been successfully used
as antivirals to treat HBV infection (Feld, 2002).
The prevalence of HBV infection varies
in different countries or regions in the world as well as in different
ethnic groups. HBV endemicity has been classified into three categories,
high (>8%), intermediate (2–8%), and low (<2%), depending on the
prevalence of hepatitis B surface antigen (HBsAg) seropositivity. The
highly endemic areas in the world include East and Southeast Asia, the
Pacific, sub-Saharan Africa(Nigeria inclusive), and parts of southern
Europe. In North America, and western and northern Europe, HBV infection
is relatively rare, with a prevalence rate of around 0.1%.Hepatitis B
virus (HBV) infection is a serious global health problem, with 2 billion
people infected world-wide, and 350 million suffering from chronic HBV
infection. HBV is the 10th leading cause of death worldwide, HBV
infections result in 600 000 deaths annually (Ott et al 2012).
1.2 million deaths per year are caused by chronic hepatitis, cirrhosis,
and hepatocellular carcinoma; the last accounts for 320 000 deaths per
year (WHO, 2000). In Western countries, the disease is relatively rare
and acquired primarily in adulthood, whereas in Asia and most of Africa,
chronic HBV infection is common and usually acquired perinatally or in
childhood.
The whole of Africa is regarded as
highly endemic, coming only behind Asia. Although overall Africa is
considered a high endemic area with 7–26% prevalence of HBsAg, Tunisia,
Morocco, and Zambia have intermediate endemicity (Andre, 2000). In West
Africa, countries like Senegal and Gambia have over 90% of their
populations exposed to and becoming infected with HBV during their lives
(Edmund WJ. et al., 1996). In Nigeria, not less than 23
million people are estimated to be infected with HBV (Bukola, 2015),
making Nigeria one of the countries with the highest incidence of HBV
infection in the world.
Hepatitis B is caused by hepatitis B
virus. The virus interferes with the functions of the liver while
replicating in hepatocytes. The immune system is then activated to
produce a specific reaction to combat and possibly eradicate the
infectious agent. As a consequence of pathological damage, the liver
becomes inflamed. HBV may cause up to 80 per cent of all cases of
hepatocellular carcinoma (HCC) worldwide, second only to tobacco among
known human carcinogens (WHO, 2001). Most people do not experience any
symptoms during the acute infection phase. However, some people have
acute illness with symptoms that last several weeks, including yellowing
of the skin and eyes (jaundice), dark urine, extreme fatigue, nausea,
vomiting and abdominal pain. In some people, the hepatitis B virus can
also cause a chronic liver infection that can later develop into
cirrhosis of the liver or liver cancer (WHO, 2014).
Susceptibility to HBV infection is
general. Only people who have been vaccinated successfully or have
developed anti-HBs antibodies after HBV infection are immune to HBV
infection. Persons with congenital or acquired immunodeficiency
including HIV infection, those with immunosuppression including those
with lymphoproliferative disease, patients treated with
immunosuppressive drugs including steroids and by maintenance
haemodyalisis are more likely to develop persistent infection with HBV.
Hepatitis B can be spread by
• unprotected sex
• sharing IV drug needles
• living in a household with an infected person
• an infected mother to her newborn child at birth
• sharing earrings, razors, or toothbrushes with an infected person
• unsterilized needles, including tattoo or piercing needles
• human bites (www.hepb.org).
People are most at risk for hepatitis B if they
• are born to mothers who are infected with HBV
• live in close household contact with a chronically infected individual
• adopt a child from a country where HBV is prevalent
• have unprotected sex or have more than one sexual partner in a six month period
• have ever been diagnosed with a sexually transmitted disease (STD)
• are men who have sex with men
• share needles and syringes
• are health care provider or emergency responder with possible contact with bodily fluids
• are a patient on kidney dialysis
• live or work in an institutional setting, such as a prison or group home (www.hepb.org).
Diagnosis of hepatitis is made by
biochemical assessment of liver function. Initial laboratory evaluation
should include: total and direct bilirubin, ALT (alanine transaminase,)
AST (aspartate aminotransferase), alkaline phosphatase, prothrombin
time, total protein albumin, globulin, complete blood count, and
coagulation studies(Hollingeret al.,2001). Diagnosis is confirmed by demonstration of specific antigens and/or antibodies.
There is yet no treatment for acute HBV
infection, but it is a vaccine-preventable infection. Several vaccines
have been used in the prevention of this infection, the prominent ones
including Lamivudine, Adefovir, Dipivoxil, Famvir, FTC, Ritonavir,
Theradigm-HBV, Ganciclovir (Hadziyannis et al.,1999).
1.1 OBJECTIVES
Hepatitis B virus infection is of global
concern. More importantly, it is of national concern as over 23 million
Nigerians are infected with HBV. The incidence of the infection in
South-Western Nigeria is of no less importance as the region is still
ravaged with high cases of immunization difficulties. Most texts have
been on HBsAg, whereas other markers are equally important.
The purpose of the this study, therefore, is
- To determine the presence of Hepatitis B envelope antibody in
patients who have been previously screened for the surface antigen.
- To determine the class of individuals mostly affected