CHAPTER TWO

                                                           CHAPTER TWO

                                                     LITERATURE REVIEW

2.0 Introduction

This chapter explains theoretical literature review ,prevalence of hepatitis B among patients attending at duflle hospital, transfusion factors associated with hepatitis B among patients attending at Dufle hospital, sexual factors associated with hepatitis B among patients attending at Dufle hospita

2.1 theoretical literature review

Hepatitis B is an infectious disease caused by the hepatitis B virus (HBV) that affects the liver [Chang MH (June 2007). (MH, (June 2007). )] Acute infection with hepatitis B virus is associated with acute viral hepatitis, an illness that begins with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, and dark urine, and then progresses to development of jaundice. The illness lasts for a few weeks and then gradually improves in most affected people. A few people may have a more severe form of liver disease known as fulminant hepatic failure and may die as a result. The infection may be entirely asymptomatic and may go unrecognized.[ Terrault N, Roche B, Samuel D (July 2005). ] ( (Terrault N, july 2005) )Chronic infection with hepatitis B virus either may be asymptomatic or may be associated with a chronic inflammation of the liver (chronic hepatitis), leading to cirrhosis over a period of several years. This type of infection dramatically increases the incidence of hepatocellular carcinoma (HCC; liver cancer). Across Europe, hepatitis B and C cause approximately 50% of hepatocellular carcinomas.[ El-Serag HB.2011]( (Gan SI, 22 subtember 2011)) Chronic carriers are encouraged to avoid consuming alcohol as it increases their risk for cirrhosis and liver cancer. Hepatitis B virus has been linked to the development of membranous glomerulonephritis (MGN).[ Gan SI, Devlin Smeta eta,2005]( (Gan SI D. S., october2005)) Transmission of hepatitis B virus results from exposure to infectious blood or body fluids containing blood. It is 50 to 100 times more infectious than human immunodeficiency virus (HIV).[ "Hepatitis B FAQs for the Public"2015] (Public", 24 august 2015)Possible forms of transmission include sexual contact,[ Fairley CK, Read TR2012] (Fairley CK, 2012)blood transfusions and transfusion with other human blood products,[ Buddeberg F,eta 2008] (Buddeberg F, 2008) re-use of contaminated needles and syringes,[ Hughes RA (March 2000).] (RA) 

transmission from mother to child (MTCT) during childbirth. Without intervention, a mother who is positive for HBsAg has a 20% risk of passing the infection to her offspring at the time of birth. This risk is as high as 90% if the mother is also positive for HBeAg. HBV can be transmitted between family members within households, possibly by contact of nonintact skin or mucous membrane with secretions or saliva containing HBV.[ "Hepatitis B – the facts:2011] (facts:, IDEAS –Victorian Government Health Information, Australia) However, at least 30% of reported hepatitis B among adults cannot be associated with an identifiable risk factor.[ Shapiro CN (May 1993).] (CN, (May 1993). )Breastfeeding after proper immunoprophylaxis does not appear to contribute to mother-tochild-transmission (MTCT) of HBV.[ ߪShi Z, Yang Y, Wang H, eta 2011] (ߪShi Z, 2011)The virus may be detected within 30 to 60 days after infection and can persist and develop into chronic hepatitis B. The incubation period of the hepatitis B virus is 75 days on average but can vary from 30 to 180 days.[WHO2014] (|, 2014)

 2.2.0 prevalence associate hapattis B virus:

 2.2.1 Age

Introduction

Hepatitis B infection (HBV) is the main source of viral hepatitis in people around the world.As of now north of two billionpeople have proof of past HBV contamination and 350 millionhave become ongoing transporters of the infection, 60 million of them dwelling in Africa [LeeWM:1997 (WM:, 1997)]. There appear to be varying dangers for HCC by geological area,with higher gamble kept in nations in sub Saharan Africa and Asiacompared to Europe[Villeneuve JP,ate (Villeneuve JP, 1994).1994]. Persistent HBV contamination is amajor reason for liver illness and is emphatically connected with the advancement of hepatocellular carcinoma(HCC) [Kirk GD,ate 2004 (ate K. G., 2004)]. Other gamble factors for HCC incorporate, male orientation, co-disease with hepatitis C infection (HCV) [Ikeda K.ate,2006 (Ikeda K, 2006)], liquor misuse [Kirk GD,ate 2005 (Kirk GD e. , 2005) (Kirk GD, eta.2005 (Kirk GD e. ,Hepatocellular carsinomaand polymorphisms in cancer-causing agent utilizing andDNA fix proteins in a populace with aflatoxin exposureand hepatitis B infection endemicity.,2005)aflatoxin openness (Kirk GD, 2005) (Kirk GD, 2005) and HBV genotype [Cougot.D.(Cougot D, 2005)2005]. Roughly 33% of HBV transporters will advance to cirrhosis what's more, 25% will foster HCC [Moyer LA, Pole EE:1994 (Moyer LA, 1994)]. The gamble of HCC is multiple times higher in patients who are steadily HBeAg positive than in HBeAg negative patients [Yang Howdy, Lu SN,eta2002 (Yang Hey, 2002)] and multiple times higher in patients with high DNA viral burden [ Chen CJ, Yang HI,eta 2006), (Chen CJ, 2006) The vast majority of the investigations of the relationship of HBeAg and viral burden with constant liver sicknesses and HCC have been directed in Southeast Asia. There is no equivalent information in Sub Saharan Africa. HBV disease is endemic in The Gambia with 15-20% unvaccinated Gambians persistently contaminated [Whittle HC,eta1983 ].( (Shave HC, 1983) ) Livercancer stays the commonest reason for death in grown-up guys in The Gambia [Bah E, Parkin DM, Corridor AJ, Jack Promotion, Shave H:.2001 ].( (Bah E, 2001) Investigations of HBV disease led in two adjoining towns of Keneba and Manduar (arranged in West Kiang area) in the period before 1986-1990, at the point when the public immunization program in The Gambia started, have shown that disease was remarkable in babies younger than a half year and kin to-kin transmission as opposed to perinatal or vertical transmission was vital [Whittle HC, estimated time of arrival 1990), (Shave HC, The example of life as a youngster hepatitisB disease in two Gambian towns., 1990) Different examinations have shown that from the get-go in the transporter state,HBV contaminated people test positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg)and have elevated degrees of HBV DNA in their serum [Mendy ME,eta2006) (Mendy ME, 2006) But the serum of more seasoned transporters, have perceptible immunizer to HBeAg (antiHBe), which seems following leeway of HBeAg and is The regular history of HBV disease is intricate and variable and is incredibly impacted by the age at contamination and the level of HBV replication. The variety of clinical result of HBV, either goal (intense disease) or perseverance (ongoing carriage) of contamination is reliant onthe have invulnerable reaction to the infection [Hui CK, Lau GK:2006]( (Hui CK, 2006)). Significant changes are happening which are affecting on the normal history of HBV contamination. These changesinclud immunization programs [Whittle HC, Maine N, Pilkington J,eta 1995] (Shave HC M. N., 1995) and the improvement of freak types of the infection chiefly pre center (pre-C)and basal center advertiser (BCP) freaks [Dumpis U, Mendy M, Slope A, estimated time of arrival 2001 ].( (Dumpis U, 2001)

We showed that one third of young carriers clear HBsAgand progressed to 'immune clearance' phase in the first 10 years after infection; thus resulting to a short lived'immune tolerance' phase. The remaining two thirds persistently test positive for HBsAg and continue to tolerate the virus. In contrast to HBsAg, clearance of HBeAg occursat steady rates over the years. By the age of 24 years only 13.6% Gambian HBsAg carriers are positive for HBeAg. Our data supports previous cross-sectional studies, that the majority of chronically infected adult Gambians have undetectable HBeAg [Mendy ME, Fortuin M, Hall eta1999 ].( (Mendy ME F. M., 1999) ) It was noted then and confirmed in the present study that HBeAg tend to  wane with increasing age and the majority of adult carriers have maintained an inactive status. It is still not clear what factors are responsible for the loss of HBsAg or HBeAg which can occur spontaneously or following treatment with interferon or nucleoside analogues [Fattovich G, Brollo L, eta 1996].( (Fattovich G, 1996) ) However, the risk for cirrhosis and HCC is low in inactive carriers with non-replicating HBV and these carriers have similar rates of liver-related morbidity and mortality when compared to uninfected individuals [Manno M, Camma C, Schepis F, Bassi F, eta 2004].( (Manno M, 2004)) The lower rates of HbeAg seropositivity in older carriers in the present study compared to carriers from Taiwan relates to the reported differences in the epidemiology of HBV between subSaharan Africa and South east Asia. Perinatal transmission is the commonest route of transmission in Asia and affects young infants (< 6 months) whilst in Africa, horizontal or sibling to sibling transmission is the most important routeof transmission and affects young children between 6–12 months of age [Chen CJ, Wang LY, Yu MW:2000]. (Chen CJ W. L., 2000)

2.2.2 Gender .

 The article reviews the reported molecular mechanisms associated with the gender disparity in HBV-related HCC to improve the understanding of its role in the development and progression of HBV-associated HCC. Most previous studies have demonstrated that there is a sexual disparity in the development of HBV-related HCC. For example, female HBV carriers generally have lower viral loads than male carriers, the risk of HBVassociated HCC is lower in females than in males, and the ratio of the estradiol level to the testosterone level tends to decrease in female patients with HBV-related HCC than in female HBV carriers who do not develop HCC(El-Serag HB.2012) (HB, 2012). To date, the mechanisms underlying that males are more susceptible to developing HCC after an HBV infection have become an important topic, drawing widespread attention from scientists. An increasing number of studies have suggested that HBV-associated HCC may be a hormone-responsive malignant tumor (Ruggieri A,2010). (Ruggieri A ,. , 2010). It was reported that high levels of serum testosterone in males with an HBV infection are associated with their development of HCC. Even when the condition of their viral hepatitis or alcoholic cirrhosis improved, their risk for HCC was still increasing (El-Serag HB. 2012). (HB, Epidemiology of viral hepatitis and hepatocellular carcinoma. , 2012)

These results suggested that the androgen receptor (AR) might be involved in HBV-related hepatocarcinogenesis and an active androgen signaling pathway might increase the risk of   HBVassociated HCC(Yang WJ, eta,2009) (Yang WJ, 2009). The AR, a ligand-dependent transcription factor of the nuclear receptor superfamily, was reported to be overexpressed in HCC. After two nuclear processes, including the AR N-C interaction (dimerization step) and the transcriptional activation of the AR N-terminal transactivation domain (NTD) (transactivation step), are completed, the AR is fully activated(Wang SH.eta.2009) (SH.eta, 2009) Interestingly, among male HBV carriers with an increased risk of HCC, both higher androgen levels and more active androgen receptor gene alleles were detected, compared with those of controls(Wang SH.eta.2009). Similarly, the ratio of estradiol to testosterone was shown to be significantly lower in female patients with HBV-associated HCC (Wang SH, 2009) The IL-1 gene family (including IL-1 α , IL-1 β and IL-1RN) is a group of inflammatory cytokines that appear to serve as tumor growth factors in hepatocarcinogenesis. Jiang et al (Jiang R, eta.2011) (Jiang R, 2011) demonstrated that IL-1α was an essential factor for the development of HBV-related HCC in males and its persistent expression was a specific predictor of chronic liver inflammation that could potentially be used as a marker in clinical diagnosis. Clinically, dynamic monitoring of IL-1α had been used and was shown to be a potentially valuable tool in detecting the recurrence of HBV-associated HCC and a possible target for pharmaceutical research. Further investigation of estrogen signaling in menopausal females indicated that the inactivation of estrogen signaling might contribute to the up-regulation of IL-1α and IL-6 expression HCC development is a multistep tumorigenic process that includes many carcinogenic-related changes at the molecular level that are affected by epigenetic and/or genetic alternations. It has been shown that many of the HCC risk factors are related to epigenetic changes, such as the regulation of mRNA levels by microRNAs (miRNAs), DNA methylation and histone modification. However, the underlying mechanisms leading to HBVrelated HCC development and their relationships with the gender disparity of this process have not been fully explored (Chen PJ.eta 2012.) (PJ.eta, 2012)

2.3.0 Transfusion Factors:

 2.3.1 Un screening

 Hepatitis B virus (HBV) infection via blood transfusion is a major concern in transfusion medicine (Perkins HA eta 2010). Screening tests for hepatitis B surface antigens (HBsAg) and anti-hepatitis B core (HBc) antibodies detect HBV transmissible blood and prevent recipient HBV infection. After the introduction of HBV nucleic acid tests (NAT) in blood donor screening, the residual risk of HBV infection by transfusion decreased( (eta P. H., 2010)(Cable R,eta (Cable R, 2013)]. Implementation of this test revealed occult hepatitis B virus infection (OBI) in blood donors. OBI is defined as the presence of HBV DNA in the liver (with detectable or undetectable HBV DNA in the serum) of individuals who tested negative for HBsAg Raimondo G,eta ( (Raimondo G, 2008).2008) The amount of viral DNA in the serum is typically very low in cases of true OBI. Because testing liver tissue is not always practical o (JH, 1978)r possible, OBI is often diagnosed through serum HBV DNA and viral marker test(Hollinger FB. [ (FB., 2008)2008 ]. A positive OBI test may be found in blood donors as a result of various clinical conditions, including: (Korelitz JJ.eta,)(1997) (JJ.eta, 1997) the incubation period of acute infections; (Wang JT) (2002) (JT, 2002) (eta H. J., 1978) the tail-end stage of chronic hepatitis B; (Candotti D, eta( (Candotti D, 2009)2009) low-level viral replication after recovery from hepatitis; and (Perkins HA ,eta,2010) (eta P. H., 2010)escape mutants not detected by current HBsAg tests(Allain JP 2004 (JP, Occult hepatitis B virus infection: implications in transfusion., 2004)). HBV transmission by blood transfusion from an OBI donor was first reported in 1978(Hoofnagle JH.eta 1978). An increasing number of studies on OBI infectivity  

of blood items have as of late been distributed (Allain JP .estimated time of arrival 2013). In this survey, we sum up the job of blood evaluating tests for HBV contaminations and update the known dangers of OBI bonding transmission (.estimated time of arrival, 2013). Hepatitis B center antigen (HBcAg) shows up in hepatocytes inside 2 wk after HBV contamination; irresistible viremia including HBsAg and polymerase are available in the blood after 3 wk. Hostile to HBc IgG structures during the recuperation period of contamination and is constant forever, accordingly, the presence of this immunizer in blood demonstrates past HBV infection(Koziel MJ,2005) (Koziel MJ, 2005). The logical awareness of HBsAg tests during the 1980s was lower than that of current examines. In 1983, Nath et al (Nath N,eta 1983) (Nath N, 1983) tracked down that 1 of 16 examples with hostile to HBc without a trace of enemies of HBs was found to have HBsAg when tried with a moretouchy test. In this manner, extra evaluating for HBV and proxy tests for non-A, non-B hepatitis were fundamental during the 1980s until the counter hepatitis C infection (HCV) immune response test opened up (Koziol DE,eta.1986) (Koziol DE, 1986) The counter HBc test was presented during the 1980s for screening of blood givers in HBV non-endemic nations, for example, the US. Indeed, even after the presentation of the counter HCV test in the mid 1990s, the antiHBc test keeps on being utilized for giver separating numerous nations to forestall potential transmission of HBV from HBsAg-negative givers (O'Brien SF.eta 2007) (.estimated time of arrival O. S., 2007) A few investigations have revealed successful screening of blood for hostile to HBc (Alla (Allain JP, 1999) in JP,1999)However, HBV endemic nations couldn't execute hostile to HBc screening in light of the fact that many blood items would be disposed of because of positive screening tests despite the fact that the vast majority of the blood would be ok for bonding. Instances of post bonding hepatitis B from positive transporter blood and posttransfusion fulminant hepatitis B from blood containing precoredefective HBV freaks have been accounted for in Norway and Japan, individually, nations that didn't evaluate contributors for against HBc (Kojima M. Estimated time of arrival 1991) (estimated time of arrival K.M., 1991). In 1989, Japan presented enemy of HBc testing with a changed calculation in which hostile to HBc-receptive blood with titers < 1:32 or ≥ 1:32 with enemies of HBs ≥ 200 mIU/mL were utilized for transfusion(Tani Y,eta. 2012). (Tani Y, 2012) Blood bonding could be a significant course for the transmission of disease particularly at the point when given blood isn't evaluated for HBV contamination (World Wellbeing Organisation.2001) (Association, Branch of Antibodies and Biologicals. Presentation of hepatitis B immunization into youth Inoculation administrations. Geneva, 2001). Screening of given blood for Hepatitis B surface Antigen (HBsAg) was presented during the 1970s (Said ZNA,2011) (ZNA,2011)This greatly reduced HBV transmission due to blood transfusions (Contreras M,eta .2005) (Contreras M, 2005) as blood found to be HBsAg positive was not transfused. In many developing countries including Nigeria, screening of blood donors or blood donated, for HBsAg alone, is still the only practice on which the prevention of HBV transmission during blood transfusion is based (Salawu L, eta 2006). Numerous scientific papers have highlighted the presence of HBV infection in some individuals negative for HBsAg but having detectable HBV DNA in the liver or blood and some of these publications have documented HBV (Salawu L, 2006) transmission resulting from transfusion of blood tested and found to be HBsAg negative (Satake M ,eta , 2007) (Satake M, 2007). Occult HBV infection (OBI) has been the subject of numerous publications focusing on different aspects of and issues relating to OBI [Lledó JL. Eta 2011.) It is a term that has been chosen by experts [33] to denote HBV infections in which HBsAg cannot be detected and the presence of infection is only established by amplifying an (JL.eta, 2011)d detecting HBV DNA(Hollinger FB .eta 2010) (eta H. F., 2010). One significant importance of OBI is the risk of transmission of HBV from individuals with OBI to recipients. This could occur if blood or blood components, stem cells or solid organs are transfused or transplanted following negative HBsAg results in donors with OBI. Such infections could manifest overtly becoming HBsAg positive with possibly fatal consequences, the risk rising with immune suppressed recipients(Hollinger FB eta .2010) (FB.eta, 2010) In Nigeria, which is highly endemic for HBV infection (Forbi JC,2010) (Forbi JC, 2010) current blood banking practices do not include procedures that would identify OBI and prevent transfusion of blood or blood products from apparently healthy donors with OBI to recipients (Salawu L,eta,2010). (Salawu L, HBsAg, anti-HCV, antiHIV and VDRL in blood donors: prevalence and trends in the last three and a half years in a tertiary health care facility in Ile-Ife, Nigeria. , 2020)

2.3.2 miss Screening

 Since the milestone introduction of hepatitis B surface antigen (HBsAg) testing in 1969, the risk of transfusion-transmitted hepatitis B virus (TTHBV) has steadily decreased, thanks to the development of increasingly more sensitive HBsAg assays; the adoption in some countries of hepatitis B core antibody (anti-HBc) screening; improved donor selection, including no remunerated intrinsically motivated blood donors; HBV vaccination programs; and finally the introduction of hepatitis B virus (HBV) nucleic acid testing (NAT) in minipools (MP) or later on as individual (ID) testing.