People with end-stage renal disease (ESRD) who have tried all other treatments and still need to clean their blood must go through hemodilysis (HD) [1]. One of the biggest risks of hemodialysis is the chance of getting an infection from blood [2,3]. Multiple types of blood-borne viruses are more likely to infect people with HD than the general population, according to research. Patients who have hemodialysis for a long time may also be more likely to get hepatitis B virus (HBV) infections [4,5]. Over 880,000 people die every year from problems related to HBV infection [6,7]. About 257 million people around the world are thought to be chronic carriers of HBV. In the 1960s, it was first shown that viral hepatitis could be spread through hemodialysis (HD). HBsAg has been found on a number of HD facility surfaces and tools. People who work in HD centers can get HBV either directly from infected equipment or indirectly through healthcare workers. The length and type of dialysis, as well as the length of end-stage renal disease (ESRD), are also risk factors in this group. We did a systematic review and meta-analysis to look at the epidemiological state of HBV infection in this patient group because HBV infection has been shown to raise the risk of death in HD patients. It is a common symptom of the condition, just as it is a common symptom of other types of hepatitis caused by other factors, such as excessive use of alcohol and drugs or metabolic abnormalities. Jaundice is a common symptom of the condition. Jaundice is also a common symptom of other types of hepatitis caused by other factors [7] An infection with the hepatitis B virus is nearly often the cause of hepatitis that occurs after receiving a blood transfusion (HBV). In addition, HBV is the primary agent responsible for the majority of cases of chronic hepatitis around the world. Sexual contact, the use of intravenous drugs or blood products, blood transfusions, and/or direct contact with blood are the most common ways that HBV is spread. It can also be transmitted through blood transfusions. Patients who had recently been diagnosed with an infection and whose illness had been present for up to six months were considered to have acute infections. On the other hand, patients whose infections had been present for more than six months were considered to have chronic infections [8-10].  The diagnosis of chronic hepatitis B has advanced from the simple detection of HBsAg to the more complex antibody response against particular viral proteins, and most recently, to the detection and quantification of viral DNA. In the past, chronic hepatitis B was diagnosed through the simple detection of HBsAg. In both the diagnosis and treatment of disease, the implementation of HBV DNA quantification methods that are ever more sensitive has proven to be of significant value [11]. Because the majority of guidelines mention that suppressing HBV replication is one of the primary therapeutic targets, monitoring the patient's viral load throughout treatment is critically crucial. HBx is the name given to the x antigen that is encoded by HBV, which is the virus that is accountable for the development of HCC. At least three important pathways are involved when it comes to HBx's contribution to the pathogenesis of disease. This suggests that HBx contributes to HCC by epigenetically altering patterns of host gene expression, whereas immune-mediated CLD is the contribution that the host makes to the development of the tumor. As a result, the significance of HBx in both the propagation of the virus and the development of HCC is emphasized in this paper that takes a more holistic approach. As a consequence of this, it offers a compelling rationale for investigating HBx as a potential therapeutic target in the design of brand new medications [12]. 

The aim of this study was to assess the association of the role hepatitis B x antigen  in pathogenicity of HBV in chronic infection among hemodialsys patients.

Kirkuk City did a cross-sectional study from February 10, 2022, to December 10, 2022.In this study, 600 people with chronic kidney disease who were on hemodialysis were included. There were people there between the ages of 20 and 75 who needed hemodialysis. Participants were interviewed using a questionnaire form created by the researcher. The questionnaire asked about the patients' age, gender, where they lived, and other information. The study included 30 healthy people (control group) between the ages of 15 and 50 who went to the Main Blood Bank in Kirkuk City to donate blood.

Method

Five milliliters of blood were taken from each patient in this study by puncturing their vein with a five-milliliter needle. Samples of blood were put into two tubes, one of which had the inhibitor EDTA in it. The second part of the sample was 3 ml and was put into flat tubes. It was left at 37 °C for 30 minutes to clot and then centrifuged at 3000 rpm for 15 minutes. The plasma from the first tube was collected using an automatic micropipette and moved to Eppendorf tubes. These tubes were then frozen at -20°C for a molecular test of HBV (HBV viral load). The sera from the second tube were also collected and moved to Eppendorf tubes, which were then frozen at -20°C for later antibody tests for specific HBx tests using the ELISA method and biochemical tests for ALT, AST, ALP, and TSB

The study showed that 8.33% (50 of 600) of HD patients  were have Positive PCR results for hepatitis B virus as compared with only 3.33% of the control group (P-value <0.01), Table 1

Table 1:  Rate of HBV positive cases in HD patients and the control group

P-value : 0.001

The study showed the highest rate of  HBV infection among HD patients were in age ≥40 years and most of them were males, Table 2.

Table 2: Distribution of studied cases according to age

According to the findings of the study, the highest rate of HBV infection (52 percent) was discovered in patients who had been undergoing dialysis for more than three years, and the risk of HBV infection increased with the rising of the length of dialysis. Table 3. 

Table 3: Relation of HCV infection with duration of hemodialysis.

The study showed that 80% of HBV patients were with HBX antigen as determined by ELISA and  20% were with negative result, Table  4 and Figure 1.

Table 4: Result of HBX among HBV patients

Figure 2: Result of HBX among HBV patients

The study showed that most of patients with cirrhosis and grade 3 of fibrosis where with positive HBX antigen and HBX may considered as a precursor for development of fibrosis and cirrhosis among hepatitis B patients ,as shown in Table 4.7.

Table 5: Relation of HBx with the development of fibrosis among hepatitis B patients

P-value: 0.001

According to estimates derived from research conducted in less developed nations, the prevalence of the hepatitis B virus in HD patients ranges anywhere from 2 percent to 20 percent [13,14]. A recent study conducted in India found that the prevalence of transfusion-transmitted illnesses including HCV and HBsAg was 45 percent and 14 percent, respectively [4]. This finding was in agreement with the result of the study that was done [5] to assess the prevalence of HBV infection among HD patients in Isfahan, Iran. That study reported that the prevalence of HBV positive among study population was 5.2 percent. In another study, the seroprevalence of HBsAg among HD patients was reported to be 8.1 percent [6]. During this time, in Basrah, Iraq, among 122 patients, HBV infections seroprevalence was found to be positive in 50% of them [7] At the international level, beginning with Iraq's neighbors, the findings of this study are in close agreement with those reported by Turkey (13.3 percent) [7] and Saudi Arabia (10 percent). 

[15] conducted a study In another study by Abuelo57, a high prevalence of HBV infection in HD patients was observed to be associated with age groups older than 50 years. The study of [16] similarly shows that the highest proportion if HD cases were diagnosed extracurrential in aged due to males. Our identification is consistent with research done by Jeele and colleagues [17], in which patient's average age was 54.6 years old The high frequency of HBV plus kidney failure in the elderly might have resulted from advanced age because increasing time to work makes various organs that finally end up being damaged due to significant factors of multiple organ failures. More precisely, it seems that the elderly had longer working lives. We found that patients over 50 years old were more likely infected by HBV infection than those under fifty. This was because a semi-immunossupressor had finally been used in hemodialysis patients, therefore to the partial lack of hepatitis viruses antbody response. There was a significant relationship between HBV positivity with patient age [18]. According to the findings of this study, the prevalence of HBV was higher among male HD patients than among female HD patients. This may have something to do with the fact that men in Iraq are more likely to engage in extracurricular activities than women are. Due to the nature of their profession, they are also more likely than women to be exposed to HBV risk factors that are associated with men (e.g. hair dressing and circumcision). This finding is consistent with research carried out on the general population of Iraq [19]. This result was in agreement with other study for the decrease of HBV infection in dialysis patients despite the implementation of universal precaution. This decrease in HBV infection is a result of the advent of recombinant human erythropoietin and HBV vaccination in recent years. The result of the present study explained that there was a high prevalence of HBV positivity in hemodialysis patients who had received treatment for more than three years [20,21]. There is a correlation between the length of time spent on hemodialysis and HCV positive; in addition, nosocomial transmission among hemodialysis patients has been recently documented by molecular analysis [21]. It is possible that the hemodialysis machine that was utilized in the unit that was investigated contributed to the spread of HBV due to the unintentional contamination of the equipment during pressure testing and the insufficient disinfection that occurred thereafter. On the other hand, even if transfusion was the primary mode of HBV transmission in the past, multiple parental exposure and the sharing of drugs (heparin) among different patients could be involved in HBV transmission. This is the case even though these units did not share any disposable equipment or syringes with one another [18]. Patients undergoing hemodialysis (HD) have an increased likelihood of contracting viral hepatitis due to the high frequency of blood transfusion sessions, the prolonged vascular access, and the potential for exposure to other infected patients and potentially contaminated equipment [19]. Patients undergoing hemodialysis have a significantly increased likelihood of contracting HBV. Immunodeficiency, on the other hand, is a possibility as to why there is such a high incidence among this community. Patients who are receiving hemodialysis on a long-term and continuous basis have an increased likelihood of becoming infected with HBV [22]. In this particular investigation, there was an HBX antigen present in eighty percent of the HBV patients. [23] also demonstrated that a high incidence of HBV patients were with the hepatitis Bx gene (HBx), and they proposed that HBxAg was a sensitive biomarker for HBV infection. This finding is in keeping with the previous findings. The results of the current investigation, which found that the expression of HBxAg corresponds with the activity of the disease as well as the probability of developing cirrhosis and fibrosis, were corroborated by the findings of a study conducted [23,24]demonstrated that a high rate of HBX antigen was present in patients with fibrosis who were in advanced cases. This finding is in keeping with what we found. It has been demonstrated that HBxAg can alter the expression and activity of a large number of genes, in addition to epigenetic molecules (such as miRNAs) and events (such as methylation and acetylation), which can result in the dysregulation of a variety of pathways and functions [12]. Previous research has demonstrated that HBx is capable of manipulating epigenetic pathways in order to influence not just host gene expression in hepatocytes but also the ability of HBV to replicate itself [25]. During a chronic infection, HBx is able to incorporate itself into the DNA of cells. Overexpression of HBxAg may disrupt the signal transduction pathways of hepatocytes, and it has the ability to bind to and activate genes that regulate negative growth, which suggests that it may play a role in fibrosis, cirrhosis, and possibly even the development of hepatocarcinogenesis [10,11]. The results of the current investigation, which found that the expression of HBxAg corresponds with the activity of the disease as well as the probability of developing cirrhosis and fibrosis, were corroborated by the findings of a study conducted [24]. An HBV infection and liver failure are both related with an imbalance of hepatocellular metabolism, including metabolites such as glucose, lipids, and amino acids. This is in addition to the direct interaction of HBx with signal transducers and interference with different pathways [26-28]. 

Most HBV patients were positive for HBX antigen. Recommendations include vaccination, isolation, universal precautions, and using HbX as a non-invasive biomarker to monitor liver progression from fibrosis to cirrhosis.

The authors declare that they have no conflict of interest

No funding sources

The study was approved by the AL-Kitab University, Kirkuk, Iraq.

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