|Year : 2015 | Volume
| Issue : 1 | Page : 32-37
Clinical, laboratory, and virological characteristics of patients with positive hepatitis B surface antigen in Upper Egypt
Khairy H Morsy MD 1, Mohamed AA Ghaliony2, Tarek T.H. El Melegy3
1 Department of Tropical Medicine and Gastroenterology, Sohag University Hospital, Faculty of Medicine, Sohag University, Sohag, Egypt
2 Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut, Egypt
3 Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
|Date of Submission||09-Jan-2015|
|Date of Acceptance||17-Feb-2015|
|Date of Web Publication||27-Apr-2015|
Khairy H Morsy
Tropical Medicine and Gastroenterology Department, Sohag University Hospital, Faculty of Medicine, Sohag University, Sohag
Source of Support: None, Conflict of Interest: None
The aim of the study was to determine the clinical, laboratory, and virological characteristics of patients with chronic HBV infection in Upper Egypt.
Patients and methods
This descriptive, cross-sectional study included 252 patients with positive hepatitis B surface antigen (HBsAg). It was conducted in the Tropical Medicine and Gastroenterology Department and Outpatient Clinic, Assiut University Hospital (Egypt), from May 2012 to May 2014. All patients underwent clinical evaluation, were administered a questionnaire about risk factors for transmission of HBV, underwent liver function tests, abdominal ultrasonographic examination, and complete blood count, evaluation of serological markers of HBV, and quantitative detection of HBV-DNA.
Of the 252 patients included, 88.5% were male with a mean age of 35.4 years. Arthralgia was the most common complaint (15.5%) and hepatomegaly was the most common finding (8.3%). As regards imaging results (ultrasonographic) the following were found: normal liver in 83.3%, coarse liver in 11.9%, hepatomegaly in 7.5%, splenomegaly in 6.3%, and cirrhosis in 5.9%. As regards laboratory results normal alanine aminotransferase was found in 79.8%, normal aspartate aminotransferase in 85.7%, reduced serum albumin in 4.4%, and low platelet count in 9.9%. The majority of patients (91.7%) were hepatitis B envelope antigen negative; 65.9% of patients were positive for HBV on PCR. No significant differences were found between positive HBV-DNA status (by PCR) and negative HBV-DNA status as regards clinical, imaging, and laboratory characteristics of patients.
Most of the patients had normal liver on ultrasonographic examination and normal liver function tests. No significant difference was found between positive HBV-DNA status (by PCR) and negative HBV-DNA status as regards clinical, imaging, and laboratory characteristics of patients.
Keywords: Egypt, hepatitis B surface antigen, hepatitis B virus infection, PCR, risk factors
|How to cite this article:|
Morsy KH, Ghaliony MA, El Melegy TT. Clinical, laboratory, and virological characteristics of patients with positive hepatitis B surface antigen in Upper Egypt. Egypt J Intern Med 2015;27:32-7
|How to cite this URL:|
Morsy KH, Ghaliony MA, El Melegy TT. Clinical, laboratory, and virological characteristics of patients with positive hepatitis B surface antigen in Upper Egypt. Egypt J Intern Med [serial online] 2015 [cited 2019 Aug 18];27:32-7. Available from: http://www.esim.eg.net/text.asp?2015/27/1/32/155853
| Introduction|| |
Hepatitis B virus (HBV) belongs to Hepadnaviridae, a family of enveloped viruses with an incomplete double-stranded DNA genome of 3.2 kb. HBV can be classified into at least eight genotypes (A-H) based on a divergence in the entire nucleotide sequence greater than 8% ,. Infection with HBV is a major public health problem . Chronic HBV infection is a major underlying etiology in liver cirrhosis and hepatocellular carcinoma (HCC) .
In countries with high HBV endemicity (prevalence >8%), the main source of infection is through perinatal transmission from the chronically infected mother or through infection during early childhood ,. Vertical (mother to infant) transmission occurs worldwide and is mainly related to transplacental transmission of HBV in utero, perinatal infection through contact with infectious blood or body fluids from the infected mother at the time of delivery, or postnatal transmission during care or through breast milk .
In areas of low HBV endemicity, most infections are acquired by horizontal transmission in early adult life, through intravenous drug use, or through unprotected sexual activities . Other risk factors include working in a healthcare setting, blood transfusions, dialysis, sharing razors or toothbrushes with an infected person, travelling in countries where the infection rate is high, and living in an institution ,. Tattooing and acupuncture led to a significant number of cases in the 1980s; however, this has become less common with improved sterility .
Chronic HBV infection in Egypt is an important medical problem. The prevalence of hepatitis B surface antigen (HBsAg) in Egypt is intermediate (2-7%) ,.
The infection may be entirely asymptomatic and may go unrecognized . Chronic infection with HBV may be asymptomatic and may progress to liver cirrhosis and HCC .
HBsAg is most frequently used to screen for the presence of HBV infection. Most hepatitis B diagnostic panels contain HBsAg and total anti-hepatitis B core (anti-HBc) (both IgM and IgG). Shortly after the appearance of HBsAg, hepatitis B envelope antigen (HBeAg) will appear . During the natural course of an infection, the HBeAg may be cleared, and antibodies to the 'e' antigen (anti-HBe) will arise immediately after. This conversion is usually associated with a marked decline in viral replication .
The aim of the current study was to determine the clinical, laboratory, and virological characteristics of patients with chronic HBV infection in Upper Egypt.
| Patients and methods|| |
Type of the study
- Study design: cross-sectional analytic study.
- Study frame: the study was performed in the Tropical Medicine and Gastroenterology Department and Outpatient Clinic, Assiut University Hospital (Egypt), from May 2012 to May 2014.
Inclusion criteria included being positive for HBsAg and negative for hepatitis C virus antibodies.
Exclusion criteria included other identifiable causes of chronic liver diseases, a history of antiviral therapy, and acute hepatitis B infection.
The following were performed:
- Clinical evaluation (history taking and clinical examination).
- Administration of a questionnaire about risk factors for transmission of viral hepatitis, such as previous blood transfusion, past history of operations, dental manipulation, receiving drugs by intravenous injection, tattooing, family history of HBV, and family history of liver diseases.
- Abdominal ultrasonographic examination.
- Liver function tests serum levels of total and direct bilirubin, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase].
- Prothrombin time estimation.
- Complete blood count.
- Serological markers of HBV: 5 ml of venous blood was aseptically drawn into plain tubes. The samples were centrifuged within 30 min at 3000 rpm for 10 min; the collected serum samples were divided into aliquots and stored at −70°C. All blood specimens were tested for HBsAg [using Monalisa HBsAg Ultra (Bio-Rad, Paris, France) detection kit], antibody against hepatitis B surface (anti-HBs Ab) [using CTK Biotech Inc. (San Diego, California, USA) detection kit], and total antibody against HBc (anti-HBc Ab) [using Wkea Med Supplies Corp. (New York, USA) detection kit] by means of the enzyme-linked immunosorbent assay technique. Reactive results were confirmed by repeating the test in duplicate. All samples that were confirmed to be HBsAg positive were further tested for HBeAg using microparticles enzyme immunoassay kits (AxSYM; Abbott Laboratories, Wiesbaden, Germany) and HBV-DNA assays.
- Quantitative detection of HBV-DNA: DNA was extracted from 200 ml of serum with a DNA extraction kit (Catalog #57704; Qiagen GmbH, Stockach, Germany), according to the manufacturer's procedure.
HBV-DNA was quantified by real-time PCR using a 7500 fast real-time PCR system (Applied PCR System; Biosystems, Life Technologies, Grand Island, New York, USA), using ready-to-use PCR kits supplied by Artus HBV PCR kit (version 1, Catalog #4506163; Qiagen GmbH) .
Before enrollment all participants signed a consent certificate after a detailed discussion about the study subject and study aim. Participants were clearly informed that refusal to participate would not prevent them from getting full benefit of the available medical service and treatment. Data were collected by means of personal interviews with participants after ensuring data confidentiality. The study was approved by the Faculty of Medicine Ethical Committee, Assiut University. The procedures followed were in accordance with the ethical standards (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008.
Statistical analysis was performed using statistical package for the social sciences (SPSS, version 17; SPSS Inc., Chicago, Illinois, USA). All data were expressed as mean ± SD or as frequencies. Continuous variables were compared through Student's t-test and proportions were compared with χ2 -test. Results were presented as mean ± SD. P values less than 0.05 were considered significant.
| Results|| |
The study included 252 patients, of whom 88.5% were male. Their median age was 35 years (mean 35.4 ± 10.2 years). All patients were native residents of Egypt. The possible risk factors for HBV infection are summarized in [Table 1].
|Table 1: Demographic characteristics and history of patients with chronic hepatitis B virus infection (n = 252)|
Click here to view
Arthralgia was the most common complaint (15.5%) and hepatomegaly was the most common finding (8.3%), as shown in [Table 2].
|Table 2: Clinical characteristics of patients with chronic hepatitis B virus infection|
Click here to view
As regards imaging results (ultrasonographic), normal liver was found in 83.3% of patients, coarse liver in 11.9%, hepatomegaly in 7.5%, splenomegaly in 6.3%, and cirrhosis in 5.9%.
As regards laboratory data elevated ALT more than two-fold was found in 4.8% of patients, elevated AST more than two-fold in 1.2%, reduced serum albumin in 4.4%, and low platelet count in 9.9%, as shown in [Table 3]. The majority of patients (91.7%) were negative for HBeAg, and 65.9% of patients were positive for HBV on PCR, as shown in [Table 4].
|Table 3: Imaging and laboratory characteristics of patients with chronic hepatitis B virus infection|
Click here to view
|Table 4: Serological markers and virological characteristics of patients with chronic hepatitis B virus infection|
Click here to view
No significant difference was seen between positive HBV-DNA status (by PCR) and negative HBV-DNA status in terms of clinical, imaging, and laboratory characteristics of patients, as shown in [Table 5].
|Table 5: Relationship between hepatitis B virus DNA status (by polymerase chain reaction) and the clinical, imaging and laboratory characteristics of patients with chronic hepatitis B virus infection|
Click here to view
| Discussion|| |
Our study disclosed some important observations. First, dental manipulations, surgical operations, previous blood transfusion, HBV infection in the family, and tattooing were the possible risk factors for HBV infection in our patients. Second, arthralgias, fatigue, and abdominal pain were the main clinical manifestations of chronic HBV infection. Third, most of the patients had normal liver on ultrasonographic examination and normal liver function tests. Fourth, the majority of patients with chronic HBV infection were negative HBeAg and about two-thirds had positive PCR. Fifth, no significant difference was found in clinical, imaging, and laboratory characteristics between patients with positive HBV-DNA status (by PCR) and negative HBV-DNA status.
The results of this study are similar to a previous study by O'Connell et al.  and to a study by Allwright et al. . They reported that HBV was found in all body secretions and excretions, but only blood, body fluids containing visible blood, semen, and vaginal secretions represented a risk of transmission. HBV is transmitted by percutaneous and mucosal exposure to infective blood or body fluids. The main modes of HBV transmission include sexual or close household contact with an infected person, perinatal mother to infant transmission, injecting drug use, and nosocomial exposure. Grogan et al.  reported that HBV can be transmitted by transfusion of infected blood or blood products, sharing unsterilized injection needles for intravenous drug use, hemodialysis, acupuncture, tattooing, and injuries from contaminated sharp instruments sustained by hospital personnel.
Our present study bears some similarities with previous reports by Liaw et al. , who found that the main clinical manifestations of chronic HBV infection were fatigue, vague abdominal discomfort, nausea and vomiting, anorexia, sometimes arthralgia and rash, followed by bleeding gums. Studies by Tosti et al.  also reported the same findings.
In the present study, our results also showed that the majority of patients had normal liver on ultrasonographic examination (83.3%) and normal liver function tests: normal ALT levels (79.8%), normal AST levels (85.7%), normal total bilirubin (93.3%), normal serum albumin (95.6%), and normal Prothrombin time (92%). Our study has some similarities with previous reports by Lok et al. , who reported that most of the patients with chronic HBV infection had normal liver and normal liver function tests.
The replicative phase of chronic HBV infection is characterized by the presence of HBeAg and HBV-DNA. The nonreplicative phase is characterized by the absence of HBeAg and HBV-DNA. Several HBeAg-negative patients have persistent high HBV replication associated with liver inflammation and ongoing fibrosis . HBeAg-negative chronic HBV infection is mostly associated with mutations in the precore and basal core promoter regions that result in prevention or reduction of HBeAg synthesis without affecting the replicative ability of the virus ,. Several studies have shown a strong relationship between HBV genotypes and mutations in the precore and core promoter regions that abolish or diminish the production of HBeAg ,,.
In the present study, we demonstrated that most of the patients (91.7%) were HBeAg negative (presumably indicating precore or core promoter mutation). Studies by Sitnik et al.  reported similar findings. Zaky et al.  mentioned that in Upper Egypt 94% of hepatitis B-infected persons were HBeAg negative and 41% had positive HBV-DNA on PCR. However, in the study by Zahran et al. , only 72% of hepatitis B-infected patients were HBeAg negative.
Most chronic HBV infections are characterized by high HBV-DNA levels (>20 000 IU/ml). Lower HBV-DNA values (2000-20 000 IU/ml) are common in HBeAg-negative chronic infection, which is associated with a low likelihood of spontaneous disease remission . Detection of HBV-DNA level is a criterion for determining the state of infection, the risk of progression toward cirrhosis and HCC, identification of patients who need antiviral therapy, determining response to therapy, and identifying the emergence of drug resistance . Chu et al.  and Ledesma et al.  confirmed the relationship between viral load level and liver damage in patients negative for HBeAg, whereas Alam et al.  reported that low-level viral load is not always an indication of improved conditions and in some patients it indicates advanced disease. In an Iranian study by Taghavi et al. , it was reported that there was no statistically significant difference between patients with positive and those with negative HBV-DNA in terms of age, sex, clinical manifestations, and liver enzyme levels.
Our results are in agreement with these studies as it showed that there was no significant difference in clinical, imaging, and laboratory characteristics between patients with positive HBV-DNA status and those with negative HBV-DNA status.
| Conclusion|| |
The main clinical manifestations of chronic HBV infection were arthralgias, fatigue, and abdominal pain, followed by bleeding gums. Most of the patients had normal liver on ultrasonographic examination and normal liver function tests. The majority of patients with chronic HBV infection were HBeAg negative. There was no significant difference in clinical, imaging, and laboratory characteristics between patients with positive HBV-DNA status (by PCR) and those with negative HBV-DNA status.
| Acknowledgements|| |
Conflicts of interest
| References|| |
Bartholomeusz A, Schaefer S. Hepatitis B virus genotypes: comparison of genotyping methods. Rev Med Virol 2004; 14:3-16.
Stuyver L, De Gendt S, Van Geyt C, Zoulim F, Fried M, Schinazi RF, Rossau R A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness. J Gen Virol 2000; 81:67-74.
Pan CQ, Zhang JX. Natural history and clinical consequences of hepatitis B virus infection. Int J Med Sci 2005; 2:36-40.
Chang MH. Hepatitis B virus infection. Semin Fetal Neonatal Med 2007; 12:160-167.
Morgolis HS, Alter MJ, Halder S. Viral hepatitis. In: Evans A, Kaslow R, editors. Viral infections of humans
. 4th ed. New York: Plenum; 1997. 363-418.
Hou J, Liu Z, Gu F. Epidemiology and prevention of hepatitis B virus infection. Int J Med Sci 2005; 2:50-57.
Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004; 11:97-107.
Akani CI, Ojule AC, Opurum HC, Ejilemele AA. Sero-prevalence of hepatitis B surface antigen (HBsAg) in pregnant women in Port Harcourt, Nigeria. Niger Postgrad Med J 2005; 12:266-270.
Jammeh S, Tavner F, Watson R, Thomas HC, Karayiannis P. Effect of basal core promoter and pre-core mutations on hepatitis B virus replication. J Gen Virol 2008; 89:901-909.
Poynard T. Hepatitis C and B: management and treatment. 2nd ed. 2004. 79-156.
Tong MJ, Blatt LM, Kao JH, Cheng JT, Corey WG. Precore/basal core promoter mutants and hepatitis B viral DNA levels as predictors for liver deaths and hepatocellular carcinoma. World J Gastroenterol 2006; 12:6620-6626.
El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007; 132:2557-2576.
El-Serag HB. Hepatocellular carcinoma. N Engl J Med 2011; 365:1118-1127.
Liaw YF, Brunetto MR, Hadziyannis S. The natural history of chronic HBV infection and geographical differences. Antivir Ther 2010; 15:25-33.
Kanbay M, Gur G, Akcay A, Selcuk H, Yilmaz U, Arslan H, et al.
Is hepatitis C virus positivity a contributing factor to occult hepatitis B virus infection in hemodialysis patients? Dig Dis Sci 2006; 51:1962-1966.
O′Connell K, Cormican M, Hanahoe B, Smyth B. Prevalence of antenatal hepatitis B virus carriage in the west of Ireland. Ir Med J 2010; 103:91-92.
Allwright S, Bradley F, Long J, Barry J, Thornton L, Parry JV. Prevalence of antibodies to hepatitis B, hepatitis C, and HIV and risk factors in Irish prisoners: results of a national cross sectional survey. BMJ 2000; 321:78-82.
Grogan L, Tiernan M, Geogeghan N, Smyth B, Keenan E. Bloodborne virus infections among drug users in Ireland: a retrospective cross-sectional survey of screening, prevalence, incidence and hepatitis B immunisation uptake. Ir J Med Sci 2005; 174:14-20.
Tosti ME, McMahon B, van der Sande M, Whittle H, Jan C-F, Poovorawan Y. Viral hepatitis. Viral Hepat 2012; 20:11-12.
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007; 45:507-539.
Lin CL, Liao LY, Liu CJ, Chen PJ, Lai MY, Kao JH, Chen DS. Hepatitis B genotypes and precore/basal core promoter mutants in HBeAg-negative chronic hepatitis B, J Gastroenterol 2002; 37:283-287.
Gandhe SS, Chadha MS, Walimbe AM, Arankalle VA. Hepatitis B virus: prevalence of precore/core promoter mutants in different clinical categories of Indian patients, J Viral Hepat 2003; 10:367-382.
Sitnik R, Pinho JR, Bertolini DA, Bernardini AP, Da Silva LC, Carrilho FJ. Hepatitis B virus genotypes and precore and core mutants in Brazilian patients. J Clin Microbiol 2004; 42:2455-2460.
Zaky S, Farghaly AM, Rashed HA, Hassan H, Faouzy E, Makhlouf N, Hussein MR Clinicopathologic features and genotyping of patients with chronic HBV infection in the Upper Egypt. Cell Immunol 2010; 265:97-104.
Zahran KM, Badary MS, Agban MN, Abdel Aziz NH. Pattern of hepatitis virus infection among pregnant women and their newborns at the Women′s Health Center of Assiut University, Upper Egypt. Int J Gynaecol Obstet 2010; 111:171-174.
Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009; 50:661-662.
Chu CJ, Hussain M, Lok AS. Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Hepatology 2002; 36:1408-1415.
Ledesma MM, Galdame O, Bouzas B, Tadey L, Livellara B, Giuliano S, et al.
Characterization of the basal core promoter and precore regions in anti-HBe-positive inactive carriers of hepatitis B virus. Int J Infect Dis 2011; 15:e314-e320.
Alam S, Ahmad N, Alam K, Mostafa G, Khan M. Correlation between hepatitis B viral DNA load and extent of liver pathology in patients with chronic hepatitis B. Hepat Mon 2008; 8:185-189.
Taghavi SA, Tabibi M, Eshraghian A, Keyvani H, Eshraghian H. Prevalence and clinical significance of hepatitis B Basal core promoter and precore gene mutations in southern Iranian patients. Hepat Mon 2010; 10:294-297.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]