|Year : 2017 | Volume
| Issue : 4 | Page : 105-112
Serological characterization of occult hepatitis B Virus infection in Riyadh regional laboratory
Fadel Hassan Al-Hababi1, Eisa Eid Al-Enazi1, Raed Hassan Al-Hababi1, Abdulwahab Bin Jomaa1, Salah Saleh Al-Sager2, Ali Eidah Al-Ahmari1
1 Department of Microbiology and Virology, Riyadh Regional Laboratory, King Saud Medical Complex, Riyadh, Kingdom of Saudi Arabia
2 Riyadh Regional Laboratory, King Saud Medical Complex, Riyadh, Kingdom of Saudi Arabia
|Date of Web Publication||18-Jun-2018|
Fadel Hassan Al-Hababi
Riyadh Regional Laboratory, King Saud Medical Complex, P. O. Box 61734, 11757 Riyadh
Kingdom of Saudi Arabia
Source of Support: None, Conflict of Interest: None
Introduction: Hepatitis B virus (HBV) infection is a major global health problem, causing chronic hepatitis, cirrhosis, hepatocellular carcinoma (HCC) and other chronic liver diseases. HBV infection is endemic in many parts of Kingdom of Saudi Arabia. Occult HBV infection (OBI) is a challenging clinical problem characterized by the absence of Hepatitis B surface Antigen (HBsAg) and low viral DNA load. Aims: This study aim is to investigate an epidemiological survey for the prevalence of OBI among Saudi healthy general population and two of most common HBV infection risks, hemodialysis and HIV patients in Riyadh Regional Laboratory. Methods: Three groups of samples were tested. 5025 blood samples healthy group were collected from Saudi citizens for pre-marriage screening testing. Second group is comprised of 658 adult patients with end-stage renal disease undergoing regular hemodialysis. Third group is comprised from 479 patients who had been previously confirmed for HIV infection. Results: Of 5025 healthy people enrolled into the study, 212 (4.2%) seropositive for HBsAg and/or anti HBc. Of them, 114/212 (53.8%) resolved infection with detectable anti-HBs (>10 mIU/mL), and 58/212 (27.36 %) had active HBV infection with detectable HBsAg. While, 40/212 (18.9%) were defined as OBI and HBV DNA was detected in two OBI patients. In 658 hemodialysis (HD) patients, 196 (27.96%) seropositive for HBsAg and/or anti-HBc. Of them 122/196 (66.3%) resolved infection with detectable anti-HBs (>10 mIU/mL), and 17/196 (9.24%) with active HBV infection with detectable HBsAg. OBI only detected in 32/196 (17.4%), HBV DNA was detected in 3 patients. Lastly, in 479 HIV patients, 152 seropositive for HBsAg and/or anti HBc. Of them 11/152 (7.23%) had active HBV infection with detectable HBsAg and 78 (51.3%) resolved infection with detectable anti-HBs (>10 mIU/mL). OBI detected in 63/152 (41.4%) and only 6 patients showed HBV DNA was detected. There were no statistically significant differences in the OBI prevalence between healthy population and HD prevalence while showed significance difference in HIV OBI prevalence compared to healthy group. Conclusions: this study proof that OBI is frequently encountered among healthy and high risk group individuals in Saudi Arabia and more support should be provided for the vaccination especially of high-risk groups, such as HIV and HD patients.
Keywords: Hemodialysis, human immunodeficiency virus, occult hepatitis B virus infection
|How to cite this article:|
Al-Hababi FH, Al-Enazi EE, Al-Hababi RH, Jomaa AB, Al-Sager SS, Al-Ahmari AE. Serological characterization of occult hepatitis B Virus infection in Riyadh regional laboratory. Saudi Crit Care J 2017;1:105-12
|How to cite this URL:|
Al-Hababi FH, Al-Enazi EE, Al-Hababi RH, Jomaa AB, Al-Sager SS, Al-Ahmari AE. Serological characterization of occult hepatitis B Virus infection in Riyadh regional laboratory. Saudi Crit Care J [serial online] 2017 [cited 2021 May 15];1:105-12. Available from: https://www.sccj-sa.org/text.asp?2017/1/4/105/234634
| Introduction|| |
Chronic hepatitis B (CHB) is a worldwide problem, with an estimated 400 million persons infected with hepatitis B virus (HBV). CHB is a leading cause of liver cirrhosis and end-stage liver disease and hepatocellular carcinoma (HCC). HBV carriers have a 100-fold increased risk of developing HCC. Therefore, early diagnosis and treatment of CHB infection is crucial for reducing morbidity and mortality.
Several studies in Saudi Arabia showed high HBV endemicity of 16.7% ranging between 9% and 25% of positive hepatitis B surface antigen (HBsAg). The overall prevalence of seropositive HBsAg among pregnant women was 1.6% with the majority (79.9%) being nonimmune and thus liable to HBV infection. Furthermore, a high prevalence of HBV infection among children was reported in 1992; approximately 7% of healthy children <10 years of age were positive for HBsAg and 20% were positive for at least one of the markers of HBV.
Despite the declining trend over the 8-year period, viral hepatitis, especially that caused by HBV and hepatitis C virus (HCV), remains a major public health problem in Saudi Arabia, while HBV continues to be the most predominant type of viral hepatitis and is a disease of adults. The availability of the vaccine leads to a significant decrease in HBV prevalence in Saudi Arabia and in many other countries worldwide during the past few decades. Currently, Saudi Arabia belongs to the intermediate endemicity countries with a wide variance of HBsAg seropositivity among different regions and various populations, ranging from 1.5% to 2.6%.
Occult HBV infection (OBI) is defined as the persistence of viral genomes in the liver tissue or the serum of individuals who are HBsAg-negative. OBI is still a distinct clinical problem, as the immunosuppressive nature of renal disease and human immunodeficiency virus (HIV) infection often leads to chronicity of the viral infection and results in an opportunity for the nosocomial spread of the infection among dialysis patients. OBI status may be due to host immunosuppression, coinfection with HCV, the window period after acute infection, genetic mutations in the S gene, or other host factors. OBI has been reported in patients with HCC  and cryptogenic or autoimmune liver diseases.
The clinical consequence and transmission risk of OBI in populations are still not fully clear. OBI may persist in individuals for years without obviously symptoms of overt HBV infection  or may associated with a higher risk of disease progression cirrhosis and HCC , and could maintain its pro-oncogenic properties in OBI and reduced response to alfa interferon and nucleotide (s) treatment.,
There has been limited data about the prevalence of OBI among chronic renal failure patients in Saudi Arabia HBV and OBI among patients living with HIV and hemodialysis (HD). This study aimed to detect the prevalence of OBI in general population and another two important groups of patients receiving HD and patients with HIV at one of the major centers in Riyadh Regional Laboratory in Riyadh, the capital city of Saudi Arabia, to define the possible implications for the safety of Saudi patients and control HBV infection among Saudi patients.
| Materials and Methods|| |
Study design, participants, and sample collection
The study population comprised three groups of samples. First, healthy group blood samples were collected from 5025 Saudi citizens referred to the Virology department in Riyadh Regional Laboratory for premarriage screening testing. Premarriage testing is routine testing for viral infection for all population in Saudi Arabia before marriage. The second group is comprised of 658 adult patients with end-stage renal disease undergoing regular HD at King Saud Medical city and its satellite dialysis units. Dialysis unit monitored patients regarding viral infections at the time of admission and every 3 months and samples were collected before dialysis. The third group is comprised of 479 patients who had been previously confirmed for HIV infection by Western blot after two positive enzyme-linked immunosorbent assay (ELISA) tests were included.
All samples were tested for HBsAg, anti-HBs, and anti-HBc by ELISA. Information was gathered on the hepatitis B surface antigen (HBsAg), core total antibody (anti-HBc), surface antibody (anti-HBs), hepatitis C (HCV), and HIV status using commercial immunoassays as described down. All samples were stored at −70°C as a policy in this laboratory. The data were then analyzed by initially identifying patients with current or past hepatitis B infection and categorizing the remaining patients according to their immune status, that is, those with an anti-HBs level >10 mIU/mL were classified as immune versus <10 mIU/mL (nonimmune). Stored serum samples from anti-HBcAb positive and HBsAg-negative patients were anonymized and tested for HBV DNA by real-time quantitative polymerase chain reaction (qPCR) assay. For further molecular testing, the sera were retrieved and checked for the quality of sera before testing; samples that showed no inhibition of PCR test were considered as valid samples and the samples that showed inhibition of PCR were excluded from the study.
Serum samples were tested for HBsAg Monolisa™ HBsAg ULTRA, Monolisa™ Anti-HBc PLUS ELISA kits by BIORAD and HCV antibodies (anti-HCV), (HIV1/2 Ag/Ab) combo at the Department of Virology, Riyadh Regional Laboratory, using commercially available assays. All anti-HBsAg reactive samples were tested for HBsAg neutralization. Samples testing anti-HCV or HIV reactive were subsequently confirmed with INNO-LIA HCV Score and INNO-LIA HCV Score (Innogenetics, Belgium), respectively, which was considered conclusive in the case of mismatch with the EIA test. All tests were performed according to the manufacturer's instructions.
HBV DNA viral load quantification
HBV DNA load was determined by qPCR. Viral DNA was extracted from 0.4 to 1.0 ml of plasma HBV DNA testing. Viral DNA was isolated using MagNA Pure Compact Nucleic Acid Isolation Kit (Roche Diagnostics, Mannheim, Germany), and quantitative real-time PCR was performed on the LightCycler instrument using LC-FastStart DNA Master HybProbes kit (Roche Diagnostics, Mannheim, Germany), targeting the HBV surface gene. The limit of quantification was 6 IU/ml.
The results are expressed in ranges, percentages, mean, and standard deviation. For comparisons between the study groups, 2 × 2 contingency table was used and the Fisher's exact test (two tailed) and the Chi-square (with Yates' correction) test was used to study independence of all other variables. P values < 5% were considered statistically significant.
The study was conducted in accordance with the ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of King Saud Medical City.
| Results|| |
For all groups tested, active HBV infection was defined as a positive HBsAg test. Both positive anti-HBs and anti-HBc tests indicated a resolved infection. Anti-HBs-positive status was an indicator of vaccine-induced immunity. Isolated anti-HBc was confirmed when an anti-HBc serological test was positive with no other positive biomarker. OBI was defined as the detection of HBV DNA by real-time PCR and HBsAg-negative results. In healthy population group, a total of 5025 were recruited. The sex of participants was almost equally with 2553 individuals (50.8%), with a mean age of 22.8 ± 10.1 years (95% confidence interval [CI] 22.52–23.08 years) [Table 1]. Approximately 4% of blood samples tested were showed an evidence of HBV infection with HBsAg positivity at 0.6%. Of 5025 healthy people blood samples, 212 (4.2%) were positive for either one or both HBsAg and/or anti-HBc. HBsAg detectable in 58/212 samples were found positive for both HBsAg and anti-HBc (27.36%) and overall prevalence (1.15%). The remaining 154 samples (72.64%) which were positive for anti-HBc were tested for the presence of anti-HBs. A total of 114/212 (53.8%) samples were resolved infection with anti-HBs positive titer (higher than 10 mIU/mL). The remaining samples 40/212 (18.87%) and (0.8%) overall samples had anti-HBc only marker and defined as OBI. These OBI samples were further investigated for HBV DNA PCR [Table 2]. Of these, only two samples of anti-HBc alone samples (2 of 40 [5%]) were HBV DNA positive.
|Table 2: Seroprevalence of different categories of hepatitis B virus status on general population individuals|
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Occult hepatitis B virus infection among dialysis patients
A total of 658 HD patients were recruited. The majority of participants were male 359 (54.56%) patients, 96 (21.1%) female, with a mean age of 48.75 ± 9.99 years (95% CI 47.98–49.51 years). There are 24 patients of unknown age and sex [Table 1]. Among all, the prevalence of HBV infection exposure was 27.96% (184 from 658), which indicated with anti-HBc positive, of them only 17 patients (2.58%) had active HBV infection with HBsAg positive and anti-HBcAb positive for over at least 6 months or more with detectable HBV DNA in blood indicating chronic HBV infection. While 122 patients (66.3% [18.54% overall]) had resolved infection with detectable anti-HBs (>10 mIU/mL), 32 patients ((17.4%) [Overall 4.86%]) isolated anti-HBc only which was defined as OBI. The immune response to HBV vaccine (titers >10 mIU/mL) was present in 296 patients (45.29%) and the remaining 176 patients (26.75%) were nonimmune to HBV and thus are susceptible to HBV infection [Table 3]. Three of 32 OBI patients with anti-HBcAb positive only had very low levels of HBV DNA detected by PCR (detected with less 20 IU/ml). Therefore, the prevalence of OBI was therefore 17.4% in the test group and 4.86% in the overall dialysis cohort. In this group of patients, we showed that there was no statistically significant differences in the OBI prevalence between healthy population and HD patients prevalence (P = 0.7941), while it was significant in active HBV infection (P = 0.0001) [Table 3].
|Table 3: Seroprevalence of different categories of hepatitis B virus status on hemodialysis-infected patients|
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Occult hepatitis B virus infection among human immunodeficiency virus samples
HIV-HBV coinfection was defined as the evidence of current exposure to HBV, including active HBV infection and OBI. A total of 479 HIV-infected patients were evaluated in the study. The majority of participants were male 359 (75.95%) with a mean age of 35.94 ± 7.78 years (95% CI 35.25–36.64) [Table 1]. All patients had a history of HBV vaccination according to the standardized vaccination schedule. Of 479 HIV-infected patients, 327 (68.27%) patients were negative HBsAg, and of them, 57 patients (11.9%) were vaccinated which anti-HBc negative. The immune response to HBV vaccine (titers ≥10 U/l) was present in of HIV patients. A total of 270 (56.4%) patients were non-immune to HBV with both anti-HBc and HBsAg are negative and thus are susceptible to HBV infection. HIV-HBV coinfection with isolated anti-HBc was found in 184 patients (29.79%). Among them, 78 (51.3%) patients had resolved infection with detectable anti-HBs (>10 mIU/mL), 11 (7.23%) active HBV infection with detectable HBsAg. While 63 (41.4%) patients were defined as OBI. Hence, the prevalence of OBI was therefore 41.4% in the test group and 13.15% in the overall HIV cohort. Among OBI HIV-infected patients, HBV-DNA was detected in six patients (9.52%) of total OBI (1.25 % overall). In this group of patients, we showed that there were statistically significant differences in the OBI prevalence between healthy population and HIV patients prevalence (P = 0.0001), and it was significant in active HBV infection too (P = 0.0001) [Table 4].
|Table 4: Seroprevalence of different categories of hepatitis B virus status on human immunodeficiency virus-infected patients|
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Coinfection with hepatitis C virus in occult hepatitis B virus infection
Several studies suggested that an OBI infection is commonly observed in patients co-infected HCV, and HIV. All three groups recruited in this study were tested for HCV serological testing. Among healthy groups samples tested for HCV Ab testing, 15 samples out of the 5025 total samples evidence showed HCV infection exposure, with current hepatitis C infection and hepatitis C RNA were positive. The prevalence of HCV-antibody positivity (with or without HCV RNA) in our cohort was (0.29%) 2 (15 out of 5025). Among these 15 patients, 13 (86.67%) patients had no previous evidence of HBV exposure. The other patients had resolved infection. No OBI cases were defined in healthy group with HCV coinfection [Table 5]. Within HD group, the prevalence of HCV infection was 15.5% (102 out of 658). Within these HCV-infected group, HBV infection exposure was (36.3%, 37 out of 102) indicated with anti-HBc positive. Of them, only 1 patient (2.7%) had active HBV infection with HBsAg positive and anti-HBcAb positive for and detectable HBV DNA in blood indicating chronic HBV infection. While 29 patients (78.48%) had resolved infection, and only isolated 7 patients (38.8%) were defined as OBI [Table 5]. One of these 7 HCV OBI patients with anti-HBcAb-positive only had very low levels of HBV DNA detected by PCR (detected with less 20 IU/ml). Finally within HIV group, the prevalence of HCV infection was 6.26% (30 out of 479). Within these HCV-infected group, HBV infection exposure was 60% (18 patients). Of them, only one patient (5.56%) had active HBV infection with HBsAg-positive and anti-HBcAb positive and detectable HBV DNA in blood indicating chronic HBV infection. While five patients (27.78%) had resolved infection and only isolated 12 patients (66.67%) defined as OBI [Table 5]. One patient of 12 HCV OBI patients with anti-HBcAb positive only had very low levels of HBV DNA detected by PCR (detected with less 20 IU/ml). We found that OBI detection was not associated with a past HBV infection and anti-HCV. No statistical significance was found comparing serological markers of HCV.
|Table 5: Seroprevalence of hepatitis C virus in Saudi samples and in occult hepatitis B virus infection-infected samples|
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| Discussion|| |
The prevalence of OBI is quite variable depending on the level of endemic disease in different parts of the world, the different assays utilized and the different populations studied. In healthy first-time blood Saudi population, we determined that 4.2% of the Saudi population blood were positive for any of the HBV markers (HBsAg and/or anti-HBc), suggesting that these group of Saudi population has been in contact with HBV at one point during their lives. About 1.36% of the population was HBsAg positive and anti-HBc markers with chronic HBV infection. Several studies from the 1980s found a high endemicity for HBV, with 5%–10% of the population infected and prevalence varying from one region to another. Saudi Arabia showed high HBV endemicity of 16.7% ranging between 9% and 25% of positive HBsAg. The overall prevalence of seropositive HBsAg among pregnant women was 1.6% with the majority (79.9%) being nonimmune and thus liable to HBV infection. In children (age 1–12 years), the prevalence was almost 7% in 1989, just before the addition of the HBV vaccine to the extended program of immunization. By 1997, the prevalence of HBV infection in children had declined to 0.3%. Blood donor results have also shown a steady decrease in HBV infection. At King Khalid University Hospital, the prevalence declined from 3.7% in 1987 to 1.7% in 2000. On the other hand, recent cross-sectional study of a representative sample of 300 college health students and 300 health college workers showed an overall seroprevalence of HBV of 1.7% and 8.7% was found among HS and HCWs, respectively. While El-Hazmi study showed the prevalence rate of HBV and infections was 1.5%. For the prevalence of anti-HBc, few studies were determined in the Saudi Arabian population. For instance, Mohammed AS showed that 5.7% (of total 1714) blood units were positive for anti-HBc among the HBsAg-negative, and/or anti-HBs- negative samples and 13.53% in blood donors from different parts of Saudi Arabia.
A number of explanations for the persistence of HBV-DNA in HBsAg-negative samples have been proposed. One possible reason for this phenotype is alteration in large HBsAg to small HBsAg envelope protein ratio associated with reduced or nonsecretion of HBsAg. This results in quantitative levels of serum HBsAg below the detection limit of enzyme immunoassays. The epidemiological studies of HBV genotypes in Saudi patients showed that the vast majority of with CHB have genotype D., Genotype D of HBV has a characteristic 33 nucleotide (nt) deletion upstream of the pre-S2/S promoter. This deletion may reduce HBsAg secretion in occult infection patients infected with genotype D HBV, while Pre-S2/S promoter deletions do not affect HBV replication.
Saudi Arabia has been implemented HBV vaccination of newborns, preschool, and school children against HBV for populations at high risk of HBV infection since 1992. As we have studied participants older than 18 years, and the rate of HBsAg positivity is an indicator of the prevalence of chronic HBV infection, whereas anti-HBc positivity can be regarded as an indicator of past exposure to HBV. This study showed that seroprevalence in general population is in the age of average 21.8± (15.1). This could suggest that neither children nor young adults were provided with catchup vaccinations. These finding supported with a recent study by Al Humayed SM in Asser region showed seroprevalence of 5.9% in overall, while a seroprevalence of 0.8% was found among persons aged 15–24 years. Persons over 25 years had a seroprevalence of 6.3%. In addition, population in this study was composed of near equal female-to-male ratio, whereas many previous studies have reported almost exclusively on males. This is especially true for blood donor studies where the female population has always been much smaller <10% of blood donors are women.
OBI infections are generally characterized by very low levels of HBV DNA in the blood (usually <1000 copies/ml or <200 IU/ml. Nevertheless many studies pointed that OBI still a concern for recipients of blood donations., However, many studies suggested potential transmission routes of occult infection and could not be neglected. For instance, in children, occult HBV may be transmitted by blood transfusion or organ transplantation. Evidence of transmission between relatives was found intrafamilial transmission among individuals with occult infection  and also can be transmitted perinatally to children from occult infected or HBsAg-positive mothers. The immunological selection pressure on the virus due to the anti-HBs immune is still possible. Collectively, these studies indicated that OBI with these potential transmission routes cannot be neglected.
Most of studies have been investigated OBI in patients with liver disease (HCV infected patients and patients with cryptogenetic liver diseases), patients at high risk of parenteral-transmitted infection (intravenous drug addicts, hemophiliacs), patients on hemodialysis, human immunodeficiency virus (HIV) infected patients and blood donors. There are few studies about OBI prevalence in healthy individuals of the general population expect for those blood donations. For instance, Minuk et al found that the prevalence of OBI is 18% of those with serological evidence of previous HBV infection and in 8% of HBV seronegative individuals. This study is the first that detects the prevalence of OBI in general Saudi population.
In this study, isolated anti-HBc was detected in 29.79% of the HIV-infected patients from whom 41.4% had OBI. The frequency of isolated anti-HBc in HIV-infected patients is very close to different studies across the world. For example, OBI in HIV infected patients in India was 45.5%, 22.1% in South Africa, and 8.7% in Columbia. This variation is attributed to the diverse prevalence of hepatitis B and HIV infections in different geographical regions and the sensitivity of the technique used to detect the HBV DNA. As most of HIV cases with OBI infection have been reported to be positive for anti-HBc represents the majority occult cases. Also it showed a high persistence of HBV genome 9.52% of total OBI and (overall 1.25%) even in those patients who are HBsAg negative. Other studies identified seropositive OBI; ~20% of occult infections are serologically negative with all negative serologic markers. Reports from India showed 7 OBI patients (2.2%) had no serological evidence of HBV infection  and (2.2%) from South Africa.
In addition, people at high risk of becoming infected with HBV could be more likely to develop OBI. This infection can represent a life-threatening risk factor if the carrier experiences an immunosuppression. Furthermore, a consideration about OBI should be taken in several conditions, when the host immune surveillance is low, an overt HBV reactivation can occur., For instance, patients undergoing immunosuppressive therapy and/or chemotherapy have the possibility of a consequent development of acute hepatitis that may lead to hepatic failure. In particular, in non-Hodgkin lymphoma, occult HBV reactivation has been reported to occur in 3%–25% of patients, OBI may occur in infants born to HBsAg-positive mothers despite the receipt of immunoprophylaxis. HBsAg loss before the onset of cirrhosis is associated with improvement of the outcome with reduced risk of cirrhosis, decompensation, and HCC.,
The prevalence of OBI in dialysis patients ranged from 0% to 58% in different surveys.,,,,,, In Egypt, OBI was detected in 12/50 (24%) of HD patients  and close results have been reported by Siagris et al., who reported that HBV DNA was detected by PCR in 10/49 (20.4%) HD patients. However, previous studies in dialysis units have reported a lower prevalence, where OBI was identified in 2.7% (5/188) in Turkey  and 3.8% (9/239) of HBs-Ag-negative North American adult HD patients using real-time PCR. This study found OBI prevalence of 17.4% in anti-core positive cases, with 4.86% in total HD patients. HBV DNA was detected in three anti-HBc positive patients. Furthermore it showed that 29.79% of HD patients had previous exposure to HBV at some time during the course of their illness. At the same time, it also suggests that a number of patients (26.75%) still need immunization and are at risk of acquiring infection with HBV. Our results showed that 62% of HD patients are considered HBV immune, either through vaccination (43%) or due to past infection (18.54%). However, HBV DNA was detected in three anti-HBc-positive patient, in this study, could indicate for a risk of nosocomial transmission.
Preventing HBV transmission within HD units is depending on a robust vaccination program. Patients with chronic kidney disease (CKD) exhibit specific and nonspecific defects in both humoral and cellular immune responses , As a result, the response to hepatitis B vaccination is lower in HD patients compared with the general population. Vaccination is therefore advised early in the course of the renal disease, using a double-vaccine dose (40 μg) and a four doses rather than three as recommended for general population  and 45%–66% of patients with CKD were estimated to develop adequate anti-HBs responses. This study showed that 43.46% developed adequate responses anti-HBs of level. However, 26.75% of studied group were susceptible for infection.
Coinfection with HCV and HBV is another factor involved in OBI. Many studies suggested showed that an OBI infection is commonly observed in patients coinfected with nonoccult HCV and HIV.,, OBI shows the highest prevalence precisely in HCV-infected patients where HCV “core” protein strongly inhibits HBV replication. HBV DNA levels in coinfected hepatocytes were lower than those in cells infected only with HBV, which leads to inhibition of HBV replication by HCV and also HBV may inhibit HCV replication. Also HCV RNA levels were lower in coinfected cells than in cells infected only with HCV. Therefore we study the impact of HCV coinfection within the groups of patients tested in this study. First HCV serology testing were performed in all study samples. This study showed that the prevalence of anti-HBc positivity in HCV seropositive was 13.33% in healthy control group compared to 37.3% and 60% in HD and HIV patients, respectively. This variation could be due to the low prevalence of HCV among the healthy group which was found to be 0.14%. This prevalence was lower that other studies showed higher HCV seropositive prevalence in Saudi Arabia. For example, in blood donors HCV seropositive prevalence ranges from 0.4% to 1.7%., On the other hand, other studies showed higher OBI prevalence in HCV infected patients 41.25% in Poland, 45.7% in Morocco  and 20% in Iran. Taken to gather, these results suggested that the risk of occult HBV infection among HCV carriers and higher risk among immunocompromised patients such as HIV and HD patients. In addition, several studies have reported that OBI may be associated with more severe liver damage and even the development of HCC may correlate with a lack of response to interferon treatment in patients with chronic HCV. Other studies found that the prevalence of OBI infection was comparable in patients with chronic HCV infection (14.8%) and healthy adults (15%) and suggested that the risk of OBI among HCV carriers is not increased compared to that of the general population in Taiwan.
| Conclusion|| |
This study proof that OBI is frequently encountered among healthy individuals in Saudi Arabia. In January 2008, the Saudi Arabian health authority included mandatory testing for HIV, HBV and HCV viruses in the premarital screening program. Currently in most MOH hospitals, pregnant women, dialysis and premarrige blood tests are screened for HBsAg alone which could cause missing of OBI detection. To eliminate the risk of HBV transmission by OBI infection, in particular hemodialysis patients and pre marriage screening and organ transplantation. Implementation of routine hepatitis B core antibody screening would be necessary. Also, periodic sampling for HBV DNA testing may be particularly appropriate for clinical groups at risk for occult HBV infection, which enable accurate HBV detection.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Tang CM, Yau TO, Yu J. Management of chronic hepatitis B infection: Current treatment guidelines, challenges, and new developments. World J Gastroenterol 2014;20:6262-78.
el-Hazmi MA. Hepatitis B virus in Saudi Arabia. J Trop Med Hyg 1989;92:56-61.
Mohammed Abdullah S. Prevalence of hepatitis B and C in donated blood from the Jazan region of Saudi Arabia. Malays J Med Sci 2013;20:41-6.
Shobokshi OA, Serebour FE, Skakni L. Hepatitis B surface gene mutants and their emerging role in the efficacy of HBV vaccination programs. Ann Saudi Med 1999;19:87-92.
Memish ZA, Knawy BA, El-Saed A. Incidence trends of viral hepatitis A, B, and C seropositivity over eight years of surveillance in Saudi Arabia. Int J Infect Dis 2010;14:e115-20.
Raimondo G, Caccamo G, Filomia R, Pollicino T. Occult HBV infection. Semin Immunopathol 2013;35:39-52.
van Hemert FJ, Zaaijer HL, Berkhout B, Lukashov VV. Occult hepatitis B infection: An evolutionary scenario. Virol J 2008;5:146.
Chan HL, Tsang SW, Leung NW, Tse CH, Hui Y, Tam JS, et al.
Occult HBV infection in cryptogenic liver cirrhosis in an area with high prevalence of HBV infection. Am J Gastroenterol 2002;97:1211-5.
Georgiadou SP, Zachou K, Liaskos C, Gabeta S, Rigopoulou EI, Dalekos GN, et al.
Occult hepatitis B virus infection in patients with autoimmune liver diseases. Liver Int 2009;29:434-42.
Bläckberg J, Kidd-Ljunggren K. Occult hepatitis B virus after acute self-limited infection persisting for 30 years without sequence variation. J Hepatol 2000;33:992-7.
Pollicino T, Saitta C, Raimondo G. Hepatocellular carcinoma: The point of view of the hepatitis B virus. Carcinogenesis 2011;32:1122-32.
Sagnelli E, Pisaturo M, Martini S, Filippini P, Sagnelli C, Coppola N, et al.
Clinical impact of occult hepatitis B virus infection in immunosuppressed patients. World J Hepatol 2014;6:384-93.
Mastroianni CM, Lichtner M, Citton R, Del Borgo C, Rago A, Martini H, et al.
Current trends in management of hepatitis B virus reactivation in the biologic therapy era. World J Gastroenterol 2011;17:3881-7.
Alrowaily MA, Abolfotouh MA, Ferwanah MS. Hepatitis B virus sero-prevalence among pregnant females in Saudi Arabia. Saudi J Gastroenterol 2008;14:70-2.
] [Full text]
Al-Faleh FZ. Changing pattern of hepatitis viral infection in Saudi Arabia in the last two decades. Ann Saudi Med 2003;23:367-71.
El-Hazmi MM. Prevalence of HBV, HCV, HIV-1, 2 and HTLV-I/II infections among blood donors in a teaching hospital in the central region of Saudi Arabia. Saudi Med J 2004;25:26-33.
Sengupta S, Panda SK, Acharya SK, Durgapal H. Role of hepatitis B virus genotype D and its mutants in occult hepatitis B infection. Indian J Med Res 2013;138:329-39.
] [Full text]
Abdo AA, Al-Jarallah BM, Sanai FM, Hersi AS, Al-Swat K, Azzam NA, et al.
Hepatitis B genotypes: Relation to clinical outcome in patients with chronic hepatitis B in Saudi Arabia. World J Gastroenterol 2006;12:7019-24.
Hajeer AH, Al Knawy B, Alhaj-Hussein BT, Al-Rubiaan SD. Hepatitis B virus: A study of genotypes in an infected Saudi cohort. Br J Biomed Sci 2007;64:93-4.
Al Humayed SM, El-Mekki AA, Mahfouz AA. Hepatitis B virus infection in Aseer region, South-Western Saudi Arabia: A call for an immediate action against a preventable disease. Public Health 2017;146:24-8.
Jutavijittum P, Andernach IE, Yousukh A, Samountry B, Samountry K, Thammavong T, et al.
Occult hepatitis B infections among blood donors in Lao PDR. Vox Sang 2014;106:31-7.
Raimondo G, Navarra G, Mondello S, Costantino L, Colloredo G, Cucinotta E, et al.
Occult hepatitis B virus in liver tissue of individuals without hepatic disease. J Hepatol 2008;48:743-6.
Allain JP. Occult hepatitis B virus infection and transfusion. J Hepatol 2006;44:617-8.
Walz A, Wirth S, Hucke J, Gerner P. Vertical transmission of hepatitis B virus (HBV) from mothers negative for HBV surface antigen and positive for antibody to HBV core antigen. J Infect Dis 2009;200:1227-31.
Minuk GY, Sun DF, Uhanova J, Zhang M, Caouette S, Nicolle LE, et al.
Occult hepatitis B virus infection in a North American community-based population. J Hepatol 2005;42:480-5.
Gutiérrez-García ML, Fernandez-Rodriguez CM, Lledo-Navarro JL, Buhigas-Garcia I. Prevalence of occult hepatitis B virus infection. World J Gastroenterol 2011;17:1538-42.
Gupta S, Singh S. Occult hepatitis B virus infection in ART-naive HIV-infected patients seen at a tertiary care centre in North India. BMC Infect Dis 2010;10:53.
Mphahlele MJ, Lukhwareni A, Burnett RJ, Moropeng LM, Ngobeni JM. High risk of occult hepatitis B virus infection in HIV-positive patients from South Africa. J Clin Virol 2006;35:14-20.
Bautista-Amorocho H, Castellanos-Domínguez YZ, Rodríguez-Villamizar LA, Velandia-Cruz SA, Becerra-Peña JA, Farfán-García AE, et al.
Epidemiology, risk factors and genotypes of HBV in HIV-infected patients in the Northeast region of Colombia: High prevalence of occult hepatitis B and F3 subgenotype dominance. PLoS One 2014;9:e114272.
Saha D, Pal A, Sarkar N, Das D, Blackard JT, Guha SK, et al.
Occult hepatitis B virus infection in HIV positive patients at a tertiary healthcare unit in Eastern India. PLoS One 2017;12:e0179035.
Bell TG, Makondo E, Martinson NA, Kramvis A. Hepatitis B virus infection in human immunodeficiency virus infected Southern African adults: Occult or overt – That is the question. PLoS One 2012;7:e45750.
Knöll A, Pietrzyk M, Loss M, Goetz WA, Jilg W. Solid-organ transplantation in HBsAg-negative patients with antibodies to HBV core antigen: Low risk of HBV reactivation. Transplantation 2005;79:1631-3.
Hui CK, Cheung WW, Zhang HY, Au WY, Yueng YH, Leung AY, et al.
Kinetics and risk of de novo
hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy. Gastroenterology 2006;131:59-68.
Niitsu N, Hagiwara Y, Tanae K, Kohri M, Takahashi N. Prospective analysis of hepatitis B virus reactivation in patients with diffuse large B-cell lymphoma after rituximab combination chemotherapy. J Clin Oncol 2010;28:5097-100.
Foaud H, Maklad S, Mahmoud F, El-Karaksy H. Occult hepatitis B virus infection in children born to HBsAg-positive mothers after neonatal passive-active immunoprophylaxis. Infection 2015;43:307-14.
Esmail MA, Mahdi WK, Khairy RM, Abdalla NH. Genotyping of occult hepatitis B virus infection in Egyptian hemodialysis patients without hepatitis C virus infection. J Infect Public Health 2016;9:452-7.
Siagris D, Christofidou M, Triga K, Pagoni N, Theocharis GJ, Goumenos D, et al.
Occult hepatitis B virus infection in hemodialysis patients with chronic HCV infection. J Nephrol 2006;19:327-33.
Yakaryilmaz F, Gurbuz OA, Guliter S, Mert A, Songur Y, Karakan T, et al.
Prevalence of occult hepatitis B and hepatitis C virus infections in Turkish hemodialysis patients. Ren Fail 2006;28:729-35.
Minuk GY, Sun DF, Greenberg R, Zhang M, Hawkins K, Uhanova J, et al.
Occult hepatitis B virus infection in a North American adult hemodialysis patient population. Hepatology 2004;40:1072-7.
McNulty CA, Bowen JK, Williams AJ. Hepatitis B vaccination in predialysis chronic renal failure patients a comparison of two vaccination schedules. Vaccine 2005;23:4142-7.
Sowole L, Labbett W, Patel M, O'Riordan A, Cross J, Davenport A, et al.
The prevalence of occult hepatitis B virus (HBV) infection in a large multi-ethnic haemodialysis cohort. BMC Nephrol 2015;16:12.
Morsica G, Ancarani F, Bagaglio S, Maracci M, Cicconi P, Cozzi Lepri A, et al.
Occult hepatitis B virus infection in a cohort of HIV-positive patients: Correlation with hepatitis C virus coinfection, virological and immunological features. Infection 2009;37:445-9.
Hofer M, Joller-Jemelka HI, Grob PJ, Lüthy R, Opravil M. Frequent chronic hepatitis B virus infection in HIV-infected patients positive for antibody to hepatitis B core antigen only. Swiss HIV cohort study. Eur J Clin Microbiol Infect Dis 1998;17:6-13.
Firnhaber C, Viana R, Reyneke A, Schultze D, Malope B, Maskew M, et al.
Occult hepatitis B virus infection in patients with isolated core antibody and HIV co-infection in an urban clinic in Johannesburg, South Africa. Int J Infect Dis 2009;13:488-92.
Raimondo G, Pollicino T, Cacciola I, Squadrito G. Occult hepatitis B virus infection. J Hepatol 2007;46:160-70.
Morales-Romero J, Vargas G, García-Román R. Occult HBV infection: A faceless enemy in liver cancer development. Viruses 2014;6:1590-611.
Szymanek-Pasternak A, Simon KA, Serafińska S, Janocha-Litwin J, Pazgan-Simon M, Madej G, et al.
The influence of anti-HBc status on the sustained virological response rate in HCV-infected patients treated with pegylated interferon alfa 2 and ribavirin. Clin Exp Hepatol 2016;2:155-60.
Kitab B, Ezzikouri S, Alaoui R, Nadir S, Badre W, Trepo C, et al.
Occult HBV infection in Morocco: From chronic hepatitis to hepatocellular carcinoma. Liver Int 2014;34:e144-50.
Vakili Ghartavol Z, Alavian SM, Amini S, Vahabpour R, Bahramali G, Mostafavi E, et al.
Prevalence of occult hepatitis B virus in plasma and peripheral blood mononuclear cell compartments of patients with chronic hepatitis C infection in Tehran-Iran. Hepat Mon 2013;13:e10134.
Chen HY, Su TH, Tseng TC, Yang WT, Chen TC, Chen PJ, et al.
Impact of occult hepatitis B on the clinical outcomes of patients with chronic hepatitis C virus infection: A 10-year follow-up. J Formos Med Assoc 2017;116:697-704.
Kao JH, Chen PJ, Lai MY, Chen DS. Occult hepatitis B virus infection and clinical outcomes of patients with chronic hepatitis C. J Clin Microbiol 2002;40:4068-71.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]