Occult Hepatitis B Infection Research Articles

SC294 - The occult hepatitis b infection (OBI) plays an important role in the pathogenesis of parenchymal renal cell carcinoma (RCC)

SC294 - The occult hepatitis b infection (OBI) plays an important role in the pathogenesis of parenchymal renal cell carcinoma (RCC)

Characterization of occult hepatitis B infection among Iranian liver transplant recipients.

BackgroundThe prevalence of occult hepatitis B infection (OBI) among Iranian liver transplant recipient patients has not been explored yet. The present study aimed to determine the OBI prevalence among Iranian liver transplant recipients.MethodsThis study encompassed 97 patients having undergone liver transplantation due to several clinical backgrounds in the Liver Transplantation Center, Tehran, Iran. After serological evaluation, two different types of PCR methods were applied for amplification of HBV DNA, followed by the direct sequencing of whole hepatitis B virus (HBV) surface genes.ResultsAt the time of admission, none of the patients were positive for HBsAg. However, 24 (25%), 12 (12.3%), and 5 (5.1%) cases were positive for anti‐HBc, hepatitis C virus (HCV), and hepatitis delta virus (HDV) antibodies, respectively. Moreover, two males were positive for OBI (2.1%). Both were positive for anti‐HBc and negative for anti‐HBs, anti‐HCV, and anti‐HDV. HBV‐related cirrhosis was the underlying reason for their liver transplantation. HBsAg sequences revealed no amino acid substitution.ConclusionsThe prevalence of OBI in the Iranian liver transplantation patients was relatively low. Future longitudinal studies with a larger sample size are suggested to explore the significance of this clinical finding, including the reactivation of cryptic HBV DNA, in liver transplant subjects.

Residual risk of hepatitis B virus transmission through blood donations in Burkina Faso screened with rapid diagnostic tests.

Background and Aimshepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) represent the major transfusion–transmissible pathogens worldwide. The risk of transmission is relatively high in African countries, mainly due to unreliable screening methods of blood donations. In Burkina Faso, predonation screening using rapid diagnostic tests (RDTs) is widespread, raising the major question of the transfusion safety in the country. The objective of this study was to assess the risk of transmission of HBV, HCV, and HIV through blood transfusion in the context of the use of RDTs for screening of the blood donations.MethodsIn this cross‐sectional study, a total of 417 serum samples obtained from blood donors tested negative for HBsAg, anti‐HCV, and anti‐HIV using RDTs were retested for the same markers using chemiluminescent immunologic assays. Total antibodies to HBV core (anti‐HBc) were tested on randomly selected samples. HBV‐DNA and HCV‐RNA viral loads (VLs) were quantified on HBsAg and anti‐HCV positive samples, respectively. To assess possible occult hepatitis B infection (OBI), HBV‐DNA‐VL was quantified on 313 randomly selected HBsAg‐negative samples.ResultsHBsAg and anti‐HCV were found respectively in 6 (6/417; 1.4%) and 11 (11/417; 2.6%) samples. No samples were reactive for anti‐HIV. Total anti‐HBc were detected in 217 out of the 319 randomly selected samples (217/319; 68.02%). HBV‐DNA was detected in four (4/313; 1.27%) samples, including two (2/6; 33.33%) of the six HBsAg positive samples and two (2/313; 0.6%) of the HBsAg‐negative samples, suggesting two cases of occult HBV infection. All anti‐HCV antibody‐positive samples were HCV‐RNA negative.ConclusionThis study shows that RDTs are not sufficiently sensitive for the screening of blood donations. Our results highlight the urgent need to think about the extension of sensitive immunological tests in all blood transfusion centers and also the implementation of nucleic acid amplification techniques.

Detection of HBV DNA among HBsAg Negative Patients

The persistence of Hepatitis B viral DNA (HBV DNA) in the blood or liver without the presence of detectable HBsAg is called Occult Hepatitis B infection (OBI)). This has become a threat when considering prevention of HBV transmission in our community. The purpose of this study was to determine prevalence as well as the HBV genotype(s) associated with OBI in Ibadan, Nigeria. HBsAg negative, using ELISA techniques, 219 blood samples were included for the study. Nested Polymerase Chain Reaction was used for the detection of HBV DNA in the samples. Data collected was processed using descriptive statistics and Chi square at p = 0.05. The number of male and female participants were 102 (46.6%) and 117 (53.4%) (P = 0.204) respectively. The participants have age range from 1 to 70 years with mean age of 32.1 years (SD =12.7) for females and 33.9years (SD = 12.4) for males. The clinical status of participants ranged from asymptomatic to those presented with acute hepatitis disease. Out of the 219 samples tested, one was positive for HBV DNA giving a prevalence of 0.5%. The positive sample was from a 30 years old female. We were unable to determine the genotype of the isolate due to poor sequence data. There is evidence of circulation of Occult Hepatitis B virus in our community as shown with prevalence of 0.5% OBI in this study. There is need for screening of blood units using Nucleic Acid Testing (NAT) technique to reduce the transmission of the virus through transfusion of infected blood and blood products. There is also need to increase awareness of HBV vaccination among the general population to forestall the danger OBI may pose.

THU391 - Estimations of the global prevalence and clinical burden of occult hepatitis B infection (OBI): a systematic review and meta-analysis

THU391 - Estimations of the global prevalence and clinical burden of occult hepatitis B infection (OBI): a systematic review and meta-analysis

What is the clinical impact of occult HBV infections and anti-HBc positivity in patients with chronic hepatitis C?

Occult hepatitis B infection (OBI) is defined by the persistence of the hepatitis B virus (HBV) genome in the liver of individuals testing negative for hepatitis B surface antigen (HBsAg). Hepatitis B core antibody (anti-HBc) is the serological marker that indicates HBV exposure. The impact of anti-HBc and OBI on patients with chronic hepatitis C remains unclear. The aim of the present study was to determine the prevalence of anti-HBc and OBI and to evaluate their impact on the clinical and pathological outcomes of patients with chronic hepatitis C. The study included 59 HBsAg-negative chronic hepatitis C patients who underwent a liver parenchymal biopsy. The presence of HBV DNA was investigated using an in-house nested PCR method. OBI was detected in 16 (27.1%) of the 59 cases and also in 10 (62.5%) of 22 (37.3%) anti-HBc-positive patients. None of the patients had positive serum HBV DNA. OBI was associated with the presence of anti-HBV antibodies (P < 0.05). There was also an association between anti-HBc positivity and the activity grades and fibrosis stages of the liver and also a prevalence of liver steatosis (P < 0.05). Positive anti-HBc results may predict OBI and may also be associated with the progression of liver injury in HBsAg-negative patients with chronic hepatitis C. Therefore, it is suggested that patients with chronic hepatitis C should be screened for anti-HBc positivity, and anti-HBc-positive patients should be carefully evaluated for disease progression.

Occult hepatitis B - the result of the host immune response interaction with different genomic expressions of the virus.

With over 40 years of history, occult hepatitis B infection (OBI) continues to remain an important and challenging public health problem. Defined as the presence of replication-competent hepatitis B virus (HBV) DNA (i.e., episomal HBV covalently closed circular DNA) in the liver and/or HBV DNA in the blood of people who test negative for hepatitis B surface antigen (HBsAg) in currently available assays, OBI is currently diagnosed using polymerase chain reaction (PCR) and real-time PCR assays. However, all efforts should be made to exclude a false negative HBsAg in order to completely follow the definition of OBI. In recent years, significant advances have been made in understanding the HBV lifecycle and the molecular mechanisms that lead to the persistence of the virus in the occult form. These factors are mainly related to the host immune system and, to a smaller proportion, to the virus. Both innate and adaptive immune responses are important in HBV infection management, and epigenetic changes driven by host mechanisms (acetylation, methylation, and microRNA implication) are added to such actions. Although greater genetic variability in the S gene of HBV isolated from OBIs was found compared with overt infection, the mechanisms of OBI are not mainly viral mutations.

Frequency of Hepatitis B Markers in Systemic Lupus Erythematosus Patients in Iran.

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Hepatitis B virus is the causative agent for chronic, acute, cirrhosis, and hepatocellular carcinoma. SLE patients with chronic or occult hepatitis B infection undergoing immunosuppressive drugs may become reactive and develop fatal hepatitis. Therefore, this study was conducted to determine HBV markers in SLE patients before the administration of immunosuppressive drugs in Ahvaz city, Iran. Materials and methods:The sera of 92 SLE patients were tested for HBs Ag and anti-HBc using ELISA, HBV DNA (by Nested PCR) testes. Real-time PCR was performed for the patients with positive anti-HBc and negative HBsAg. The positive HBV DNA samples were checked for HBV genotype and HBV subtypes. Results: Among the 92 SLE patients, three (3.3%) were males and 89 (96.7%) females . The patients’ ages ranged from 14 to 70 years [mean age of 38.9±10.1]. Three of 92 (3.26%) subjects [2/3 males and 1/89 female] were positive for HBsAg, anti-HBc Ab, and HBV DNA detected with PCR (p=0.000003)]. Five of 89 (5.61%) subjects [1 male and 4/88 females were only positive for anti-HBc and negative for HBs Ag, HBV DNA(PCR) using Real-time PCR (p=0.05). The results of the nucleotide data and phylogenetic tree showed all three HBV patients were genotype D1. The results of amino acid sequencing revealed all three HBV patients were HBV subtype ayw2. Conclusion:This study proved that 3.26% of SLE patients were positive for overt HBV infection (positive for anti-HBc, HBsAg and HBV-DNA using PCR). All the three isolated HBV were genotype D1 and subtype ayw2. The fact that 5.61% of the patients were only positive for anti-HBc characterized the occult hepatitis B infection (OBI) although further investigation is needed. To prevent HBV or OBI reactivation for SLE patients before immunosuppression treatment, HBV markers including anti-HBc, HBsAg, HBV-DNA should be implemented using PCR and Real-time PCR .

High resolution HLA-DRB1 analysis and shared molecular amino acid signature of DR\u03b21 molecules in Occult hepatitis B infection

AimTo investigate the association of human leukocyte antigen (HLA)-DRB1 alleles and the variations of polymorphic amino acid changes in DRβ1 chain in Shaanxi Han population with Occult hepatitis B infection (OBI).MethodsHigh-resolution HLA-DRB1 genotyping was performed in 107 OBI carriers and 280 normal controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. Three-dimensional modeling was performed to explore the effect of the key residues on the HLA-DRB1 molecule.ResultsStrong susceptible association for allele DRB1*07:01 was observed in OBI carriers. The amino acid variation at HLA-DRβ1 molecule revealed susceptible associations for residues Gln4β, Val57β(P9), Ser60β(P9) and Val78β(P4), the amino acids Arg4β, Asp57β(P9), Tyr60β(P9) and Tyr78β(P4) showed protective associations.ConclusionAlleles DRB1*07:01 showed strong susceptible associations in OBI carriers. The amino acid variations in DRβ molecules revealed significant molecular markers for susceptibility and protection from OBI in Shaanxi Han population.

Prevalence of viral hepatitis B markers among blood donors in the Republic of Guinea

The problem of transfusion safety in relation to parenteral viral hepatitis still remains relevant. Viral hepatitis B (HB) remains the most common viral infection transmitted through transfusion procedures. One of the natural phases of chronic hepatitis B (CHB) is occult hepatitis B infection (OBI), characterized by an undetectable HBsAg (regardless of the other serological markers content) in the presence of hepatitis B virus (HBV) DNA in the liver tissue and an extremely low, up to undetectable, level of viral load in the blood. In the Republic of Guinea, as in most countries on the continent, the prevention of HBV transmission through transfusion is still based on HBsAg serological testing of donors only. In this connection, OBI remains as a potential threat to blood transfusion safety. Detection of HBV DNA is a reliable preventive measure against transmission of the virus from donors with HBsAg-negative HBV infection, especially in highly endemic regions. In this regard, the study was conducted to substantiate recommendations for improving blood safety against the background of significant HBV prevalence in the Republic of Guinea.The aim of the work was the evaluation of serological and molecular markers of HBV infection in blood donors in the Republic of Guinea. We examined 250 blood samples obtained from donors living in Conakry, Republic of Guinea. Samples were tested for the presence of serological (surface antigen, HBsAg; antibodies (ABs) to surface (anti-HBs IgG) and core (anti-HBc IgG) antigens) and molecular (DNA) markers of HBV infection. The overall detection rate of hepatitis B markers was 83.2%; HBsAg was detected in 16.4% of all individuals. The high incidence of HBsAg in men (19.55%) compared to women (8.45%) was shown, the relative risk of HBV infection with the formation of HBsAg-positive chronic hepatitis B in males was also significantly higher. The prevalence of the HBV DNA in the study group was 30.4%, the OBI cases accounted for 15.6%. The prevalence of this form of the disease was shown in donors aged 30-49 years (24.78%), in the group of people younger than 30 years, the incidence was lower (8.73%), and at the age of over 50 years, OBI was not detected. Based on the phylogenetic analysis of 76 virus isolates, it was shown that genotype E prevails in the examined group (85.53%).Cases of pathogen DNA detection occurred in HBsAg-negative blood donors in the presence of anti-HBs IgG (n = 4), as well as in the simultaneous presence of ABs anti-HBs IgG and anti-HBc IgG (n = 7). The viral load exceeded 200 IU/ml in OBI samples. Escape mutations were detected by sequencing in each OBI sample, contributing to the virus escaping from diagnostic based on screening for HBsAg. Assessment of the prevalence viral hepatitis B markers in blood donors, determination of genotypes and clinically significant mutations of virus variants are necessary to ensure safe medical manipulations, control and prevention of the spread of this infectious agent.

Absence of chronicity in infants born to immunized mothers with occult HBV infection in Taiwan

In the Taiwanese population born in the universal vaccination era, HBsAg carrier rates have fallen below 2%, while approximately 5% develop occult hepatitis B infection (OBI). However, the potential for transmission from mothers with OBI to their infants has not been well studied. We aimed to investigate whether mothers with OBI could transmit HBV to their babies. A total of 253 pregnant women who were born after July 1986 and had been fully vaccinated against HBV during infancy were recruited from a tertiary hospital in Northern Taiwan. HBV serology and DNA levels were determined. Babies born to mothers with OBI were followed-up until 1 year of age. The surface genes were sequenced. HBV infection was documented in 18 vaccinated mothers, 2 of whom were HBsAg-reactive (0.79 %). Seventeen were positive for HBV DNA, among whom 16 (6.32%) presented with OBI with a median DNA level of 145 IU/ml (interquartile range: 37.8-657.3 IU/ml). Eleven babies born to 10 mothers with OBI were recruited. Three babies were HBsAg-reactive, and 2 were positive for HBV DNA (17.0 and 212.0 IU/ml). Seven mothers with OBI carried multiple surface gene variants. Two transiently infected babies harbored variants originating from their mother's HBV quasi-species. All infants received complete hepatitis B vaccines. At 12 months of age, none of the babies were positive for HBsAg or HBV DNA. It was possible for mothers with OBI to transmit HBV to their babies, who consequently harbored surface gene variants originating from their mothers' minor variants. Viremia was cleared 1 year after completing the hepatitis B vaccination series. Since initiating the hepatitis B vaccination program in Taiwan, the rate of young individuals (i.e. born after 1986) carrying the HBV surface antigen has fallen below 2%, although around 5% of vaccinated individuals develop occult HBV infections. Herein, we show that pregnant mothers with occult HBV infections can transmit HBV to their offspring. However, no infant had sustained infection at 1 year of age having completed a full HBV vaccination series.

Occult Hepatitis B Virus Infection and Its Risks of Cryptic Transmission in Southern Ethiopia.

BackgroundThe detection of hepatitis B virus surface antigen (HBsAg) in serum remains the mainstay in diagnosing and screening of hepatitis B virus (HBV) in most developing countries. The absence of HBsAg in the blood may not indicate the absence of circulating HBV and might be infectious. Thus, this study aimed to estimate the burden and its cryptic transmission risks of occult hepatitis B infection (OBI) among HBsAg negative healthy individuals in Southern Ethiopia.MethodsA community-based cross-sectional study was conducted from September 2020 to January 2021. Serum samples were collected and assayed for HBsAg and HBV core antibody (anti-HBc) seromarkers using enzyme-linked immunosorbent assay (ELISA). In anti-HBc positive samples, HBV DNA was detected using real-time polymerase chain reaction (RT-PCR). Data were entered into Epi-Data version 3.1, cleaned, and analyzed using SPSS version 21.0. Descriptive and logistic regression analyses were employed. Statistical significance was decided at p < 0.05.ResultsA total of 346 were individuals included in this study; 34 (9.8%) were tested positive for HBsAg. The rest 312 (90.2%) negatively tested were further assayed for anti-HBc, and 115 (36.7%) were found positive implying previous exposure to HBV, and 21 (18.3%) out of 115 anti-HBc positives had HBV DNA signifying OBI. The HBV DNA concentration below 200 IU/mL was 85.7%. A high rate of OBI was observed among individuals who had multiple sexual contacts, a family history of hepatitis, and tattooing.ConclusionIn this study, the prevalence of OBI is high. This indicates the burden of HBV is considerable since screening is exclusively dependent on HBsAg which will not eliminate the possibility of residual cryptic transmission through blood donation, organ transplantation, perinatal transmission, and other contacts. Our results demonstrate that nucleic acid-based testing (NAT) should be an essential part of screening to prevent missing OBI.

Occult Hepatitis B Virus Infection among β-Thalassemia Major Patients in Ahvaz City, Iran.

Occult Hepatitis B Infection (OBI) is a critical risk factor for triggering post-transfusion hepatitis (PTH), cirrhosis, hepatocellular carcinoma, and hepatitis B virus (HBV) reactivation, which β-thalassemia major (BTM) patients are at risk of it due to multiple blood transfusions. This study was aimed at determining the prevalence of OBI among BTM patients from Khuzestan Province, Iran. In this cross-sectional study, 90 thalassemia patients, who have received blood 36 to 552 times, participated referred to the Shafa hospital of Ahvaz city from January 2018 to April 2019. ELISA for determining serological markers (HBsAg, anti-HBc, anti-HBs, and anti-HCV) and real-time PCR for detecting HBV-DNA were performed; Nested PCR was conducted for DNA sequencing and determining the genotype of OBI case. Phylogenetic and statistical analyses were done by R package. Of 90 subjects enrolled in this study; 95.5% (86/90) were HBsAg negative, and the frequency of OBI among them was 1.16% (1/86). The anti-HBs, anti-HBc, and anti-HCV were detected in 80.00%, 7.78%, and 12.2% of patients, respectively. HBV-DNA was assessed at four HBsAg-positive subjects as well, and all of them were negative. The phylogenetic analysis showed that the detected HBV DNA in the OBI case belongs to the genotype D. This research, for the first time, demonstrated that OBI is present among β-thalassemia patients in Iran. Also, further studies are necessary to determine the actual prevalence of OBI among BTM patients in Iran to decisions concerning OBI screening, especially in transfusion centers.

Detection of the Hepatitis B Surface Antigen in Patients with Occult Hepatitis B by Use of an Assay with Enhanced Sensitivity

Patients with occult hepatitis B infection (OBI) have undetectable hepatitis B surface antigen (HBsAg) by conventional assays but detectable hepatitis B virus (HBV) DNA in blood/liver. We evaluated the key performance characteristics of a sensitive HBsAg assay (Architect HBsAg Next qualitative assay, referred to as NEXT) with respect to HBsAg detection. Assay precision, sample carryover, and seroconversion sensitivity of NEXT were evaluated. HBsAg was measured by NEXT in 1,138 individuals, including 1,038 patients who attended liver clinics in a tertiary hospital (200 HBV DNA-positive blood donors whose HBsAg was undetectable by conventional assays, 38 patients receiving immunosuppressive therapy, and 800 chronic hepatitis B patients with HBsAg seroclearance) and 100 HBsAg-negative subjects recruited from a community project. The within-run and within-laboratory coefficients of variation were <6% for the positive sample pools. In 9 seroconversion panels tested, NEXT allowed an earlier HBsAg detection than conventional assays. NEXT detected HBsAg in 10/200 (5%) HBsAg-negative blood donors, 1/20 (5%) and 0/18 HBsAg-negative patients with and without HBV reactivation, respectively, and 59/800 (7.3%) patients with HBsAg seroclearance. HBsAg was detectable by NEXT in 27.8%, 8.2%, 6.9%, 3.8%, and 1.9% samples at <3, 3 to 5, >5 to 8, >8 to 11, and >11 years after HBsAg seroclearance, respectively. Seven out of 100 HBsAg-negative community-identified subjects were tested positive by NEXT. Compared with conventional HBsAg assays, NEXT demonstrated a higher sensitivity and conferred an increment of 5 to 7% detection rate in patients with OBI, thereby helping in identifying HBV carriers and prevention of OBI-associated HBV transmission and reactivation.

Detection of Occult Hepatitis B Virus in Patients Undergoing Chemotherapy in Iran

Aim: Occult hepatitis B infection (OBI) is life threatening and has a high mortality rate despite applying antiviral treatments in cancer patients. This study aimed to investigate the prevalence of OBI in patients undergoing chemotherapy in Iran. Materials &amp; methods: A total of 342 patients undergoing chemotherapy were enrolled. OBI detection in anti-HBc positive individuals was conducted using nested PCR. Results: Among 342 subjects, 103 (30.1%) were positive for anti-HBc. Fifteen (14.6%) cases of 103 anti-HBc positive samples were also positive for HBsAg. Overall, HBV DNA was positive in three (3.4%) of 88 anti-HBc subjects. Conclusion: Our results indicated that OBI might occur in almost one in 25 anti-HBc-positive patients undergoing chemotherapy.

E2 Site Mutations in S Protein Strongly Affect Hepatitis B Surface Antigen Detection in the Occult Hepatitis B Virus.

The mechanism of occult hepatitis B infection (OBI) has not yet been fully clarified. Our previous research found that novel OBI-related mutation within S protein, E2G, could cause the hepatitis B surface antigen (HBsAg) secretion impairment, which resulted in intracellular accumulation in OBI of genotype B. Here, to further explore the role of E2 site mutations in the occurrence of OBI, we analyzed these site mutations among 119 OBI strains identified from blood donors. Meanwhile, 109 wild-type HBV strains (HBsAg positive/HBV DNA positive) were used as control group. Furthermore, to verify the E2 site mutations, two conservative 1.3-fold full-gene expression vectors of HBV genotype B and C (pHBV1.3B and pHBV1.3C) were constructed. Then, the E2 mutant plasmids on the basis of pHBV1.3B or pHBV1.3C were constructed and transfected into HepG2 cells, respectively. The extracellular and intracellular HBsAg were analyzed by electrochemical luminescence and cellular immunohistochemistry. The structural characteristics of S proteins with or without E2 mutations were analyzed using relevant bioinformatics software. E2 mutations (E2G/A/V/D) existed in 21.8% (26/119) of OBIs, while no E2 mutations were found in the control group. E2G/A/V/D mutations could strongly affect extracellular and intracellular level of HBsAg (p < 0.05). Notably, unlike E2G in genotype B that could cause HBsAg intracellular accumulation and secretion decrease (p < 0.05), E2G in genotype C could lead to a very significant HBsAg decrease both extracellularly (0.46% vs. pHBV1.3C) and intracellularly (11.2% vs. pHBV1.3C) (p < 0.05). Meanwhile, for E2G/A mutations, the relative intracellular HBsAg (110.7–338.3% vs. extracellular) and its fluorescence intensity (1.5–2.4-fold vs. with genotype-matched pHBV1.3B/C) were significantly higher (p < 0.05). Furthermore, N-terminal signal peptides, with a typical cleavage site for peptidase at positions 27 and 28, were exclusively detected in S proteins with secretion-defective mutants (E2G/A). Our findings suggest that: (1) E2G/A/V/D mutations were confirmed to significantly influence the detection of HBsAg, (2) the underlying mechanism of OBI caused by E2G mutation is quite different between genotype B and genotype C, and (3) E2G/A could produce a N-terminal truncated S protein, which might attribute to the HBsAg secretion impairment in the OBIs.

Prevalence and Clinical Significance of Occult Hepatitis B Infection in The Gambia, West Africa.

BackgroundPrevalence and clinical outcomes of occult hepatitis B infection (OBI) have been poorly studied in Africa.MethodsUsing the PROLIFICA cohort, we compared the prevalence of OBI between hepatitis B surface antigen (HBsAg)-negative healthy adults screened from the general population (controls) and HBsAg-negative patients with advanced liver disease (cases), and estimated the population attributable fraction for the effect of OBI on advanced liver disease.ResultsOBI prevalence was significantly higher among cases (15/82, 18.3%) than controls (31/330, 9.4%, P = .03). After adjusting for age, sex, and anti-hepatitis C virus (HCV) serology, OBI was significantly associated with advanced liver disease (odds ratio, 2.8; 95% confidence interval [CI], 1.3–6.0; P = .006). In HBsAg-negative people, the proportions of advanced liver disease cases attributable to OBI and HCV were estimated at 12.9% (95% CI, 7.5%–18.1%) and 16.9% (95% CI, 15.2%–18.6%), respectively.ConclusionsOBI is endemic and an independent risk factor for advanced liver disease in The Gambia, West Africa. This implies that HBsAg-negative people with liver disease should be systematically screened for OBI. Moreover, the impact of infant hepatitis B immunization to prevent end-stage liver disease might be higher than previous estimates based solely on HBsAg positivity.

Evaluation of the Immunological Status in Occult Hepatitis B Virus-infected Patients Attending Rivers State University Teaching Hospital

Background: Occult hepatitis B infection (OBI) is a rare form of infection that is characterized by the presence of replication-competent HBV DNA in the liver but without detectable HBsAg in the serum.&#x0D; Aim: This study aimed to determine the comparative levels of immunological variables particularly CD4 counts and differential white blood cell (WBC) counts in occult hepatitis B and HBsAg positive subjects among prospective blood donors in Port Harcourt Metropolis in Nigeria.&#x0D; Methods: The CD4 count and total and differential WBC counts were analyzed with automated techniques using BD Fascount and Sysmex XP-300 respectively. Data were analyzed as mean (standard deviation) and significance was assumed at 95% confidence interval using student t-test and one-way ANOVA on GraphPad prism.&#x0D; Results: The mean values for CD4, WBC, LYM (lymphocyte), MXD (differential mixed cells), and NEU (neutrophils) were 607±286 µ/l, 16±24 /l, 1.8±0.55 %, 0.46±0.15 % and 3.1±1.1 % respectively for occult hepatitis B subjects; 609±222 µ/l, 5.4±1.7 /l, 2.3±1.2 %, 0.54±0.31 % and 2.7±1.2 % respectively for HbsAg positive subjects and 823±256 µ/l, 10±5.4 /l, 2.4±1.6 %, 0.69±0.49 % and 6.4±4.7 % respectively for hepatitis B negative subjects. CD4 levels for male and female occult hepatitis B subjects are 729±309 µ/l and 461±190 µ/l respectively; 582±210 µ/l and 643±250 µ/l respectively for HBsAg positive subjects while that of hepatitis B negative subjects were 824±305 µ/l and 821±199 µ/l respectively. OBI showed a significant negative association between differential mixed cells and lymphocytes (r= -0.89 and p= 0.001) alone signifying that increment in former could reduce the latter. Only the HBsAg positive subjects showed a significant positive correlation of age to differential mixed cells (r=0.94 and p=0.000) which imply as the age increase the level of differential mixed cells will rise. Again, the HBsAg positive subjects showed a significant positive correlation between the differential mixed cells against neutrophil and WBC (r=0.53 and p=0.050), (r=0.56 and 0.036) respectively. Smoking and alcohol consumption caused raised levels of CD4 cells in OBI.&#x0D; Conclusion: This study revealed a significant decrease in CD4 count, increase in total WBC and neutrophil counts while lymphocyte counts were decreased in occult hepatitis B subjects. Gender difference affect the level of CD4 cells and significant correlation were observed especially with the differential mixed cells.

Drug-resistant andimmune-escapehepatitis B virus mutants,occult hepatitis B infection and coinfections in public hospital patients from Argentina.

Argentina exhibits low serological prevalence for Hepatitis B virus (HBV); however, occult hepatitis B infection (OBI) has been reported in blood donors, Amerindians and individuals coinfected with hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV). The aim of this study was to analyze the genetic diversity of HBV and to evaluate serological marker associations and coinfections with HCV and HIV in patients attending and treated in a public hospital in the province of Buenos Aires, Argentina. A total of 189 HBV reactive samples (HBsAg and/or anti-HBc) were analyzed for HBV DNA characterization. All reactive samples were tested for anti-HCV and HIV-antigen/antibody using CMIA assays. Thirty-six samples exhibited detectable HBV DNA, 7 of which were OBI. HBV sequences were classified as subgenotypes A1, A2, B2, D3, F1b, F3 and F4. Mutations related to the ability to escape the host's immune response, resistance to antiviral therapy and progression to disease were found in patients, partly due to the variable sensitivity of HBsAg, the reverse transcriptase, the basal core promoter and the preCore. HCV and HIV prevalence was 10% and most of the genotypes found in the sequences were genotype 1 and B/F recombinant subtype, respectively. Of the total samples analyzed, 7 exhibited coinfections. This study shows the frequency of OBI, subgenotypedistribution, HBV mutations and coinfections, which may have important clinical implicationsin public hospital patients. Planned prevention, detection and treatment adherence are needed to reduce transmission and morbidity in vulnerable populations.

Serum Th17 and TNF-α distinguish between patients with occult hepatitis B infection, chronic hepatitis B infection and healthy individuals.

Chronic hepatitis B (CHB) is classified into five phases based on virus-host interactions: immune tolerance, immune clearance, inactive carrier state, reactive phase and occult hepatitis B infection (OBI). OBI is an uncommon asymptomatic phase of CHB that can be reactivated when the immune system is compromised, occasionally giving rise to severe liver disease. Host immune factors play essential roles in all phases of the CHB infection. Cytokines may alter infection course, influencing the propensity for and the progression of CHB and thus warrant study. Three clinical groups were studied: 48 healthy individuals (HI), 28 patients with persistent positive anti-HBc serological markers and negative HBsAg over time, who were diagnosed as OBI and 12 patients with active CHB. OBI patients were defined by three independent detections of the hepatitis B virus genome through nested PCR and real-time PCR. Quantitative measurement of 20 Th1, Th2 and Th17 human cytokines was performed in the sera of HI, OBI and CHB patients. Levels of IFN-γ, TNF-β, IL-28A, IL-4, IL-5, IL-13, IL-1β, IL-6, IL-21, IL-22, IL-23, GM-CSF and MIP-3α were similar between groups. IL-2, IL-12p70, IL-10, IL-17F and TGF-β1 were similar in HI and OBI, but higher in CHB. TNF-α and the IL-17A:IL-17F ratio were significantly different between the three groups. TNF-α was progressively higher in HI, OBI and CHB (P = 0.004), while the IL-17A:IL-17F ratio was 1.1 in HI, 3.4 in OBI and 0.4 in CHB. Detection and levels of these pro-inflammatory cytokines in OBI patients suggest that they are undergoing a silent hepatic inflammatory process.