Occult HBV Infection In Patients Research Articles

Does the ultrasensitive HBsAg Next assay enhance Hepatitis B diagnosis? An evaluation of analytical performances

BackgroundAccurate laboratory confirmation for Hepatitis B diagnosis and monitoring are crucial. Recently an ultrasensitive immunoassay test, the HBsAg Next (HBsAgNx), has been reported approximately eight times more sensitive than current HBsAg assays. The aim of our study was to assess the analytical performances of this new test. Methodology253 clinical samples from Saint Louis University Hospital were analyzed, splitted into four panels: (1) routine prospectively screening serums (n = 196), (2) retrospective serum samples before HBV reactivation (HBV-R) (n = 18), (3) occult HBV infection (OBI) (n = 10) and (4) a selection of wild type HBV genotypes (n = 29) ResultsPanel 1, showed robust agreement with the HBsAg Qualitative II (HBsAgQII) assay (Cohen's kappa = 0.83). Despite this agreement, 7 false positive with the HBsAgQII assay were found negative with HBsAgNx. One OBI was detected only with HBsAgNx. Panel 2 showed potential time savings in diagnosing HBV-R using HBsAgNx among 4/18 HBsAg positives samples. Panel 3 highlighted the ability of HBsAgNx to detect HBsAg in OBI patients defined by negative for HBsAg with HBsAgQII assay and positive for HBV DNA. Furthermore, the HBsAgNx assay detected all different genotypes. ConclusionThe study highlights the effectiveness of the HBsAgNx assay, showing its performance. It excels in detecting weakly positive samples and addressing challenging cases. HBsAgNx assay demonstrates promising analytical performances, with improved sensitivity and specificity compared to standard HBsAgQII assay, able to detect all genotypes. Its potential impact on early detecting and monitoring reactivations, and occult infections could be very useful in clinical practice.

Cross sectional study on the molecular detection of Hepatitis B virus in patients with chronic liver disease in Guntur, India revealed mutations in Genotype A of occult HBV

The present study was aimed at the molecular detection of HBV infection among patients with chronic liver disease (CLD) and to study the mutation spectrum S-gene region in the occult HBV strains. An observational study conducted on 200 clinically diagnosed CLD cases enrolled from the Gastroenterology unit. Two hundred serum samples were screened with Fibroscan and for HBsAg, HBCT and estimated liver enzymes. Samples positive for either HBsAg or Anti HBc total were further evaluated for other HBV markers and presence of HBV DNA. The S region was amplified in occult CHB cases and sequenced. 70.5% (141) of the patients with CLD were suffering with Chronic Hepatitis B virus (CHB). The HBV DNA was detected in 19.14% patients. Four cases were in occult phase. Two samples of them could be amplified. The isolates belong to the genotype A, and revealed certain mutations leading to novel amino acids. Mutations in the S gene sequences of HBV virus from the Occult HBV infection (OBI) patients would lead to immune escape or cause occult infection. In the Genotype A at two positions, amino acids that are likely to cause occult infection are observed apart from mutations at certain positions leading to novel amino acids.

Control of occult hepatitis B virus infection.

The diagnosis of hepatitis B virus (HBV) infection requires HBV DNA testing and serologic testing for detection of the surface antigen (HBsAg) and the hepatitis B core antibody (anti-HBc). There is a population of patients with occult HBV infection (OBI), which is not detected by HBsAg or HBV DNA quantification in blood, despite the presence of active replication in the liver. This document provides a definition of OBI and describes the diagnostic techniques currently used. It also addresses the detection of patients with risk factors and the need for screening for OBI in these patients. Correct diagnosis of OBI prevents HBV reactivation and transmission. Diagnosis of OBI is based on the detection of HBV DNA in patients with undetectable HBsAg in blood. A high number of patients with OBI may remain undiagnosed; therefore, screening for OBI in patients with factor risks is essential. For a correct diagnosis of OBI, it is necessary that new markers such as ultrasensitive HBsAg are incorporated, and a more comprehensive marker study is performed by including markers such as cccDNA.

The Investigation of Hepatitis B Vaccine Immune Responses in Occult Hepatitis B Virus-Infected Patients.

ObjectivesThere is no effective treatment for occult hepatitis B virus infection (OBI) patients, and immunotherapy may be one of the most promising options. We aim to investigate the underlying mechanism and therapeutic potential of hepatitis B vaccine immunotherapy for OBI patients.MethodsOutpatient OBI patients were screened and randomly divided into treatment (Group A) and control (Group B) groups. At weeks 0, 4, and 24, patients in Group A received a subcutaneous/intramuscular injection of hepatitis B vaccine (Engerix-B, 20 μg/time) according to the standard vaccination schedule; patients in Group B served as blank control. The patients were followed for 36 weeks, with clinical, biochemical, virological, immunological, and imaging data collected and analyzed at weeks 0, 12, 24, and 36, respectively, and the relation between the virology and immunology results was analyzed.ResultsOf the 228 OBI patients, 28 were excluded, and 200 were enrolled for observation. In the end, 44 patients were included in Group A and 39 in Group B after excluding lost cases. At week 0 (baseline), some patients in two groups had liver disease symptoms, HBV-related liver function damage, and liver fibrosis. 86.36% (38/44) and 82.05% (32/39) patients were positive for serum hepatitis B surface antibodies (anti-HBs) in Group A and Group B, respectively, with the median (quartile) of 42.47 (16.85, 109.1) and 39.27 (16.06, 117.4) mIU/ml, respectively. Reduced peripheral blood CD4+T, CD8+T, and B lymphocytes were found in some patients in two groups. These results were not statistically different between Group A and Group B (P>0.05). At week 36, all patients were serum anti-HBs (+) in Group A, with a median (quartile) of 1000 (483.9, 1000) mIU/ml, which was significantly higher than that at week 0 (P<0.05) and that in Group B (P<0.05). Compared to week 0, the number of CD8+ T and B lymphocytes increased significantly and were significantly higher than Group B at the same point. Two patients in Group B were found to have hepatitis B virus reactivation from week 12 to week 36.Correlation AnalysisAnti-HBs in Group A patients were positively correlated with B lymphocytes (r=0.3431, 0.3087, and 0.3041, respectively) and positively correlated with CD8+ T lymphocytes (r=0.4954, 0.3054, and 0.3455, respectively) at weeks 12, 24, and 36.ConclusionVirological reactivation is a risk for OBI patients. Serum hepatitis B surface antibodies were significantly increased after hepatitis B vaccine treatment, the same as the numbers of peripheral blood B and CD8+ T lymphocytes; changes in hepatitis B surface antibody levels were positively correlated with the changes in peripheral blood B and CD8+ T lymphocytes.

Identification and functional characterization of miR-451a as a novel plasma-based biomarker for occult hepatitis B virus infection

BackgroundNumerous studies have indicated that miRNAs might play significant roles in the development of hepatitis B virus (HBV) infection. while the miRNAs in occult HBV infection (OBI) are still largely unknown. MethodsInitially, 15 HBV infection-related miRNAs in plasma of 10 OBI and 10 healthy controls (HCs) was analyzed by qRT-PCR. Significantly dysregulated miRNAs were subsequently validated in another 64 OBI, 20HCs, 31 chronic hepatitis B (CHB) and 20 asymptomatic HBsAg carriers (ASC). Furthermore, the potential biological functions and molecular mechanisms of miR-451a in HBV infection were investigated using HBV-expressing hepatoma cell lines. ResultsCompared to HCs, plasma miR-451a and miR-340-3p were significantly up-regulated in OBI, ASC and CHB patients, while no significant difference was found among OBI, ASC and CHB patients. ROC curve analysis indicated that both plasma miR-451a and miR-340-3p could moderately distinguish OBI from HCs, with AUCs of 0.76 and 0.78, respectively. When combined, the differentiation efficiency of this miRNA panel was better, with an AUC of 0.82. While, they both could not specifically separate the stage of chronic HBV infection. Functional experiments showed that overexpression of miR-451a might suppress HBV replication and gene expression in hepatoma cell lines. Mechanistically, miR-451a might inhibit HBV replication and gene expression by directly targeting ATF2. ConclusionsA plasma panel, including miR-340-3p and miR-451a that might suppress HBV replication by targeting ATF2, has the potential as biomarkers for HBV infection. In the setting of blood donations, this panel would be more practical to moderately differentiate OBI in HBsAg-negative donors.

Identification and characterization of lncRNA AP000253 in occult hepatitis B virus infection

BackgroundRecent studies suggest that lncRNAs may play significant roles in the development of hepatitis B virus (HBV) infection. However, as a special stage of HBV infection, the lncRNA expression in occult HBV infection (OBI) remains unclear.MethodsThe plasma level of 15 HBV infection-related lncRNAs was initially detected using qRT-PCR in 10 OBI and 10 healthy controls (HCs) in discovery phase. Significantly dysregulated lncRNAs were subsequently validated in another 64 OBI, 20 HCs, 31 chronic hepatitis B (CHB) and 20 asymptomatic HBsAg carriers (ASC). Moreover, the AP000253 expression in liver tissues and its potential biological functions in HBV infection were further investigate with public transcriptomic data and HBV-expressing cell lines.ResultsAmong candidate lncRNAs, the plasma level of AP000253 decreased significantly in OBI, ASC and CHB patients compared to HCs, while no difference was found among OBI, ASC and CHB patients. In liver tissues, similar AP000253 expression was also observed from the GSE83148 dataset, while that in HBV-expressing hepatoma cells was opposite. ROC curve analysis indicated that plasma AP000253 yielded an AUC of 0.73 with 60% sensitivity and 75% specificity when differentiating OBI from HCs, but it could not specifically separate the stage of chronic HBV infection. Furthermore, functional experiments suggested that AP000253 could promote HBV transcription and replication in hepatoma cell lines.ConclusionsAP000253 might be involved in HBV replication, and be served as a potential biomarker for HBV infection. In the setting of blood donations, plasma AP000253 would be more useful to moderately distinguish OBI in HBsAg-negative donors. However, the AP000253 expression in liver tissues and associated molecular mechanism of HBV infection deserve further study in future.

Treatment or Prophylaxis against Hepatitis B Virus Infection in Patients with Rheumatic Disease Undergoing Immunosuppressive Therapy: An Update.

Chronic hepatitis B virus (HBV) flares or reactivations are serious causes of morbidity or mortality in rheumatologic patients undergoing immunosuppressive therapy. The recent insights in the pathogenesis of rheumatic diseases led to the use of new immunosuppressive therapies indicated in case of failure, partial response, or intolerance of conventional synthetic disease-modifying anti-rheumatic drugs. Based on these premises, this review examines and discusses the main rheumatologic treatments that could require the initiation of prophylactic treatment or close monitoring of occult HBV infection in patients beginning antiviral therapy at the first signs of HBV reactivation, or antiviral treatment in chronic HBV-infected patients. We searched for relevant studies published in the last five years. Studies suggested that the presence of HBV infection is common in rheumatic patients and HBV reactivation during these immunosuppressant treatments is quite frequent in these kinds of patients. Therefore, before starting an immunosuppressive therapy, patients should be screened for HBsAg, anti-HBs, and anti-HBc and, on the basis of markers positivity, they should be carefully characterized for HBV infection phases. In conclusion, screening of HBV infection in patients undergoing immunosuppressive therapy with subsequent HBV monitoring, prophylaxis or treatment consistently reduces the risk of clinical consequences.

Occult Hepatitis B Virus Infection Among Hemodialysis Patients in Fakous General Hospital

Background: Occult HBV infection (OBI) is defined as the presence of a small amount of HBV in patients with negative serum for hepatitis B surface antigen (HBs Ag). The serum HBV DNA level in these patients is generally lower than 104 copies/mL, there is a high prevalence of OBI in patients with chronic hepatitis C, HCC cryptogenic liver disease, and HIV. Objectives: Assessment of prevalence of Occult Hepatitis B Virus infection among hemodialysis patients in Fakous General Hospital. Patients and Methods: A total of 40 patients with end-stage renal disease undergoing regular HD (for at least 6 months underwent a complete physical examination. Serum samples were collected between before hemodialysis and then stored at -80C° until tested. Serological markers of HBV infection (HBsAg, anti-HBs, anti-HBc) were determined using standard third generation commercially available enzyme immunoassays). Results: The 40 patients who have been included in this study had a minimum age of 25 years and a maximum age of 78 years. The number of females was 25 with a percentage of 62.5% and the percentage of males was about 37.5% (15 males). 22 patients (55%) had negative sera for anti-HCV antibody and a percentage of 37% and 63% for the distribution of females and males, respectively. 18 patients (45%) had positive sera for anti-HCV antibody and 37% of them were females and 63% of them were males. Conclusions: OBI infection is a relatively common infection (37.5%) among chronic hemodialysis patients in the dialysis unit of Fakous general hospital.

ESCV/PASCV Membership

Occult HBV infection (OBI) is of great concern due to their complicated diagnosis and potential for public transmission.The study aimed to determine the clinical prevalence of OBI and if viral immune escape-associated mutations contribute to the occurrence of OBI.A total of 91,037 HBV-infected patients with different related illnesses who were admitted to the Fifth Medical Center of Chinese PLA General Hospital from January 2005 to December 2017 were tested for OBI. Serum samples from 62 patients with OBI manifestations (OBI patients) and 124 matched non-OBI patients were sequenced for possible immune escape-associated mutations within the major hydrophilic region of HBV S protein. HBsAg and HBV DNA levels in representative viral strains were measured.Of the 91,037 tested patients, 487 (0.53 %) were negative for HBsAg but positive for HBV DNA and were defined as OBI patients. The prevalence in different illness categories varied. Immune escape-associated mutations were more frequently detected in OBI patients than in non-OBI patients (59.68 % vs. 35.48 %, P < 0.01), as did the coexistence of multiple mutations (43.55 % vs. 22.58 %, P < 0.01). Specifically, the prevalence rates of sT118 K, sK122R, and sV168A were increased in OBI patients. Strains with sK122R mutants (sK122R, sK122R + D144E, sK122R + C121R + D144E, and sK122R + F134L + D144E) from a follow-up OBI patient all showed significantly lower levels of HBsAg production than a wild-type strain.The study clarified the clinical prevalence of OBI, verified the influence of immune escape-associated mutations, and identified the role of the sK122R mutation in multiple OBI patients.

The sK122R mutation of hepatitis B virus (HBV) is associated with occult HBV infection: Analysis of a large cohort of Chinese patients.

Occult HBV infection (OBI) is of great concern due to their complicated diagnosis and potential for public transmission. The study aimed to determine the clinical prevalence of OBI and if viral immune escape-associated mutations contribute to the occurrence of OBI. A total of 91,037 HBV-infected patients with different related illnesses who were admitted to the Fifth Medical Center of Chinese PLA General Hospital from January 2005 to December 2017 were tested for OBI. Serum samples from 62 patients with OBI manifestations (OBI patients) and 124 matched non-OBI patients were sequenced for possible immune escape-associated mutations within the major hydrophilic region of HBV S protein. HBsAg and HBV DNA levels in representative viral strains were measured. Of the 91,037 tested patients, 487 (0.53 %) were negative for HBsAg but positive for HBV DNA and were defined as OBI patients. The prevalence in different illness categories varied. Immune escape-associated mutations were more frequently detected in OBI patients than in non-OBI patients (59.68 % vs. 35.48 %, P < 0.01), as did the coexistence of multiple mutations (43.55 % vs. 22.58 %, P < 0.01). Specifically, the prevalence rates of sT118 K, sK122R, and sV168A were increased in OBI patients. Strains with sK122R mutants (sK122R, sK122R + D144E, sK122R + C121R + D144E, and sK122R + F134L + D144E) from a follow-up OBI patient all showed significantly lower levels of HBsAg production than a wild-type strain. The study clarified the clinical prevalence of OBI, verified the influence of immune escape-associated mutations, and identified the role of the sK122R mutation in multiple OBI patients.

Evaluation of Occult Hepatitis B Infection in Individuals with Chronic Hepatitis C Before Treatment with Oral Direct-Acting Antivirals

: Occult hepatitis B virus infection (OBI) is one of the most challenging entities in the field of viral hepatitis. The virological and clinical relevance of OBI in patients treated with novel direct-acting antivirals (DAA) for hepatitis C virus (HCV) infections is currently a topic of hot debate. In cases where hepatitis B surface antigen (HBsAg) is not detected, DAA treatment is often initiated without examining for the presence of hepatitis B virus (HBV) DNA. In this study, the incidence of OBI was investigated in 114 HCV patients prior to application of DAAs who did not respond to pegylated interferon and ribavirin (PEG-INF and RBV) treatment. Serum samples were screened for HBV serological markers (antibody to hepatitis B core antigen [anti-HBc] and HBsAg). Samples positive for anti-HBc without HBsAg were further examined via real-time PCR (qPCR), nested PCR and S-gene mutational analyses. Overall, anti-HBc was detected in 37.7% chronic HCV patients and 2.6% had OBI with a baseline HBV DNA viral load < 2000 IU/mL before DAA therapy. One patient was identified as HBV genotype A1 without mutations in surface protein. Our collective data highlight the importance of clinicians being aware of potential anti-HBc positivity in patients with hepatitis C and the issues surrounding OBI screening before initiation of treatment with novel DAAs.

Circulating miRNA expression profile and bioinformatics analysis in patients with occult hepatitis B virus infection.

Emerging suggest that microRNAs (miRNAs) play vital roles in the occurrence and development of hepatitis B virus (HBV) infectious disease. However, miRNAs in occult hepatitis B virus infection (OBI), a special stage of HBV infection, remain largely unknown. Herein, we conducted this study to identify differentially expressed miRNAs and then to investigate the potential roles of these miRNAs in OBI. Plasma miRNA expression profiles of three OBI patients and three healthy controls were analyzed with high through-put miRNA sequencing technology. Altered expression of miRNAs was further confirmed with reverse transcription quantitative polymerase chain reaction (qRT-PCR). Finally, bioinformatics analysis was conducted to investigate the involved pathways and target genes for these differentially expressed miRNAs. Totally, 32 differentially expressed miRNAs were identified between OBI and healthy controls by miRNA sequencing (fold change ≥ 1.5, P < .1, and counts per million reads ≥ 1), including 16 downregulated and 16 upregulated miRNAs. Differential expression of hsa-miR-486-5p, -25-3p, and -92a-3p and -1-3p was further validated by qRT-PCR analysis, which was consistent with miRNA sequencing analysis. Moreover, these four miRNAs might distinguish OBI from HCs efficiently. Bioinformatics analyses indicated that the differentially expressed miRNAs were primarily involved in various biological processes related to gene expression and transcription, cell development and metabolism, protein modification and kinase activity regulation, as well as multiple signaling pathways such as PI3K/Akt signaling pathway. This study provided a global view of miRNA expression in plasma from OBI patients. These differentially expressed miRNAs might play important roles in the development of OBI, which provided intriguing insights into the screening and molecular mechanism of OBI.

Among Patients with Undetectable Hepatitis B Surface Antigen and Hepatocellular Carcinoma, a High Proportion Has Integration of HBV DNA into Hepatocyte DNA and No Cirrhosis

In some individuals with undetectable serum levels of hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV) DNA can still be detected in serum or hepatocytes and HBV replicates at low levels-this is called occult HBV infection (OBI). OBI has been associated with increased risk of hepatocellular carcinoma (HCC). We investigated the incidence of OBI in patients with HCC and other liver diseases. We also investigated whether, in patients with OBI and HCC, HBV DNA has integrated into the DNA of hepatocytes. We collected clinical information and liver tissues from 110 HBsAg-negative patients (90 with HCC and 20 without HCC; median ages at surgical resection and biopsy collection, 64.1 and 48.6 years, respectively) who underwent liver resection or liver biopsy from November 2002 through July 2017 in Hong Kong. HBV DNA and covalently closed circular DNA (cccDNA) were analyzed and quantified by PCR in liver tissues. Integration of HBV DNA into the DNA of liver cells was detected by Alu-PCR. Of the 90 HBsAg-negative patients with HCC, 18 had alcoholic liver disease (20%), 14 had non-alcoholic fatty liver disease or steatohepatitis (16%), 2 had primary biliary cholangitis, 2 had recurrent pyogenic cholangitis, 1 had autoimmune hepatitis, and 53 had none of these (59%). Among the 20 patients without HCC, 7 had non-alcoholic fatty liver disease or steatohepatitis, 7 had primary biliary cholangitis, and 6 had autoimmune hepatitis. OBI was detected in 62/90 patients with HCC (69%) and 3/20 patients without HCC (15%) (P < .0001). cccDNA was detectable in liver cells of 29 patients with HCC and OBI (47%) and HBV DNA had integrated into DNA of liver cells of 43 patients with HCC and OBI (69%); cccDNA and integrated HBV DNA were not detected in the 3 patients who had OBI without HCC. There were 29 patients with integration of HBV DNA among 33 patients with undetectable cccDNA in liver tissues (88%) and 14 patients with integration of HBV DNA among the 29 patients with cccDNA in liver tissues (48%) (P = .001). HBV DNA was found to integrate near genes associated with hepatocarcinogenesis, such as those encoding telomerase reverse transcriptase, lysine methyltransferase 2B, and cyclin A2. Among the 43 patients with integration of HBV DNA, 39 (91%) did not have cirrhosis. In an analysis of clinical data and liver tissues from 90 HBsAg-negative patients with HCC, we found that almost 70% had OBI, of whom 70% had integration of HBV DNA into liver cell DNA; 90% of these patients did not have cirrhosis. HBV DNA integrated near hepatic oncogenes; these integrations might promote development of liver cancer.

Occult HBV infection in patients with autoimmune hepatitis: A virological and clinical study.

Occult HBV infection (OBI) could have serious clinical consequences in patients receiving immunosuppressive therapy. We aimed to investigate the prevalence of OBI in Chinese patients with autoimmune hepatitis (AIH) and to analyze its clinical and virological features. 103 AIH cases were enrolled. Hepatitis B virus (HBV) serological markers were screened by chemiluminescence. HBV-DNA were detected by nest-PCR and real-time PCR. HBV genotyping and mutation analysis were performed by Sanger sequencing. Twenty-four out of 103 (23.30%) AIH patients had OBI as evidenced by positive HBV-DNA and negative hepatitis B surface antigen (HBsAg). HBV genotype C is the predominant genotype (57.89%), which had more amino acid (AA) substitutions in S region than that of B-genotype group (P=0.001). The distribution of AA substitution in the 'α' determinant region between genotype C and B were significantly different (P=0.042). In addition to those already reported OBI-associated AA substitutions (e.g., sG145R and sV184A), some new OBI-associated AA substitutions (e.g., sV106A, sC137* and sL176P) were found in AIH patients in our study. Three out of 24 (12.50%) OBI patients were diagnosed as decompensated cirrhosis, one patient with S deletion mutation and two patients with HBV extensive AA substitutions. There was a higher proportion of AIH patients with OBI than the general population in China, which can be either seropositive or seronegative-OBI in AIH patients is associated with some specific AA substitutions. The presence of deletion mutations and the extent of AA substitutions in the HBV S region may have predictive clinical implications.

Recent Advances in HBV Reactivation Research.

Hepatitis B virus (HBV) is an important public health problem that poses a serious threat to human health. HBV reactivation generally occurs in overt or occult HBV infection patients who suffered DDAs, chemotherapy, or immunosuppressive therapy, especially when some solid tumors and leukemia patients are using hormones such as prednisolone and imatinib. The approximate incidence of HBV reactivation ranged from about 10% to 40%. Scientists often explore the molecular mechanisms from both the virus and the host. But some studies have reported that some drugs (cisplatin, rituximab, imatinib, and glucocorticoid) could induce HBV reactivation directly. However, the specific molecular mechanisms were unclear. With the emergence of new antiviral drugs and molecular targeted drugs, the risk of HBV reactivation will increase significantly. Therefore this review was expected to be used to provide recommendations for future research in HBV reactivation.

Determining Occult HBV Infection in Patients with Isolated Hepatitis B Core Antibody Positivity

Patients with isolated hepatitis B core antibody (HBcAb) positivity (i.e., negative for hepatitis B surface antigens and antibodies but HBcAb-positive)

Behaviour of occult HBV infection in HCV-infected patients under treatment with direct-acting antivirals.

There is controversial data on possible occult HBV reactivation in HCV patients successfully treated with direct-acting antivirals (DAA). However, diagnosis of occult HBV infection (OBI) was not performed by gold standard procedures in any study. By using several highly sensitive assays, we examined serially collected serum samples from 40 HBV-surface-negative DAA-treated HCV patients with OBI identified by testing liver biopsy specimens through nested-PCR technique. Serum samples were obtained at four time points from each patient (at baseline, at 4 weeks after starting, at the end and 12 weeks after stopping therapy) and tested for HBV DNA by nested-PCR and real-time PCR techniques. All tested serum samples were negative by both quantitative HBV surface antigen (HBsAg) and HBV core-related antigen assays. 26/40 patients were anti-HBs-positive and in all of them, the amount of this antibody was stable at the four time points evaluated. Serum HBV DNA was detected in 10 samples at baseline, in 6 samples 4 weeks after starting therapy, in 11 samples at the end of therapy and in 21 samples 12 weeks after stopping treatment (P=0.001). Aminotransferase values dropped within the normal levels at week 4 of therapy and persisted normal over time in all cases. A slight increase in the amount of HBV DNA 3 months after stopping DAA therapy was the only parameter showing a possible reappearance of HBV activity in OBI patients cured for a concomitant HCV infection, but it was insufficient to lead toward a virological reactivation capable of inducing liver injury.

Reactivation of Occult HBV Infection in Patients Cured of HCV With Direct-Acting Antivirals

The era of hepatitis C virus (HCV) treatment with direct-acting antiviral (DAA) therapy has remarkably improved liver-related morbidity and overall mortality with patients achieving rapid and sustained clearance of HCV infection. The initial DAA clinical trials excluded patients with hepatitis B virus (HBV) co-infection, and thus potential complications were unforeseen until case reports of HBV reactivation associated with DAA therapy began to emerge. A recent United States Food and Drug Administration (FDA) drug safety communication has brought public attention to the issue of HBV reactivation in patients treated with DAA for HCV co-infection. Reactivation of HBV is well known to occur with a variety of immune-suppressive therapies notably in the context of cancer, rheumatologic treatments, and organ transplantation. While HBV reactivation in the setting of DAA therapy remains rare, the severity of hepatitis can be profound and deadly. Early recognition and treatment are keys to improving patient outcomes. Therefore, it is currently recommended to screen all patients for current or prior HBV infection prior to starting DAA therapy. If either hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc) is positive, HBV DNA should be obtained. With active viremia, prophylactic therapy should be started with DAA treatment with an agent with a high barrier for resistance. If there is no evidence of active viremia, the risks and benefits of prophylactic therapy should be weighed. Those with positive HBsAg should consider prophylactic therapy. Those with an isolated anti-HBc in the absence of HBsAg have an option of monitoring their liver enzymes, HBV DNA, and HBsAg at regular intervals during DAA therapy. If prophylactic HBV therapy is initiated, it should be continued for at least 3 months after DAA therapy is complete. After this period, the risks and benefits of continuing their HBV therapy should be re-addressed.

Serological characterization of occult hepatitis B Virus infection in Riyadh regional laboratory

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.

High risk of occult hepatitis B virus infection in leukemia patients from China.

In this study, we assessed the prevalence of overt and occult hepatitis B virus (HBV) infection among leukemia patients. Among 256 leukemia patients and 377 fracture patients (control group), we found that the hepatitis B surface-antigen-positive rate was greater in leukemia patients than in the controls (odds ratio, 2.08; p = 0.01). Moreover, the prevalence of occult HBV infection was higher in leukemia patients than in the controls (10.5% vs. 2.9%; odds ratio, 3.92; p<0.001). The HBV genotype distribution differed significantly between the leukemia and chronic hepatitis B or control groups (p < 0.001 and 0.01, respectively); specifically, genotype C was primarily observed in occult HBV infection patients with leukemia. The stop codon mutation rate or amino acid substitutions in the major hydrophilic region did not differ between the groups. Thus, the prevalence of occult hepatitis B is higher in leukemia patients, and the HBV genotype distribution differs between patients with leukemia and chronic hepatitis B virus infection.