Occult Hepatitis Research Articles

False occult hepatitis B virus infection with negative HBsAg while positive HBeAg & overt DNA levels: Case report and literature review

Background: Occult Hepatitis B Infection (OBI) is characterized by the detection of Hepatitis B Virus (HBV) DNA in serum (usually HBV DNA < 200 IU/ml) or liver but negativity for hepatitis B surface antigen. The diagnosis of OBI is based on the sensitivity of assays used in the detection of HBV DNA and HBsAg. HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to a false negative HBsAg result and misdiagnosis of OBI in people with overt HBV infection. An OBI patient was followed 4 years with the analysis of HBV detection.

Naturally occurring pre-S mutations promote occult HBV infection by affecting pre-S2/S promoter activity

Occult hepatitis B virus (HBV) infection (OBI) has non-negligible clinical significance, but the mechanism of its occurrence remains unclear. Growing evidence suggests that mutations in the pre-S region of HBV genome may be associated with the occurrence of OBI. However, the role of pre-S mutations in OBI and its molecular mechanism was not fully understand. Here, the pre-S sequences from 307 OBI blood donors and 293 hepatitis B surface protein (HBsAg)-positive blood donors were obtained, and we observed a higher frequency of naturally occurring pre-S mutations in OBI donors infected with genotype B/C HBV than in HBsAg-positive donors, suggesting their potential positive role in OBI. In both genotype B and C, several pre-S mutants resulted in markedly reduced HBsAg production in vitro. In particular, the T68I, S78N and N98T mutants of genotype B were proven to significantly decrease the HBsAg synthesis by affecting the pre-S2/S promoter activity, and thereby promoting the occurrence of OBI.

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)

Age and Gender are Predictors for Occult Hepatitis C in Egyptian Sustained Responders to Directly Acting Antivirals

Age and Gender are Predictors for Occult Hepatitis C in Egyptian Sustained Responders to Directly Acting Antivirals

Hepatitis B virus infection reactivation in patients under immunosuppressive therapies: Pathogenesis, screening, prevention and treatment.

With a 5.3% of the global population involved, hepatitis B virus (HBV) is a major public health challenge requiring an urgent response. After a possible acute phase, the natural history of HBV infection can progress in chronicity. Patients with overt or occult HBV infection can undergo HBV reactivation (HBVr) in course of immunosuppressive treatments that, apart from oncological and hem-atological diseases, are also used in rheumatologic, gastrointestinal, neurological and dermatological settings, as well as to treat severe acute respiratory syndrome coronavirus 2 infection. The risk of HBV reactivation is related to the immune status of the patient and the baseline HBV infection condition. The aim of the present paper is to investigate the risk of HBVr in those not oncological settings in order to suggest strategies for preventing and treating this occurrence. The main studies about HBVr for patients with occult hepatitis B infection and chronic HBV infection affected by non-oncologic diseases eligible for immunosuppressive treatment have been analyzed. The occurrence of this challenging event can be reduced screening the population eligible for immunosuppressant to assess the best strategies according to any virological status. Further prospective studies are needed to increase data on the risk of HBVr related to newer immunomodulant agents employed in non-oncological setting.

Prevalence of occult hepatitis B virus infection among patients receiving haemodialysis in Sana'a city

Occult hepatitis B virus infection (OBI) is a challenging entity. Due to the increase in invasive procedures, blood transfusions, and difficulties in diagnosing OBI, patients are more likely to acquire OBI. This cross-sectional study was conducted to assess the prevalence of OBI by hepatitis B virus (HBV)-DNA detection, the prevalence of HBV infection by total hepatitis B core antibody (HBcAb) detection, and the potential risk factors for HBV infection in patients receiving haemodialysis regularly. This study included 80 patients receiving haemodialysis regularly, without acute or chronic HBV infection. They were selected from the dialysis units in Sana'a city, Yemen from June 2016 to June 2017. Patients who were positive for hepatitis B surface antigen and hepatitis B surface antibody were excluded from this study. Blood samples were taken prior to each haemodialysis session, and serological markers of HBV were included. HBcAb was measured by enzyme-linked immunosorbent assay, and HBV-DNA was measured by polymerase chain reaction. HBV-DNA was detected in four patients (5%) and HBcAb was detected in 38 patients (47.5%). There was a significant association between HBV-DNA and HBcAb in patients receiving haemodialysis regularly. Patients who test positive for HBcAb should undergo additional HBV-DNA testing to allow accurate HBV screening and prevent infection of other patients.

Causes and outcomes of hepatic fibrosis in persons living with HIV.

The epidemiology of liver disease in people living with HIV has evolved since the arrival of effective hepatitis C virus (HCV) treatment. Nonalcoholic fatty liver disease (NAFLD) in HIV patients is highly prevalent while hepatitis D, hepatitis E, and occult hepatitis B remain underappreciated. We discuss mechanisms of fibrosis in HIV and review clinical outcomes of HIV-associated liver diseases. HIV-HCV co-infection is receding as a cause of progressive liver disease, but fibrosis biomarkers after HCV treatment remain elevated. Antiretroviral therapy (ART) with anti-hepatitis B virus (HBV) activity promotes stable liver disease, but oversimplifying ART regimens in unrecognized suppressed HBV may lead to activation of HBV. A high prevalence of fibrosis and rapid progression of fibrosis are seen in HIV-associated NAFLD, with visceral fat as a major risk factor. Newer ART such as integrase strand inhibitors may have limited intrinsic hepatoxicity but do increase weight, which may secondarily lead to hepatic steatosis. Promising therapies for HIV-associated NAFLD include tesamorelin and CCR5 blockade agents. Our understanding of the natural history and pathogenesis of liver diseases in HIV has advanced and adapted to the changing landscape of liver disease in this population. Future research should evaluate long-term clinical and histological outcomes, prevention strategies, and treatment options to improve morbidity and mortality in HIV-related liver diseases.

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.

Occult infection with hepatitis B virus PreS variants synergistically promotes hepatocellular carcinoma development in a high-fat diet context by generating abnormal ceramides

BackgroundSome occult hepatitis B virus (HBV) infections are resulted from PreS mutations that reduce secretion of envelope protein (HBsAg). We investigated the ceramide amounts and species in hepatocytes infected with PreS variants that were isolated from HBsAg-seronegative patients with hepatocellular carcinoma (HCC) and the ceramide effects on autochthonous HCC development in murine models.MethodsHBV PreS/S regions from 35 HBsAg-seronegative HCC patients were sequenced. Hepatocyte cell lines and male C57BL/6J mouse livers were transfected with two PreS variant representatives. The ceramides with variated lengths of fatty acyl chains were quantified. Tumour development was examined in the HBV-transfected mice fed different diet types.ResultsIn HBsAg-seronegative HCC patients, nonneoplastic liver tissues harboured HBsAg and replication-competent HBV. The most frequently detected PreS/S variants carried mutations of altered amino acid properties in HBsAg compared with an isolate from one HBsAg-seronegative HCC patient. Hepatocyte infection with PreS variants caused HBsAg retention within the endoplasmic reticulum and generated more amounts of ceramides with C16:0 ceramide elevated the highest. Saturated fatty acids aggravated the PreS variant-infected hepatocytes to generate abnormal amounts and species of ceramides, which with HBV proteins synergistically activated NLRP3 inflammasome in liver inflammatory macrophages. Liver tumours were only detected in HBV-transfected mice fed high-fat diet, with higher tumour loads in the PreS variant-transfected, associated with abnormal ceramide generation.ConclusionsHBV PreS mutations which altered amino acid properties of envelope proteins inhibited HBsAg secretion. Hepatocyte infection with PreS variants generated abnormal ceramides which with HBV proteins coactivated NLRP3 inflammasome in liver macrophages to promote autochthonous HCC development.

Detection of Occult Hepatitis C Virus Infection in Egyptian Patients Who Achieved a Sustained Virologic Response to Direct-Acting Antiviral Agents.

Occult hepatitis C virus (HCV) infection (OCI) is diagnosed based on the detection of HCV-RNA in non-serum reservoirs, such as peripheral blood mononuclear cells (PBMCs) and/or hepatocytes with undetectable HCV-RNA in the serum. The current study was designed to shed more light on the presence of occult HCV in a population of cases who achieved an SVR after receiving treatments for HCV-infection and its significance. This cross-sectional study evaluated 111 chronic HCV patients treated at Theodor Bilharz Research Institute, Egypt and achieved a sustained virological response (SVR) 12 -24 weeks after treatment with Direct acting antiviral drugs (DAAs). The treatment lasted 12 or 24 weeks using generic medications including Sofosbuvir (SOF) 400 mg/day and Daclatasvir (DCV) 60 mg/day ± weight-based Ribavirin (RBV) 600-1000 mg/day. After achieving the SVR 12 -24 weeks, all patients were subjected to clinical examination and full laboratory investigations. All the candidates were assessed for fibrosis pre/post-treatment by transient elastography (Fibroscan©). Eighty-seven patients (78.4%) received dual therapy (SOF/DCV) and 24 patients (21.6%) received triple therapy (SOF/DCV/RBV). One hundred and seven patients received the regimen for 12 weeks (96.4%) and only four patients received the regimen for 24 weeks (3.6%). All patients were examined in terms of HCV RNA in plasma and PBMCs. Nine patients (8.1%) were positive for PBMCs HCV RNA. The presence of Occult HCV infection (OCI) was significantly correlated with age, level of AFP, and the degree of liver stiffness. The OCI was present in 8.1% of the patients who achieved an SVR 12 - 24 weeks. These patients were mostly aged and with elevated AFP and advanced fibrosis. Monitoring and follow-up of those patients may help to assess the outcomes.

UTILITY OF MINI-POOL NAT STRATEGY FOR IMPROVING BLOOD SAFETY BY DETECTING OCCULT HEPATITIS B VIRUS INFECTION : A 5 YEAR STUDY

Introduction: The prevalence of transfusion transmitted infections (TTIs) is high in India. The aim of our study was to evaluate the sero-prevalence of TTIs using Nucleic acid technology (NAT) and detection of Occult Hepatitis B virus infection by Minipool NAT Strategy. A total of 89,639 units of blood donated at Dhanvanta Materials and Methods: ri Voluntary Blood Bank, Rajahmundry during the period from January 2012 to July 2016. The sero-prevalence for HIV, HBV and HCV was tested by 4th generation ELISA. Only sero-negative samples were tested on mini pool nucleic acid test (MP-NAT) to detect HIV1, HIV2, HCV and HBV viral nucleic acids. Combined NAT yield was calculated and compared the NAT yield with MPX test and MPX V2.0. We also evaluated the optical density (OD) values of ELISA for MP-NAT reactive donor samples to evaluate the efcacy of NAT in detecting window period cases. The Results: overall sero-prevalence of TTIs was 2.41% and HBV was predominantly present (66%). Total 29 ELISA negative blood donor samples were found reactive on NAT. All NAT reactive donors were of HBV only. Out of 29 cases, 12 were detected by MPX test from 26,008 donations and 17 by MPX V2.0 from 25,619 donations, providing NAT yield of 1:2169 and 1:1507 respectively. OD and Signal cut off values of ELISA for NAT reactive samples were found to be much below extended grey zone value (<0.3). Additiona Conclusion: l testing of nucleic acids by MP-NAT in combination of mandated primary serology by ELISA provides 99.99% of safe blood to needy patients; thus signicantly reduces the risk of TTIs by identifying the window period cases.

Estimates of the prevalence of occult HBV infection in Asia: a systematic review and meta-analysis

Purpose Occult Hepatitis B virus infection (OBI) is of great significance to the transmission of Hepatitis B virus (HBV) and the evolution of the patient’s clinical outcome. We conducted a systematic review and meta-analysis to estimate the prevalence of OBI in Asia. Methods Literature search was conducted in PubMed, Cochrane Library database, Web of Science and Embase with the keywords of ‘Hepatitis B virus’, ‘occult infection’, ‘prevalence’. 70 studies were included in the meta-analysis. Meta-analysis was performed using random-effects models to calculate the pooled prevalence of OBI and 95% confidence interval (CI). The data were analyzed in R 4.1.2. Results The overall prevalence of OBI was 4% (95%CI: 0.03–0.06) in Asia. Subgroup analysis based on geographic region showed a prevalence of 3% (95%CI 0.02–0.06) in East Asia, 9% (95%CI 0.05–0.15) in West Asia, 3% (95%CI 0.01–0.11) in Southern Asia and 9% (95%CI 0.05–0.15) in Southeast Asia. Subgroup analysis demonstrated a prevalence of 1% (95%CI 0.00–0.02) in general population, 5% (95%CI: 0.03–0.08) in high-risk population, 9% (95%CI: 0.03–0.22) in the human immunodeficiency virus (HIV)-infected patient, 18% (95%CI: 0.09–0.32) in the hepatopathy patients. Conclusion Based on the meta-analysis of the prevalence of OBI in different populations, we concluded that the prevalence of OBI in the high-risk population, hepatopathy patients, and HIV-infected patients was higher than that in the general population. A systematic review showed that OBI was associated with disease progression and prognosis. Therefore, these populations should be routinely screened for OBI and promptly intervened to avoid promoting disease progression.

Anti-HBc-nonreactive occult hepatitis B infections with HBV genotypes B and C in vaccinated immunocompetent adults.

Absence of anti-HBc reactivity with detectable anti-HBs was observed in blood donors with occult hepatitis B virus (HBV) infection (OBI). The prevalence and mechanisms underlying this uncommon condition were investigated over time in Chinese blood donors with OBI. Isolated anti-HBs OBI status was identified from 466,911 donors from Dalian, China, and monitored in follow-up (range: 2.6-84.3months). HBV vaccination status was documented, and infecting viral strains were characterized. Of 451 confirmed OBIs (1:1035), 43 (9.5%; 1:10,858) had isolated anti-HBs as only serological marker. Isolated anti-HBs OBIs differed from anti-HBc-reactive OBIs by significantly younger age (median 24 years), higher HBV DNA (median: 20 IU/ml) and anti-HBs (median 60.5IU/L) levels, paucity of mutations in HBV Core and S proteins, and high vaccination rate (72%). Vaccinated isolated anti-HBs OBIs (n=31) differed from unvaccinated (n=11) by significantly younger age (22 vs 38 years), higher anti-HBs level at index (48% vs 9% with anti-HBs >100 IU/L) and higher frequency of anti-HBs immune response (44% vs 20%). Of 15 vaccinated and 5 unvaccinated OBIs follow-up, 65% (8 vaccinated and 5 unvaccinated) became HBV DNA negative suggesting aborted recent infection, while 35% (7 vaccinated) had low persistent viraemia 2 to 65 months post index. In conclusion, isolated anti-HBs OBI in Chinese blood donors appears associated with young, vaccinated, adults exposed to HBV who predominantly develop low level aborted infection revealed by transient HBV DNA and immune anti-HBs response. However, a subset of individuals still experienced low but persistent viral replication whose clinical outcome remains uncertain.

Global epidemiology of occult hepatitis B virus infections in blood donors, a systematic review and meta-analysis

This study aimed to assess the global prevalence of occult hepatitis B in blood donors. We searched PubMed, Web of Science, Global Index Medicus, and Excerpta Medica Database. Study selection and data extraction were performed by at least two independent investigators. Heterogeneity (I2) was assessed using the χ2 test on the Cochran Q statistic and H parameters. Sources of heterogeneity were explored by subgroup analyses. This study is registered with PROSPERO, number CRD42021252787. We included 82 studies in this meta-analysis. The overall prevalence of OBI was 6.2% (95% CI: 5.4-7.1) in HBsAg negative and anti-HBc positive blood donors. Only sporadic cases of OBI were reported in HBsAg negative and anti-HBc negative blood donors. The overall prevalence of OBI was 0.2% (95% CI: 0.1-0.4) in HBsAg negative blood donors. The prevalence of OBI was generally higher in countries with low-income economic status. The results of this study show that despite routine screening of blood donors for hepatitis B, the transmission of HBV by blood remains possible via OBI and/or a seronegative window period; hence there is a need for active surveillance and foremost easier access to molecular tests for the screening of blood donors before transfusion.

Role of S protein transmembrane domain mutations in the development of occult hepatitis B virus infection

ABSTRACT Occult HBV infection (OBI) is a special infection status during Hepatitis B virus (HBV) infection. The underlying mechanism of its occurrence remains unclear. This study conducted sequencing analysis on 104 OBI plasma samples and 524 HBsAg positive samples from 29 blood centres, and searched for high-frequency mutations in transmembrane domain (TMD) of S protein in the OBI population. Plasmids with TMD high-frequency mutations were constructed, in vivo and in vitro functional experiments were performed to investigate possible molecular mechanisms of OBI occurrence. We found 22 high-frequency TMD mutations in genotype B OBI strains. Among them, five mutations can lead to impairment of HBsAg secretion; seven mutations had accumulated intracellular HBsAg while extracellular HBsAg didn’t decrease compared to wildtype. This study chose C85R from TMD2, F220C, and F220Y from TMD4 for further exploration. Protein structure predication showed these three mutant HBsAg displayed changed hydrophilic properties and tended to accumulate in the phospholipid bilayer of cell membrane. Mutant HBsAg’s secretion disorder may induce OBI. On the other hand, V168A + V177A from TMD3 expressed increased HBsAg both in intracellular and extracellular levels. This mutation had most unstable natural conformation and may be inclined to transition into V177A or V168A + S174N + V177A. These three mutations were more prone to mixed infection, presenting a state of coexistence, thus approaching the impaired secretion pattern of OBI. This study demonstrated TMD mutations could contribute to the occurrence of OBI and provided a theoretical basis for OBI study and the functional cure of chronic hepatitis B virus infection.

Comparative analysis of hepatitis B virus infections in blood donors born before and after the implementation of universal HBV vaccination in southern China.

In China, the vaccinated blood donors have rapidly increased by recent years, which may impact blood safety. The true prevalence of HBV between vaccinated blood donors and non-vaccinated blood donors should be explored. The samples of blood donors were collected and detected for serologic markers of HBV in the Shenzhen Blood Centre (SZBC). The discrepant results were tested with commercial electrochemiluminescence immunoassay (ELCI) for HBsAg, anti-HBs, HBeAg, Anti-HBe and Anti-HBc, alternative MPX ID NAT, nested PCR, and a quantitative real-time polymerase chain reaction (qPCR) assay for HBV DNA. The serological and molecular characteristics of HBV infected blood donors were analysed, and the effects on blood safety for donors born before and after the implementation of universal HBV vaccination were compared. Out of 242 presumed HBV infected donors from 26 318 donations, 131 (0.49%, [95% CI, 0.43-0.59]) chronic HBV infections (CHB, HBsAg detected with or without DNA), 58 (0.22%, [95% CI, 0.17-0.28]) occult hepatitis B infections (OBI, HBsAg not detected, assume anti-HBc positive and/or anti-HBs with HBV DNA) and 3 (0.011%, [95% CI, 0.0023-0.033]) window period (WP) infections were confirmed respectively. There were 28 CHBs (0.44%), 7 OBIs (0.11%) and 1 WP (0.016%) from vaccinated blood donor and 103 CHBs (0.52%), 51 OBIs (0.26%) and 2 WPs (0.01%) from non-vaccinated blood donor. The HBV+ (CHBs, OBIs and WPs) rate (0.56%) in vaccinated donors was lower than in non-vaccinated donors (0.78%, p < 0.05). The HBsAg titers of vaccinated infected blood donors (Median: 128.8IU/ml) were much higher than non-vaccinated infected blood donors (58.4IU/ml). The OBI yield rates in the vaccinated blood donors was significantly lower than the non-vaccinated blood donors (p < 0.05). There 102/124 (82.3%) samples were genotype B, 22/124 (17.7%) were genotype C respectively. There was no significant difference in the distribution of genotype between non-vaccinated blood donors (B/C, 86/17) and vaccinated blood donors (B/C, 23/6; p > 0.05). High frequency of vaccine escape mutations M133L (32.4%) and E164G in S region of genotype B strains and substitution L175S (40.9%) related to vaccine escape in S region of genotype C strains were identified. The universal HBV vaccination program markedly reduces the risk of HBV infection in blood donors, and provides a significant guarantee for the safety of blood transfusion. Several important mutations detected related vaccine escape and notable mutations needed further investigated.

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.

Screening of Occult Hepatitis B and C Virus Infection in Working Children, Tehran, Iran

Background: Working children are susceptible to infection with various infectious microorganisms. Unfortunately, the difficulties of working children are growing at a remarkable speed worldwide. Objectives: The aim of this research was to determine the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, as well as to evaluate the level of anemia, calcium, and phosphorus in working children. Methods: This cross-sectional research was performed on 370 Iranian and Afghan working children from February 2018 to May 2019. Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb), and anti-HCV Ab were evaluated using an enzyme-linked immunosorbent assay (ELISA). Furthermore, HCV-RNA and genomic HBV-DNA in the plasma and peripheral blood mononuclear cell (PBMC) specimens of the participants were investigated. The restriction fragment length polymorphism (RFLP) method was used to determine the genotype of HCV, and sequencing was performed to confirm. Results: The mean age of the participants was 10.1 ± 2.1 years (range, 6 - 15 years), and 229 (61.9%) were male. None of the studied children had any detectable HBV-DNA in the plasma and PBMC. The HCV genome was not detected in the plasma of the children, but HCV-RNA was assessed in the PBMC sample of 1 child (0.3%). Therefore, one of the children had occult HCV infection (OCI). The genotype of HCV in this child was subtype 1a. Furthermore, HBsAb was detected in Iranian (41.5%) and Afghan children (40.0%), and 2 (0.54%) of the working children were HBsAg positive. In 3 participants (0.8%), a positive HBcAb test result was noted. Conclusions: The prevalence of HCV and HBV infection in working children in Iran is extremely rare. However, there is a possibility of the presence of OCI in these children.

Global burden of occult hepatitis B virus infection: where we are and what to do

Occult hepatitis B virus (HBV) infection is characterised by the persistence of replication-competent HBV DNA in the liver (with or without HBV DNA in the blood) of individuals testing negative for HBsAg, using currently available assays.1 Occult HBV infection represents a phase of the natural history of HBV infection,2 in which HBV DNA in the form of a covalently closed circular DNA minichromosome has suppressed replicative activity and gene expression with extremely low rates of virion production.

Prevalence of occult hepatitis B virus infection in adults: a systematic review and meta-analysis

Despite growing concerns about transmissibility and clinical impact, occult hepatitis B virus (HBV) infection has received little attention in the hepatitis elimination agenda. We aimed to estimate the prevalence of occult HBV infection at a global and regional scale and in specific populations. For this systematic review and meta-analysis, we searched the MEDLINE, Embase, Global Health, and Web of Science databases for articles published in any language between Jan 1, 2010, and Aug 14, 2019. We included original articles and conference abstracts of any study design that reported the proportion of HBsAg-negative adults (aged ≥18 years) who are positive for HBV DNA (ie, people with occult HBV infection). The prevalence of occult HBV infection was pooled, using the DerSimonian-Laird random-effects model, in the general population and specific groups defined by the type of study participants (blood donors; other low-risk populations; high-risk populations; and people with advanced chronic liver disease), and stratified by HBV endemicity in each country. We also assessed the performance of anti-HBc as an alternative biomarker to detect occult HBV infection. The study was registered with PROSPERO, CRD42019115490. 305 of 3962 articles were eligible, allowing a meta-analysis of 140 521 993 individuals tested for HBV DNA. Overall, only two studies evaluated occult HBV infection in the general population, precluding unbiased global and regional estimates of occult HBV infection prevalence. In blood donors, occult HBV infection prevalence mirrored HBV endemicity: 0·06% (95% CI 0·00-0·26) in low-endemicity countries, 0·12% (0·04-0·23) in intermediate-endemicity countries, and 0·98% (0·44-1·72), in high-endemicity countries (p=0·0012). In high-risk groups, occult HBV infection prevalence was substantial, irrespective of endemicity: 5·5% (95% CI 2·9-8·7) in low-endemicity countries, 5·2% (2·5-8·6) in intermediate-endemicity countries, and 12·0% (3·4-24·7) in high-endemicity countries. The pooled sensitivity of anti-HBc to identify occult HBV infection was 77% (95% CI 62-88) and its specificity was 76% (68-83). A substantial proportion of people carry occult HBV infection, especially among high-risk groups across the globe and people living in highly endemic countries. Occult HBV infection should be part of the global viral hepatitis elimination strategy. None.