Virus Surface Antigen Research Articles

Presence of hepatitis B virus in synovium and its clinical significance in rheumatoid arthritis

BackgroundPrevious studies have revealed that hepatitis B virus (HBV) infection may be related to rheumatoid arthritis (RA), but there are no studies on the presence of HBV antigens or nucleic acid in synovium from patients with RA with HBV infection. In the present study, we investigated the presence of HBV in the synovium and its clinical significance in RA.MethodsFifty-seven consecutive patients with active RA (Disease Activity Score 28-joint assessment based on C-reactive protein ≥ 2.6) and available synovial tissue who had completed 1 year of follow-up were recruited from a prospective cohort. The patients were divided into chronic HBV infection (CHB, n = 11) and non-CHB groups according to baseline HBV infection status. Clinical data were collected at baseline and at 1-, 3-, 6-, and 12-month follow-up. Radiographic changes of hand/wrist at baseline and month 12 were assessed with the Sharp/van der Heijde-modified Sharp score (mTSS). HBV in synovium was determined by immunohistochemical staining for hepatitis B virus surface antigen and hepatitis B virus core antigen (HBcAg) and by nested PCR for the HBV S gene.ResultsHBcAg was found in the synovium of patients with RA with CHB (7 of 11, 64%), which was confirmed by PCR for the HBV S gene. Compared with the non-CHB group, more CD68-positive macrophages, CD20-positive B cells, and CD15-positive neutrophils infiltrated the synovium in the CHB group (all p < 0.05). There were smaller improvements from baseline in most disease activity indicators mainly at month 12, and a significantly higher percentage of CHB patients experienced 1-year radiographic progression (ΔmTSS ≥ 0.5 unit/yr, 64% vs. 26%, p = 0.024). Multivariate logistic regression analysis showed that CHB status (OR 14.230, 95% CI 2.213–95.388; p = 0.006) and the density of synovial CD68-positive macrophages (OR 1.002, 95% CI 1.001–1.003; p = 0.003) were independently associated with 1-year radiographic progression.ConclusionsThe presence of HBV in RA synovium may be involved in the pathogenesis of local lesions and exacerbate disease progression in RA.

A photoelectrochemical immunosensor based on gold nanoparticles/ZnAgInS quaternary quantum dots for the high-performance determination of hepatitis B virus surface antigen

ZnAgInS quaternary quantum dots were prepared using glutathione as the capped reagent. Gold nanoparticles (GNPs) were integrated with ZnAgInS QDs to provide a GNPs/ZnAgInS QDs nanocomposite. The morphological image, component and crystal structure of GNPs/ZnAgInS QDs were characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). A glassy carbon electrode surface was coated with GNPs/ZnAgInS QDs nanocomposites to construct an interface for immobilizing the antibody of hepatitis B virus surface antigen (anti-HBsAg). By employing GNPs/ZnAgInS QDs as a photoactive element, a photoelectrochemical immunosensor for hepatitis B virus surface antigen (HBsAg) was developed. The results indicate that gold nanoparticles can dramatically enhance the photocurrent response of ZnAgInS QDs and thus improving the sensing performances of the immunosensor. The experimental conditions including incubation time, incubation temperature, and ascorbic acid concentration were optimized. The relative photocurrent decline [Ri = ΔI/I0= (I0 − I)/I0] shows a linear relationship to the logarithm of HBsAg concentration [lg(c, ng mL−1)] in the range from 0.005 to 30 ng mL−1. A detection limit of 0.5 pg mL−1 was obtained. The immunosensor shows excellent sensitivity, selectivity, stability and reproducibility. The HBsAg concentrations in clinical serum samples were also accurately determined with this new photoelectrochemical immunosensor.

Contrasting Timing of Virological Relapse After Discontinuation of Tenofovir or Entecavir in Hepatitis B e Antigen-Negative Patients.

Stopping long-term nucleos(t)ide analogue therapy increases hepatitis B virus (HBV) surface antigen (HBsAg) loss rates in HBV e antigen (HBeAg)-negative patients. Viral rebound may induce immune responses facilitating functional cure. We analyzed which factors are associated with timing of virological relapse in 220 Asian HBeAg-negative patients from the prospective ABX203 vaccine study. Unexpectedly, only the type of antiviral therapy was significantly associated with early virological relapse, defined as an HBV DNA load of >2000 IU/mL until week 12, and relapse occurred earlier in patients treated with tenofovir versus those treated with entecavir (median time, 6 vs 24 weeks; P < .0001). This should be considered for future trials and monitoring of patients after treatment discontinuation.

Anti-Hepatitis B Antibody status in children with coeliac disease

Objective: This study aimed to compare the antibodies response to hepatitis B virus (HBV) vaccine between Libyan children with coeliac disease (CD) and healthy control. Subjects and Methods: A total of 66 children with CD on a gluten-free diet (GFD) and 31 randomly allocated healthy children who received HBV vaccination according to the standard immunization schedule were included. Hepatitis B virus surface antigen (HBsAg) and the production of specific anti-HBs antibodies were evaluated in all patients and control participants using standard techniques. Patients with &lt;10 IU/L anti-HBs antibodies were considered nonresponses to the vaccination. Results: None of the participants were HBsAg reactive. Forty-one of the 66 patients (62%) were female, and 25 (37.8%) were male. The mean age of the CD patients was 8.2 years (range, 22 months-15 years). Anti-HBs titers were positive in 40 (60.6%) patients and negative in 26 (39.3%) patients, whereas they were positive in 19 (61.2%) of the children in the control group and negative in 12 (38.7%).There was no significant difference in response to vaccine between the two groups (P = 0.83), the study revealed a statistically significant relation between negative anti-HBs titers and duration from the last dose of HBV vaccine (P = 0.004). Conclusion: In the present study, the response rate in Libyan children with CD on GFD was not different from healthy control. However, not all children need booster dose; only nonresponders need an intradermal test-booster dose to reassess the state of their memory cell before considering revaccination.

Reviewing of Research Finding of Hepatitis B Virus Infection in Lao People's Democratic Republic.

The seroprevalence of hepatitis B virus (HBV) surface antigen (HBsAg)-positive blood donors was 8.7%. The prevalence among males (9.7%) was higher than among females (6.2%). The prevalence of antihepatitis C virus (HCV)-positive blood donors was 1.1%, with no significant differences between males (1.1%) and females (1.0%). Annual positive rates for HBsAg and anti-HCV donors during the years 2003 to 2005 did not differ significantly. In Lao People’s Democratic Republic (PDR), HBV is highly endemic. However, blood donations are only screened for HBsAg, leaving a risk of transmission by HBsAg-negative occult infected donors. Here, we characterized first-time blood donors to assess prevalence of HBV infections and occult infected donors. Despite hepatitis B vaccination at birth and at 6, 10, and 14 weeks of age, HBV infection continues to be endemic in Lao PDR. We carried a cross-sectional serological study in infants, preschool children, school pupils, and pregnant women to determine their burden of disease, risk of infection, and vaccination status. The prevalence of HBsAg carriage in pregnant women is a relevant marker for the risk of mother-to-child HBV transmission. This study aimed to assess the changes in prevalence of HBV infection among pregnant women attending Mahosot Prenatal Clinic (Vientiane).How to cite this article: Ounavong A. Reviewing of Research Finding of Hepatitis B Virus Infection in Lao People’s Democratic Republic. Euroasian J Hepato-Gastroenterol 2018;8(1):75-76.

An ultra-sensitive Abbott ARCHITECT® assay for the detection of hepatitis B virus surface antigen (HBsAg)

BackgroundCritical to the identification of HBV infection and the prevention of transfusion transmitted disease is the sensitive and accurate detection of Hepatitis B virus surface antigen (HBsAg). Improvements in HBsAg assay sensitivity approaching the performance of nucleic acid testing (NAT) are essential to further reduce the detection window for acute HBV infection in regions where NAT is not widely available. Objectives and study designAn improved HBsAg assay on the fully-automated Abbott ARCHITECT® platform was developed to improve sensitivity, mutant and genotype detection. ResultsThe analytical sensitivity of the improved prototype assay is 5.2 mIU/ml, which is 3.86- to 14.54-fold more sensitive than comparator assays based on the WHO International Reference Standard. The enhanced sensitivity was also demonstrated with 27 HBV seroconversion panels, detecting more panel members (191 of 364) vs. the ARCHITECT® Qual I (144), Qual II (160) and PRISM® (148) HBsAg assays. Further, the assay detected 7 of 12 HBV DNA positive/HBsAg negative samples, and detected all evaluated mutants and genotypes with higher sensitivity than the comparator assays. The improvement in sensitivity did not diminish assay specificity, attaining 100% (95% CI, 99.97-100%) on 10,633 blood donors. ConclusionsAn Abbott ARCHITECT® HBsAg assay with clinical performance approaching that of mini-pool NAT (approximately 100 copies/ml was developed. The assay has superior HBsAg mutant and genotype detection and specificity, all of which are important for the diagnosis and management of HBV infection.

Digital Microarrays: Single-Molecule Readout with Interferometric Detection of Plasmonic Nanorod Labels.

DNA and protein microarrays are a high-throughput technology that allow the simultaneous quantification of tens of thousands of different biomolecular species. The mediocre sensitivity and limited dynamic range of traditional fluorescence microarrays compared to other detection techniques have been the technology's Achilles' heel and prevented their adoption for many biomedical and clinical diagnostic applications. Previous work to enhance the sensitivity of microarray readout to the single-molecule ("digital") regime have either required signal amplifying chemistry or sacrificed throughput, nixing the platform's primary advantages. Here, we report the development of a digital microarray which extends both the sensitivity and dynamic range of microarrays by about 3 orders of magnitude. This technique uses functionalized gold nanorods as single-molecule labels and an interferometric scanner which can rapidly enumerate individual nanorods by imaging them with a 10× objective lens. This approach does not require any chemical signal enhancement such as silver deposition and scans arrays with a throughput similar to commercial fluorescence scanners. By combining single-nanoparticle enumeration and ensemble measurements of spots when the particles are very dense, this system achieves a dynamic range of about 6 orders of magnitude directly from a single scan. As a proof-of-concept digital protein microarray assay, we demonstrated detection of hepatitis B virus surface antigen in buffer with a limit of detection of 3.2 pg/mL. More broadly, the technique's simplicity and high-throughput nature make digital microarrays a flexible platform technology with a wide range of potential applications in biomedical research and clinical diagnostics.

Tarin, a Potential Immunomodulator and COX-Inhibitor Lectin Found in Taro (Colocasia esculenta).

Taro (Colocasia esculenta) corm is a rustic staple food, rich in small starch granules, fibers, and bioactive phytoconstituents such as flavonoids, alkaloids, sterols, tannins, phytates, micronutrients, and proteins, including tarin, a GNA‐related lectin. Tarin exhibits recognized biocide activities against viruses and insects, has antitumoral properties and is an immunomodulator molecule candidate. It has been isolated in highly purified form (>90%) from taro corms through low‐cost and single‐step affinity chromatography. It comprises 2‐domain 27 to 28 kDa protomer, posttranslational cleaved into 2 nonidentical monomers, 11.9 and 12.6 kDa, held by noncovalent binding. At least 10 tarin isoforms sharing over 70% similarity have been described. The monomers assume the β‐prism II fold, consisting of 3 antiparallel β‐sheets formed by 4 β‐strands each. Tarin exhibits an expanded‐binding site for complex and high‐mannose N‐glycan chains 49, 212, 213, 358, 465, and 477 found on cell surface antigens of viruses, insects, cancer, and hematopoietic cells, explaining its broad biological activities. Tarin may stimulate innate and adaptive immune responses, enabling hosts to recover from infections or immunosuppressed status inherent to several pathological conditions. In a murine model, tarin stimulates the in vitro and in vivo proliferation of total spleen and bone marrow cells, especially B lymphocytes. Granulocyte repopulation has also been demonstrated in long‐term mice bone marrow cell cultures. As a potential immunomodulator, tarin, administered to immunosuppressed mice, attenuated cyclophosphamide‐induced leukopenia. We propose a molecular model that unites the potential prophylactic and therapeutic action of tarin on hematopoietic and cancer cells, as a potential immunomodulator.

Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses.

T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh and GC B cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional, antigen-specific, CD4+ T cell responses and potent neutralizing antibody responses in mice and nonhuman primates. Importantly, the strong antigen-specific Tfh cell response and high numbers of GC B cells and plasma cells were associated with long-lived and high-affinity neutralizing antibodies and durable protection. Comparative studies demonstrated that nucleoside-modified mRNA-LNP vaccines outperformed adjuvanted protein and inactivated virus vaccines and pathogen infection. The incorporation of noninflammatory, modified nucleosides in the mRNA is required for the production of large amounts of antigen and for robust immune responses.

Performance of point of care assays for hepatitis B and C viruses in chronic kidney disease patients

AimsPoint of care testing (POCT) has been used for hepatitis B and C diagnosis in general population, but little is known about the influence of clinical conditions in the accuracy...

Extended screening for infectious diseases among newly-arrived asylum seekers from Africa and Asia, Verona province, Italy, April 2014 to June 2015.

Background and aimManagement of health issues presented by newly-arrived migrants is often limited to communicable diseases even though other health issues may be more prevalent. We report the results of infectious disease screening proposed to 462 recently-arrived asylum seekers over 14 years of age in Verona province between April 2014 and June 2015. Methods: Screening for latent tuberculosis (TB) was performed via tuberculin skin test (TST) and/or QuantiFERON-TB Gold in-tube assay and/or chest X-ray. An ELISA was used to screen for syphilis. Stool microscopy was used to screen for helminthic infections, and serology was also used for strongyloidiasis and schistosomiasis. Screening for the latter also included urine filtration and microscopy. Results: Most individuals came from sub-Saharan Africa (77.5%), with others coming from Asia (21.0%) and North Africa (1.5%). The prevalence of viral diseases/markers of human immunodeficiency virus (HIV) infection was 1.3%, HCV infection was 0.85% and hepatitis B virus surface antigen was 11.6%. Serological tests for syphilis were positive in 3.7% of individuals. Of 125 individuals screened for TB via the TST, 44.8% were positive and of 118 screened via the assay, 44.0% were positive. Of 458 individuals tested for strongyloidiasis, 91 (19.9%) were positive, and 76 of 358 (21.2%) individuals from sub-Saharan Africa were positive for schistosomiasis. Conclusions: The screening of viral diseases is questionable because of low prevalence and/or long-term, expensive treatments. For opposing reasons, helminthic infections are probably worth to be targeted by screening strategies in asylum seekers of selected countries of origin.

Immunogenicity, safety, and tolerability of a recombinant hepatitis B vaccine manufactured by a modified process in healthy young Japanese adults

ABSTRACTHepatitis B vaccines are highly effective in preventing hepatitis B virus infection and have been included in the national immunization program of Japan since 2016. Heptavax®-II is one of two hepatitis B vaccine products licensed in Japan, and its manufacturing process is being modified to reduce variability of manufacturing and optimize immunogenicity. In this study (NCT01463683), the immunogenicity and safety of a modified-process hepatitis B vaccine (mpHBV) were compared to those of the licensed Heptavax®-II. Overall, 722 Japanese adults aged 20-to-35 years old were randomized in a 3:3:1 ratio to either the mpHBV subcutaneous (SC) injection group (mpHBV SC), the Heptavax®-II SC injection group (Heptavax®-II SC), or the mpHBV intramuscular (IM) injection group (mpHBV IM). All participants received a 3-dose series of either mpHBV or Heptavax®-II at Day 1, Month 1, and Month 6. Serum antibody to hepatitis B virus surface antigen (anti-HBs) was assayed on Day 1 prior to the first vaccination and Month 7 (1 month Postdose 3). Seroprotection rates in mpHBV SC were non-inferior to that in Heptavax®-II SC and anti-HBs geometric mean titers were numerically higher in mpHBV SC as compared to Heptavax®-II SC. The incidences of injection-site and systemic adverse events (AEs) observed in mpHBV SC were comparable to those in Heptavax®-II SC, except for erythema which was higher in mpHBV SC than in Heptavax®-II SC. Most injection-site and systemic AEs were mild-to-moderate in intensity and there were no reports of vaccine-related serious AEs in any group. IM administration of mpHBV was well-tolerated and more immunogenic compared to SC administration. In conclusion, mpHBV and Heptavax®-II were well-tolerated and elicited satisfactory immune responses for the prevention against hepatitis B virus-associated diseases.

Diterpenes from buds of Wikstroemia chamaedaphne showing anti-hepatitis B virus activities

Phytochemical study of the buds of Wikstroemia chamaedaphne Meisn. led to the isolation of seven previously undescribed diterpenes, including one tigliane diterpene (wikstchalide A), two daphnane diterpenes (wikstroelides W-X), and four lathyrane diterpenes (laurifoliosides A-B and 2-epi-laurifoliosides A-B), along with four known diterpenes. The structures of these compounds were established by extensive spectroscopic evidence and electronic circular dichroism (ECD) calculations. Wikstchalide A possesses a 5,6-epoxy ring in the tigliane skeleton. Two compounds exhibited potential anti-hepatitis B virus activities, with IC50 values of 46.5 and 88.3 μg/mL against hepatitis B virus (HBV) surface antigen (HBsAg), and six compounds showed certain inhibitory effects on HBV-DNA replication with the inhibition ratios ranging from 2.0% to 33.0% at the concentrations ranging from 0.39 to 6.25 μg/mL.

Serum hepatitis B core antibody levels predict HBeAg seroconversion in chronic hepatitis B patients with high viral load treated with nucleos(t)ide analogs.

BackgroundPatients with chronic hepatitis B virus (HBV) infection who are hepatitis B virus e antigen (HBeAg) positive are increasingly being treated with nucleos(t)ide analogs (NUCs). However, the predictive value of serum hepatitis B virus core antibody (HBcAb) levels for HBeAg seroconversion among patients with high viral load remains unclear.MethodsThis study consisted of 74 patients with high viral load (HBV DNA >1 × 107 copies/mL) enrolled in a multicenter, randomized, controlled trial, treated with lamivudine and adefovir (N = 32) or entecavir (N = 42) for up to 96 weeks. Serum HBV DNA, quantitative hepatitis B virus surface antigen (HBsAg), HBeAg, and HBeAb was tested at each visit. Quantitative HBcAb evaluation was conducted for all the available samples in the trial, by using a newly developed double-sandwich anti-HBc immunoassay.ResultsSerum HBcAb levels were significantly higher in patients with a serum alanine aminotransferase (ALT) level more than five times the upper limit of normal (ULN) compared with patients with ALT levels within 5 × ULN (4.25 ± 0.61 vs. 3.94 ± 0.47 log10 IU/mL, P = 0.0345). Patients with HBeAg seroconversion were associated with a higher level of HBcAb at baseline, compared with those without HBeAg seroconversion (4.38 ± 0.54 vs. 4.02 ± 0.58 log10 IU/mL, P = 0.029). The area under receiver operating characteristic curve of baseline HBcAb for HBeAg seroconversion was 0.71 (95% CI: 0.55–0.86, P = 0.013). When the baseline HBcAb level was >4.375 log10 IU/mL, the sensitivity and specificity to predict HBeAg seroconversion at week 96 were 62.5% and 74.2%, and the positive likelihood ratio (LR) and negative LR were 2.42 and 0.51, respectively. The multivariate analysis result indicated that baseline serum HBcAb level was the only independent predictor for HBeAg seroconversion at week 96, with an odds ratio of 4.78.ConclusionBaseline serum HBcAb level >4.375 log10 IU/mL could satisfactorily predict HBeAg seroconversion among patients with high viral load treated with NUC.

Eliciting unnatural immune responses by activating cryptic epitopes in viral antigens.

Antigenic variation in viral surface antigens is a strategy for escaping the host’s adaptive immunity, whereas regions with pivotal functions for infection are less subject to antigenic variability. We hypothesized that genetically invariable and immunologically dormant regions of a viral surface antigen could be exposed to the host immune system and activated by rendering them susceptible to antigen-processing machinery in professional antigen-presenting cells (APCs). Considering the frequent antigen drift and shift in influenza viruses, we identified and used structural modeling to evaluate the conserved regions on the influenza hemagglutinin (HA) surface as potential epitopes. Mutant viruses containing the cleavage motifs of cathepsin S within HA were generated. Immunization of mice showed that the mutant, but not the wild-type virus, elicited specific antibodies against the cryptic epitope. Those antibodies were purified, and specific binding to HA was confirmed. These results suggest that an unnatural immune response can be elicited through the processing of target antigens in APCs, followed by presentation via the major histocompatibility complex, if not subjected to regulatory pathways. By harnessing the antigen-processing machinery, our study shows a proof-of-principle for designer vaccines with increased efficacy and safety by either activating cryptic, or inactivating naturally occurring, epitopes of viral antigens.—Lee, Y. J., Yu, J. E., Kim, P., Lee, J.-Y., Cheong, Y. C., Lee, Y. J., Chang, J., Seong, B. L. Eliciting unnatural immune responses by activating cryptic epitopes in viral antigens.

Development of sandwich ELISA systems for the diagnosis of hepatitis B virus surface antigen and its antibody in human sera

Hepatitis B is an infection of the liver caused by the Hepatitis B virus HBV HBV is one of the major causes of acute and chronic hepatitis cirrhosis and hepatocellular carcinoma and it is a serious global public health problem It is estimated that million individuals worldwide are infected with the virus which causes deaths each year People most at risk include antibody who has unprotected sexual intercourse drug users who share needles and syringes health care workers in contact with potentially contaminated blood or body fluids anyone in intimate contact with the infected person Therefore the development of economic and accurate detection systems and potential alternative antiviral approaches for HBV detection could be important for fighting viral hepatitis Hepatitis B diagnosis has been based on the detection of serologic markers Testing for these markers helps to determine the presence of past or ongoing HBV infection the acute chronic or subclinical carrier state of the disease response to therapy and or the immune status of the patient Hepatitis B virus surface antigen HBsAg is the first serological marker to appear in the circulation well before clinical symptoms and is the viral component usually found in the highest concentration in the serum of HBV infected patients The presence of anti HBs in serum indicates previous exposure to HBV and long lasting acquired immunity Low serum titres of anti HBs however it can signal a lack of immunity to future HBV infection In this study diagnostic systems based on the use of monoclonal antibody MAb and polyclonal antibodies PAb were developed and conjugated enzyme and biotin for early and sensitive diagnosis of Hepatitis B which is still one of the important infectious diseases in Turkey Sandwich ELISA kit systems were generated by using both G MAb as capturing agent and G HRP or G biotin conjugates as detecting agents Homemade sandwich ELISA tests were compared with the other conventional sandwich ELISA tests by using hepatitis B positive and negative infection serum They were shown that our system gave reliable results When the homemade HBsAg ELISA system were compared with the other commercial kit by using patients sera it was shown that our system corresponded with the results of negative and positive samples at ratio of When the homemade anti HBsAg ELISA system was compared with the commercial kit by using patients sera it was shown that our system corresponded with the results of negative and positive samples at ratio of In subsequent studies by the final tests of homemade ELISA kit it was observed that Biotin labeled kits responded very close results with the conformity level when compared with commercial kits

The clinicopathological and prognostic value of HSP27 in hepatocellular carcinoma: a systematic review and meta-analysis.

BackgroundIn the recent past, there is increasing evidence demonstrating that HSP27 plays a key role in tumor progression. However, the relationship between HSP27 expression and the clinicopathological features of hepatocellular carcinoma (HCC), as well as its prognostic value in HCC patients remain controversial. Accordingly, we conducted a meta-analysis to assess the correlation between HSP27 expression and HCC, and determine the prognostic value of HSP27 in HCC.MethodsThe data included clinicopathological features and survival information extracted from the published literature in the databases PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, and Wan Fang. The pooled odds ratios and hazard ratios with 95% CIs were calculated using Forest plot analysis.ResultsThe meta-analysis results indicated that the positive HSP27 expression was significantly correlated with HCC incidence, tumor differentiation, and α-fetoprotein level in patients with HCC. However, the expression of HSP27 was not associated with metastasis, hepatitis B virus surface antigen, gender, tumor size, TNM stage, and vascular invasion. Additionally, HSP27 expression indicated a poor overall survival rate, but it was not related to disease-free survival rate.ConclusionThis meta-analysis revealed that HSP27 may play a key role in the development of HCC and could be a reliable biomarker for the prognosis of patients with HCC. However, additional high-quality research is needed to support the results.

53P - Impact of chronic hepatitis virus infection on the feasibility and efficacy for Asian patients with hepatocellular carcinoma in phase I clinical trials

Background: In Asia, chronic hepatitis B and C virus infections (CHVI) are major risk factors for liver fibrosis and hepatocellular carcinoma (HCC). Patients with advanced HCC have limited effective therapeutic options and are potential candidates for early phase clinical trials for new anti-cancer agents. The impact of CHVI on the feasibility and efficacy for patients with HCC in Phase I trials (P-Is) has not been reported or elucidated in Western countries. Methods: We retrospectively analyzed the characteristics and outcomes of HCC patients participating in P-Is, with emphasis on CHVI. Patients testing positive for anti-hepatitis C virus (HCV) antibody or hepatitis B virus surface antigen (HBsAg) were diagnosed with CHVI. Results: Eighty-five patients were enrolled in P-Is at our center. There were no significant differences in the clinical and laboratory variables, including the liver function test results, between the 46 (54%) CHVI-positive and 39 (46%) CHVI-negative patients in this study. The median time to treatment failure (TTF) and overall survivals (OS) from enrollment of the P-I were 60 days (95% confidence interval [CI]: 51–85) and 412 days (95% CI: 267–478), respectively. There is no significant difference between positive and negative for hepatitis virus in the best response based on the RECIST. The frequency of abnormal liver function test (LFT) adverse events (grade ≥ 3) was significantly different among CHVI-positive and -negative patients. No patient discontinued P-I treatment secondary to abnormal LFT results or developed reactivation of hepatitis virus, and no treatment-related mortality was observed. Multivariate analysis revealed that the number of prior systemic treatments significantly contributed to poor TTF (≥2; HR: 2.1, 95% CI: 1.3–3.6, P = 0.004) and that poor Eastern Cooperative Oncology Group Performance Status significantly contributed to poor OS (≥1; HR: 1.9, 95% CI: 1.0–3.4, P = 0.04). Conclusions: CHVI did not independently predict TTF and OS. Abnormal LFT adverse events could be related to CHVI but did not lead to discontinuation of P-I treatment. Thus, patients advanced HCC with CHVI can be enrolled in the P-Is. Legal entity responsible for the study: N/A Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest.

Seroclearance of hepatitis B surface antigen following hepatitis E exacerbation on chronic hepatitis E and B dual infection in a renal transplant recipient: a case report

BackgroundHepatitis E virus infection usually causes an acute and self-resolving hepatitis. In areas where chronic hepatitis B virus infection is prevalent, acute hepatitis E virus superinfection on chronic hepatitis B virus infection occurs sporadically. In recent years, however, chronic hepatitis E virus infection has been recognized in patients under immunosuppressant therapy. To the best of our knowledge, cases involving patients with chronic hepatitis E virus and hepatitis B virus dual infection have never been reported.Case presentationA 47-year-old Taiwanese woman who was a renal transplant recipient with chronic hepatitis B virus infection was under immunosuppressant and antiviral treatment. An episode of hepatitis B exacerbation developed due to withdrawal of antiviral treatment against advice, but the flare subsided following antiviral re-treatments. However, an episode of hepatitis exacerbation developed following removal of the renal graft because of graft failure. During the hepatitis flare, she was still under successful antiviral suppression against hepatitis B virus, while her serum samples were positive for hepatitis E virus RNA. Following the hepatitis flare, seroclearance of hepatitis B virus surface antigen developed. From then on, she was under regular hemodialysis. Five years later, another episode of mild hepatitis exacerbation occurred again with positive serum hepatitis E virus RNA. Tracing back the longitudinal serum samples, serum hepatitis E virus RNA was persistently positive throughout the course. This patient was thus recognized to have chronic hepatitis E virus and hepatitis B virus dual infection with intermittent hepatitis E exacerbations.ConclusionsIn areas where chronic hepatitis B virus infection is prevalent, chronic hepatitis E virus coinfection can occur in organ transplant recipients receiving immunosuppressant. Intermittent hepatitis E exacerbations may develop, interfering with the status of hepatitis B virus infection.

Nucleic acid polymer REP 2139 and nucleos(T)ide analogues act synergistically against chronic hepadnaviral infection in vivo in Pekin ducks.

Nucleic acid polymer (NAP) REP 2139 treatment was shown to block the release of viral surface antigen in duck HBV (DHBV)‐infected ducks and in patients with chronic HBV or HBV/hepatitis D virus infection. In this preclinical study, a combination therapy consisting of REP 2139 with tenofovir disoproxil fumarate (TDF) and entecavir (ETV) was evaluated in vivo in the chronic DHBV infection model. DHBV‐infected duck groups were treated as follows: normal saline (control); REP 2139 TDF; REP 2139 + TDF; and REP 2139 + TDF + ETV. After 4 weeks of treatment, all animals were followed for 8 weeks. Serum DHBsAg and anti‐DHBsAg antibodies were monitored by enzyme‐linked immunosorbent assay and viremia by qPCR. Total viral DNA and covalently closed circular DNA (cccDNA) were quantified in autopsy liver samples by qPCR. Intrahepatic DHBsAg was assessed at the end of follow‐up by immunohistochemistry. On‐treatment reduction of serum DHBsAg and viremia was more rapid when REP 2139 was combined with TDF or TDF and ETV, and, in contrast to TDF monotherapy, no viral rebound was observed after treatment cessation. Importantly, combination therapy resulted in a significant decrease in intrahepatic viral DNA (>3 log) and cccDNA (>2 log), which were tightly correlated with the clearance of DHBsAg in the liver. Conclusion: Synergistic antiviral effects were observed when REP 2139 was combined with TDF or TDF + ETV leading to control of infection in blood and liver, associated with intrahepatic viral surface antigen elimination that persisted after treatment withdrawal. Our findings suggest the potential of developing such combination therapy for treatment of chronically infected patients in the absence of pegylated interferon. (Hepatology 2018;67:2127‐2140).