Accurate quantification of within- and between-host HBV evolutionary rates requires explicit transmission chain modelling.

Posted by on 15 Oct 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Accurate quantification of within- and between-host HBV evolutionary rates requires explicit transmission chain modelling. Virus Evol. 2017 Jul;3(2):vex028 Authors: Vrancken B, Suchard MA, Lemey P Abstract Analyses of virus evolution in known transmission chains have the potential to elucidate the impact of transmission dynamics on the viral evolutionary rate and its difference within and between hosts. Lin et al. (2015, Journal of Virology, 89/7: 3512-22) recently investigated the evolutionary history of hepatitis B virus in a transmission chain and postulated that the ‘colonization-adaptation-transmission’ model can explain the differential impact of transmission on synonymous and non-synonymous substitution rates. Here, we revisit this dataset using a full probabilistic Bayesian phylogenetic framework that adequately accounts for the non-independence of sequence data when estimating evolutionary parameters. Examination of the transmission chain data under a flexible coalescent prior reveals a general inconsistency between the estimated timings and clustering patterns and the known transmission history, highlighting the need to incorporate host transmission information in the analysis. Using an explicit genealogical transmission chain model, we find strong support for a transmission-associated decrease of the overall evolutionary rate. However, in contrast to the initially reported larger transmission effect on non-synonymous substitution rate, we find a similar decrease in both non-synonymous and synonymous substitution rates that cannot be adequately explained by the colonization-adaptation-transmission model. An alternative explanation may involve a transmission/establishment advantage of hepatitis B virus variants that have accumulated fewer within-host substitutions, perhaps by spending more time in the covalently closed circular DNA state between each round of viral replication. More generally, this study illustrates that ignoring phylogenetic relationships can lead to misleading evolutionary estimates. PMID: 29026650 [PubMed]

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Accurate quantification of within- and between-host HBV evolutionary rates requires explicit transmission chain modelling.

In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging.

Posted by on 30 Sep 2017 | Tagged as: Hepatitis B Alternative Medicine

In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging. Virulence. 2017 Sep 29;:0 Authors: Gupta A, Avci P, Karimi M, Sadasivam M, Antunes-Melo WC, Carrasco E, Hamblin MR Abstract Traditional methods of localizing and quantifying the presence of pathogenic microorganisms in living experimental animal models of infections have mostly relied on sacrificing the animals, dissociating the tissue and counting the number of colony forming units. However the discovery of several varieties of the light producing enzyme, luciferase, and the genetic engineering of bacteria, fungi, parasites and mice to make them emit light, either after administration of the luciferase substrate, or in the case of the bacterial lux operon without any exogenous substrate, has provided a new alternative. Dedicated bioluminescence imaging (BLI) cameras can record the light emitted from living animals in real time allowing non-invasive, longitudinal monitoring of the anatomical location and growth of infectious microorganisms as measured by strength of the BLI signal. BLI technology has been used to follow bacterial infections in traumatic skin wounds and burns, osteomyelitis, infections in intestines, Mycobacterial infections, otitis media, lung infections, biofilm and endodontic infections and meningitis. Fungi that have been engineered to be bioluminescent have been used to study infections caused by yeasts (Candida) and by filamentous fungi. Parasitic infections caused by malaria, Leishmania, trypanosomes and toxoplasma have all been monitored by BLI. Viruses such as vaccinia, herpes simplex, hepatitis B and C and influenza, have been studied using BLI. This rapidly growing technology is expected to continue to provide much useful information, while drastically reducing the numbers of animals needed in experimental studies. PMID: 28960132 [PubMed – as supplied by publisher]

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In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging.

Clinical outcomes and prognostic factors of cyberknife stereotactic body radiation therapy for unresectable hepatocellular carcinoma.

Posted by on 29 Sep 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Clinical outcomes and prognostic factors of cyberknife stereotactic body radiation therapy for unresectable hepatocellular carcinoma. BMC Cancer. 2016 Jul 12;16:451 Authors: Que J, Kuo HT, Lin LC, Lin KL, Lin CH, Lin YW, Yang CC Abstract BACKGROUND: Stereotactic body radiation therapy (SBRT) has been an emerging non-invasive treatment modality for patients with hepatocellular carcinoma (HCC) when curative treatments cannot be applied. In this study, we report our clinical experience with Cyberknife SBRT for unresectable HCC and evaluate the efficacy and clinical outcomes of this highly sophisticated treatment technology. METHODS: Between 2008 and 2012, 115 patients with unresectable HCC treated with Cyberknife SBRT were retrospectively analyzed. Doses ranged from 26 Gy to 40 Gy were given in 3 to 5 fractions for 3 to 5 consecutive days. The cumulative probability of survival was calculated according to the Kaplan-Meier method and compared using log-rank test. Univariate and multivariate analysis were performed using Cox proportional hazard models. RESULTS: The median follow-up was 15.5 months (range, 2-60 months). Based on Response Evaluation and Criteria in Solid Tumors (RECIST). We found that 48.7 % of patients achieved a complete response and 40 % achieved a partial response. Median survival was 15 months (4-25 months). Overall survival (OS) at 1- and 2-years was 63.5 ) and 41.3 % (31.6-50.6 %), respectively, while 1- and 2- years Progression-free Survival (PFS) rates were 42.8 ) and 38.8 % (29.0-48.4 %). Median progression was 6 months (3-16 months). In-field recurrence free survival at 1 and 2 years was 85.3 % (76.2-91.1 %) and 81.6 % (72.2-88.6 %), respectively, while the 1- and 2-years out-field recurrence free survival were 52.5 % (41.2-60.8 %) and 49.5 ), respectively. Multivariate analysis revealed that Child-Pugh score (A vs. B), Portal vein tumor thrombosis (positive vs. negative), Tumor size (≤4 cm vs >4-9 cm /≥10 cm), and tumor response after SBRT (CR vs. PR/stable) were independent predictors of OS. Acute toxicity was mostly transient and tolerable. CONCLUSIONS: Cyberknife SBRT appears to be an effective non-invasive treatment for local unresectable HCC with low risk of severe toxicity. These results suggested that Cyberknife SBRT can be a good alternative treatment for unresectable HCC unsuitable for standard treatment. PMID: 27405814 [PubMed – indexed for MEDLINE]

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Clinical outcomes and prognostic factors of cyberknife stereotactic body radiation therapy for unresectable hepatocellular carcinoma.

Genetic variants in the regulatory region of SLC10A1 are not associated with the risk of hepatitis B virus infection and clearance.

Posted by on 28 Sep 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Genetic variants in the regulatory region of SLC10A1 are not associated with the risk of hepatitis B virus infection and clearance. Infect Genet Evol. 2016 Oct;44:495-500 Authors: Chen X, Wang Y, Chen X, Cheng K, Li J, Lou J, Ke J, Yang Y, Gong Y, Zhu Y, Wang L, Zhong R Abstract The Na/taurocholate cotransporter NTCP (encoded by SLC10A1) was identified as a cellular entry receptor for the human hepatitis B virus (HBV), advancing our understanding of the molecular mechanism of HBV infection. An alternative hypothesis was put forward that regulatory variants in SLC10A1 might play an important role in HBV susceptibility by potentially influencing expression levels of NTCP. The three regulatory SNPs (rs8011311, rs7154439, rs111409076) were genotyped in 1023 HBV-persistent carriers, 735 subjects with HBV natural clearance and 732 HBV marker-negative subjects in a Han Chinese population. Real-time reverse transcription PCR analysis and luciferase assays have been performed to dissect the potential functionality. In logistic regression analysis, when subjects with HBV natural clearance were compared with HBV marker-negative subjects, no significant associations with the risk of HBV infection were observed for any of the three SNPs after adjusting for age, sex, smoking status and alcohol consumption (P>0.05). Similar negative results were also found for the three SNPs when HBV-persistent carriers were compared with HBV marker-negative subjects. Likewise, no significant associations with the risk of HBV clearance were observed when HBV-persistent carriers were compared with subjects with HBV natural clearance (P>0.05). Quantitative RT/PCR showed no significant difference in NTCP expression levels in normal liver tissue amongst individuals with different rs111409076 genotypes (P=0.317 for the general linear model). Moreover, no evident effect of the SLC10A1 rs111409076 AACA/- polymorphism on transcriptional activity was found by luciferase assay in either HepG2 (P=0.161) or Hep3b (P=0.129) cell lines. The present study indicated that the common variants in the regulatory region of SLC10A1 may not influence the expression of NTCP at the level of transcriptional regulation, and ultimately may not be associated with HBV susceptibility in this Chinese population. PMID: 27491457 [PubMed – indexed for MEDLINE]

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Genetic variants in the regulatory region of SLC10A1 are not associated with the risk of hepatitis B virus infection and clearance.

Clinical utility of HCV core antigen detection and quantification using serum samples and dried blood spots in people who inject drugs in…

Posted by on 28 Sep 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Clinical utility of HCV core antigen detection and quantification using serum samples and dried blood spots in people who inject drugs in Dar-es-Salaam, Tanzania. J Int AIDS Soc. 2017 Sep 14;20(1):1-7 Authors: Mohamed Z, Mbwambo J, Shimakawa Y, Poiteau L, Chevaliez S, Pawlotsky JM, Rwegasha J, Bhagani S, Simon D TR, Makani J, Thursz MR, Lemoine M Abstract INTRODUCTION: A lack of access to hepatitis C virus (HCV) diagnostics is a significant barrier to achieving the World Health Organization 2030 global elimination goal. HCV core antigen (HCVcAg) quantification and dried blood spot (DBS) are appealing alternatives to conventional HCV serology and nucleic acid testing (NAT) for resource-constraint settings, particularly in difficult-to-reach populations. We assessed the accuracy of serum and DBS HCVcAg testing in people who inject drugs in Tanzania using HCV NAT as a reference. METHOD: Between May and July 2015, consecutive HCV-seropositive patients enrolled in the local opioid substitution treatment centre were invited to participate in the study. All had HCV RNA detection (Roche Molecular Systems, Pleasanton, CA, USA), genotyping (NS5B gene phylogenetic analysis) and HCVcAg on blood samples and DBS (Architect assay; Abbott Diagnostics, Chicago, IL, USA). RESULTS: Out of 153 HCV-seropositive individuals, 65 (42.5%) and 15 (9.8%) were co-infected with HIV (41 (63%) were on anti-retroviral therapy (ARVs)) and hepatitis B respectively. In total, 116 were viraemic, median viral load of 5.7 (Interquartile range (IQR); 4.0-6.3) log iU/ml (75 (68.2%) were genotype 1a, 35 (31.8%) genotype 4a). The median alanine transaminase (ALT) (iU/l), aspartate transaminase (AST) (iU/l) and gamma-glutamyl transferase (GGT) (iU/l) were 35 (IQR; 23-51), 46 (32-57) and 69 (35-151) respectively. For the quantification of HCV RNA, serum HCVcAg had a sensitivity at 99.1% and a specificity at 94.1%, with an area under the receiver operating curve (AUROC) at 0.99 (95% CI 0.98-1.00). DBS HCVcAg had a sensitivity of 76.1% and a specificity of 97.3%, with an AUROC of 0.87 (95% CI 0.83-0.92). HCVcAg performance did not differ by HIV co-infection or HCV genotype. Conclusions Our study suggests that HCVcAg testing in serum is an excellent alternative to HCV polymerase chain reaction in Africa. Although HCVcAg detection and quantification in DBS has a reduced sensitivity, its specificity and accuracy are good and it could therefore be used for scaling up HCV testing and care in resource-limited African settings. PMID: 28953324 [PubMed – in process]

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Clinical utility of HCV core antigen detection and quantification using serum samples and dried blood spots in people who inject drugs in…

Fucoidan from Fucus vesiculosus suppresses hepatitis B virus replication by enhancing extracellular signal-regulated Kinase activation.

Posted by on 17 Sep 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Fucoidan from Fucus vesiculosus suppresses hepatitis B virus replication by enhancing extracellular signal-regulated Kinase activation. Virol J. 2017 Sep 16;14(1):178 Authors: Li H, Li J, Tang Y, Lin L, Xie Z, Zhou J, Zhang L, Zhang X, Zhao X, Chen Z, Zuo D Abstract BACKGROUND: Hepatitis B virus (HBV) infection is a serious public health problem leading to cirrhosis and hepatocellular carcinoma. As the clinical utility of current therapies is limited, the development of new therapeutic approaches for the prevention and treatment of HBV infection is imperative. Fucoidan is a natural sulfated polysaccharide that extracted from different species of brown seaweed, which was reported to exhibit various bioactivities. However, it remains unclear whether fucoidan influences HBV replication or not. METHODS: The HBV-infected mouse model was established by hydrodynamic injection of HBV replicative plasmid, and the mice were treated with saline or fucoidan respectively. Besides, we also tested the inhibitory effect of fucoidan against HBV infection in HBV-transfected cell lines. RESULTS: The result showed that fucoidan from Fucus vesiculosus decreased serum HBV DNA, HBsAg and HBeAg levels and hepatic HBcAg expression in HBV-infected mice. Moreover, fucoidan treatment also suppressed intracellular HBcAg expression and the secretion of the HBV DNA as well as HBsAg and HBeAg in HBV-expressing cells. Furthermore, we proved that the inhibitory activity by fucoidan was due to the activation of the extracellular signal-regulated kinase (ERK) pathway and the subsequent production of type I interferon. Using specific inhibitor of ERK pathway abrogated the fucoidan-mediated inhibition of HBV replication. CONCLUSION: This study highlights that fucoidan might be served as an alternative therapeutic approach for the treatment of HBV infection. PMID: 28915824 [PubMed – in process]

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Fucoidan from Fucus vesiculosus suppresses hepatitis B virus replication by enhancing extracellular signal-regulated Kinase activation.

Antiretroviral therapy for pregnant women living with HIV or hepatitis B: a systematic review and meta-analysis.

Posted by on 13 Sep 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Antiretroviral therapy for pregnant women living with HIV or hepatitis B: a systematic review and meta-analysis. BMJ Open. 2017 Sep 11;7(9):e019022 Authors: Siemieniuk RA, Foroutan F, Mirza R, Mah Ming J, Alexander PE, Agarwal A, Lesi O, Merglen A, Chang Y, Zhang Y, Mir H, Hepworth E, Lee Y, Zeraatkar D, Guyatt GH Abstract OBJECTIVE: To assess the impact of various antiretroviral/antiviral regimens in pregnant women living with HIV or hepatitis B virus (HBV). DESIGN: We performed random effects meta-analysis for HIV-related outcomes and network meta-analysis for HBV outcomes, and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess quality separately for each outcome. DATA SOURCES: Embase and Medline to February 2017. ELIGIBILITY CRITERIA: For maternal outcomes, we considered randomised controlled trials (RCTs) comparing tenofovir-based regimens with those with alternative nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). For child outcomes, we included RCTs and comparative observational studies of tenofovir-based regimens versus alternative NRTIs regimens or, for HBV, placebo. RESULTS: Ten studies (seven RCTs) met the inclusion criteria for maternal and child outcomes, and an additional 33 studies (12 RCTs) met the inclusion criteria for HBV-specific outcomes. The most common comparison was tenofovir and emtricitabine versus zidovudine and lamivudine. There was no apparent difference between tenofovir-based regimens and alternatives in maternal outcomes, including serious laboratory adverse events (low certainty) and serious clinical adverse events (moderate certainty). There was no difference between NRTIs in vertical transmission of HIV: 1 more per 1000, 8 fewer to 10 more, low certainty; or vertical transmission of HBV: 7 fewer per 1000, 10 fewer to 38 more, moderate certainty. We found moderate certainty evidence that tenofovir/emtricitabine increases the risk of stillbirths and early neonatal mortality (51 more per 1000, 11 more to 150 more) and the risk of early premature delivery at <34 weeks (42 more per 1000, 2 more to 127 more). CONCLUSIONS: Tenofovir/emtricitabine is likely to increase stillbirth/early neonatal death and early premature delivery compared with zidovudine/lamivudine, but certainty is low when they are not coprescribed with lopinavir/ritonavir. Other outcomes are likely similar between antiretrovirals. TRIAL REGISTRATION NUMBER: PROSPERO CRD42017054392. PMID: 28893758 [PubMed – in process]

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Antiretroviral therapy for pregnant women living with HIV or hepatitis B: a systematic review and meta-analysis.

MiRNA-target network analysis identifies potential biomarkers for Traditional Chinese Medicine (TCM) syndrome development evaluation in hepatitis B…

Posted by on 10 Sep 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles MiRNA-target network analysis identifies potential biomarkers for Traditional Chinese Medicine (TCM) syndrome development evaluation in hepatitis B caused liver cirrhosis. Sci Rep. 2017 Sep 08;7(1):11054 Authors: Liu Y, Wang M, Luo Y, Chen C, Lu Y, Shi Y, Tang C, Zhou Q, Zhang H, Hu Y, Su S, Chen Q Abstract Hepatitis B is one of most etiologies of Liver cirrhosis in China, and clinically lacks the effective strategy for Hepatitis B caused cirrhosis (HBC) therapy. As a complementary and alternative medicine, Chinese Traditional Medicine (TCM) has special therapeutic effects for HBC. Here, we focus on the evolution process of HBC TCM syndromes, which was from Excessive (Liver-Gallbladder Dampness-Heat Syndrome, LGDHS) to Deficient (Liver-Kidney Deficiency Syndrome, LKYDS) via Excessive-Deficient syndrome (Liver-Depression and Spleen-Deficiency Syndrome, LDSDS). Using R package, 16 miRNAs in LGDHS/Normal, 48 miRNAs in LDSDS/LGDHS, and 16 miRNAs in LKYDS/LDSDS were identified, respectively. The miRNA-target networks show that the LDSDS was most stability and complicated. Subsequently, 4 kernel miRNAs with LGDHS-LDSDS process, and 5 kernel miRNAs with LDSDS-LKYDS process were screened. Using RT-qPCR data, p1 (hsa-miR-17-3p, -377-3p, -410-3p and -495) and p2 miRNA panel (hsa-miR-377-3p, -410-3p, -27a-3p, 149-5p and 940) were identified by Logistic Regression Model, which clearly improve the accuracy of TCM syndrome classification. The rebuilt miRNA-target network shows that the LDSDS is a critical point and might determine the evolution directions of HBC TCM syndrome. This study suggests that the identified kernel miRNAs act as potential biomarkers and benefit to evaluate the evolution tendency of HBC TCM syndromes. PMID: 28887510 [PubMed – in process]

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MiRNA-target network analysis identifies potential biomarkers for Traditional Chinese Medicine (TCM) syndrome development evaluation in hepatitis B…

HBsAg mutations related to occult hepatitis B virus infection in HIV-positive patients result in a reduced secretion and conformational changes of…

Posted by on 08 Sep 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles HBsAg mutations related to occult hepatitis B virus infection in HIV-positive patients result in a reduced secretion and conformational changes of HBsAg. J Med Virol. 2017 Feb;89(2):246-256 Authors: Sadeghi A, Shirvani-Dastgerdi E, Tacke F, Yagmur E, Poortahmasebi V, Poorebrahim M, Mohraz M, Hajabdolbaghi M, Rasoolinejad M, Abbasian L, Jafari R, Fakhari Z, Norouzi M, Ebrahimian A, Geravand B, Alavian SM, Jazayeri SM Abstract BACKGROUND: Occult hepatitis B infection (OBI) is a frequent finding in human immunodeficiency virus (HIV)-infected patients. While several related mutations in the hepatitis B virus (HBV) genome have been reported, their distinct impact on HBsAg synthesis is largely obscure. METHODS: Thirty-one (18%) out of 172 HIV-infected patients, who were selected from HBsAg-negative patients, were positive for HBV-DNA assigned as being OBI-positive. We generated a series of expression constructs of variant HBsAg with “a” determinant amino acid substitutions including P127L, P127T, S136Y, and P127T + S136Y using site-directed mutagenesis. The expression of variant HBsAg was examined by transient transfection in hepatoma cells, followed by HBsAg immunoassay and immunofluorescence stained with specific anti-HBs antibodies. The potential impact of amino acid substitutions at different positions for conformational changes in the HBsAg was investigated using bioinformatics. RESULTS: All variants comprising either single or combined mutations resulted in significantly reduced HBsAg detection in supernatants and in cell lysates of hepatoma cells transfected with the constructs. Moreover, intracellular immunofluorescence staining of cytoblocks showed perinuclear and cytoplasmic fluorescence of HBsAg constructs with significantly diminished fluorescent intensity in comparison to the wild type. Altered protein conformations by predictive models, indicating an impaired detection by the host’s immune response as well as by commercial antibody-based test assays. CONCLUSION: Mutations in the “a” determinant region of HBV as often found in OBI remarkably impair the detection of HBsAg from serum and infected cells, emphasizing the relevance of alternative methods such as HBV-DNA quantification for high-risk groups like HIV-infected individuals. J. Med. Virol. 89:246-256, 2017. © 2016 Wiley Periodicals, Inc. PMID: 27381922 [PubMed – indexed for MEDLINE]

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HBsAg mutations related to occult hepatitis B virus infection in HIV-positive patients result in a reduced secretion and conformational changes of…

Short Course of Postoperative Hepatitis B Immunoglobulin Plus Antivirals Prevents Reinfection of Liver Transplant Recipients.

Posted by on 08 Sep 2017 | Tagged as: Hepatitis B Alternative Medicine

Short Course of Postoperative Hepatitis B Immunoglobulin Plus Antivirals Prevents Reinfection of Liver Transplant Recipients. Transplantation. 2017 Sep;101(9):2079-2082 Authors: Radhakrishnan K, Chi A, Quan DJ, Roberts JP, Terrault NA Abstract BACKGROUND: Hepatitis B immune globulin (HBIG) has been an integral component of prophylaxis against hepatitis B virus (HBV) recurrence in liver transplantation (LT) recipients, but HBIG is costly and inconvenient to administer, prompting consideration of alternative regimens. METHODS: In this retrospective cohort, we report on the success of antiviral therapy combined with a short course (in hospital only) HBIG in liver transplant recipients with HBV DNA less than 100 IU/mL pre-LT. RESULTS: A total of 42 hepatitis B surface antigen (HBsAg) positive, human immunodeficiency virus and hepatitis D virus-negative patients with pretransplant HBV DNA undetectable to 100 IU/mL who received HBIG 5000 IU in anhepatic phase and daily for 5 days together with nucleos(t)ide analogues indefinitely yielded 1- and 3-year cumulative incidences of recurrence, defined by positive serum HBsAg, of 2.9% (upper 95% confidence interval, 19%). One patient had HBV viremia 16 months post-LT without detectable HBsAg. Both patients with either HBsAg positivity or viremia had recurrent hepatocellular carcinoma diagnosed within a month of detection. Post-LT survival was 98% and 94% at 1 and 5 years, respectively. CONCLUSIONS: We conclude that a very short course of HBIG combined with long-term antiviral therapy is highly effective in preventing HBV recurrence and should be the preferred strategy for LT recipients with undetectable or low-level viremia at time of LT. PMID: 28880197 [PubMed – in process]

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Short Course of Postoperative Hepatitis B Immunoglobulin Plus Antivirals Prevents Reinfection of Liver Transplant Recipients.

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