A novel toolbox for the in vitro assay of hepatitis D virus infection.

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

Related Articles A novel toolbox for the in vitro assay of hepatitis D virus infection. Sci Rep. 2017 Jan 12;7:40199 Authors: Zhao JH, Zhang YL, Zhang TY, Yuan LZ, Cheng T, Chen PJ, Yuan Q, Xia NS Abstract Hepatitis D virus (HDV) is a defective RNA virus that requires the presence of hepatitis B virus (HBV) for its life cycle. The in vitro HDV infection system is widely used as a surrogate model to study cellular infection with both viruses owing to its practical feasibility. However, previous methods for running this system were less efficient for high-throughput screening and large-scale studies. Here, we developed a novel method for the production of infectious HDV by adenoviral vector (AdV)-mediated transduction. We demonstrated that the AdV-based method yields 10-fold higher viral titers than the transient-transfection approach. The HDV-containing supernatant derived from AdV-infected Huh7 cells can be used as the inoculum in infectivity assays without requiring further concentration prior to use. Furthermore, we devloped a chemiluminescent immunoassay (HDV-CLEIA) to quantitatively determine intracellular HDAg with a dynamic range of 5-11,000 pg/mL. HDV-CLEIA can be used as an alternative approach to assess HDV infection. The advantages of our updated methodology were demonstrated through in vitro HDV infection of HepaRG cells and by evaluating the neutralization activity using antibodies that target various regions of the HBV/HDV envelope proteins. Together, the methods presented here comprise a novel toolbox of in vitro assays for studying HDV infection. PMID: 28079152 [PubMed – in process]

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A novel toolbox for the in vitro assay of hepatitis D virus infection.

Semi-quantitative real-time PCR: a useful approach to identify persons with low replicative chronic hepatitis B.

Posted by on 11 Jan 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Semi-quantitative real-time PCR: a useful approach to identify persons with low replicative chronic hepatitis B. J Virol Methods. 2017 Jan 06;: Authors: Castéra-Guy J, Rubbo PA, Kania D, Lemoine M, Van de Perre P, Tuaillon E Abstract Antiviral therapy can be avoided during the low replicative phase of chronic Hepatitis B virus (HBV) infection which is characterized notably by HBV DNA concentration below 2000 IU/ml. Simplified diagnostic tests can improve access to HBV DNA monitoring in resource-limited settings. The capacity of a new semi-quantitative real-time PCR approach based on sample-to-standard relative detection of the target to discriminate samples with HBV DNA levels above or below the clinical threshold of 2000 IU/ml was compared to a quantitative assay (Roche CobasAmpliPrep/CobasTaqMan HBV Test v2.0). The semi-quantitative assay correctly identified 40/40 (100%) low replicative HBV DNA patients and 58/61 (95%) samples from HBV-infected subjects with moderate/high levels of viral DNA. Our results suggested that this alternative PCR test is efficient to guide therapeutic decision based on identification of low replicative HBV infection from all of the chronic hepatitis B carriers requiring treatment, and may be useful in resource-limited settings where the vast majority of cases live. PMID: 28069472 [PubMed – as supplied by publisher]

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Semi-quantitative real-time PCR: a useful approach to identify persons with low replicative chronic hepatitis B.

[The enhanced expression of Toll-like receptor 2 in CD8(+)T cells of chronic HBV infected patients].

Posted by on 07 Jan 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles [The enhanced expression of Toll-like receptor 2 in CD8(+)T cells of chronic HBV infected patients]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2016 Jun;32(6):812-5 Authors: Yun C, Xiao J, Kang D, Wang Q, Peng L, Liu X, Leng J Abstract Objective To detect the level of Toll-like receptor 2 (TLR2) in CD8(+)T cells of chronic HBV infected patients without antiviral treatment. Methods Forty chronic HBV infected donors without antivirus treatment and 19 healthy donors were enrolled in our study. All donors were divided into three groups: a high viral load (HBV DNA>1×10(4) copies/mL) group, a low viral load (HBV DNA>1×10(4) copies/mL) group, and a healthy control group. After the isolation and staining of peripheral blood mononuclear cells (PBMCs), the levels of TLR2, CD38, HLA-DR, CD95, programmed death-1 (PD-1) in CD8(+)T cells were detected by flow cytometry to further analyze the correlations between TLR2 and CD38, HLA-DR, CD95, PD-1. Results The expression of TLR2 in CD8(+)T cells of the HBV infected patients were significantly higher than that in the healthy donors. The expression of TLR2 in CD8(+)T cells of the low viral load group was significantly higher than that in the high viral load group. There were no correlations between the expression of TLR2 and the expressions of CD38, HLA-DR, CD95 and PD-1 in CD8(+)T cells in the chronic HBV infected patients. Conclusion The expression of TLR2 in CD8(+)T cells increases in chronic HBV infected patients. PMID: 27371850 [PubMed – indexed for MEDLINE]

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[The enhanced expression of Toll-like receptor 2 in CD8(+)T cells of chronic HBV infected patients].

Discontinuation of Hepatitis B Immunoglobulin by Long-term Hepatitis B Vaccine Inoculation in Preventing Hepatitis B Recurrence After Liver…

Posted by on 06 Jan 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Discontinuation of Hepatitis B Immunoglobulin by Long-term Hepatitis B Vaccine Inoculation in Preventing Hepatitis B Recurrence After Liver Transplantation. Transplant Proc. 2016 May;48(4):1179-83 Authors: Usui M, Sugimoto K, Kato H, Murata Y, Tanemura A, Kuriyama N, Azumi Y, Kishiwada M, Mizuno S, Sakurai H, Takei Y, Isaji S Abstract INTRODUCTION: For the patients undergoing liver transplantation for hepatitis B virus (HBV)-related diseases, hepatitis B immunoglobulin (HBIG) should be administered to prevent reinfection. Because HBIG is highly expensive and a blood product, an alternative strategy using HBV vaccination has been made in an attempt to discontinue use of HBIG. The aim of this study was to evaluate the impact of long-term HBV vaccination for discontinuation of HBIG, paying attention to the status of active immunization using T-cell proliferation assay. PATIENTS AND METHODS: Among the 144 recipients who underwent liver transplantation in our hospital, 16 had HBV-related liver diseases; the 14 patients who had received vaccination were subjects in our study. To evaluate the status of active immunization, T-cell proliferation was examined by counting the number of T cells after adding HBV vaccine to the culture supernatant of T cells, and tumor necrosis factor α and interferon γ were measured in the culture supernatant. RESULTS: The ratio of male/female was 13/1 (median age: 55 years; range: 37 years to 67 years). The median follow-up time was 102 months (range: approximately 14 months to 148 months). All 14 patients were free of HBV recurrence. HBIG-free status could be achieved in 9 patients (64.3%) during the treatment period for more than 50 months after beginning of HBV vaccination, of whom 5 (35.7%) became HBV vaccine-free. T-cell proliferation was confirmed by fact that the stimulation index ranged from 2.34 to 5.2 in the patients who were HBIG-free. CONCLUSION: Long-term HBV vaccination after LT is a useful and effective treatment in preventing HBV recurrence, allowing the discontinuation of HBIG treatment. PMID: 27320582 [PubMed – indexed for MEDLINE]

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Discontinuation of Hepatitis B Immunoglobulin by Long-term Hepatitis B Vaccine Inoculation in Preventing Hepatitis B Recurrence After Liver…

Comparable Short- and Long-term Outcomes in Living Donor and Deceased Donor Liver Transplantations for Patients With Model for End-stage Liver Disease…

Posted by on 24 Dec 2016 | Tagged as: Hepatitis B Alternative Medicine

Comparable Short- and Long-term Outcomes in Living Donor and Deceased Donor Liver Transplantations for Patients With Model for End-stage Liver Disease Scores ≥35 in a Hepatitis-B Endemic Area. Ann Surg. 2017 Jan;265(1):173-177 Authors: Chok KS, Fung JY, Chan AC, Dai WC, Sharr WW, Cheung TT, Chan SC, Lo CM Abstract OBJECTIVE: To evaluate if living donor liver transplantation (LDLT) should be offered to patients with Model for End-stage Liver Disease (MELD) scores ≥35. BACKGROUND: No data was available to support LDLT of such patients. METHODS: Data of 672 consecutive adult liver transplant recipients from 2005 to 2014 at our center were reviewed. Patients with MELD scores ≥35 were divided into the deceased donor liver transplantation (DDLT) group and the LDLT group and were compared. Univariate analysis was performed to identify risk factors affecting survival. RESULTS: The LDLT group (n = 54) had younger (33 yrs vs 50 yrs, P < 0.001) and lighter (56 Kg vs 65 Kg, P = 0.004) donors, lighter grafts (627.5 g vs 1252.5 g, P < 0.001), lower graft-weight-to-recipient-standard-liver-volume rates (51.28% vs 99.76%, P < 0.001), shorter cold ischemic time (106.5 min vs 389 min, P < 0.001), and longer operation time (681.5 min vs 534 min, P < 0.001). The groups were comparable in postoperative complication, hospital mortality, and graft survival and patient survival at one year (88.9% vs 92.5%; 88.9% vs 94.7%), three years (87.0% vs 86.9%; 87.0% vs 88.8%), and five years (84.8% vs 81.8%; 84.8% vs 83.3%). Univariate analysis did not show inferior survival in LDLT recipients. CONCLUSIONS: At centers with experience, the outcomes of LDLT can be comparable with those of DDLT even in patients with MELD scores ≥35. When donor risks and recipient benefits are fully considered and balanced, an MELD score ≥35 should not be a contraindication to LDLT. In Hong Kong, where most waitlisted patients have acute-on-chronic liver failure from hepatitis B, LDLT is a wise alternative to DDLT. PMID: 28009743 [PubMed – in process]

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Comparable Short- and Long-term Outcomes in Living Donor and Deceased Donor Liver Transplantations for Patients With Model for End-stage Liver Disease…

Patients’ perspectives on the delivery of hepatitis B management and care.

Posted by on 15 Dec 2016 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Patients’ perspectives on the delivery of hepatitis B management and care. Aust Fam Physician. 2015 Jun;44(6):346 Authors: Richmond J, Hajarizadeh B, Wallace J PMID: 26427092 [PubMed – indexed for MEDLINE]

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Patients’ perspectives on the delivery of hepatitis B management and care.

Alternative Therapies for Chronic Hepatitis B Patients With Partial Virological Response to Standard Entecavir Monotherapy.

Posted by on 15 Dec 2016 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Alternative Therapies for Chronic Hepatitis B Patients With Partial Virological Response to Standard Entecavir Monotherapy. J Clin Gastroenterol. 2016 Apr;50(4):338-44 Authors: Chaung KT, O’Brien C, Ha NB, Nguyen NH, Trinh HN, Nguyen MH Abstract BACKGROUND: Entecavir (ETV) is a first-line, oral antinucleoside agent for the treatment of chronic hepatitis B patients. Despite its high potency, some patients may still be viremic after prolonged therapy with ETV monotherapy. Long-term outcome data comparing maintained ETV monotherapy to alternative therapies in persistently viremic patients are limited. Our goal was to compare complete viral suppression (CVS) rates [hepatitis B DNA (HBV DNA)<40 to 60 IU/mL] with alternative therapies to continued ETV monotherapy in ETV partial responders. METHODS: This is a retrospective cohort study consisting of 86 consecutive treatment-naive, ETV=0.5 mg partial responders (detectable HBV DNA after ≥12 mo on ETV) who maintained ETV=0.5 mg daily (n=29) or switched to either ETV=1.0 mg daily (n=32) or ETV/tenofovir (TDF)=0.5 mg/300 mg (n=25) in 3 US GI/liver clinics from January 2005 to January 2012. Patients were identified by International Classification of Diseases, Ninth Revision query and data were collected by individual chart review. For those who remained on ETV=0.5 mg, comparison at regimen “switch time” was done using values at 12 months from initial ETV therapy. Rates of CVS were evaluated using Kaplan-Meier methods. Multivariate Cox proportional hazard models were used to estimate hazard ratio (HR) relating to potential predictors to the desirable outcomes of CVS. RESULTS: In all therapy groups, the majority of patients were Asian (93.1% to 100.0%), male (64.0% to 68.8%), and hepatitis B e antigen-positive (95.8% to 100.0%) and had similar baseline alanine aminotransferase (ALT) levels. However, baseline HBV DNA (7.0 vs. 7.9 vs. 7.8 log10 IU/mL, P=0.05) and HBV DNA at regimen switch point (2.9 vs. 3.7 vs. 3.6 log10 IU/mL, P=0.0014) were lower in the ETV=0.5 mg cohort compared with those switched to ETV=1.0 mg or ETV/TDF, respectively. The ETV=0.5 mg cohort also had the shortest duration of ETV=0.5 mg therapy before switch (11.8 vs. 13.5 vs. 19.2 mo, P<0.0001). After the switch point, more patients on ETV/TDF achieved CVS compared with those on ETV=0.5 mg or ETV=1.0 mg at month 6 (77.3% vs. 13.8% vs. 9.4%), month 12 (86.4% vs. 40.5% vs. 25.0%), and month 18 (100% vs. 70.2% vs. 33.3%). Compared with the ETV=0.5 mg and ETV=1.0 mg groups, the ETV/TDF group also had higher rates of ALT normalization at month 6 (73.0% vs, 46.4% vs. 63.0%), month 12 (79.7% vs. 69.5% vs. 77.9%), and month 18 (100.0% vs. 69.5% vs. 86.8%), respectively. The multivariate analyses, inclusive of baseline age and treatment duration on initial therapy with ETV=0.5 mg, indicated that the ETV/TDF combination (HR=12.19, P<0.0001) was independently and positively associated with CVS, whereas high HBV DNA levels at baseline (HR=0.77, P=0.02) and at switch point (HR=0.46, P=0.002) were negatively associated with CVS. ETV=1.0 mg dose was not a predictor for CVS compared with ETV=0.5 mg. CONCLUSIONS: Following adjustments for HBV DNA levels and prior treatment duration, ETV/TDF combination therapy independently predicted superior viral suppression and ALT normalization in partial responders to ETV=0.5 mg daily compared with ETV=0.5 mg or ETV=1.0 mg monotherapy. In patients who continued to be viremic after 12 months of ETV=0.5 mg, one third were still viremic after another 18 months on the same therapy. Alternative therapies should be considered for these patients. PMID: 26646801 [PubMed – indexed for MEDLINE]

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Alternative Therapies for Chronic Hepatitis B Patients With Partial Virological Response to Standard Entecavir Monotherapy.

Baseline HBsAg and HBcrAg titres allow peginterferon-based ‘precision medicine’ in HBeAg-negative chronic hepatitis B patients.

Posted by on 03 Nov 2016 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Baseline HBsAg and HBcrAg titres allow peginterferon-based ‘precision medicine’ in HBeAg-negative chronic hepatitis B patients. J Viral Hepat. 2016 Nov;23(11):905-911 Authors: Martinot-Peignoux M, Lapalus M, Maylin S, Boyer N, Castelnau C, Giuily N, Pouteau M, Moucari R, Asselah T, Marcellin P Abstract Quantitative hepatitis B core-related antigen (qHBcrAg) has been proposed as an additional marker to quantitative HBsAg (qHBsAg), for management of chronic hepatitis B. Evaluate baseline combination of qHBsAg and qHBcrAg for identification of patients that could benefit from pegylated interferon-alpha-2a (PegIFN)-based therapy. Sixty-two HBeAg-negative patients treated with PegIFN or PegIFN plus tenofovir disoproxil fumarate (PegIFN+TDF). HBsAg and HBcrAg titres were evaluated at baseline. Thirty patients received PegIFN and 32 PegIFN+TDF. SR was 10 of 30 and 17 of 32 in PegIFN and PegIFN+TDF patients, respectively. Cut-offs determined by maximized Youden’s index for identifying patients likely to respond to therapy were as follows: 3.141 log10 IU/mL and 3.450 log10 U/mL for HBsAg and HBcrAg, respectively. At the end of 3 years post-treatment follow-up, HBsAg loss was observed in 7 of 30 and 6 of 32 in PegIFN and PegIFN+TDF patients, respectively. The AUC was estimated to be 0.716 (95% CI [0.578, 0.855]) for HBsAg and 0.668 (95% CI [0.524, 0.811]) for HBcrAg (P=.5541). PPVs for AUCs(95%CI) were 0.762(0.590-0.947), 0.714(0.533-1.000) and 0.800(0.611-1.000), and NPVs for AUCs(95%CI) were 0.756(0.660-0.899), 0.718(0.630-0.857) and 0.765(0.675-0.889) for qHBsAg, qHBcrAg and the combination of both markers, respectively. Baseline qHBsAg 3.141 log10 IU/mL and qHBcrAg 3.450 log10 U/mL thresholds used separately or in combination allow prediction of response, prior to PegIFN-based therapy, with a PPV of 80.3% and NPV of 76.5%. Baseline qHBsAg is predictive of HBsAg loss. Both markers could be used, separately or in combination, for PegIFN-based ‘precision therapy’. Our results emphasize that the combination of PegIFN alpha-2a plus TDF with 53% of SR might be an alternative to finite therapy. PMID: 27375231 [PubMed – in process]

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Baseline HBsAg and HBcrAg titres allow peginterferon-based ‘precision medicine’ in HBeAg-negative chronic hepatitis B patients.

Transient elastography for the diagnosis of liver fibrosis: a systematic review of economic evaluations.

Posted by on 25 Oct 2016 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Transient elastography for the diagnosis of liver fibrosis: a systematic review of economic evaluations. Liver Int. 2016 Oct 3;: Authors: van Katwyk S, Coyle D, Cooper C, Pussegoda K, Cameron C, Skidmore B, Brener S, Moher D, Thavorn K Abstract BACKGROUND: Liver biopsy remains the gold standard for the diagnosis of liver fibrosis, but its use as a diagnostic tool is limited by its invasive nature and high cost. OBJECTIVE: The aim of this study was to systematically review the cost-effectiveness of transient elastography (TE) with and without controlled attenuation parameter (CAP) for the diagnosis of liver fibrosis or steatosis in patients with hepatitis B, hepatitis C, alcoholic liver disease and non-alcoholic fatty liver disease. METHODS: An economic literature search was performed. Eligibility criteria included systematic reviews, health technology assessments or economic evaluations of TE compared to liver biopsy and other non-invasive tests. After abstract screening, full-text reports of potentially relevant articles were assessed in duplicate. The methodological quality of the included studies was also appraised. RESULTS: The database search yielded 253 records; four cost-effectiveness and four cost-utility studies were included. The methodological quality of the included studies varies. High-quality cost-effectiveness studies not only suggested that TE is less costly but also less accurate than liver biopsy. The incremental cost-effectiveness ratio (ICER) of TE improves with a greater level of diagnostic accuracy and a higher degree of liver fibrosis. High-quality cost-utility studies indicated that TE is a cost-effective alternative to biopsy with ICER between $9000 and $14 000 per QALY for patients with hepatitis C. We did not find studies that assessed the cost-effectiveness of TE with CAP for the diagnosis of liver steatosis. CONCLUSIONS: Transient elastography is an economically attractive alternative to liver biopsy and other non-invasive diagnostic tests especially for patients with a higher degree of liver fibrosis. PMID: 27699993 [PubMed – as supplied by publisher]

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Transient elastography for the diagnosis of liver fibrosis: a systematic review of economic evaluations.

MR elastography of the liver at 3.0 T in diagnosing liver fibrosis grades; preliminary clinical experience.

Posted by on 19 Oct 2016 | Tagged as: Hepatitis B Alternative Medicine

Related Articles MR elastography of the liver at 3.0 T in diagnosing liver fibrosis grades; preliminary clinical experience. Eur Radiol. 2016 Mar;26(3):656-63 Authors: Yoshimitsu K, Mitsufuji T, Shinagawa Y, Fujimitsu R, Morita A, Urakawa H, Hayashi H, Takano K Abstract OBJECTIVES: To clarify the usefulness of 3.0-T MR elastography (MRE) in diagnosing the histological grades of liver fibrosis using preliminary clinical data. MATERIALS AND METHODS: Between November 2012 and March 2014, MRE was applied to all patients who underwent liver MR study at a 3.0-T clinical unit. Among them, those who had pathological evaluation of liver tissue within 3 months from MR examinations were retrospectively recruited, and the liver stiffness measured by MRE was correlated with histological results. Institutional review board approved this study, waiving informed consent. RESULTS: There were 70 patients who met the inclusion criteria. Liver stiffness showed significant correlation with the pathological grades of liver fibrosis (rho = 0.89, p < 0.0001, Spearman’s rank correlation). Areas under the receiver operating characteristic curve were 0.93, 0.95, 0.99 and 0.95 for fibrosis score greater than or equal to F1, F2, F3 and F4, with cut-off values of 3.13, 3.85, 4.28 and 5.38 kPa, respectively. Multivariate analysis suggested that grades of necroinflammation also affected liver stiffness, but to a significantly lesser degree as compared to fibrosis. CONCLUSIONS: 3.0-T clinical MRE was suggested to be sufficiently useful in assessing the grades of liver fibrosis. KEY POINTS: MR elastography may help clinicians assess patients with chronic liver diseases. Usefulness of 3.0-T MR elastography has rarely been reported. Measured liver stiffness correlated well with the histological grades of liver fibrosis. Measured liver stiffness was also affected by necroinflammation, but to a lesser degree. 3.0-T MRE could be a non-invasive alternative to liver biopsy. PMID: 26060066 [PubMed – indexed for MEDLINE]

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MR elastography of the liver at 3.0 T in diagnosing liver fibrosis grades; preliminary clinical experience.

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