[Correlation study on Chinese medical syndrome types of chronic hepatitis B patients and HLA-DR13 gene, BCP mutation, and T-lymphocyte subsets].

Posted by on 20 May 2015 | Tagged as: Hepatitis B Alternative Medicine

Related Articles [Correlation study on Chinese medical syndrome types of chronic hepatitis B patients and HLA-DR13 gene, BCP mutation, and T-lymphocyte subsets]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014 Nov;34(11):1315-8 Authors: Yang XR, Liu Y, Ouyang J, Wang XK, Diao WX Abstract OBJECTIVE: To explore the correlation between the HLA-DR13, basic core promoter (BCP), changes of T lymphocyte subset and clinical Chinese medical syndromes of chronic hepatitis B (CHB). METHODS: Totally 102 CHB patients were syndrome typed as Gan depression Pi deficiency syndrome (GDPDS), Pi-Shen yang deficiency syndrome (PSYDS), Gan-gallbladder dampness heat syndrome (GGDHS), Gan-Shen yin deficiency syndrome (GSYDS), and static blood blocking collaterals syndrome (SBBCS). Besides, 30 healthy subjects were recruited as the normal control group. The blood HBV-DNA level and HLA-DR13 gene were detected with real time fluorescent PCR. The expression of CD4+ and CD8+ in T lymphocytes was detected using flow cytometry. The mutation of serum A1762T/G1764A was detected using PCR sequencing. Hepatitis Be antigen (HBeAg) was detected with ELISA, and correlation between various Chinese medical syndrome types and objective indicators were analyzed. RESULTS: There was no statistical difference in HBV-DNA quantitative results among various syndrome types (P > 0.05). HBeAg positive rate was higher in GDPDS than in other syndrome types (P < 0.05). It was sequenced as GDPDS > GSYDS > SBBCS > GGDHS > PSYDS. Compared with the normal control group, percentages of CD3+ and CD3+ CD4+ were lower in PSYDS (P < 0.05). The ratio of CD3+ CD4+/CD3+ CD8 was lower in GGDHS and PSYDS than in the normal control group (P < 0.05). There was no statistical difference in the CD3+ CD8+ percentage among various syndrome types (P > 0.05). The quantitation of HLA-DR13 gene was lower in GDPDS and GSYDS than in the normal control group (P < 0.05). The positive rate of BCP mutation was higher in GSYDS than in other syndrome types (P < 0.05). CONCLUSION: Co-detection results of HLA-DR13 and BCP could be used as reference indices of Chinese medical syndrome typing of CHB. PMID: 25566621 [PubMed – indexed for MEDLINE]

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[Correlation study on Chinese medical syndrome types of chronic hepatitis B patients and HLA-DR13 gene, BCP mutation, and T-lymphocyte subsets].

[Differential expression of microRNA in chronic hepatitis B patients of pi-wei dampness-heat syndrome and of gan depression Pi deficiency syndrome: a…

Posted by on 20 May 2015 | Tagged as: Hepatitis B Alternative Medicine

Related Articles [Differential expression of microRNA in chronic hepatitis B patients of pi-wei dampness-heat syndrome and of gan depression Pi deficiency syndrome: a primary research]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014 Nov;34(11):1324-8 Authors: Wang EC, Zhang L, Liu HW, Guo YL, Zhang F, He CW, Shen MM, Feng QS Abstract OBJECTIVE: To explore different microRNA expression profiles between chronic hepatitis B (CHB) patients of Pi-Wei dampness-heat syndrome (PWDHS) and Gan depression Pi deficiency syndrome (GDPDS). METHODS: By applying gene chip technology, blood samples from CHB patients of PWDHS (3 cases), GDPDS (3 cases), and healthy volunteers (3 cases) were withdrawn and microRNA detected. The microRNA was screened and functional analyses performed by using SAS system. RESULTS: Totally 77 microRNAs with differential expression were screened from CHB patients of PWDHS and healthy volunteers, including 60 up-regulated microRNAs and 17 down-regulated microRNAs. Functions of target genes were mainly associated with transcription factors, gas exchange, adverse stimulating, regulation of enzyme activities, developing of the immune system, and the process of actin filaments. Totally 41 microRNAs with differential expression were screened from CHB patients of GDPDS and healthy volunteers, including 32 up-regulated microRNAs and 9 down-regulated microRNAs. Functions of target genes were mainly associated with binding to nucleotide or chromatin, inhibition and activation of transcription, biosynthesis, regulation of metabolic process, regulation of enzyme activities, developing of the immune system, the process of actin filaments, and IL-12. Totally 6 microRNAs with differential expression were screened from CHB patients of PWDHS and CHB patients of GDPDS, including 1 up-regulated microRNA and 5 down-regulated microRNAs. Functions of target genes were mainly associated with transmembrane transport, regulation of transcription factors, metabolism of hormones, developing of the immune system, the process of actin filaments, regulation of metabolic process, response to exterior stimulation, and so on. CONCLUSION: There existed differentially expressed microRNAs (spectrum) between CHB patients of PWDHS and CHB patients of GDPDS. PMID: 25566623 [PubMed – indexed for MEDLINE]

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[Differential expression of microRNA in chronic hepatitis B patients of pi-wei dampness-heat syndrome and of gan depression Pi deficiency syndrome: a…

Development of a novel IGRA assay to test T cell responsiveness to HBV antigens in whole blood of chronic Hepatitis B patients.

Posted by on 15 May 2015 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Development of a novel IGRA assay to test T cell responsiveness to HBV antigens in whole blood of chronic Hepatitis B patients. J Transl Med. 2015 May 13;13(1):157 Authors: Dammermann W, Bentzien F, Stiel EM, Kühne C, Ullrich S, Zur Wiesch JS, Lüth S Abstract BACKGROUND: Interferon gamma release assays (IGRA) have been developed to support easy and fast diagnosis of diseases like tuberculosis, and CMV in transplant patients. IGRAs focus on cellular immunity especially memory T cells and thus also allow rapid screening prior to complex flow cytometric testing. Here, we describe a novel, sensitive whole blood based cytokine release assay capable of assessing T cell responsiveness to HBV antigens in Hepatitis B patients and assessing hepatitis B vaccination status in healthy individuals. METHODS: Seventy two chronic Hepatitis B patients (CHB), 8 acute hepatitis B patients (AHB) and 80 healthy controls (HC) were tested by ELISA for IFNγ- and IL2-secretion in whole blood after challenge with synthetic peptide libraries of hepatitis B core antigen (HBcAg) or hepatitis B surface antigen (HBsAg). RESULTS: The developed IGRA test reliably differentiated between Hepatitis B patients, vaccinees and unvaccinated healthy controls. Treatment naïve and treated CHB patients showed a weaker IFNγ response to HBcAg (16 ± 5 and 35 ± 28 pg/ml, respectively) compared to the AHB group (82 ± 39 pg/ml), whereas HC remained unresponsive (6 ± 1 pg/ml). IL2 levels after HBcAg challenge were also higher in the AHB group compared to naive and treated CHB as well as HC (47 ± 21 vs. 12 ± 3, 15 ± 10 and 12 ± 9 pg/ml, respectively). HBsAg stimulation led to increased IFNγ and IL2 levels in the AHB group (33 ± 12 and 22 ± 12 pg/ml) and even higher levels in HC due to a high hepatitis B vaccination rate (41 ± 10 and 167 ± 58 pg/ml). Naive and treated CHB patients developed no or only weaker IFNγ or IL2 responses to HBsAg (5 ± 2 and 12 ± 7 pg/ml, for naive CHB, 12 ± 10 and 18 ± 15 pg/ml, for treated CHB). For HC, IL2 release after HBsAg stimulation depicted hepatitis B vaccination status with a diagnostic sensitivity and specificity of 85 % and 90 %. CONCLUSION: Our novel whole blood based cytokine release assay constitutes an easy and robust tool for screening HBV specific cellular immunity as alternative to flow cytometry or ELISPOT assays. PMID: 25968473 [PubMed – as supplied by publisher]

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Development of a novel IGRA assay to test T cell responsiveness to HBV antigens in whole blood of chronic Hepatitis B patients.

Oral delivery of wafers made from HBsAg-expressing maize germ induces long-term immunological systemic and mucosal responses.

Posted by on 07 May 2015 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Oral delivery of wafers made from HBsAg-expressing maize germ induces long-term immunological systemic and mucosal responses. Vaccine. 2015 May 2; Authors: Hayden CA, Fischer ME, Andrews BL, Chilton HC, Turner DD, Walker JH, Tizard IR, Howard JA Abstract BACKGROUND: The hepatitis B surface antigen (HBsAg) has been administered over the last 20 years as a parenteral vaccine against the hepatitis B virus (HBV). Despite high seroconversion rates, chronic infection rates are still high worldwide. Orally delivered vaccines provide a practical alternative to injected vaccines, potentially helping poorly responding populations and providing a viable alternative for populations in remote locations. Anamnestic responses are vital to establishing the efficacy of a given vaccine and have been assessed in this study using a plant-based oral delivery platform expressing the hepatitis B surface antigen (HBsAg). METHODS: Long-term immunological memory was assessed in mice injected with a primary dose of Recombivax(®) and boosted with orally-delivered HBsAg wafers, control wafers, or parenterally-delivered commercial vaccine (Recombivax(®)). RESULTS: Mice boosted with HBsAg orally-administered wafers displayed sharp increases in mucosal IgA titers in fecal material and steep increases in serum IgA, whereas mice boosted with Recombivax(®) showed no detectable levels of IgA in either fecal or serum samples following four boosting treatments. Long-term memory in the orally-treated mice was evidenced by sustained fecal IgA, and serum IgA, IgG, and mIU/mL over one year, while Recombivax(®)-treated mice displayed sustained serum IgG and mIU/mL. Furthermore, sharp increases in these same antibodies were induced after re-boosting at 47 and 50 weeks post-primary injection. CONCLUSIONS: Orally-delivered vaccines can provide long-term immune responses mucosally and systemically. For sexually-transmitted diseases that can be acquired at mucosal surfaces, such as HBV, an oral delivery platform may provide added protection over a conventional parenterally administered vaccine. PMID: 25944300 [PubMed – as supplied by publisher]

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Oral delivery of wafers made from HBsAg-expressing maize germ induces long-term immunological systemic and mucosal responses.

Nucleoside-Nucleotide Analog Combination Therapy Is Effective in Preventing Recurrent Hepatitis B After Liver Transplantation.

Posted by on 06 May 2015 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Nucleoside-Nucleotide Analog Combination Therapy Is Effective in Preventing Recurrent Hepatitis B After Liver Transplantation. Dig Dis Sci. 2015 May 5; Authors: Khemichian S, Hsieh MJ, Zhang SR, Limurti J, Kim J, Fong TL Abstract BACKGROUND: Hepatitis B immune globulin (HBIg) in combination with a nucleos(t)ide analog is the mainstay of prophylactic regimen to prevent recurrence of hepatitis B following orthotopic liver transplantation (OLT). HBIg therapy is costly and inconvenient for the patients. There is a growing experience converting HBIg/nucleos(t)ide to combination nucleotide/nucleoside analogs from. METHODS: Twenty-six patients that underwent OLT between March 2001 and July 2011 who had received at least 12 months of HBIg and single nucleos(t)ide were enrolled. HBsAg and HBV DNA were undetectable, and anti-HBs were detectable at the time of switch. HBV DNA and HBsAg were measured every 3 months following discontinuation of HBIg and addition of nucleos(t)ide. RESULTS: Patients included 23 Asians/3 Caucasian, 21 males/5 females. Mean time of conversion from HBIg/nucleos(t)ide to nucleoside/nucleotide combination was 77.5 (range 11-132) months after OLT. Mean duration of follow-up after conversion was 31.9 (range 14-70) months. All patients had undetectable HBV DNA, and 24 patients remained HBsAg negative during follow-up. Two patients recurred 7 and 9 months later, respectively, with detectable HBsAg. Both patients continued to have undetectable HBV DNA and normal ALT. HBsAg was neutralized by reinfusion of HBIg. CONCLUSION: Nucleoside/nucleotide combination is an effective alternative to HBIg/nucleos(t)ide to prevent recurrence of hepatitis B after OLT. PMID: 25939541 [PubMed – as supplied by publisher]

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Nucleoside-Nucleotide Analog Combination Therapy Is Effective in Preventing Recurrent Hepatitis B After Liver Transplantation.

Reactivation of Hepatitis B Virus in HBsAg-Negative Patients with Hepatocellular Carcinoma.

Posted by on 22 Apr 2015 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Reactivation of Hepatitis B Virus in HBsAg-Negative Patients with Hepatocellular Carcinoma. PLoS One. 2015;10(3):e0122041 Authors: Jang JW, Kim YW, Lee SW, Kwon JH, Nam SW, Bae SH, Choi JY, Yoon SK, Chung KW Abstract BACKGROUND & AIMS: Despite increasing attention to hepatitis B virus (HBV) reactivation in hematologic settings, information on reactivation in hepatitis B surface (HBsAg)-negative patients with hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine the incidence and risk factors of HBV reactivation in HBsAg-negative patients undergoing transarterial chemoembolization (TACE). METHODS: A total of 109 HBsAg-negative patients with HCC were consecutively recruited for this study and treated with either mono- (n = 75), combination-drug TACE (n = 20), or combination-drug TACE plus radiotherapy (n = 14). With serial monitoring of virological markers every 2-3 months, patients were observed for HBV reactivation (defined as the reappearance of HBV DNA or sero-reversion of HBsAg) in comparison with control subjects with HBsAg-negative cirrhosis (n = 16) or HBsAg loss (n = 46). RESULTS: During the study period, HBV reactivation occurred in 12 (11.0%) and 1 (1.6%) patients in the TACE and control groups, respectively. The median level of HBV DNA at reactivation was 5,174 copies/ml (range: 216-116,058). Of the 12 patients with HBV reactivation, four (33.3%) developed clinical hepatitis, including one patient who suffered from decompensation. All antiviral-treated patients achieved undetectable HBV DNA or HBsAg loss after commencement of antiviral drugs. TACE was significantly correlated with a high incidence of HBV reactivation, with increasing risk of reactivation with intensive treatment. On multivariate analysis, treatment intensity and a prior history of chronic hepatitis B remained independently predictive of reactivation. CONCLUSIONS: TACE can reactivate HBV replication in HBsAg-negative patients, with a dose-risk relationship between treatment intensity and reactivation. Patients with prior chronic HBV infection who are to undergo intensive TACE should be closely monitored, with an alternative approach of antiviral prophylaxis against HBV reactivation. PMID: 25894607 [PubMed – in process]

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Reactivation of Hepatitis B Virus in HBsAg-Negative Patients with Hepatocellular Carcinoma.

Safety and efficacy of angiographic occlusion of duodenal varices as an alternative to TIPS: review of 32 cases.

Posted by on 13 Apr 2015 | Tagged as: Hepatitis B Alternative Medicine

Safety and efficacy of angiographic occlusion of duodenal varices as an alternative to TIPS: review of 32 cases. Ann Hepatol. 2015 May-jun 2015;14(3):369-379 Authors: Copelan A, Chehab M, Dixit P, Cappell MS Abstract Backgroud/rationale of study. Analyze safety and efficacy of angiographic-occlusion-with-sclerotherapy/embolotherapy-without-transjugular-intrahepatic-portosystemic-shunt (TIPS) for duodenal varices. Although TIPS is considered the best intermediate-to-long term therapy after failed endoscopic therapy for bleeding varices, the options are not well-defined when TIPS is relatively contraindicated, with scant data on alternative therapies due to relative rarity of duodenal varices. Prior cases were identified by computerized literature search, supplemented by one illustrative case. Favorable clinical outcome after angiography defined as no rebleeding during follow-up, without major procedural complications. RESULTS: Thirty-two cases of duodenal varices treated by angiographic-occlusion-with-sclerotherapy/embolotherapy- without-TIPS were analyzed. Patients averaged 59.5 ± 12.2 years old (female = 59%). Patients presented with melena-16, hematemesis & melena-5, large varices-5, growing varices-2, ruptured varices-1, and other- 3. Twenty-nine patients had cirrhosis; etiologies included: alcoholism-11, hepatitis C-11, primary biliary cirrhosis- 3, hepatitis B-2, Budd-Chiari-1, and idiopathic-1. Three patients did not have cirrhosis, including hepatic metastases from rectal cancer-1, Wilson’s disease-1, and chronic liver dysfunction-1. Thirty-one patients underwent esophagogastroduodenoscopy before therapeutic angiography, including fifteen undergoing endoscopic variceal therapy. Therapeutic angiographic techniques included balloon-occludedretrograde-transvenous-obliteration (BRTO) with sclerotherapy and/or embolization-21, DBOE (double-balloon-occluded-embolotherapy)-5, and other-6. Twenty-eight patients (87.5%; 95%-confidence interval: 69-100%) had favorable clinical outcomes after therapeutic angiography. Three patients were therapeutic failures: rebleeding at 0, 5, or 10 days after therapy. One major complication (Enterobacter sepsis) and one minor complication occurred. CONCLUSIONS: This work suggests that angiographic-occlusion-withsclerotherapy/ embolotherapy-without-TIPS is relatively effective (~90% hemostasis-rate), and relatively safe (3% major-complication-rate). This therapy may be a useful treatment option for duodenal varices when endoscopic therapy fails and TIPS is relatively contraindicated. PMID: 25864218 [PubMed – as supplied by publisher]

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Safety and efficacy of angiographic occlusion of duodenal varices as an alternative to TIPS: review of 32 cases.

Serum Golgi Protein 73 (GP73) is a Diagnostic and Prognostic Marker of Chronic HBV Liver Disease.

Posted by on 31 Mar 2015 | Tagged as: Hepatitis B Alternative Medicine

Serum Golgi Protein 73 (GP73) is a Diagnostic and Prognostic Marker of Chronic HBV Liver Disease. Medicine (Baltimore). 2015 Mar;94(12):e659 Authors: Xu Z, Liu L, Pan X, Wei K, Wei M, Liu L, Yang H, Liu Q Abstract Alanine aminotransferase (ALT) is the most commonly used marker of liver injury, but normal ALT levels are seen in a proportion of chronic hepatitis B virus (HBV)-infected patients with severe liver injury. Golgi protein 73 (GP73) is a promising alternative marker of liver injury. This study assessed the relation between GP73 levels and liver disease severity, monitored the kinetic changes in GP73 levels in chronic HBV patients receiving entecavir (ETV) therapy, and investigated the potential diagnostic and prognostic values of serum GP73 as a new liver injury biomarker in chronic HBV infections.This study enrolled 1150 patients with chronic HBV infections, 200 of whom were retrospectively enrolled in this study after receiving 1 year of ETV treatment. GP73 expression in liver tissue was detected by immunohistochemistry. GP73 levels in single or serial serum samples were measured by enzyme-linked immunosorbent assay.Immunohistochemical analysis indicated that GP73 protein expression in the liver increased progressively with pathologic progression from nonexistent or mild hepatitis to severe hepatitis and cirrhosis during chronic HBV infection. Serum GP73 levels were positively correlated with the disease severity of chronic HBV infections (r = 0.58, P < 0.001). In patients with normal ALT levels, serum GP73 concentrations were significantly higher in patients with prominent hepatic inflammatory injury and fibrosis than in patients without hepatic inflammatory injury or fibrosis. Serum GP73 concentrations and GP73 protein expression were decreased in the liver tissues of patients whose ALT levels normalized after 1 year of ETV antiviral therapy.Changes in serum GP73 levels were closely associated with changes in liver injury severity, and, therefore, GP73 may be an effective new liver inflammatory injury biomarker, and could be useful for monitoring the prognosis of chronic HBV infectious patients with normal ALT levels. PMID: 25816035 [PubMed – in process]

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Serum Golgi Protein 73 (GP73) is a Diagnostic and Prognostic Marker of Chronic HBV Liver Disease.

Gene therapeutic approaches to inhibit hepatitis B virus replication.

Posted by on 03 Mar 2015 | Tagged as: Hepatitis B Alternative Medicine

Gene therapeutic approaches to inhibit hepatitis B virus replication. World J Hepatol. 2015 Feb 27;7(2):150-64 Authors: Gebbing M, Bergmann T, Schulz E, Ehrhardt A Abstract Acute and chronic hepatitis B virus (HBV) infections remain to present a major global health problem. The infection can be associated with acute symptomatic or asymptomatic hepatitis which can cause chronic inflammation of the liver and over years this can lead to cirrhosis and the development of hepatocellular carcinomas. Currently available therapeutics for chronically infected individuals aim at reducing viral replication and to slow down or stop the progression of the disease. Therefore, novel treatment options are needed to efficiently combat and eradicate this disease. Here we provide a state of the art overview of gene therapeutic approaches to inhibit HBV replication. We discuss non-viral and viral approaches which were explored to deliver therapeutic nucleic acids aiming at reducing HBV replication. Types of delivered therapeutic nucleic acids which were studied since many years include antisense oligodeoxynucleotides and antisense RNA, ribozymes and DNAzymes, RNA interference, and external guide sequences. More recently designer nucleases gained increased attention and were exploited to destroy the HBV genome. In addition we mention other strategies to reduce HBV replication based on delivery of DNA encoding dominant negative mutants and DNA vaccination. In combination with available cell culture and animal models for HBV infection, in vitro and in vivo studies can be performed to test efficacy of gene therapeutic approaches. Recent progress but also challenges will be specified and future perspectives will be discussed. This is an exciting time to explore such approaches because recent successes of gene therapeutic strategies in the clinic to treat genetic diseases raise hope to find alternative treatment options for patients chronically infected with HBV. PMID: 25729471 [PubMed]

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Gene therapeutic approaches to inhibit hepatitis B virus replication.

Successful use of hepatitis B surface antigen-positive liver grafts – an effective source for donor organs in endemic areas: a single-center…

Posted by on 24 Feb 2015 | Tagged as: Hepatitis B Alternative Medicine

Successful use of hepatitis B surface antigen-positive liver grafts – an effective source for donor organs in endemic areas: a single-center experience. Ann Transplant. 2015;20:103-11 Authors: Jeng LB, Thorat A, Yang HR, Yeh CC, Chen TH, Hsu CH, Hsu SC, Poon KS, Li PC, Lai HC, Su WP, Peng CY Abstract Background Due to high prevalence of hepatitis B virus (HBV) infection in Taiwan, liver grafts from donors positive for hepatitis B surface antigen (HBsAg) without progressive disease can be effective alternative source of donor organs. This study aims to prove the safety of living donor liver transplantation (LDLT) using HBsAg-positive liver grafts and its long-term outcome. Material and Methods We studied 14 consecutive LDLT recipients that received HBsAg-positive grafts from November 2009 to December 2013 for various indications. All donors were chronic HBsAg carriers with normal liver function tests. Median follow-up was 46 months (range, 35-59). Results All the donors and recipients recovered well post-transplant with no reactivation of HBV to date. Two of the recipients died due to extra-hepatic recurrence of HCC. At median follow-up of 46 months, 4-year cumulative survival of recipients was 77.38%. Conclusions In endemic areas, HBsAg-positive donor organs can clearly be used effectively under viral immunoprophylaxis. HBV disease reactivation does not appear to be a threat even with hepatitis B immunoglobulin (HBIG)-free antiviral monoprophylaxis regimen. This study thus proves the safety and feasibility of the option of using HBsAg-positive grafts in high-prevalence areas. PMID: 25703063 [PubMed – in process]

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Successful use of hepatitis B surface antigen-positive liver grafts – an effective source for donor organs in endemic areas: a single-center…

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