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…

Endogenous antiviral microRNAs determine permissiveness for hepatitis B virus replication in cultured human fetal and adult hepatocytes.

Posted by on 19 Feb 2015 | Tagged as: Hepatitis B Alternative Medicine

Endogenous antiviral microRNAs determine permissiveness for hepatitis B virus replication in cultured human fetal and adult hepatocytes. J Med Virol. 2015 Feb 17; Authors: Kumar M, Sharma Y, Bandi S, Gupta S Abstract Superior cell culture models for hepatitis B virus (HBV) will help advance insights into host-virus interactions. To identify mechanisms regulating HBV replication, this study used cultured human HepG2 cells and adult or fetal hepatocytes transduced with adenoviral vector to express HBV upstream of green fluorescent protein. The vector efficiently transduced all cell types. In HepG2 cells, replicative viral intermediates, nucleocapsid-associated HBcAg, and HBsAg were expressed. However, in fetal or adult hepatocytes, pregenomic HBV RNA and viral RNAs were expressed, but nucleocapsid-associated HBcAg in cells or HBsAg in culture medium were absent, indicating interruptions in viral replication due to possible microRNA-related interference. MicroRNA profiling demonstrated that a large number of microRNAs with antiviral potential were differentially expressed in hepatocytes after culture. In transfection assays using HepG2 cells, candidate antiviral microRNAs, e.g., hsa-miR-24 or hsa-miR-638 decreased the levels of HBV transcripts or HBV gene products. Since candidate microRNAs could have targeted interferon response genes as an alternative explanation interferon signaling was examined. However, HBV replication in cultured hepatocytes was not restored despite successful inhibition of JAK1/2-STAT signaling by the inhibitor, ruxolitinib. Therefore, HBV was unable to complete replication in cultured hepatocytes due to expression of multiple antiviral microRNAs. This mechanism should help understand restrictions in HBV replication for developing HBV models in cultured cells while providing frameworks for pathophysiological studies of HBV replication in subsets of hepatocytes or stem/progenitor cells during hepatitis. J. Med. Virol. 00: 1-16, 2015. © 2015 Wiley Periodicals, Inc. PMID: 25690916 [PubMed – as supplied by publisher]

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Endogenous antiviral microRNAs determine permissiveness for hepatitis B virus replication in cultured human fetal and adult hepatocytes.

Accuracy of transient elastography in assessing liver fibrosis in chronic viral hepatitis: A multicenter, retrospective study.

Posted by on 17 Feb 2015 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Accuracy of transient elastography in assessing liver fibrosis in chronic viral hepatitis: A multicenter, retrospective study. Liver Int. 2015 Feb 14; Authors: Seo YS, Kim MY, Kim SU, Hyun BS, Jang JY, Lee JW, Lee JI, Suh SJ, Park SY, Park H, Jung EU, Kim BS, Kim IH, Lee TH, Um SH, Han KH, Kim SG, Paik SK, Choi JY, Jeong SW, Jin YJ, Lee KS, Yim HJ, Tak WY, Hwang SG, Lee YJ, Lee CH, Kim DC, Kang YW, Kim YS, The Korean Transient Elastography Study Group Abstract BACKGROUND/AIMS: Transient elastography (TE) has become an alternative to liver biopsy (LB). This study investigated the diagnostic performance of liver stiffness (LS) measurement using TE in Korean patients with chronic hepatitis B and C (CHB and CHC). METHODS: From April 2006 to June 2014, 916 patients (567 CHB and 349 CHC) who underwent LB and TE at 15 centers were analyzed. The Batts and Ludwig scoring system was used for histologic assessment. Aspartate aminotransferase (AST)-to-platelet ratio indexes (APRI) were calculated. Area under the receiver operating characteristic curve (AUROC) was used. RESULTS: The median age, LS value, and APRI score were 45 years, 8.8 kPa, and 0.61, respectively, in CHB patients versus 51 years, 6.8 kPa and 0.55, respectively in CHC patients. TE was significantly superior to APRI in CHB patients (AUROC 0.774 vs. 0.72 for ≥F2, 0.849 vs. 0.812 for ≥F3, and 0.902 vs. 0.707 for F4, respectively; all P<0.05). Furthermore, TE was significantly superior for predicting ≥ F3 stage (AUROC 0.865 vs. 0.840, P=0.009) whereas it was similar for predicting ≥ F2 and F4 stage (AUROC 0.822 vs. 0.796; 0.910 vs. 0.884; all P>0.05) in CHC patients. In CHB patients, optimal cutoff LS values were 7.8 kPa for ≥ F2, 8.2 kPa for ≥ F3, and 11.6 kPa for F4, versus 6.8 kPa, 8.6 kPa, and 14.5 kPa, respectively, in CHC patients. CONCLUSIONS: TE can accurately assess the degree of liver fibrosis in Korean patients with CVH. TE was superior to APRI for predicting each fibrosis stage. This article is protected by copyright. All rights reserved. PMID: 25682719 [PubMed – as supplied by publisher]

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Accuracy of transient elastography in assessing liver fibrosis in chronic viral hepatitis: A multicenter, retrospective study.

The global burden of liver disease: the major impact of China.

Posted by on 12 Feb 2015 | Tagged as: Hepatitis B Alternative Medicine

Related Articles The global burden of liver disease: the major impact of China. Hepatology. 2014 Dec;60(6):2099-108 Authors: Wang FS, Fan JG, Zhang Z, Gao B, Wang HY Abstract Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus [HBV]), nonalcoholic fatty liver disease, and alcoholic liver disease, affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second-most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its “leader in liver diseases” title by investing large amounts of money in funding research, vaccines, and drug development for liver diseases and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management, and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China. PMID: 25164003 [PubMed – indexed for MEDLINE]

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The global burden of liver disease: the major impact of China.

Validation of rapid point-of-care (POC) tests for the detection of hepatitis B surface antigen (HBsAg) in field and laboratory settings in The Gambia,…

Posted by on 30 Jan 2015 | Tagged as: Hepatitis B Alternative Medicine

Validation of rapid point-of-care (POC) tests for the detection of hepatitis B surface antigen (HBsAg) in field and laboratory settings in The Gambia, West Africa. J Clin Microbiol. 2015 Jan 28; Authors: Freeya Njai H, Shimakawa Y, Sanneh B, Ferguson L, Ndow G, Mendy M, Sow A, Lo G, Toure-Kane C, Tanaka J, Taal M, D’alessandro U, Njie R, Thursz M, Lemoine M Abstract Hepatitis B virus (HBV) infection is a leading cause of death in sub-Saharan Africa (SSA). Point-of-care tests for hepatitis B surface antigen (HBsAg) could be an ideal tool for large scale HBV screening/treatment programme in SSA. Using data from the PROLIFICA programme, we conducted a cross-sectional study to assess the diagnostic accuracy of three point-of-care tests (Determine™, VIKIA® and Espline®) for the detection of HBsAg in the field or laboratory settings in The Gambia. In the field, we used finger-prick whole blood for the Determine™ and VIKIA®, and dried blood spots for the reference standard test (AxSYM®HBsAg ELISA). In the laboratory we used serum for the Determine™, Espline®, and reference test (Architect® chemiluminescent microparticle immunoassay). Of 773 participants recruited at the community and 227 known chronic HBV carriers (1,000 subjects in total), 293 were positive for HBsAg. The sensitivity and specificity of the Determine™ test was 88.5% and 100% in the field and 95.3% and 93.3% in the laboratory settings, respectively. The sensitivity and specificity of the VIKIA® test (in the field) and Espline® (in the laboratory) were 90.0% and 99.8%, and 93.9% and 94.7%, respectively. There was no evidence that one kit was better than another. Most of the patients with false negative results (18/19) were classified as inactive chronic carriers. In summary, the three point-of-care tests had acceptable range of diagnostic accuracy. These tests may represent an accurate, rapid and inexpensive alternative to serology testing for the screening of HBV infection at field level in SSA. PMID: 25631805 [PubMed – as supplied by publisher]

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Validation of rapid point-of-care (POC) tests for the detection of hepatitis B surface antigen (HBsAg) in field and laboratory settings in The Gambia,…

Polyacetylenes and anti-hepatitis B virus active constituents from Artemisia capillaris.

Posted by on 08 Jan 2015 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Polyacetylenes and anti-hepatitis B virus active constituents from Artemisia capillaris. Fitoterapia. 2014 Jun;95:187-93 Authors: Zhao Y, Geng CA, Sun CL, Ma YB, Huang XY, Cao TW, He K, Wang H, Zhang XM, Chen JJ Abstract Three new polyacetylenes, 8-(Z)-decene-4, 6-diyne-1, 3, 10-triol (1), 1, 3S, 8S-trihydroxydec-9-en-4, 6-yne (2), 3S, 8S-dihydroxydec-9-en-4, 6-yne 1-O-β-D-glucopyranoside (3), and one new glucosyl caffeoate, 1-O-ethyl-6-O-caffeoyl-β-D-glucopyranose (4), together with 34 known compounds were isolated from Artemisia capillaris. The structures of the new compounds were determined by extensive spectroscopic analyses including 1D and 2D NMR, HRESIMS, [α]D and CD experiments. Among them, 19 compounds showed activity inhibiting HBsAg secretion; 20 compounds showed activity inhibiting HBeAg secretion; and 25 compounds possessed inhibitory activity against HBV DNA replication according to our anti-HBV assay on HepG 2.2.15 cell line in vitro. The most active compound 12 could inhibit not only the secretions of HBsAg and HBeAg, but also HBV DNA replication with IC50 values of 15.02 μM (SI=111.3), 9.00 μM (SI=185.9) and 12.01 μM (SI=139.2). PMID: 24685503 [PubMed – indexed for MEDLINE]

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Polyacetylenes and anti-hepatitis B virus active constituents from Artemisia capillaris.

A new phenylethanoid glycoside with antioxidant and anti-HBV activity from Tarphochlamys affinis.

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

Related Articles A new phenylethanoid glycoside with antioxidant and anti-HBV activity from Tarphochlamys affinis. Arch Pharm Res. 2014 May;37(5):600-5 Authors: Zhou XL, Wen QW, Lin X, Zhang SJ, Li YX, Guo YJ, Huang RB Abstract A new phenylethanoid glycoside, named taraffinisoside A (1), together with five known glycosides were isolated from the stems and leaves of Tarphochlamys affinis. The structure of taraffinisoside A was identified on the basis of detailed spectral analysis. Compounds 1-4 and 6 showed potent antioxidant activities with IC50 values of 10.36, 19.73, 43.95, 15.30 and 46.04 μM by 1,1-diphenyl-2-picryhydrazyl radical-scavenging assay. Compounds 1, 2 and 4 showed anti-HBV activities, with IC50 values of 0.50, 0.72 and 0.26 mM for HBsAg and 0.93, 0.42 and 0.07 mM for HBeAg, respectively. PMID: 23893479 [PubMed – indexed for MEDLINE]

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A new phenylethanoid glycoside with antioxidant and anti-HBV activity from Tarphochlamys affinis.

[Auxiliary treatment of HBV correlated hepatic failure by Chinese herbs: a systematic review of randomized controlled trials].

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

Related Articles [Auxiliary treatment of HBV correlated hepatic failure by Chinese herbs: a systematic review of randomized controlled trials]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013 Nov;33(11):1449-56 Authors: Wang RY, Zhou YF, Fei YT, Sun KW Abstract OBJECTIVE: To evaluate the effectiveness and safety of Chinese herbs as an adjuvant treatment for hepatitis virus B (HBV)-related hepatic failure. METHODS: Data were retrieved through the Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, PubMed, CNKI, VIP, Wanfang Database, and ChiCTR by key words or free words such as hepatic failure, severe hepatitis, HBV, Chinese medicine, randomization, and control. Appendix references of related papers were taken as supplementary indices. According to requirement for Cochrane systematic evaluation, randomized clinical trials on assessing the effectiveness and safety of Chinese herbs as main or adjuvant treatment in treating HBV-related hepatic failure were methodologically assessed, data extracted and analyzed. RESULTS: Totally 21 trials on Chinese herbal medicine therapy versus standard medical therapy (involving 1 881 patients) were included. Most trials had unclear risk bias. In 5 studies on the mortality, 3 trials showed that the mortality was lower in the test group than in the control group [RR 0.40, 95% CI (0.20, 0.79), P = 0.0002]. In 6 randomized control trials, totally 20 papers reported the control of complications. Eight results showed Chinese herbal medicine therapy had better effect in controlling complications. The recurrence rate and assessment of the survival quality were reported. Considering secondary indicators, four trials showed Chinese herbal medicine therapy had better effect in lowering the ineffective rate, decreasing total bilirubin (TBIL), and elevating prothrombin activity (PTA). Other prescriptive analyses found that the overall effect on secondary indicators was better in the test group than in the control group, but not all the indicators were statistically different. Adverse reactions were only reported in two papers, showing no severe adverse reaction. CONCLUSION: According to present evidence, till now, we could not judge whether Chinese herbs, as an adjuvant treatment, could do any favor for lowering the incidence and recurrence of hepatic failure patients, and improving their survival qualities. PMID: 24483102 [PubMed – indexed for MEDLINE]

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[Auxiliary treatment of HBV correlated hepatic failure by Chinese herbs: a systematic review of randomized controlled trials].

[Intervention of chronic hepatitis B liver fibrosis patients in different stages by syndrome typing and different activating blood removing stasis…

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

Related Articles [Intervention of chronic hepatitis B liver fibrosis patients in different stages by syndrome typing and different activating blood removing stasis methods: a clinical study]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013 Nov;33(11):1457-61 Authors: Liu SY, Zhang YQ, Liu YL, Guo P, Zhou CM Abstract OBJECTIVE: To observe the clinical efficacy of treating chronic hepatitis B liver fibrosis (CHBLF) in different stages by syndrome typing and different activating blood removing stasis methods (ABRSM). METHODS: Totally 100 CHBLF patients of vital qi deficiency blood stasis syndrome (VQDBSS) treated at the Department of Liver Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences from July 2008 to December 2011, were randomly assigned to the treatment group and the control group, 50 in each group. Those in the treatment group were treated by self-formulated decoctions for activating blood nourishing blood (ABNB), activating blood removing stasis (ABRS), and activating blood softening hard mass (ABSHM) according to their stages of disease conditions (mild, moderate, and severe). Those in the control group were treated with Compound Biejia Ruangan Tablet (CBRT). Integrals of Chinese medical syndromes, liver functions [mainly including alanine aminotransferase (ALT), albumin/globulin (A/ G)], ultrasonographic examinations of liver (mainly including echoes of liver, width of spleens, width of portal vein), four indicators of serum hepatic fibrosis [including serum hyaluronic acid (HA), laminin (LN), type IV collagen (IV-C), type III collagen peptide (P-III-P)] were statistically analyzed. The therapeutic course was 6 months for all. RESULTS: Compared with before treatment in the same group, the integrals of Chinese medical syndromes both decreased after treatment in the two groups (P < 0.05). The width of spleens decreased in the treatment group more obviously after treatment than before treatment (P < 0.05). Compared with the control group, the integrals of Chinese medical syndromes and the width of spleens were more obviously improved in the treatment group, showing statistical difference (P < 0.05). Compared with before treatment in the same group, levels of ALT, HA, and LN significantly decreased, and the level of A/G significantly increased after treatment in the two groups, showing statistical difference (P < 0.05). Compared with the control group, the A/G level, HA, and LN were more obviously improved in the treatment group, showing statistical difference (P < 0.05). The total effective rate was 76% in the treatment group and 46% in the control group, showing statistical difference (P < 0.05). CONCLUSIONS: Treating CH-BLF in different stages by ABRSM got better effect than using CBRT alone. It could favorably improve clinical symptoms of CHBLF patients and their serum biochemical indicators. PMID: 24483103 [PubMed – indexed for MEDLINE]

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[Intervention of chronic hepatitis B liver fibrosis patients in different stages by syndrome typing and different activating blood removing stasis…

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