December 2014

Monthly Archive

Regulation of Multiple Stages of Hepadnavirus Replication by Carboxyl-Terminal Domain of Viral Core Protein in Trans.

Posted by on 30 Dec 2014 | Tagged as: Hepatitis B Alternative Medicine

Regulation of Multiple Stages of Hepadnavirus Replication by Carboxyl-Terminal Domain of Viral Core Protein in Trans. J Virol. 2014 Dec 24; Authors: Liu K, Ludgate L, Yuan Z, Hu J Abstract Mutational analyses have indicated that the carboxyl-terminal domain (CTD) of hepadnavirus core protein, and its state of phosphorylation, are critical for multiple steps in viral replication. Also, CTD interacts with host proteins in a phosphorylation state-dependent manner. To ascertain the role of CTD in viral replication without perturbing its sequence and the role of CTD-host interactions, CTD of the human hepatitis B virus (HBV) or duck hepatitis B virus (DHBV) core protein, either wild type (WT) or with alanine or glutamic acid/aspartic acid substitutions at the phosphorylation sites, were expressed in cells replicating DHBV with WT core protein. A dramatic decrease in phosphorylation of the DHBV core protein (DHBc) was observed when the WT and most HBV core protein CTD (HCTD) variants were co-expressed in trans, which was accompanied by a profound reduction of viral core DNA and in particular, the double-stranded DNA. One HCTD variant that failed to change DHBc phosphorylation also had no effect on DHBV core DNA. All WT and variant HCTDs and DHBc CTDs (DCTDs) decreased the DHBV covalently closed circular (CCC) DNA. Identification of CTD-host interactions indicated that CDK2 binding by CTD may mediate its inhibitory effect on DHBc phosphorylation and reverse transcription via competition with DHBc for the host kinase, whereas importin α binding by CTD may contribute to inhibition of CCC DNA production by competitively blocking the nuclear import of viral nucleocapsids. These results suggest the possibility of blocking multiple steps of viral replication, especially CCC DNA formation, via inhibition of CTD functions. IMPORTANCE: Mutational analyses have suggested that the carboxyl-terminal domain (CTD) of hepadnavirus core protein is critical for viral replication. However, results from mutational analyses are subject to alternative interpretations. Also, how CTD affects virus replication remains unclear. In this study, we took an alternative approach to mutagenesis by overexpressing CTD alone in cells replicating the virus with the wild type core protein to determine the roles of CTD in viral replication. Our results revealed that CTD can inhibit multiple stages of viral replication, and its effects may be mediated at least in part through specific host interactions. They suggest that CTD, or its mimics, may have therapeutic potential. Furthermore, our experimental approach should be broadly applicable as a complement to mutagenesis for studying protein functions and interactions while at the same time providing a means to identify the relevant interacting factors. PMID: 25540387 [PubMed – as supplied by publisher]

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Regulation of Multiple Stages of Hepadnavirus Replication by Carboxyl-Terminal Domain of Viral Core Protein in Trans.

Study of ZHENG differentiation in hepatitis B-caused cirrhosis: a transcriptional profiling analysis.

Posted by on 23 Dec 2014 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Study of ZHENG differentiation in hepatitis B-caused cirrhosis: a transcriptional profiling analysis. BMC Complement Altern Med. 2014;14:371 Authors: Lu YY, Chen QL, Guan Y, Guo ZZ, Zhang H, Zhang W, Hu YY, Su SB Abstract BACKGROUND: In traditional Chinese medicine (TCM) clinical practice, ZHENG (also known as TCM syndrome) helps to understand the human homeostasis and guide individualized treatment. However, the scientific basis of ZHENG remains unclear due to limitations of current reductionist approaches. METHODS: We collected the leukocyte samples of three hepatitis B-caused cirrhosis (HBC) patients with dampness-heat accumulation syndrome (DHAS) and three HBC patients with liver depression and spleen deficiency syndrome (LDSDS) for microarray analysis. We generated Gene-Regulatory-Networks (GeneRelNet) from the differentially expressed genes (DEGs) of microarray date. Core genes were validated using anther independent cohort of 40 HBC patients (20 DHAS, 20 LDSDS) with RT-PCR. RESULTS: There were 2457 mapped genes were differentially expressed between DHAS and LDSDS (Fold change ≥ 2.0, P < 0.05). There were markedly different genes co-expression patterns in DHAS and LDSDS. Furthermore, three differential co-expression genes including purine nucleoside phosphorylase (PNP); aquaporin 7 (AQP7) and proteasome 26S subunit, non-ATPase 2 (PSMD2) were screened by GeneRelNets, and their mRNA expressions were further validated by real time RT-PCR. The results were consistent with microarray. The PNP (P = 0.007), AQP7 (P = 0.038) and PSMD2 (P = 0.009) mRNA expression is significant difference between DHAS and LDSDS using the non-parametric test. Furthermore, we constructed an mRNA panel of PNP, AQP7 and PSMD2 (PAP panel) by logistic regression model, and evaluated the PAP panel to distinguish DHAS from LDSDS by area under the receiver operating characteristic curve (AUC) analysis, which showed a higher accuracy (AUC = 0.835). Gene ontology (GO) analysis indicated that the DHAS is most likely related to system process while the functions overrepresented by LDSDS most related to the response to stimulus. CONCLUSIONS: This study suggested that there are particular transcriptional profiles, genes co-expressions patterns and functional properties of DHAS and LDSDS, and PNP, AQP7, and PSMD2 may be involved in ZHENG differentiation of DHAS and LDSDS in HBC. PMID: 25280538 [PubMed – indexed for MEDLINE]

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Study of ZHENG differentiation in hepatitis B-caused cirrhosis: a transcriptional profiling analysis.

[Therapeutic efficacy and quality of life investigation of traditional Chinese medicine-based therapy of chronic hepatitis B-related liver fibrosis].

Posted by on 17 Dec 2014 | Tagged as: Hepatitis B Alternative Medicine

Related Articles [Therapeutic efficacy and quality of life investigation of traditional Chinese medicine-based therapy of chronic hepatitis B-related liver fibrosis]. Zhonghua Gan Zang Bing Za Zhi. 2014 Jan;22(1):30-2 Authors: An J, Ni W, Qiao J Abstract OBJECTIVE: To prospectively evaluate the efficacy of a traditional Chinese medicine (TCM)-based therapy for treating liver fibrosis in patients with chronic hepatitis B (CHB), and to investigate the patients’ perception of the treatment’s effects on quality of life (QoL). METHODS: A total of 430 patients with CHB-related liver fibrosis were randomly assigned to treatment groups for receipt of a 12-month course of the antiviral drug entecavir alone (control group) or in combination with the TCM Liuweiwuling tablets. Patients were assessed before (pre-treatment) and after therapy and the treatment-related differences in clinical manifestations, levels of liver function markers and liver fibrosis indexes, color ultrasound images, and hepatitis B virus (HBV) DNA load were compared between the two groups by statistical analysis. The generic QoL scale developed by the World Health Organization (WHOQOL-BREF) was used to score the patients’ perceptions of treatment outcome. RESULTS: After treatment, the patients in both groups showed significant improvement in the majority of clinical manifestations (both P less than 0.05), with the exception of bloating. In addition, both groups showed significant improvements of liver function markers and in signs of liver fibrosis (both P less than 0.05). Both groups also showed significant reductions in the diameters of the portal and splenic (both P less than 0.05), as well as increases in the rate of undetectable HBV DNA (with a statistically similar outcome achieved in the two groups). Finally, both groups had higher QoL scores after treatment, with all assessed parameters except environment showing a significant improvement (all P less than 0.05). CONCLUSION: When used in combination with entecavir, the TCM Liuweiwuling tablet is a safe therapy for CHB and its related liver fibrosis and may help to improve the QoL of these patients. PMID: 24721240 [PubMed – indexed for MEDLINE]

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[Therapeutic efficacy and quality of life investigation of traditional Chinese medicine-based therapy of chronic hepatitis B-related liver fibrosis].

[Clinical effect of combination therapy with Fufang Biejia Ruangan tablet and entecavir in patients with hepatitis B virus-related cirrhosis].

Posted by on 17 Dec 2014 | Tagged as: Hepatitis B Alternative Medicine

Related Articles [Clinical effect of combination therapy with Fufang Biejia Ruangan tablet and entecavir in patients with hepatitis B virus-related cirrhosis]. Zhonghua Gan Zang Bing Za Zhi. 2014 Aug;22(8):604-8 Authors: Wu G, He H, Li H, Chen W Abstract OBJECTIVE: To investigate the clinical effect of combination therapy with Fufang Biejia Ruangan tablet and entecavir in patients with hepatitis B virus (HBV)-related cirrhosis. METHODS: A total of 163 patients with HBV-related cirrhosis were recruited for treatment between March 2010 and August 2012, and divided into the following three groups:group A (n =56) received Fufang Biejia Ruangan Tablet plus entecavir; group B (n =52) received entecavir only; and group C (n =55) received Fufang Biejia Ruangan tablet only. Enzyme-linked immunoassay methods were used to measure serum levels of hyaluronic acid (HA), laminin (LN), collagen (PCIV) and prolyl endopeptidase (PLD). The grade of liver fibrosis was determined upon liver biopsy, and score of liver stiffness was measured by FibroScan. RESULTS: All three treatment groups showed significant decreases from baseline in serum levels of alanine aminotransferase, aspartate aminotransferase, HBV DNA, HA, LN, PCIV and PLD (all P < 0.05). However, the changes in HA, LN, PCIV and PLD levels were significantly greater in group A than in either group B or C (P < 0.05). All three treatment groups showed significant improvements from baseline in liver fibrosis grade and liver stiffness score (P < 0.05). The total effective rate of group A was 82.14%, which was significantly higher than that of groups B and C (P < 0.05). CONCLUSION: Combination therapy of Fufang Biejia Ruangan tablet plus entecavir is effective for treating HBV-related cirrhosis. PMID: 25243962 [PubMed – indexed for MEDLINE]

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[Clinical effect of combination therapy with Fufang Biejia Ruangan tablet and entecavir in patients with hepatitis B virus-related cirrhosis].

[Supplemental Fuzhenghuayu capsule therapy for improving liver fibrosis markers in patients with chronic hepatitis B following unsatisfactory outcome…

Posted by on 15 Dec 2014 | Tagged as: Hepatitis B Alternative Medicine

Related Articles [Supplemental Fuzhenghuayu capsule therapy for improving liver fibrosis markers in patients with chronic hepatitis B following unsatisfactory outcome of nucleos(t)ide analogue monotherapy]. Zhonghua Gan Zang Bing Za Zhi. 2013 Jul;21(7):514-8 Authors: Tian YL, Zhu XY, Yin WW, Zang ZD, Wang L, Fu XL Abstract OBJECTIVE: To investigate the ability of Fuzhenghuayu capsule to improve markers of liver fibrosis when provided as supplemental therapy in patients with chronic hepatitis B (CHB) who achieved complete virological response but unsatisfactory resolution of fibrosis markers with nucleos(t)ide analog (NAs) monotherapy. METHODS: One-hundred-and-ten patients with CHB-related liver fibrosis who had received NA for more than or equal to 2 years and achieved sustained virological response (SVR) but no improvement in liver fibrosis index were randomly divided into two equal groups: experimental group, continued oral NAs (one tablet, 1 time/day) with simultaneous Fuzhenghuayu capsule (1.5 g, 3 times/day) for 48 weeks; control group, continued oral NAs only for 48 weeks. Serum fibrosis markers (hyaluronic acid (HA), laminin (LN), amino terminal propeptide of type III procollagen (PIIIP) and IV collagen (IV-C)), liver fibrosis stages, B ultrasonic wave, and liver function were observed before (baseline) and after treatment and compared by statistical analysis. RESULTS: The baseline levels of fibrosis markers were not significantly different between the experimental and control groups. After treatment, the levels of all of the fibrosis markers were lower in the experimental group (P less than 0.05 vs. control group; HA t = 19.548, LN t = 2.264, PIIIP t = 2.230, and IV-C t = 6.649) and lower than the baseline levels (P less than 0.01; HA t = 12.458, LN t = 7.402, PIIIP t = 4.620, IV-C t = 8.937). The control group also showed a significant reduction in HA and LN levels after treatment (P less than 0.01 vs. baseline; t = 5.202 and 3.444), but PIIIP and IV-C were unaffected. The baseline liver fibrosis stages were not significantly different between the experimental and control groups. After treatment, only the experimental group showed significant improvement in liver fibrosis stages (P less than 0.01). The rates of excellent therapeutic outcome, effectiveness, and non-effectiveness were significantly different between the experimental group (11.3%, 43.4%, and 45.3%) and the control group (1.0%, 22.2%, and 75.6%) (x2 = 9.408, P less than 0.01). Similar trends were observed for improvements in B ultrasonic wave for liver and spleen and in markers of liver function. Finally, neither treatment group experienced adverse effects. CONCLUSION: For CHB patients who achieve SVR by antiviral treatment with NAs, but unsatifactory improvement in liver fibrosis indices, administration of supplemental Fuzhenghuayu capsule with continued NAs therapy may represent a safe and effective treatment. PMID: 24074710 [PubMed – indexed for MEDLINE]

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[Supplemental Fuzhenghuayu capsule therapy for improving liver fibrosis markers in patients with chronic hepatitis B following unsatisfactory outcome…

Clinical Events after Cessation of Lamivudine Therapy in Patients Recovered from a Hepatitis B Flare with Hepatic Decompensation.

Posted by on 03 Dec 2014 | Tagged as: Hepatitis B Alternative Medicine

Clinical Events after Cessation of Lamivudine Therapy in Patients Recovered from a Hepatitis B Flare with Hepatic Decompensation. Clin Gastroenterol Hepatol. 2014 Oct 28; Authors: Chang ML, Jeng WJ, Liaw YF Abstract BACKGROUND: & Aims: Before guidelines were issued, instead of indefinite therapy, many patients with hepatitis B flare and hepatic decompensation had discontinued lamivudine therapy. We investigated heir outcomes. METHODS: We performed a retrospective cohort study of 263 consecutive patients with chronic hepatitis B (94 with cirrhosis) who recovered from a flare of hepatitis with hepatic decompensation and were followed after cessation of lamivudine therapy. Clinical events that occurred during the follow-up period were assessed by chart review and retrospective analysis of results from assays. RESULTS: The mean duration of lamivudine therapy was 12.1±8.6 months; data were collected from patients for 89.1±38.7 months after therapy ended. In the first year off therapy, 29.9% of patients had clinical relapse, 16.2% had hepatitis flares, and 8.2% had hepatic decompensation. There was no significant difference in the incidence of hepatic decompensation between patients with and without cirrhosis. Hepatocellular carcinoma developed in 14 patients after cessation of therapy (within 20-109 months), with a 5-year cumulative incidence of 5.2% in patients with cirrhosis. Three patients with cirrhosis died of hepatic decompensation after cessation of therapy (within 38-76 months; 5 year cumulative mortality, 2.9%). Multivariate analyses showed that men were more likely than women to have recurrence of hepatic decompensation (hazard ratio [HR], 4.339; P=.014). Liver cirrhosis (HR, 2.766; P=.041) and age (HR, 1.054; P=.023) increased risk for hepatocellular carcinoma. CONCLUSIONS: Cessation of lamivudine therapy after recovery from a hepatitis B flare with decompensation was safe for most patients. However, 8.2% develop decompensation within 1 year and can be rescued by timely retreatment. With close monitoring, the stopping strategy could be a feasible alternative to indefinite therapy, especially in low resource settings. PMID: 25445774 [PubMed – as supplied by publisher]

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Clinical Events after Cessation of Lamivudine Therapy in Patients Recovered from a Hepatitis B Flare with Hepatic Decompensation.