Treatment of hepatitis B

Chronic hepatitis B virus (HBV) infection affects approximately 350 million people worldwide. Treatment of chronic hepatitis B is aimed at sustained suppression of HBV replication and remission of liver disease. Currently, antiviral treatment is indicated for hepatitis B e antigen (HBeAg)-positive patients in the immune clearance phase, and for HBeAg-negative patients with evidence of active liver disease and continued high levels of HBV replication. Treatment is not recommended for patients in the immune tolerance phase or the inactive carrier state, due to lack of efficacy of current treatment. This review updates safety and efficacy data of interferon alpha and lamivudine in the treatment of chronic hepatitis B. Management strategies in different clinical scenarios and future treatments are also discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42442/1/20370771.pd

HBV genotype B is associated with better response to interferon therapy in HBeAg( + ) chronic hepatitis than genotype C

Hepatitis B virus (HBV) genotype and precore/core promoter mutations have been implicated in spontaneous and interferon alfa (IFN-Α)—related hepatitis B e antigen (HBeAg) seroconversion. We performed a retrospective analysis of a previously reported randomized controlled trial to determine the effects of HBV genotype and precore/core promoter mutations on IFN-Α response in patients with HBeAg-positive chronic hepatitis. Clinical data and stored sera from 109 (95%) patients in the original trial were analyzed. Seventy-three patients received IFN-Α and 34 received no treatment (controls). Almost all patients had HBV genotypes B (38%) and C (60%). Antiviral response was achieved in 39% and 17% of IFN-Α—treated patients ( P = 0.03) and in 10% and 8% of untreated controls ( P = 0.88) with HBV genotype B and C, respectively. Multivariate analysis identified HBV genotype B, elevated pretreatment alanine aminotransferase (ALT) levels, and low pretreatment HBV-DNA levels but not IFN-Α treatment as independent factors associated with antiviral response. Among the 66 patients with elevated pretreatment ALT level, antiviral response was achieved in 57% and 21% of IFN-Α—treated patients ( P = 0.019), and in 25% and 8% of untreated controls ( P = 0.45) with HBV genotype B and C, respectively. Multivariate analysis showed that genotype B and low pretreatment HBV-DNA levels were independent predictors of antiviral response. In conclusion, our data showed that HBV genotype B was associated with a higher rate of IFN-induced HBeAg clearance compared with genotype C. Stratification for HBV genotypes should be considered in future clinical trials of antiviral therapy of chronic hepatitis B. (H EPATOLOGY 2002;36:1425–1430).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38415/1/1840360619_ftp.pd

Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72563/1/j.1365-2893.2005.00581.x.pd

A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C

Information on the stage of liver fibrosis is essential in managing chronic hepatitis C (CHC) patients. However, most models for predicting liver fibrosis are complicated and separate formulas are needed to predict significant fibrosis and cirrhosis. The aim of our study was to construct one simple model consisting of routine laboratory data to predict both significant fibrosis and cirrhosis among patients with CHC. Consecutive treatment-naive CHC patients who underwent liver biopsy over a 25-month period were divided into 2 sequential cohorts: training set (n = 192) and validation set (n = 78). The best model for predicting both significant fibrosis (Ishak score ≥ 3) and cirrhosis in the training set included platelets, aspartate aminotransferase (AST), and alkaline phosphatase with an area under ROC curves (AUC) of 0.82 and 0.92, respectively. A novel index, AST to platelet ratio index (APRI), was developed to amplify the opposing effects of liver fibrosis on AST and platelet count. The AUC of APRI for predicting significant fibrosis and cirrhosis were 0.80 and 0.89, respectively, in the training set. Using optimized cut-off values, significant fibrosis could be predicted accurately in 51% and cirrhosis in 81% of patients. The AUC of APRI for predicting significant fibrosis and cirrhosis in the validation set were 0.88 and 0.94, respectively. In conclusion, our study showed that a simple index using readily available laboratory results can identify CHC patients with significant fibrosis and cirrhosis with a high degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among CHC patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34794/1/510380230_ftp.pd

Sport-specific balance ability in Taekwondo practitioners

ABSTRACT Fong SSM, Cheung CKY, Ip JY, Chiu JHN, Lam KLH, Tsang WWN. Sport-specific balance ability in Taekwondo practitioners. J. Hum. Sport Exerc. Vol. 7, No. 2, pp. 520-526, 2012. Taekwondo is a combat sport emphasizing on kicking techniques and dynamic footwork. Specialized balance ability is crucial for Taekwondo practitioners. This study aimed to compare (1) the postural stability during turning, and (2) the forward lunge distance between adolescent TKD practitioners and non-practitioners. Nineteen TKD practitioners (12 males, 7 females; Mean age ± SD: 15.58 ± 1.07 years) and nineteen control participants (13 males, 6 females; Mean age ± SD: 16.21 ± 0.98 years) were recruited in the study. Balance performance was assessed by the Forward Lunge Test and Step/Quick Turn Test with the NeuroCom Balance Master system. Forward lunge distance, turn time and turn sway were measured. TKD practitioners were found to turn faster by 35.37% (p=0.004) and sway less during turning by 15.23% (p=0.034) than non-practitioners. The forward lunge distance in TKD practitioners was 5.67% shorter than that in control participants (p=0.046). This study shows that TKD practitioners might have sport-specific balance ability. The findings of this study inspire the exploration of the longitudinal training effect of TKD so as to develop the evidence base for this exercise option to improve the postural control of adolescents with balance problems

Carboxyl-terminal truncated HBx regulates a distinct microRNA transcription program in Hepatocellular carcinoma development

Background: The biological pathways and functional properties by which misexpressed microRNAs (miRNAs) contribute to liver carcinogenesis have been intensively investigated. However, little is known about the upstream mechanisms that deregulate miRNA expressions in this process. In hepatocellular carcinoma (HCC), hepatitis B virus (HBV) X protein (HBx), a transcriptional trans-activator, is frequently expressed in truncated form without carboxyl-terminus but its role in miRNA expression and HCC development is unclear. Methods: Human non-tumorigenic hepatocytes were infected with lentivirus-expressing full-length and carboxyl-terminal truncated HBx (Ct-HBx) for cell growth assay and miRNA profiling. Chromatin immunoprecipitation microarray was performed to identify the miRNA promoters directly associated with HBx. Direct transcriptional control was verified by luciferase reporter assay. The differential miRNA expressions were further validated in a cohort of HBV-associated HCC tissues using real-time PCR. Results: Hepatocytes expressing Ct-HBx grew significantly faster than the full-length HBx counterparts. Ct-HBx decreased while full-length HBx increased the expression of a set of miRNAs with growth-suppressive functions. Interestingly, Ct-HBx bound to and inhibited the transcriptional activity of some of these miRNA promoters. Notably, some of the examined repressed-miRNAs (miR-26a, -29c, -146a and -190) were also significantly down-regulated in a subset of HCC tissues with carboxyl-terminal HBx truncation compared to their matching non-tumor tissues, highlighting the clinical relevance of our data. Conclusion: Our results suggest that Ct-HBx directly regulates miRNA transcription and in turn promotes hepatocellular proliferation, thus revealing a viral contribution of miRNA deregulation during hepatocarcinogenesis. © 2011 Yip et al.published_or_final_versio

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Sport-specific balance ability in Taekwondo practitioners

Taekwondo is a combat sport emphasizing on kicking techniques and dynamic footwork. Specialized balance ability is crucial for Taekwondo practitioners. This study aimed to compare (1) the postural stability during turning, and (2) the forward lunge distance between adolescent TKD practitioners and non-practitioners. Nineteen TKD practitioners (12 males, 7 females; Mean age ± SD: 15.58 ± 1.07 years) and nineteen control participants (13 males, 6 females; Mean age ± SD: 16.21 ± 0.98 years) were recruited in the study. Balance performance was assessed by the Forward Lunge Test and Step/Quick Turn Test with the NeuroCom Balance Master system. Forward lunge distance, turn time and turn sway were measured. TKD practitioners were found to turn faster by 35.37% (p=0.004) and sway less during turning by 15.23% (p=0.034) than non-practitioners. The forward lunge distance in TKD practitioners was 5.67% shorter than that in control participants (p=0.046). This study shows that TKD practitioners might have sport-specific balance ability. The findings of this study inspire the exploration of the longitudinal training effect of TKD so as to develop the evidence base for this exercise option to improve the postural control of adolescents with balance problems