ABSTRACT
Since the first FDA approval of Lamivudine in 1998, many nucleo(t)side analogs such as Lamivudine, Adefovir, and Entecavir have been used. However, they only inhibit DNA synthesis, and if their administration is stopped a viral breakthrough can develop, making long-term administration necessary, ultimately followed by the development of resistance. Tenofovir has been developed and drug-resistant mutations have decreased significantly, but the problem of resistance due to long-term drug use still remains, along with the drug safety problem. In this review, we introduce the recent trend in the development of hepatitis B treatment agents and the Korea National Research Institute of Health (KNIH) research for the development of a novel treatment for hepatitis B (drug repositioning) without resistance and which targets the various life cycles of HBV.
ABSTRACT
Hepatitis B virus (HBV) infection is a major public health problem, with some 250 million people currently at high risk of developing chronic liver diseases. The current antiviral treatment for chronic hepatitis B (CHB) is effective in controlling viral replication but fails to achieve a complete cure. Since the identification of sodium taurocholate cotransport polypeptide (NTCP) as an HBV receptor, anti-HBV drugs targeting viral entry, capsid assembly, cccDNA, transcription, and secretion have been developed. In this paper, the potential inhibitors in various steps of the HBV life cycle are summarized.
ABSTRACT
Since the first FDA approval of Lamivudine in 1998, many nucleo(t)side analogs such as Lamivudine, Adefovir, and Entecavir have been used. However, they only inhibit DNA synthesis, and if their administration is stopped a viral breakthrough can develop, making long-term administration necessary, ultimately followed by the development of resistance. Tenofovir has been developed and drug-resistant mutations have decreased significantly, but the problem of resistance due to long-term drug use still remains, along with the drug safety problem. In this review, we introduce the recent trend in the development of hepatitis B treatment agents and the Korea National Research Institute of Health (KNIH) research for the development of a novel treatment for hepatitis B (drug repositioning) without resistance and which targets the various life cycles of HBV.
ABSTRACT
Hepatitis B virus (HBV) infection is a major public health problem, with some 250 million people currently at high risk of developing chronic liver diseases. The current antiviral treatment for chronic hepatitis B (CHB) is effective in controlling viral replication but fails to achieve a complete cure. Since the identification of sodium taurocholate cotransport polypeptide (NTCP) as an HBV receptor, anti-HBV drugs targeting viral entry, capsid assembly, cccDNA, transcription, and secretion have been developed. In this paper, the potential inhibitors in various steps of the HBV life cycle are summarized.
ABSTRACT
Background : Endoscopic vessel harvesting (EVH) is one of the less-invasive graft harvesting techniques for CABG. On the other hand, it needs certain amount of a learning curve to acquire sufficient technique. Inappropriate manipulation will cause damage of the vein, decrease the patency and affect the patient's long-term survival. Off-the-job training has the potential to shorten the length of the learning curve. In this study we evaluated the effectiveness of a newly developed saphenous vein harvesting model provided by EBM corporation. Purpose : To evaluate the effectiveness of concentrated training with the EVH simulator. Objective and Methods : One novice trainee doctor was recruited for this study. After 20 procedures using the simulator training clinical device, EVH was performed under supervision. This procedure was compared with the last case before the training in terms of setup for the EVH, visualization by endoscope, dissection, division of branches, duration of the procedure, and number required for repair. Results : The duration required to train with the simulator showed a stable average of 10 cases. All the elements in terms of EVH procedure were improved after the simulator training. Discussion : It is important to prepare an appropriate simulator, trainer, and clear purpose for effective training. It was beneficial to enhance the clinical level with the concentrated simulator training. Conclusions : The newly developed EVH model is an effective simulator before performing the initial clinical case.
ABSTRACT
BACKGROUND/AIMS: Direct sequencing is the gold standard for the detection of drug-resistance mutations in hepatitis B virus (HBV); however, this procedure is time-consuming, labor-intensive, and difficult to adapt to high-throughput screening. In this study, we aimed to develop a dendron-modified DNA microarray for the detection of genotypic resistance mutations and evaluate its efficiency. METHODS: The specificity, sensitivity, and selectivity of dendron-modified slides for the detection of representative drug-resistance mutations were evaluated and compared to those of conventional slides. The diagnostic accuracy was validated using sera obtained from 13 patients who developed viral breakthrough during lamivudine, adefovir, or entecavir therapy and compared with the accuracy of restriction fragment mass polymorphism and direct sequencing data. RESULTS: The dendron-modified slides significantly outperformed the conventional microarray slides and were able to detect HBV DNA at a very low level (1 copy/μL). Notably, HBV mutants could be detected in the chronic hepatitis B patient sera without virus purification. The validation of our data revealed that this technique is fully compatible with sequencing data of drug-resistant HBV. CONCLUSIONS: We developed a novel diagnostic technique for the simultaneous detection of several drug-resistance mutations using a dendron-modified DNA microarray. This technique can be directly applied to sera from chronic hepatitis B patients who show resistance to several nucleos(t)ide analogues.
Subject(s)
Humans , DNA , Drug Resistance , Hepatitis B virus , Hepatitis B , Hepatitis B, Chronic , Hepatitis , Lamivudine , Mass Screening , Oligonucleotide Array Sequence Analysis , Sensitivity and SpecificityABSTRACT
BACKGROUND/AIMS: Occult HBV infection can persist following HBsAg loss and be transmitted, but the virological features are not well defined. METHODS: Here we investigated 25 Korean patients who lost HBsAg during follow up, either spontaneously or subsequent to therapy. RESULTS: Whereas subtype adr (genotype C) was found in 96% of HBsAg positive patients, 75 % of patients who lost HBsAg spontaneously were seemed to be infected with the ayw subtype with sequence similar to genotype D. Mutations in the major hydrophilic region (MHR) of HBsAg were found in 7 patients who lost HBsAg spontaneously. The mutations include T123S, M125I/N, C139R, D144E, V177A, L192F, and W196L, some of which have not been reported before. Functional analysis via transfection experiments indicate that the C139R and D144E mutations drastically reduced HBsAg antigenicity, while the Y225del mutation found in one interferon-treated patient impaired HBsAg secretion. CONCLUSIONS: Lack of detectable HBsAg in patient serum could be explained by low level of ccc DNA in liver tissue, low antigenicity of the surface protein, or its secretion defect.