RESUMEN
Any experimental Thermoluminescent (TL) glow-peak contains the activation energy information of its corresponding energy level within the band gap in insulating materials. The theory of peak shape methods (PSM) correlates the macroscopic geometrical characteristics of a single TL peak with activation energy of the level responsible for the TL peak by assuming that the area under a TL peak can be approximated by the area of a triangle. In this way the geometrical characteristics becomes the measure of the activation energy. In the present work new PSM expressions are derived, which are not empirical as the existing ones but are based of the physical model of one trap one recombination (OTOR) center. Three cases are considered. (I) Delocalized OTOR for re-trapping probability smaller than the recombination probability. (II) Delocalized OTOR for re-trapping probability greater than recombination probability. (III) Localized transitions OTOR model. The system of differential equations of each case model were solved analytically using the Lambert W function (or equivalently the Wright ω function). Then the resulted analytical expressions of TL intensity as a function of temperature were used to derive new PSM. The new PSM from all cases are formally exactly the same, having, however, strong differentiation in their coefficients. The functionality of the new expressions is tested and its comparison with pre-existing PSM is performed.
RESUMEN
Simulation studies of thermoluminescence (TL) and other stimulated luminescence phenomena are a rapidly growing area of research. The presence of competition effects between luminescence pathways leads to the complex nature of luminescence signals, and therefore, it is necessary to investigate and validate the various methods of signal analysis by using simulations. The present study shows that in simulations of luminescence signals originating from multilevel phenomenological models, it is not possible to extract mathematically the individual information for each peak in the signal. It is further shown that computerized curve deconvolution analysis is the only reliable tool for extracting the various kinetic parameters. Simulation studies aim to explain experimental results, and therefore, it is necessary to validate simulation results by comparing with experiments. In this paper, testing of simulation results is performed using two methods. In the first method, the influence of competition effects is tested by comparing the input model parameters with the output values from the deconvolution analysis. In the second method, the agreement with experimental results is tested using the properties of well-known glow peaks with very high repeatability among TL laboratories, such as the 110 °C glow peak of quartz.
RESUMEN
This study provides a unified presentation of thermoluminescence (TL) glow-curve deconvolution within the framework of the open source R package "tgcd", according to various analytical expressions that describe first-, second-, general-, and mixed-order kinetics as well as the recently developed semi-analytical expressions that derive from the one trap-one recombination center (OTOR) model that utilizes the Lambert W function or the Wright Omega function. We provide a comprehensive, flexible, convenient, and openly accessible program to analyze TL glow curves according to different models and expressions. The consistency of kinetic parameters determined using different model expressions was assessed using measured TL glow curve of CaF2:Dy. The performance of the computerized glow curve deconvolution (CGCD) method was also tested using simulated glow curves. Results revealed the benefits of comparing kinetic parameters determined from different model expressions and those obtained using experimental TL evaluation methods to assess the reliability of deconvolution results. The accuracy of the CGCD method is dependent upon both the model expressions used and the intrinsic trapping parameters of the TL material.
RESUMEN
A recently introduced material for dental restorations, Zirconia reinforced Lithium Silicate (ZLS), is examined for its properties, in order to be used as a personal accidental thermoluminescence dosimeter. For this purpose, its main thermoluminescence characteristics are studied, such as its sensitivity, signal reproducibility, fading, dose response and lower detectable dose limit. Furthermore, the material is characterized by means of microscopic, spectroscopic and crystallographic techniques. The results propose that ZLS is promising to be used as a personal accidental thermoluminescence dosimeter for post-irradiation detection, with single aliquot protocols.
Asunto(s)
Materiales Dentales/química , Compuestos de Litio/química , Dosímetros de Radiación , Liberación de Radiactividad Peligrosa , Silicatos/química , Circonio/química , Restauración Dental Permanente , Límite de DetecciónRESUMEN
This paper reviews developments in phenomenological models of stimulated luminescence phenomena. A set of five master equations is presented, which describe a wide variety of stimulated luminescence signals: thermoluminescence, isothermal luminescence, optically stimulated luminescence and infrared stimulated luminescence. Both delocalized and localized models are reviewed, and analytical solutions are presented for these models. The master equations are tested against the solutions of the differential equations in the models, as well by fitting experimental data for a variety of luminescencent dosimetric materials. Three out of the five master equations involve the Lambert W(z) function, thus establishing this function as the theoretical cornerstone of the phenomenological luminescence models. The applicability of the superposition principle is discussed, in connection with computerized curve deconvolution analysis.
RESUMEN
The present study constitutes the first part of a meteorite project, currently in progress, towards the full and thorough dosimetric study (TL and OSL) of two different meteorites of recent fall, Norton County and Holbrook. Both meteorites exhibit strong TL sensitivity, linear dose response and no saturation for doses up to 2kGy. However, the two meteorites exhibited a very dissimilar TL glow curve and behaviour regarding sensitization and fading. Notably, the Norton County aubrite achondrite was found to exhibit a strong fading of the high-temperature peak (~300°C), attributed to anomalous fading, whereas Holbrook did not seem to show signs of anomalous fading. Since quantitative conclusions regarding the thermal and irradiation history of meteorites, require knowledge of the detailed peak structure of the glow curve and deeper understanding of the trapping mechanism, the glow curves, after irradiation in the range 10-2000Gy, were deconvoluted using general order kinetics. The fitting parameters extracted point towards complex non-strictly first order mechanisms with a multitude of traps acting very differently. All the above, combined with future OSL measurements, currently in progress, are expected to shed light on the nature of the involved traps in both phenomena (energy depth, light-resistance etc), which would allow to extract more concrete conclusions about their history.
RESUMEN
Natural calcium fluoride has been commonly used as thermoluminescence (TL) dosimeter due to its high luminescence intensity. The aim of this work includes attempting a correlation between specific TL glow curves after bleaching and components of linearly modulated optically stimulated luminescence (LM-OSL) as well as continuous wave OSL (CW-OSL). A component resolved analysis was applied to both integrated intensity of the RTL glow curves and all OSL decay curves, by using a Computerized Glow-Curve De-convolution (CGCD) procedure. All CW-OSL and LM-OSL components are correlated to the decay components of the integrated RTL signal, apart from two RTL components which cannot be directly correlated with either LM-OSL or CW-OSL component. The unique, stringent criterion for this correlation deals with the value of the decay constant λ of each bleaching component. There is only one, unique bleaching component present in all three luminescence entities which were the subject of the present study, indicating that each TL trap yields at least three different bleaching components; different TL traps can indicate bleaching components with similar values. According to the data of the present work each RTL bleaching component receives electrons from at least two peaks. The results of the present study strongly suggest that the traps that contribute to TL and OSL are the same.
RESUMEN
Drug sterilization with ionizing radiation is a well-established technology, which is constantly extending to several products due to its numerous advantages, since it allows the heat-free sterilization of heat-sensitive pharmaceutical preparations. In a previous study, the possibility to identify irradiated solid-state drugs by means of OSL and TL was examined with very promising findings. In the same respect, the present work aims, for the first time to the authors' best knowledge, to explore whether TL can be employed as a method for post-sterilization dosimetry on commercial liquid-state drugs, by studying the properties of their glass containers. Two different types of glass containers (bottle and ampoule) of two widely used liquid drugs, i.e., Hexalen® and Voltaren®, are used for this purpose. Both glass containers exhibit a linear TL dose response for doses up to 6kGy with a stable behavior through time, while no significant sensitization of the main peaks is observed. Thus, preliminary findings are very promising towards the post-sterilization dosimetry of liquid drugs and the use of the containers of commercial liquid drugs for normal and/or accidental dosimetry.
Asunto(s)
Composición de Medicamentos/métodos , Embalaje de Medicamentos , Vidrio , Esterilización/métodos , Dosimetría Termoluminiscente/métodos , Relación Dosis-Respuesta en la Radiación , Estabilidad de Medicamentos , Humanos , RadiometríaRESUMEN
Signals acquired during thermoluminescence or optically stimulated luminescence measurements must be completely free of any spurious and/or contamination signals to assure the credibility of the results, especially during exploratory research investigating the luminescence behavior of new materials. Experiments indicate that such unwanted signals may also stem from new (unused) and used empty sample carriers, namely cups and discs, which are widely used for such measurements, probably due to contamination from a fluorite and/or silica-related source. Fluorite and/or silicone oil appear to be the most likely sources of contamination, thus, their removal, along with any other possible source that exhibits undesirable luminescence behavior, is necessary. Conventional cleaning methods fail to eliminate such contaminants from empty cups and discs. In this work a new cleaning method is proposed incorporating off-the-shelf chemical agents. Results of thermoluminescence measurements highlight the efficiency of the new cleaning process, since it can completely remove any observed contaminants from both new and used sample carriers, of various shapes and/or materials. Consequently their signal is minimized even at relatively high beta-doses, where it is prominent, resulting in a clean and only sample-attributed signal.
RESUMEN
Drug sterilization with ionizing radiation is a well-established technology and is gaining ground the last decades due to its numerous advantages. Identification of irradiated drugs would be interesting and, in this respect, the present work aims, for the first time to the authors' best knowledge, to explore whether OSL and TL can be employed as methods for post-sterilization dosimetry on commercial drugs, i.e., as tools for the detection of irradiated drugs. Five widely used drugs, i.e., Daktarin(®), Aspirin(®), Panadol(®), Brufen(®) and Procef(®), are used for this purpose. Preliminary findings are very promising towards the post-sterilization dosimetry and the use of commercial drugs for normal and/or accidental dosimetry.
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Dosimetría con Luminiscencia Ópticamente Estimulada/métodos , Preparaciones Farmacéuticas/análisis , Preparaciones Farmacéuticas/efectos de la radiación , Esterilización/métodos , Dosimetría Termoluminiscente/métodos , Dosimetría con Luminiscencia Ópticamente Estimulada/normas , Dosimetría Termoluminiscente/normasRESUMEN
The present work studies the thermally assisted photo transfer OSL (TAPT OSL) signal in the case of Al(2)O(3):C samples showing double-structured main dosimetric TL peaks. The measurement signal provides indirect experimental evidence regarding the presence of deep traps along with one transfer mechanism extremely powerful and efficient. The experimental features of this signal are presented along with those yielded for samples with narrow TL peaks for the sake of comparison. In the framework of a dosimetric characterization, the straightforward relation observed between the TAPT OSL integrated intensity and the dose, even if non-linear, implies that this signal could be effectively used towards dosimetry purposes in the high dose region up to 250 Gy. Furthermore, the study on the influence of the annealing temperature on the TL glow curve shape on Al(2)O(3):C grains is attempted. The variety of glow curve shapes reported especially in the case of single grains is not affected by high temperature annealing, since its effect is dominant even after heating at 1085°C. Thus, this variety should not be correlated to the different deep trap occupancies, but rather be attributed to a possible structural defect. The main dosimetric TL peak af all grains is considered to be a composite of two unambiguously different traps of non-first-order kinetics. The low temperature part of these traps, reaching a maximum at ~190°C is an electron trap and the high temperature part with maximum at ~250°C is a hole trap. TL dose response of Al(2)O(3):C grains presenting double peak structures is presented for the first time in literature, suggesting the usefulness on the applicability of Al(2)O(3):C in the dose regime up to 100 Gy.
RESUMEN
In the present study we report dosimetric properties of iodized salt aiming at using it as an accidental luminescent dosimeter. It was found that the very good sensitivity of its main dosimetric peak is strongly affected by thermal treatments. This is also the case for OSL emission. The sensitivity loss due to heating implies that caution should be exercised while applying single aliquot protocols for dose evaluation. The sequence of dissolution and subsequent re-crystallization was established to be an extremely effective zeroing mechanism for the TL signal. The linearity in the dose response was also monitored in the case of dissolved and subsequently re-crystallized salt. In the case of naturally occurring salt, zeroing of the TL signal due to dissolution as well as the linearity of dose response up to doses as large as 100 Gy were found to be very promising features for dating applications.
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Yodo/química , Radiometría/métodos , Cloruro de Sodio/química , Dosimetría Termoluminiscente/métodos , Cristalización , Cloruro de Sodio Dietético , Dosimetría Termoluminiscente/instrumentaciónRESUMEN
BACKGROUND & AIMS: Long-term treatment with entecavir resulted in durable virologic suppression and continued histologic improvement in nucleoside-naive chronic hepatitis B patients. Patients with advanced fibrosis or cirrhosis, who received long-term entecavir treatment, were evaluated for improvement in liver histology. METHODS: The study included a subset of patients from phase III and long-term rollover studies, who received entecavir for at least 3 years, had advanced fibrosis or cirrhosis, and evaluable biopsies at baseline and after long-term treatment. RESULTS: Ten patients had advanced fibrosis or cirrhosis at baseline (Ishak fibrosis score, ≥ 4). After approximately 6 years of cumulative entecavir therapy (range, 267-297 wk), all 10 patients showed improvement in liver histology and Ishak fibrosis score. The mean change from baseline in Ishak fibrosis and Knodell necroinflammatory scores were -2.2 and -7.6, respectively. A reduction in Ishak fibrosis score to 4 or less was observed for all 4 patients who had cirrhosis at baseline. CONCLUSIONS: Chronic hepatitis B patients with advanced fibrosis or cirrhosis demonstrated histologic improvement and reversal of fibrosis and cirrhosis after long-term treatment with entecavir.
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Antivirales/administración & dosificación , Guanina/análogos & derivados , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Cirrosis Hepática/patología , Ensayos Clínicos como Asunto , Guanina/administración & dosificación , Histocitoquímica , Humanos , Masculino , Microscopía , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: Treatment with pegylated interferon (PEG-IFN) alpha-2b results in hepatitis B e antigen (HBeAg) loss in 36% of patients at 6 months post treatment. The aim of this study was to determine whether a long-term response to PEG-IFN is dependent on the timing of HBeAg loss. METHODS: A total of 91 patients treated with PEG-IFN alpha-2b alone (100 microg per week) and 81 patients treated with PEG-IFN alpha-2b and lamivudine (100 mg/day) for 52 weeks were enrolled in this study. Patients were initially followed up at 4-week intervals and had one additional long-term follow-up (LTFU) visit (mean: 3.03+/-0.77 years 26 weeks post treatment). RESULTS: Of the 172 patients included, 78 patients (46%) did not have loss of HBeAg, 47 (27%) lost HBeAg within 32 weeks, and 47 patients (27%) had loss of HBeAg after week 32. At LTFU, patients with HBeAg loss< or =32 weeks had hepatitis B virus DNA of <400 copies/ml significantly more often than did those who lost HBeAg after week 32 (47 vs. 21%, respectively; P=0.009). Hepatitis B surface antigen (HBsAg) negativity was also observed significantly more often in patients with early HBeAg loss (36 vs. 4%, respectively, P<0.001). Early HBeAg loss tended to occur more often in patients treated with PEG-IFN and lamivudine combination therapy than in those treated with PEG-IFN alone (35 vs. 21%; P=0.10), as did HBsAg loss (15 vs. 8%; P=0.14). CONCLUSIONS: Early PEG-IFN-induced HBeAg loss results in a high likelihood of HBsAg loss and may be associated with more profound viral suppression during the first 32 weeks of therapy in patients treated with lamivudine combinations.
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Antivirales/uso terapéutico , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/sangre , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Adulto , Área Bajo la Curva , Distribución de Chi-Cuadrado , Quimioterapia Combinada , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Humanos , Interferón alfa-2 , Lamivudine/uso terapéutico , Estudios Longitudinales , Masculino , Proteínas Recombinantes , Estadísticas no ParamétricasRESUMEN
BACKGROUND/AIMS: Acute pancreatitis is the most serious complication of endoscopic retrograde cholangiopancreatography (ERCP) but is not very common. A test that could predict the occurrence of pancreatitis would help to decide whether to discharge a patient after ERCP or not. The aim of this prospective study was to compare the value of serum amylase and elastase in the prediction of post-ERCP pancreatitis and its severity. METHODOLOGY: Ninety-seven patients underwent ERCP. Serum samples were taken before, two and six hours after ERCP for amylase and elastase measurement. Fifty-four patients (group A) were treated with continuous intravenous infusion of octreotide, beginning 6 hours before ERCP and terminating 24 hours after. Forty-three patients (group B) received no preventive treatment. RESULTS: In group A, 9 patients (16.6%) developed pancreatitis, 8 of them (14.8%) mild and 1 (1.8%) severe. Two patients in group B developed mild pancreatitis (p = 0.1). In all patients the predictive accuracy in the second hour for amylase >3N, >5N and elastase >N was 79%, 87% and 86% respectively. The likelihood ratio of positivity (LRP) was 3.6, 6.5 and 6.1. In the sixth hour the respective values were 76%, 86%, 85% and 4, 7.3 and 6.4. In group A, the respective values in the second hour were 85%, 91%, 94% and 5, 25.2, infinity, and in the sixth hour 85%, 94%, 98% and 5.7, 11.5, infinity. CONCLUSIONS: Serum amylase (with cutoff value >5N) and elastase (>N), 6 hours after ERCP, were the most accurate tests for the prediction of post-ERCP pancreatitis, especially in patients receiving octreotide. The measurement of serum elastase could supplement that of serum amylase in the prediction of more cases of post-ERCP pancreatitis.
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Amilasas/sangre , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Elastasa Pancreática/sangre , Pancreatitis/diagnóstico , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Octreótido/administración & dosificación , Pancreatitis/enzimología , Pancreatitis/prevención & control , Valor Predictivo de las Pruebas , Premedicación , Estudios Prospectivos , Curva ROCRESUMEN
BACKGROUND & AIMS: Treatment with adefovir dipivoxil for 48 weeks resulted in clinical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B that was lost when treatment was discontinued. We investigated the efficacy, safety, and resistance profile of adefovir dipivoxil treatment for up to 240 weeks. METHODS: HBeAg-negative patients were treated double blind with placebo or adefovir dipivoxil 10 mg once daily for 48 weeks, followed by adefovir dipivoxil from week 49 to 96. At week 97, 125 patients enrolled in a 144-week, open-label phase. Patients received adefovir dipivoxil for up to 192 or 240 weeks. RESULTS: Serum hepatitis B virus (HBV) DNA levels were less than 1000 copies per milliliter in 67% of patients, and alanine aminotransferase (ALT) levels normalized in 69% after 240 weeks. After 192 or 240 weeks of treatment, over 83% of patients had improvement in necroinflammation, and over 73% had improvement in fibrosis. Ishak fibrosis scores improved compared with baseline in 35%, 55%, and 71% of patients after 48, 192, and 240 weeks of adefovir dipivoxil, respectively. After 240 weeks, the cumulative probability of HBV polymerase mutations was 29%, but the cumulative probability of mutations with virologic resistance was 20% and of mutations, virologic resistance, and ALT elevations was 11%. Slight elevations in creatinine were confirmed in 4 (3%) patients. CONCLUSIONS: Treatment with adefovir dipivoxil for up to 240 weeks was well tolerated and produced significant, increasing improvement in hepatic fibrosis, durable suppression of HBV replication, normalization of liver enzymes, and delayed development of resistance.
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Adenina/análogos & derivados , Antivirales/uso terapéutico , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Organofosfonatos/uso terapéutico , Adenina/administración & dosificación , Adenina/efectos adversos , Adenina/uso terapéutico , Adulto , Anciano , Alanina Transaminasa/sangre , Antivirales/administración & dosificación , Antivirales/efectos adversos , Carcinoma Hepatocelular/etiología , ADN Viral/sangre , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Virus de la Hepatitis B/genética , Hepatitis B Crónica/patología , Humanos , Cirrosis Hepática , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Organofosfonatos/administración & dosificación , Organofosfonatos/efectos adversosRESUMEN
The study of the thermoluminiscence (TL) sensitivity of quartz due to heat and irradiation treatments is of importance in dating and retrospective dosimetry. A comprehensive comparative study of the predose effect was carried out for three types of quartz of different origin. Complete TL vs. dose and sensitivity S vs. predose curves were obtained for the dose range of 0.1 < D < 400 Gy. Additional complete sensitivity vs. predose curves were obtained for samples which underwent a combined predose irradiation and a subsequent heat treatment to 500 degrees C. Although the TL vs. dose curves showed very different behaviours, the sensitivity vs. predose curves showed several common characteristics. The sensitivity vs. predose curves showed abrupt changes approximately 10 Gy. The sensitivity after a combined predose irradiation and heat treatment to 500 degrees C showed a very gradual change in the whole dose range studied. These results are explained qualitatively by using the modified Zimmerman model for quartz.
Asunto(s)
Modelos Químicos , Cuarzo/química , Cuarzo/efectos de la radiación , Dosimetría Termoluminiscente/instrumentación , Dosimetría Termoluminiscente/métodos , Simulación por Computador , Cristalización , Relación Dosis-Respuesta en la Radiación , Diseño de Equipo , Análisis de Falla de Equipo , Ensayo de Materiales , Dosis de RadiaciónRESUMEN
The pre-dose technique in thermoluminescence (TL) is used for dating archaeological ceramics and for accident dosimetry. During routine applications of this technique, the sensitisation of the quartz samples is measured as a function of the annealing temperature, yielding the so-called thermal activation characteristic (TAC). The measurement of multiple TACs and the study of the effect of UV-radiation on the TL sensitivity of quartz are important analytical and diagnostic tools. In this paper, it is shown that a modified Zimmerman model for quartz can successfully model the experimental steps undertaken during a measurement of multiple TACs.
Asunto(s)
Algoritmos , Modelos Químicos , Cuarzo/análisis , Cuarzo/química , Dosimetría Termoluminiscente/métodos , Simulación por Computador , Relación Dosis-Respuesta en la Radiación , Dosis de Radiación , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Treatment with adefovir dipivoxil for 48 weeks resulted in histologic, virologic, and biochemical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. We evaluated the effect of continued therapy as compared with cessation of therapy. METHODS: One hundred eighty-five HBeAg-negative patients with chronic hepatitis B were assigned to receive 10 mg of adefovir dipivoxil or placebo once daily for 48 weeks (ratio, 2:1). After week 48, patients receiving adefovir dipivoxil were again randomly assigned either to receive an additional 48 weeks of the drug or to switch to placebo. Patients originally assigned to placebo were switched to adefovir dipivoxil. Patients treated with adefovir dipivoxil during weeks 49 through 96 were subsequently offered continued therapy. The primary end points were changes in hepatitis B virus (HBV) DNA and alanine aminotransferase levels. RESULTS: Treatment with adefovir dipivoxil resulted in a median decrease in serum HBV DNA of 3.47 log copies per milliliter (on a base-10 scale) at 96 weeks and 3.63 log copies per milliliter at 144 weeks. HBV DNA levels were less than 1000 copies per milliliter in 71 percent of patients at week 96 and 79 percent at week 144. In the majority of patients who were switched from adefovir dipivoxil to placebo, the benefit of treatment was lost (median change in HBV DNA levels from baseline, -1.09 log copies per milliliter; only 8 percent of patients had levels below 1000 copies per milliliter at week 96). Side effects during weeks 49 through 144 were similar to those during the initial 48 weeks. Resistance mutations rtN236T and rtA181V were identified in 5.9 percent of patients after 144 weeks. CONCLUSIONS: In patients with HBeAg-negative chronic hepatitis B, the benefits achieved from 48 weeks of adefovir dipivoxil were lost when treatment was discontinued. In patients treated for 144 weeks, benefits were maintained, with infrequent emergence of viral resistance.
Asunto(s)
Adenina/análogos & derivados , Adenina/uso terapéutico , Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Organofosfonatos/uso terapéutico , Adenina/administración & dosificación , Adenina/efectos adversos , Adolescente , Adulto , Animales , Antivirales/administración & dosificación , Antivirales/efectos adversos , ADN Viral/sangre , Método Doble Ciego , Esquema de Medicación , Farmacorresistencia Viral , Femenino , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Organofosfonatos/administración & dosificación , Organofosfonatos/efectos adversos , Estudios Prospectivos , Factores de TiempoRESUMEN
We determined the clinical outcome of hepatitis e antigen (HBeAg)-negative chronic hepatitis B patients treated with long-term nucleos(t)ide analog therapy starting with lamivudine. We evaluated 201 such patients treated for 3.8 +/- 1.4 years and 2 historical similar cohorts: 1 treated with interferon-alfa (n = 209) and 1 untreated (n = 195). Virological or biochemical remission rate at 48 months under lamivudine was 34% or 36%, respectively, whereas adefovir was administered in 79 patients with virological-biochemical breakthroughs or no response. Of the lamivudine-treated patients, 4 died, 1 underwent a transplantation, and another 8 developed major events, all having advanced fibrosis at baseline and all but 1 having experienced breakthroughs or no response. At 5 years, survival was 96%, and major event-free survival was 93%. The major event-free survival was significantly better in patients with than in those without virological remission under lamivudine. At the end of follow-up, both survival and major event-free survival were independently associated with type of and response to treatment, being significantly better in patients under long-term antiviral therapy or interferon sustained responders than in interferon non-sustained responders or untreated cases (5-year survival: 96% or 98% vs. 88% or 90%, respectively). In conclusion, in HBeAg-negative chronic hepatitis B, long-term nucleos(t)ide analog therapy starting with lamivudine significantly improves survival and reduces the risk of major complications, compared with interferon non-sustained responders or untreated patients. In such patients with advanced fibrosis, close follow-up for lamivudine resistance and prompt onset of additional antiviral therapy is required or the ab initio use of agent(s) with low resistance rates should be considered.