La fibrosis hepática es la respuesta a estímulos dañinos al hígado y consiste en la deposición excesiva de matriz extracelular de manera progresiva. Es reversible si se trata y erradica la causa de la enfermedad y si las lesiones no son demasiado graves, es decir, si el diagnóstico es oportuno y se da un tratamiento efectivo, el hígado puede recuperar su estructura normal. Sin embargo, detectar la enfermedad en una etapa inicial es poco probable dado que un paciente presenta síntomas cuando se encuentra en la última fase: la cirrosis hepática. El método de elección para determinar el grado de fibrosis es la biopsia hepática que consiste en la toma de una muestra y su posterior análisis morfológico por observación al microscopio. Esta muestra corresponde a 1/50,000 del hígado. Para evaluar la biopsia, se han propuesto múltiples escalas que evalúan distintos aspectos histopatológicos, la utilizada convencionalmente es Metavir. De acuerdo a esta escala, se define el grado fibrótico en cuatro fases: F1, fibrosis portal (leve); F2, fibrosis portal con septos (moderada); F3, fibrosis con numerosos septos y nódulos de regeneración incompletos (grave); F4, cirrosis, con nódulos de regeneración completos. Este método presenta varios problemas como variabilidad inter-observador, baja resolución entre los grados intermedios de fibrosis y la limitante de ser una prueba cualitativa. Recientes terapias y herramientas de diagnóstico para este problema demandan métodos para establecer un grado de avance en la enfermedad según aspectos cuantitativos. Existe incertidumbre en el diagnóstico que repercute en imprecisión en la calibración de nuevas técnicas. Por lo anterior el objetivo general de este trabajo fue evaluar del comportamiento térmico del tejido hepático afectado por fibrosis, por medio de un sensor de flujo de calor. Así como la identificación de la fase de fibrosis del tejido hepático aplicando el enfoque lógico-combinatoriose aplicó bajo dos esquemas, uno donde la definición de las clases se hizo con el diagnóstico de la escala Metavir encontrando un 25% de acierto en esta clasificación y como resultado de aplicar el segundo esquema, con el porcentaje de fibrosis como clasificador, se obtuvo un 75% de acierto. Si bien, la muestra se limitó a 16 individuos, lo que puede no ser concluyente al utilizar este enfoque en un modelo animal, de los resultados destaca que la variable Metavir, utilizada en un inicio para definirlas clases, es de tipo ordinal y cualitativa, y pretendía diferenciar a individuos definidos con variables físicas cuantitativas; es por ello que se obtuvo un resultado de clasificación más favorable cuando se utilizó el porcentaje de fibrosis. Los resultados de este trabajo representan una contribución, no solamente para el desarrollo de herramientas para el diagnóstico de la fibrosis hepática, sino también, en la caracterización del tejido con parámetros físicos, de tal modo que se tenga mayor información que a su vez, coadyuvar en nuevas alternativas de tratamiento y prevención.
Hepatic fibrosis is the response to harmful stimuli to the liver and consists of the progressive deposition of excessive extracellular matrix. It is reversible if the cause of the disease is treated and eradicated and also if the lesions are not too serious, meaning that there is a timely diagnosis and effective treatment, then the liver can regain its normal structure. However, detecting the disease at an early stage is unlikely since a patients presents symptoms when they are in the last phase: liver cirrhosis. The method of choice to determine the degree of fibrosis is the liver biopsy consisting of taking a sample and its subsequent morphological analysis by observation under a microscope. This sample corresponds to 1 / 50,000 of the liver. To evaluate the biopsy, multiple scales have been proposed that evaluate different histopathological aspects, the most frequently used is Metavir. According to this scale, the fibrous grade is defined in four phases: F1, portal fibrosis (mild); F2, portal fibrosis with septa (moderate); F3, fibrosis with numerous septa and incomplete regeneration nodules (severe); F4, cirrhosis, with complete regeneration nodules. This method presents several problems such as inter-observer variability, low resolution between the intermediate degrees of fibrosis thus limiting this to be a qualitative test. Recent therapies and diagnostic tools for this problem require methods to establish a degree of progression in the disease according to quantitative aspects. There is uncertainty in the diagnosis that affects the imprecision in the calibration of new techniques. Due to the above, the general objective of this study was to evaluate the thermal behavior of fibrous tissue with the use of a heat flux sensor. As well as the identification of the fibrosis phase of the hepatic tissue applying the logic-combinatorial approach of pattern recognition theory. To study the disease, hepatic fibrosis was induced in a rat model of the Wistar strain with Carbon Tetrachloride (CCl4). A hepatectomy was performed in the individuals of the model according to the established induction times to collect the tissue samples. A methodology was established for the evaluation of progression of fibrosis in the liver samples, based on the Metavir scale, supported by three observers. Measurements were made on the samples to determine their thermal behavior, using a heat flow sensor. Also, a morphometric tool is applied for the quantification of histopathological findings that send a quantitative measure on a continuous scale of the problem that was studied. Finally, applying the logic-combinatorial approach of pattern recognition theory, a similarity function was designed using seven quantitative characteristics, allowing the description of the individuals and the classification of the stages of fibrosis through a more descriptive integral of hepatic samples. Heat flow measurements showed a relationship between the progression of liver fibrosis in rats and the thermal properties of hepatic tissue where, the greater the progression of the disease, the greater the heat flows in the sample. However, this relationship was found only in samples with strong diagnoses of fibrosis, so it is desirable to increase the sensitivity of the heat flow sensor to continue with the evaluation of this methodology as a tool for the analysis of liver samples. The quantification of histopathological findings shows that the amount of fibrosis has a progressive increase according to the evolution of the disease. In the results of the steatosis quantification, the percentages were limited between 0.06 and 0.87% for 15 of the 16 individuals in the rat model. Only an individual was counted an atypical value of 9.76%. No correlation was found between this condition and the other acquired variables. The combinatorial-logic approach was applied under two schemes, one where the definition of the classes was made with the diagnosis of the Metavir scale finding a 25% success in this classification and as a result of applying the second scheme, with the percentage of fibrosis as classifier, a 75% success rate was obtained. Although the sample was limited to 16 individuals, which may not be conclusive when using this approach in an rat model, the results point out that the variable Metavir, initially used to define classes, is ordinal and qualitative, and intended to differentiate individuals defined with quantitative physical variables; that is why a more favorable classification result was obtained when the percentage of fibrosis was used. The results of this work represent a contribution, not only for the development of tools for the diagnosis of hepatic fibrosis, but also, in the characterization of the tissue with physical parameters, in such a way that it has more information for the development of new alternatives of treatment and prevention.
Beziehungen
Beschreibungen
| Attributname | Werte |
|---|
| Creador |
|
|---|
| Mitwirkende |
|
|---|
| Tema |
|
|---|
| Editor |
|
|---|
| Idioma |
|
|---|
| Identificador |
|
|---|
| Stichwort |
|
|---|
| Año de publicación |
|
|---|
| Tipo de Recurso |
|
|---|
| Derechos |
|
|---|
| División académica |
|
|---|
| Línea académica |
|
|---|
| Licencia |
|
|---|
