Progression et tests diagnostiques de la stéatose hépatique non alcoolique

• Main Author: Fedchuk, Larysa
• Other Authors: Paris 6
• Language: fr
• Published: 2014
• Subjects: La stéatose hépatique non alcoolique; La stéatohépatite non-alcoolique; La progression de la maladie; L'insulinorésistance; La fibrose; Les méthodes non-invasives; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; 612
• Online Access: http://www.theses.fr/2014PA066210/document

La stéatose hépatique non alcoolique, regroupant la stéatose isolée (NAFLD) et la stéatohépatite non-alcoolique (NASH), est un enjeu de santé publique mondial en raison d’une incidence croissante, en grande partie expliquée par l’augmentation de la prévalence du diabète et de l’obésité. La stéatose hépatique prédit la survenue des complications métaboliques associées à l’insulinorésistance, comme le diabète ou les événements cardiovasculaires. La connaissance de l’histoire naturelle de la NAFLD comporte encore de nombreuses incertitudes. Actuellement le modèle explicatif repose sur une dichotomie entre la stéatohépatite (NASH), qui peut progresser vers la cirrhose et la stéatose isolée ou avec inflammation minime (NAFL) qui jusqu'à présent était considérée comme une condition non évolutive ne progressant pas vers la cirrhose et n'augmentant pas la morbi-mortalité d'origine hépatique. Cette dichotomie conditionne en grande partie la prise en charge de ces patients, ceux avec NAFL étant souvent rassurés par le praticien quant à leur devenir et ne bénéficiant pas d'une surveillance hépatique spécifique. La ponction biopsie du foie est considérée comme un examen de référence, mais son usage en pratique clinique reste limité en raison d’effets indésirables, d’erreurs d'échantillonnage et de la variabilité d’interprétation inter-observateur. Les méthodes non invasives de lésions hépatiques sont devenues une vraie alternative à la biopsie du foie pour la prise en charge des patients ayant une maladie chronique du foie, au cours des dix dernières années. === Non-alcoholic fatty liver disease (NAFLD) covers a spectrum ranging from isolated steatosis to non-alcoholic steatohepatitis (NASH) and is becoming one of the most frequent causes of chronic liver disease, mainly because of its close association with the worldwide epidemic of diabetes and obesity. Liver steatosis can predict the occurrence of metabolic complications associated with insulin resistance, such as diabetes and cardiovascular events. Our understanding of the natural history of NAFLD is still incomplete. Currently, the explicative model is based on a dichotomy between steatohepatitis, considered the progressive form of the disease, which can lead to cirrhosis and isolated steatosis with or without minimal inflammation, which is considered a non-progressive condition that does not impact overall survival or result in liver-related mortality and morbidity. This dichotomy largely determines the management of NAFLD patients: patients without steatohepatitis usually do not undergo specific monitoring for liver disease progression. Liver biopsy is considered the reference diagnostic method but its implementation in clinical practice remains limited due to procedure complexity, invasiveness, cost, potential complications, sampling error and inter-observer variability. Non-invasive methods of hepatic injury have become a real alternative to liver biopsy for the diagnosis of patients with chronic liver disease in the past decade. The aims of this thesis were: 1) to better understand the histological course of the disease, to better identify patients at risk of histological progression based on initial histological findings and to establish a correlation between histological changes and the course of metabolic co-morbidities often associated with NAFLD : 2) to establish factors associated with short-term variability of repeated measurements of elastometry in patients with chronic liver diseases in order to understand how this non invasive procedure can be used for patient monitoring 3) to determine the diagnostic value and limitations of several steatosis biomarkers using liver biopsy as a reference standard in a large cohort of patients with suspected NAFLD. Our study shows that a fraction of patients with isolated steatosis can unambiguously evolve towards well-defined steatohepatitis, and in some of them, bridging fibrosis. The presence of mild lobular inflammation or any amount of fibrosis substantially increases the risk of histological progression in the mid-term while those with steatosis alone are at lowest risk. Patients with disease progression experienced a deterioration of cardio-metabolic risk factors. Our data if validated by independent studies, allow for better stratification of patients at risk of disease progression. The results of this study favor a change in the practices of monitoring and risk assessment of patients with steatosis but without steatohepatitis.