Portal Hypertension in Non-alcoholic Fatty Liver Disease: Association With Cardiovascular Risk and Identification of Non-invasive Biomarkers
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 170
- 主要终点
- Number of patients with NAFLD without advanced fibrosis and severe steatosis with portal hypertension
研究概览
简要总结
Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver disease in our environment. Preliminary data suggest that portal hypertension may exist in the initial phases of NAFLD due to mechanisms that have not yet been elucidated. The clinical relevance of its development in these initial phases is unknown, while in more advanced phases new data are required to confirm the close relationship between portal hypertension and the risk of decompensation described in other etiologies. Likewise, the influence of fibrosis and portal hypertension on the cardiovascular risk of patients with NAFLD is unknown. The aim of the present multicenter project is to characterize the presence of portal hypertension and the mechanisms involved in its development in the different stages of NAFLD, to assess the association between the degree of portal hypertension and the development of portal hypertension-related complications, to know the early cardiovascular risk in the different stages of the disease, and to identify noninvasive biomarkers of the presence and severity of portal hypertension.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 65 years.
- •Clinical suspicion of NAFLD.
- •Severe (controlled attenuation parameter (CAP) ≥330 dB/m) or mild steatosis (CAP: 298-317 dB / m), and FibroScan® grade 2 fibrosis (M probe: 7-9 kpa; XL probe: 5-7.5 kpa) in patients with grade 1 or 2 obesity and insulin resistance (HOMA index> 2.6) or diabetes mellitus.
- •Fibroscan® grade 3 or 4 fibrosis (M probe:> 9 kpa; XL probe:> 7.5 kpa).
- •Decompensated NAFLD cirrhosis (i.e. development of ascites, variceal hemorrhage, and/or hepatic encephalopathy) up to Child B (9 points).
- •Signature of informed consent.
排除标准
- •Concomitant liver disease and patients with acute on chronic liver failure.
- •Excessive alcohol consumption (≥ 30 grams per day in men and ≥ 20 grams per day in women).
- •Comorbidities (HIV infection, connective diseases, prothrombotic disorders) and/or drugs (didanosine, azathioprine, oxaliplatin) associated with the presence of idiopathic non-cirrhotic portal hypertension.
- •Clinical history of cardiovascular disease (ischemic cardiomyopathy, atrial fibrillation, valvular defects, severe arterial hypertension, previous hospitalizations secondary to heart failure, cerebrovascular disease).
- •Severe renal impairment, defined by creatinine clearance <15 ml/min/1.73m
- •Any previous or current thrombosis in any venous territory.
- •Uncontrolled psychiatric illness
- •Contraindication to liver biopsy or any of the complementary tests included in the project.
- •Hepatocellular carcinoma that does not meet Milan criteria.
- •Pregnancy or breastfeeding
- •Significant comorbidities that entail a functional limitation and/or a life expectancy of less than 12 months.
结局指标
主要结局
Number of patients with NAFLD without advanced fibrosis and severe steatosis with portal hypertension
时间窗: 1 months
number of the mechanisms responsible for the appearance of portal hypertension by specifically assessing the following
时间窗: 1 months
An increase in sinusoidal vascular resistance and the relative importance of its structural (sinusoidal compression) and functional (endothelial dysfunction and activation of starry cells) components, Splanchnic vasodilatation leading to portal hyperflow and hyperdynamic circulation, proinflammatory state and Activation of angiogenesis.
Number of patients with NAFLD and advanced fibrosis with portal hypertension
时间窗: 1 months
Threshold of portal hypertension leading to portal hypertension-related complications in patients with NAFLD
时间窗: 1months
次要结局
- Impact of portal hypertension and hepatic fibrosis on early cardiovascular risk and the degree of liver and kidney function.(1 months)
- Non-invasive biomarkers of the presence and severity of portal hypertension through metabolomics, extracellular vesicles and / or other analytical markers(1 months)