Progression of LIver Damage and Cardiometabolic Disorders in Non-alcoholic Fatty Liver dIsease: an Observational Cohort STUDY. The Plinio Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 2,000
- 试验地点
- 1
- 主要终点
- Clinical, biochemical and genetic factors associated to progression of liver fibrosis in a large cohort of patients with NAFLD
研究概览
简要总结
Liver fibrosis is the most important prognostic factor in patients with non-alcoholic factor disease. Clinical and biological condition, as diabetes or mutation for PNPLA3, are well known factors associated with liver fibrosis onset and progression. However, little is known about biochemical factors predicting liver fibrosis evolution in large NAFLD populations.
详细描述
Non-alcoholic fatty liver disease (NAFLD) is a common liver disease worldwide. NAFLD includes a spectrum of diseases raging from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma.
The prevalence of NAFLD ranges from 20% in the general population to 80-90% in obese and/or diabetic patients. Type 2 diabetes is also associated with disease progression. Some genetic conditions are known to be related with NAFLD pathophysiology. Mutation of patatin like phospholipase domain containing 3 (PNPLA3) is the most frequent genetic disorder associated with NAFLD onset and its accelerated progression. Both type 2 diabetes and PNPL3 mutation are the better-known factors associated with liver fibrosis.
More than the amount of lipid accumulation in the hepatocytes or of liver inflammation, the most important prognostic factors in NAFLD is fibrosis, which can occur in all stage of NAFLD disease, also in simple steatosis without inflammation or ballooning. Advanced fibrosis (F stage ≥ 3) has been related not only with liver-related death but also with death from all causes.
In 2007 a noninvasive system, the NAFLD fibrosis score (NFS), was validated to identify NAFLD patients with advanced fibrosis. NFS ≥ 0.676 detects an advanced fibrosis (F3-F4) with a positive predictive value of 90%-82% while NFS ≤ -1.455 excludes advanced fibrosis with a negative predictive value of 93%-88%.
In addition, in different settings, a score named Fibrosis-4 (FIB-4) was also validated to detect advanced fibrosis in patients with hepatitis B virus and hepatitis C virus /human immunodeficiency virus coinfection. Fib-4 ≤ 1.45 excludes advanced fibrosis with a negative predictive value of 90%, while Fib-4 ≥ 3.25 detects advanced fibrosis with a positive predictive value of 65%.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18 years old or more
- •Patients with at least on of the following metabolic disorders
- •Arterial hypertension
- •Dyslipidemia
排除标准
- •Average daily consumption of alcohol >20 g in women and of >30 g in men (assessed by Alcohol Use Disorders Identification Test, AUDIT;
- •presence of hepatitis B surface antigen and antibody to hepatitis C virus;
- •positive tests for autoimmune hepatitis;
- •cirrhosis and other chronic liver diseases;
- •diagnosis of oncological diseases
- •concomitant therapy with drugs known to promote liver steatosis (e.g. amiodarone);
- •other chronic infectious or autoimmune disease;
结局指标
主要结局
Clinical, biochemical and genetic factors associated to progression of liver fibrosis in a large cohort of patients with NAFLD
时间窗: Patients will be followed for an expected mean time of 120 months
To detect non conventional factors associated with the progression of liver fibrosis in patients with NAFLD. Progression of liver fibrosis will be assessed by non invasive markers (such as FIB-4, Nafld Fibrosis Score e liver elastography). The predictive role of the following factors will be assessed: plasmatic and urinary isoprostanes, thromboxane, platelet recruitment, reactive species of oxygen, nadph oxidase (nox2). Genes of interested will be sequenced.
次要结局
- The predictive role of non-invasive markers of fibrosis on the incidence of major cardiovascular events.(Patients will be followed for an expected mean time of 60 months)
- Nutritional factors associated to NAFLD(At Baseline)
- Platelet activation in NAFLD and NASH(At Baseline)
- The predictive role of systemic markers of oxidative stress and antioxidant status on the incidence of cardiovascular events in NAFLD patients(Patients will be followed for an expected mean time of 120 months)
- Factors associated with chronic kidney disease in NAFLD patients(At Baseline)
- Predictors of kidney disease progression in patients with NAFLD(Patients will be followed for an expected mean time of 60 months)
- Role of gut microbiota in NAFLD(At Baseline)
- Reactive species of oxygen in NAFLD and NASH(At Baseline)
- Nadph oxidase (nox2) activation in NAFLD and NASH(At Baseline)
- Echocardiographic changes in patients with NAFLD(At Baseline)
- Score of cardiovascular risk in patients with NAFLD(Patients will be followed for an expected mean time of 120 months)
- Dyslipidemia and cardiovascular events in patients with NAFLD(Patients will be followed for an expected mean time of 120 months)
- Plasmatic and urinary isoprostanes(At Baseline)
研究者
Francesco Violi
Department Head
University of Roma La Sapienza