Portal Hypertension in Non-alcoholic Fatty Liver Disease: Association With Cardiovascular Risk and Identification of Non-invasive Biomarkers (THESIS)

Instituto de Investigación Marqués de Valdecilla

Status: Unknown

Conditions: Fatty Liver Disease

Treatments: Other: A complete cardiovascular and liver characterization will be carried out

Study type: Observational

Funder types: Other

Identifiers

NCT04191044

THESIS

Details and patient eligibility

About

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.

Enrollment: 170 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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/1.73m2.
• 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.

Trial design

170 participants in 4 patient groups

NAFLD with mild steatosis and grade <3 fibrosis in patients

Description:

NAFLD with mild steatosis and grade \<3 fibrosis in patients with grade 1 or 2 obesity and insulin resistance (HOMA index\> 2.6) or diabetes mellitus.

Treatment:

Other: A complete cardiovascular and liver characterization will be carried out

NAFLD with severe steatosis and grade <3 fibrosis in patients

Description:

NAFLD with severe steatosis and grade \<3 fibrosis in patients with grade 1 or 2 obesity and insulin resistance (HOMA index\> 2.6) or diabetes mellitus.

Treatment:

Other: A complete cardiovascular and liver characterization will be carried out

NAFLD with advanced fibrosis

Description:

NAFLD with advanced fibrosis (i.e. grade 3 or 4 fibrosis) without previous portal hypertension-related complications

Treatment:

Other: A complete cardiovascular and liver characterization will be carried out

Decompensated NAFLD cirrhosis

Description:

Decompensated NAFLD cirrhosis (i.e. development of ascites, variceal hemorrhage, and/or hepatic encephalopathy) up to Child B (9 points)

Treatment:

Other: A complete cardiovascular and liver characterization will be carried out