Portal Hypertension in Non-alcoholic Fatty Liver Disease: Association With Cardiovascular Risk and Identification of Non-invasive Biomarkers (THESIS)
THESIS
1 other identifier
observational
170
0 countries
N/A
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started Jan 2020
Shorter than P25 for all trials
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 5, 2019
CompletedFirst Posted
Study publicly available on registry
December 9, 2019
CompletedStudy Start
First participant enrolled
January 10, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 10, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
July 10, 2020
CompletedDecember 12, 2019
December 1, 2019
Same day
December 5, 2019
December 10, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Number of patients with NAFLD without advanced fibrosis and severe steatosis with portal hypertension
1 months
Number of patients with NAFLD and advanced fibrosis with portal hypertension
1 months
number of the mechanisms responsible for the appearance of portal hypertension by specifically assessing the following
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.
1 months
Threshold of portal hypertension leading to portal hypertension-related complications in patients with NAFLD
1months
Secondary Outcomes (2)
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
Study Arms (4)
NAFLD with mild steatosis and grade <3 fibrosis in patients
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.
NAFLD with severe steatosis and grade <3 fibrosis in patients
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.
NAFLD with advanced fibrosis
NAFLD with advanced fibrosis (i.e. grade 3 or 4 fibrosis) without previous portal hypertension-related complications
Decompensated NAFLD cirrhosis
Decompensated NAFLD cirrhosis (i.e. development of ascites, variceal hemorrhage, and/or hepatic encephalopathy) up to Child B (9 points)
Interventions
A complete cardiovascular and liver characterization will be carried out, including some supplementary tests with minimal risks (e.g. hemodynamic study). If any disease is detected, patients will be referred to the corresponding specialized care following the usual clinical practice.
Eligibility Criteria
Non-alcoholic fatty liver disease.
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Publications (4)
Baffy G. Origins of Portal Hypertension in Nonalcoholic Fatty Liver Disease. Dig Dis Sci. 2018 Mar;63(3):563-576. doi: 10.1007/s10620-017-4903-5. Epub 2018 Jan 22.
PMID: 29368124BACKGROUNDFrancque S, Verrijken A, Mertens I, Hubens G, Van Marck E, Pelckmans P, Van Gaal L, Michielsen P. Noncirrhotic human nonalcoholic fatty liver disease induces portal hypertension in relation to the histological degree of steatosis. Eur J Gastroenterol Hepatol. 2010 Dec;22(12):1449-57. doi: 10.1097/MEG.0b013e32833f14a1.
PMID: 21389796BACKGROUNDMendes FD, Suzuki A, Sanderson SO, Lindor KD, Angulo P. Prevalence and indicators of portal hypertension in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2012 Sep;10(9):1028-33.e2. doi: 10.1016/j.cgh.2012.05.008. Epub 2012 May 18.
PMID: 22610002BACKGROUNDRodrigues SG, Montani M, Guixe-Muntet S, De Gottardi A, Berzigotti A, Bosch J. Patients With Signs of Advanced Liver Disease and Clinically Significant Portal Hypertension Do Not Necessarily Have Cirrhosis. Clin Gastroenterol Hepatol. 2019 Sep;17(10):2101-2109.e1. doi: 10.1016/j.cgh.2018.12.038. Epub 2019 Jan 6.
PMID: 30625404BACKGROUND
Biospecimen
Blood samples will be used to measure inflammation markers and other laboratory parameters.
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- OTHER
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 5, 2019
First Posted
December 9, 2019
Study Start
January 10, 2020
Primary Completion
January 10, 2020
Study Completion
July 10, 2020
Last Updated
December 12, 2019
Record last verified: 2019-12