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

NCT ID: NCT04191044

Last Updated: 2019-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

170 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-01-10

Study Completion Date

2020-07-10

Brief Summary

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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.

Detailed Description

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Conditions

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Fatty Liver Disease

Keywords

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Non-alcoholic fatty liver disease

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

A complete cardiovascular and liver characterization will be carried out

Intervention Type OTHER

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.

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.

A complete cardiovascular and liver characterization will be carried out

Intervention Type OTHER

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.

NAFLD with advanced fibrosis

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

A complete cardiovascular and liver characterization will be carried out

Intervention Type OTHER

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.

Decompensated NAFLD cirrhosis

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

A complete cardiovascular and liver characterization will be carried out

Intervention Type OTHER

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.

Interventions

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A complete cardiovascular and liver characterization will be carried out

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.

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Universitario Ramon y Cajal

OTHER

Sponsor Role collaborator

Hospital General Universitario Gregorio Marañon

OTHER

Sponsor Role collaborator

Puerta de Hierro University Hospital

OTHER

Sponsor Role collaborator

Instituto de Investigación Marqués de Valdecilla

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Central Contacts

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Jose Ignacio Fortea

Role: CONTACT

Phone: +34 942 204084

Email: [email protected]

Lucia Lavin Alconero

Role: CONTACT

Phone: +34 942 204084

Email: [email protected]

References

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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.

Reference Type BACKGROUND
PMID: 29368124 (View on PubMed)

Francque 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.

Reference Type BACKGROUND
PMID: 21389796 (View on PubMed)

Mendes 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.

Reference Type BACKGROUND
PMID: 22610002 (View on PubMed)

Rodrigues 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.

Reference Type BACKGROUND
PMID: 30625404 (View on PubMed)

Other Identifiers

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THESIS

Identifier Type: -

Identifier Source: org_study_id