Integrated Approaches for Identifying Molecular Targets in Liver Disease

NCT03915002 | Completed

• 1 other identifier: STUDY19120198
• Study Type: observational
• Target: 155
• Locations: 1 country
• Sites: 1

Brief Summary

To provide a framework for successful clinical trials testing novel targets for therapy in liver disease. To identify molecular and cellular drivers of liver disease to provide a molecular classification and study the determinants or key drivers of disease progression. Consecutive patients admitted with steatohepatitis (alcoholic or non-alcoholic) will be enrolled in this study where liver tissue, blood and stool will be collected to discover and validate factors associated with diagnosis, severity, histological characteristics, development of decompensations, progression of disease and survival.

Conditions

Alcoholic Liver Disease; Non-Alcoholic Fatty Liver Disease; Steatohepatitis, Nonalcoholic; Steatohepatitis

Outcome Measures

Primary Outcomes (3)

• Molecular Subtypes for Targeted Therapies in Liver disease

  * Generation of consistent non-invasive molecular footprints of disease severity and prognosis: plasma and peripheral blood cells from groups of patients with different disease prognosis will be analyzed by means of high throughput proteomics (Mass Spectrometry and aptamer mediated identification) and single cell RNA sequencing, respectively. Data will be integrated with liver RNA-sequencing to detect relevant liver fingerprints in plasma. * Mechanisms of ductular reaction and hepatocyte de-differentiation will be studied by micro-dissection and region-specific RNA-sequencing. * Mechanisms of hepatocyte dedifferentiation will be evaluated using methylation bead chip and chromatin immunoprecipitation coupled to DNA sequencing (ChIP-seq) of histone marks related with activation, enhancement, poisoning and repression of gene expression.

  5 years

• Determination of key drivers of the disease progression

  * To describe and identified the histological patters in each phase of the disease (using imaging technics, including second harmonic generation imaging microscopy and electronic microscopy as well as classical IHC technics) * To quantified and compare the degree of hepatic steatosis and fibrosis assessed by non-invasive techniques such as FibroScan® (CAP controlled attenuation parameter) across different cohorts of patients and across the different stages of the disease within the same patient's phenotype. * To identify the main genetic. psychosocial, and environmental factors influencing the development of advanced liver fibrosis among patients with known or suspected excessive alcohol intake. Through DNA

  5-10 years

• repository capable of providing a framework fro the other outcomes

  To develop a bio-specimen bank comprised of plasma, DNA, and other biological specimens obtained from patients with alcoholic hepatitis, control disease and healthy controls

  2-10 years

Study Arms (3)

Patients

Steatohepatitis: 1. Alcoholic Steatohepatitis and Alcoholic liver disease 2. Nonalcoholic fatty liver disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH)

Disease control

Patients 18 years or older with a diagnosis of cholestatic liver diseases (primary biliary cholangitis or primary sclerosing cholangitis) or hepatotropic virus (hepatitis C or B virus), according to the current international guidelines.

Control subjects

Patients over 18 years old without a diagnosis of liver disease that for any other reason (i.e candidate to liver donor, patients with liver metastasis that require surgery, patients with any type of benign liver tumor or HCC in a healthy liver). Patient over 18 years old with a documented alcoholic used disorder in their clinical records and without any evidence of liver disease.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

1. Alcoholic Steatohepatitis and Alcoholic liver disease 2. Nonalcoholic fatty liver disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH)

You may qualify if:

• Patients with a previous probable or possible AH episode will be defined following the guidelines proposed by the NIAAA.
• Terminal illness with less than 6 months live expectancy (e.g. advanced hepatocellular
• carcinoma).
• Patients who are pregnant or breastfeeding.
• Complete portal vein thrombosis (PVT).
• Previous liver transplant recipient
• Patients with cirrhosis due to alcohol related liver disease without AH with or without a prior episode of decompensation.
• Patients with a diagnosis of cirrhosis due to alcohol related liver disease according to clinical and/or analytic and/or radiological criteria.
• Terminal illness with less than 6 months live expectancy (e.g. advanced hepatocellular carcinoma).
• Patients who are pregnant or breastfeeding.
• Complete portal vein thrombosis
• Previous liver transplant recipient
• Current alcoholic hepatitis episode
• Alcoholic liver disease with compensated never decompensated liver disease.
• Patients diagnosed with an alcohol use disorder identification test (AUDIT) total scores of 8 or more OR Patients with a score lower than 8 in the AUDIT test but for whom there is a high suspicion of current or recent (within one year) AUD based on medical history, self reported history of excessive alcohol use, stigmata of alcohol use on physical exam, liver chemistry abnormalities, or alcohol induced organ involvement other than decompensated liver disease.

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

University of Pittsburgh Medical center

Pittsburgh, Pennsylvania, 15213, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

-Serum, plasma, whole blood, urine, stool, liver tissue, visceral fat and saliva

MeSH Terms

Conditions

Liver Diseases, Alcoholic; Non-alcoholic Fatty Liver Disease; Fatty Liver

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Study Officials

• Jaideep Behari, MD, PhD

  Associate Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 5, 2019
• First Posted: April 16, 2019
• Study Start: June 13, 2019
• Primary Completion: April 12, 2023
• Study Completion: April 12, 2023
• Last Updated: November 7, 2023

Record last verified: 2023-11

Locations

US (1)