Human Liver ORganoids as a Model to Study the Development of Non-Alcoholic SteatOhepatitis (NASH)

Recruiting · NCT06856252 · Interventional (participants receive a specific treatment) · Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

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NASH

Interventions studied

Liver resection to isolate cells

What this trial is about

The primary objective of the study is to generate and characterize three-dimensional models, called "assembloids", composed of the main liver cell populations (in particular from the co-culture of organoids with stellate cells, responsible for fibrogenesis, deriving from clinical samples). These models will be used in order to imitate the first phases of the onset of steatohepatitis, in conditions of altered lipid metabolism (induced through exposure to the main environmental determinants of this condition: excess fatty acids, fructose, cholesterol) in the presence or absence of the mutation I148M of PNPLA3. Other genetic variants will also be analyzed, such as TM6SF2, MBOAT7 and GCKR, which have previously been correlated with the development of non-alcoholic steatohepatitis. Further objectives will be: 1) identify new biomarkers of pathological activation of human stellate cells and progression of liver damage, to be subsequently validated in clinical case series for future use in clinical management for individual risk stratification; 2) study the epigenetic factors that underlie the onset of non-alcoholic steatohepatitis and its progression to fibrosis, cirrhosis and HCC; 3) evaluate the impact of antisense oligonucleotides directed against PNPLA3 on the severity of the "steatohepatitic" phenotype (lipid accumulation, lipotoxicity and inflammation and fibrogenesis) in assembloids

Who can take part

Age range

18 Years and older

Sex

All (male and female)

Healthy volunteers

No - a diagnosis or condition is required

Phase

Not applicable (e.g. observational or device study)

Study type

Interventional (participants receive a specific treatment)

Eligibility criteria (as published)

Adult patients who have given consent to participate in the study and listed for the following procedures will be included: * liver biopsy for suspected non-alcoholic steatohepatitis (NASH) at the time of diagnosis; * liver resection for hepatocarcinoma or other liver lesions (including secondaries from other neoplasms and benign focal lesions, which will allow obtaining healthy starting liver tissue); * post-transplant healthy liver biopsies; * cholecystectomies. It will also be required: * availability to sign informed consent for the study * availability of DNA sample for genetic analysis and clinical data, * blood sampling for genetic and epigenetic analyzes and analysis of non-coding RNAs (lncRNAs, miRNAs and circRNAs). Patients will be excluded who present: * positivity for chronic viral hepatitis (HCV-RNA and/or HBsAg); * positivity to other liver diseases such as autoimmune and viral hepatitis (hepatitis B and C), hereditary hemochromatosis, alpha-1-antitrypsin deficiency, Wilson's disease.

Where it is running

1 location listed.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Istituto di Ricovero e Cura a Carattere Scientifico di natura pubblica - Milan, Milano, Italy

Read the full protocol, contacts and eligibility on ClinicalTrials.gov →