Fibrosis Reduction in Non Alcoholic Steatohepatitis (FRIN)

Institute of Hospitalization and Scientific Care (IRCCS)

Status

Active, not recruiting

Conditions

Weight Loss

Bariatric Surgery Candidate

NASH With Fibrosis

Treatments

Dietary Supplement: intensive life style modification

Procedure: roux -en-y- gastric bypass

Study type

Interventional

Funder types

Other

Identifiers

NCT05798702

4103

Details and patient eligibility

About

Background: Non-Alcoholic Steatohepatitis (NASH) represents one of the stages of Non-Alcoholic Fatty Liver Disease (NAFLD) with a very high risk to evolve in cirrhosis and hepato-carcinoma.

Currently, the only diagnostic method is a liver biopsy that remains the gold standard for characterizing liver histologic alterations and fibrosis stages. There is no specific treatment for NASH, in fact no drugs are currently licensed specifically for treating this disease.

Aim: Our aim is to conduct a non-inferiority, randomized-controlled trial (RCT) comparing Roux-en-Y Gastric bypass (RYGB) with an intensive lifestyle modification plan (Very low-calorie diet, VLCD) for the reduction of advanced stages of fibrosis in subjects with obesity and NASH after 25% weight loss.

Full description

Materials and Methods: The Investigators will screen patients with obesity, NAFLD fibrosis score (NFS) >0.676 and FibroScan > 9.5 kPA who have a high probability of NASH with advanced stage of fibrosis.

Participants will undergo liver biopsy to make diagnosis according to the Steatosis Activity Fibrosis (SAF) score algorithm. Subjects with BMI ≥ 30 and ≤50 kg/m2, age 25-65 years and F3-F4 fibrosis stage at liver biopsy will be included and randomized 1:1 to RYGB or VLCD. Anthropometric parameters, body composition with DEXA and liver function with blood samples will be assessed at the enrolment. A mixed meal metabolic test will be also performed to evaluate insulin sensitivity and secretion. These procedures will be repeated after 25% weight loss. Expectation: The Investigators expect a reduction of 2 points of histological fibrosis after 25% weight loss following either metabolic surgery or dieting. The investigators foresee also reversal of NASH, improvement of metabolic syndrome and glycemic control, changes in insulin sensitivity and secretion, changes in lipid profile, in NASH liver markers, in Fibroscan variables and in body composition

Enrollment

20 estimated patients

Sex

All

Ages

25 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Informed Consent signed before starting any procedure foreseen by the study;
Liver Ultrasound shoving steatosis and Fibroscan>9,5 KPa;
NAFLD fibrosis score>0,676;
diagnosis of NASH with stage F3-F4 of fibrosis according to SAF score, documented by liver biopsy and no evidence of another form of liver disease;
BMI≥ 30 and ≤50 kg/m2;
Age 25-65 years.

Exclusion criteria

Chronic liver disease other than NAFLD (e.g. hemochromatosis, viral or autoimmune hepatitis, Wilson's disease, α1 -antitrypsin deficiency);
Presence of esophageal varices and/or ascites;
INR ≥ 1,4;
Platelet count ≤ 100000;
Substantial alcohol consumption (>20 g/day for women or >30 g/day for men) and/or toxin exposure;
Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous 6 months;
End stage renal failure;
Participation in any other concurrent therapeutic clinical trial;
Any other life-threatening, non-cardiac disease;
Pregnancy;
Type 1 diabetes, or LADA;
Lipodystrophy;
Abetalipoproteinemia;
Interfering medications (e.g., amiodarone, methotrexate, tamoxifen, corticosteroids);
Inability to give informed consent.