Prebiotics in Patients With Non-alcoholic Liver Disease

A Randomized, Double - Blind Study With Two Parallel Arms for 4 Months (20 Weeks), Evaluating the Effectiveness of the Prebiotics in Patients With Non-alcoholic Liver Disease.

The purpose of this present study is to evaluating whether prebiotics - ITF (Inulin/OFS 75/25) is effective in treating patients with non-alcoholic liver disease.

The study will include 60 patients with Non-alcoholic fatty liver disease (NAFLD) which will randomize to two groups, receiving either ITF (Inulin/oligofructose-OFS 75/25) or maltodextrin (placebo). The trial will last for 26 weeks: Stage 1-Run-in period: Subjects will be followed to ascertain weight maintenance. Stage 2- Randomized intervention period: Subjects will be assigned to receive 16 gram/day of ITF or maltodextrin. Both ITF and placebo will be provided in identical opaque packages and both subjects and researchers will be blinded to the content. After signing informed (-2 week) consent, the following data will be collected: demographics, lifestyle habits including dietary questionnaires, and medical history. At week 0, week 12 and week 24 all the following tests will be performed: Vital Signs: blood pressure, anthropometric measurements, body composition determined by bioelectrical impedance analysis (BIA). Biochemical blood tests: liver function tests fasting glucose insulin & lipid profile, CRP (an inflammation marker), SCFA, BCAA, and LBP and FGF 19. Fecal samples: fecal samples will be used for microbiota composition analysis, and BA analysis. Assessment of liver status At week 0 and 24 by using magnetic resonance spectroscopy (1H-MRS), SteatoTest and NashTest (FibroMax™) and by liver enzymes for evaluating steohepatitis.

Determined by liver fat fraction measured by magnetic resonance spectroscopy (1H-MRS) Blood test for calculate Inflammation score using SteatoTest and NashTest (FibroMax™) Blood test for liver enzyme

Which will be determined by a fasting Glucose and Insulin blood tests and Calculate homeostasis model assessment (HOMA).

Which will be determined by blood test for lipid profile - Triglycerides, cholesterol-LDL and cholesterol-HDL

Inclusion Criteria: Diagnosis of NAFLD based on fatty infiltration detection by ultrasonography and alanine aminotransferase levels of (ALT) ≥ 30 U/L male ≥ 19 U/L females. Over-weight (BMI ≥ 27 kg/m2) who fulfill the criteria of the National Cholesterol Education Program (NCEP) metabolic syndrome Willing to sign informed consent to participate in the study Patients without diabetes or with well-controlled diabetes (HbA1C < 7.5%) who are treated by diet ± metformin Exclusion Criteria: Pregnancy Uncontrolled diabetes Diabetic treatment other than metformin, unusual diets (vegetarian, vegan), usage of antibiotics, probiotics or prebiotics up to 6 months prior to study, alcohol abuse, presence of gastrointestinal or mental disorders, weight-loss treatment, bariatric surgery Serious medical conditions Evidence of another etiology for chronic liver disease such as: hepatitis B, hepatitis C, HIV, autoimmune diseases and metabolic diseases, medications with known hepatotoxicity.

Dewulf EM, Cani PD, Claus SP, Fuentes S, Puylaert PG, Neyrinck AM, Bindels LB, de Vos WM, Gibson GR, Thissen JP, Delzenne NM. Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Gut. 2013 Aug;62(8):1112-21. doi: 10.1136/gutjnl-2012-303304. Epub 2012 Nov 7.