Mediterranean Lifestyle Intervention in Patients With Non-alcoholic Fatty Liver Disease
Condition: Non-alcoholic Fatty Liver Disease (NAFLD); Non-alcoholic Steatohepatitis (NASH)
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Interventional

Summary: 
      Non-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of the
      metabolic syndrome. NAFLD is a pathologic condition which involves both hepatic steatosis and
      non alcoholic steatohepatitis (NASH), as the result of fat accumulation in the liver (liver
      fat >5-10% of liver weight), not due to excess alcohol consumption or other causes of
      steatosis.

      At present, no medication or surgical procedure has been approved for treating NAFLD and
      lifestyle modifications remain the cornerstone therapy targeting both at weight reduction for
      overweight subjects and at prevention of overweight for the normal weight individuals. Given
      that a Mediterranean dietary pattern has a beneficial effect both on the prevention and the
      resolution of the metabolic syndrome, the main aim of the present study is to implement and
      evaluate the potential benefits of an intervention based on the Mediterranean lifestyle in a
      sample of patients with NAFLD.
    

Detailed description: 
      Non-alcoholic fatty liver disease (NAFLD) is a pathologic condition which involves both
      hepatic steatosis and non alcoholic steatohepatitis (NASH), as the result of fat accumulation
      in the liver (liver fat >5-10% of liver weight), not due to excess alcohol consumption or
      other causes of steatosis. Its prevalence ranges in the general population from 10-35%, while
      in obese individuals can reach the 75% and is particularly worrying because these people
      appear to have a higher mortality from both liver and non-liver-related disease, such as
      cardiovascular disease, and therefore a greater economic burden of health costs.

      At present, no medication or surgical procedure has been approved for treating NAFLD and
      lifestyle modifications remain the cornerstone therapy targeting both at weight reduction for
      overweight subjects and at prevention of overweight for the normal weight individuals. Given
      that a Mediterranean dietary pattern has a beneficial effect both on the prevention and the
      resolution of the metabolic syndrome, the main aim of the present study is to implement and
      evaluate the potential benefits of an intervention based on the Mediterranean lifestyle in a
      sample of patients with NAFLD. A secondary aim will be to produce material, for both health
      professionals (namely dietitians and doctors) and patients to help them implementing such an
      intervention based on the Mediterranean lifestyle.

      This study will be a prospective, randomized, blinded and controlled study. Participants with
      NAFLD and BMI>25Kg/m2 (range 25-40 Kg/m2) will be included. NAFLD's diagnosis will be based
      on increased serum levels of alanine aminotransferase (ALT), with or without increased
      gamma-glutamyl transpeptidase (GGT) serum levels, the presence of hepatic steatosis and
      absence of other causes of hepatic steatosis and hepatic failure.

      At baseline, patients will be informed about the study and will give their written consent.
      Then subjects will be randomly assigned to one of 3 groups: (a) Control group, receiving
      written general advice for a healthy lifestyle; (b) Mediterranean diet Group or (c)
      Mediterranean lifestyle group. Participants in (b) and (c) groups will attend a more
      comprehensive program, comprising seven 60-min group counseling sessions, conducted every two
      weeks for the first 2 months and every month for the following 4 months, until the 6-month
      evaluation. Participants will be also assessed 12 months after their entry in the study.

      The dietary intervention and the monitoring will be carried out in the laboratory of Clinical
      Nutrition & Dietetics at Harokopio University, where experienced clinical dietitians will
      conduct all consultations. Counseling will be based on the goal setting theory. Motivational
      and behavioral strategies will be also used. In the Mediterranean diet group, all food groups
      of the Mediterranean diet will be targeted, whereas in the Mediterranean lifestyle group
      culinary practices, seasonality, and locality of food products, socialization during meals,
      rest during the day, as well as the adoption of an active living will be additionally
      addressed. Intervention will also aim at achieving a 5-10% weight loss within the first 6
      months.

      Patients will be evaluated at baseline, at the end of the 6-mo intervention and 1 year after
      the study entry. At baseline, all patients will undergo a brief medical history assessment,
      complete physical examination and routine laboratory testing. History of alcohol consumption
      will be obtained from both patients and friends/relatives where possible. Evaluation of
      anthropometric measurements, dietary intake, physical activity and lifestyle habits, will be
      continuously assessed throughout the study. Dietary intake will be assessed through two
      24-hour recalls and a food frequency questionnaire (FFQ). Data from recalls will be analyzed
      in terms of energy, macro- and micronutrient intake (using the Nutritionist Pro, version 2.2
      software), as well as of food group intake and meal patterns. Conditions around eating will
      be also recorded and analyzed. Furthermore, a semi-quantitative FFQ, including the main food
      groups of the Mediterranean diet will be used for the overall assessment of eating habits.
      Physical activity will be assessed using the Harokopio Physical Activity Questionnaire
      (HPAQ). Sleep duration and quality will be evaluated through the Athens Insomnia Scale,
      consisting of items related to sleep induction, awakenings during the night, final awakening,
      total sleep duration, and sleep quality, well-being, functioning capacity, and sleepiness
      during the day. Current and past smoking habits will be also recorded.

      At baseline and at 6 and 12 months, blood samples will be collected after an overnight food
      deprivation for the assessment of biochemical markers, and stored at -80oC. Lipid profile,
      markers of glucose metabolism and liver function, and adipokines, inflammatory markers and
      markers of oxidative stress will be determined using automated analyzers and/or commercial
      ELISA kits.

      All patients will pass through liver stiffness measurements with liver elastography at
      baseline, as well as at the end of the intervention and after one year of the study entry.
      Patients without a recent liver biopsy (within the previous 12 months) will also undergo
      liver biopsy at baseline. Liver biopsies will be repeated one year after and will be
      evaluated by the same hepato-pathologist, who will have access to patient's clinical data.
    

Intervention name(s): Mediterranean lifestyle; Mediterranean Diet
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Counseling will be based on the goal setting theory. Motivational and behavioral strategies will be also used. In the Mediterranean lifestyle group culinary practices, seasonality, and locality of food products, socialization during meals, rest during the day, as well as the adoption of an active living will be additionally addressed.; Counseling will be based on the goal setting theory. Motivational and behavioral strategies will be also used. In the Mediterranean diet group, all food groups of the Mediterranean diet will be targeted.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: NAFLD; NASH; Mediterranean diet; Mediterranean lifestyle