Investigation of Synbiotic Treatment in NAFLD
Investigation of Synbiotic Treatment in NAFLD
Non-alcoholic fatty liver disease (NAFLD) is a liver condition in which fat builds up in the
 liver not caused by alcohol. The liver is an organ that is not designed to build up fat.
 NAFLD is common in people who have too much body fat in their abdomen or who have diabetes
 (high blood sugar), but does not always exist with these conditions. NAFLD can also occur in
 thin people too. NAFLD can be harmful to the liver and may cause the liver to fail over time.
 NAFLD may also cause adult (or type 2) diabetes and also heart disease. In people who already
 have diabetes, NAFLD can cause glucose (sugar) levels to be too high.

 Our intestines (guts) contain healthy bacteria and some harmful bacteria (bugs). This balance
 of healthy and harmful bugs is essential for the normal workings of our intestine to digest
 food. Providing these bacteria do not leak out into the blood they do not cause harm. If the
 balance of healthy to harmful bugs is upset, the harmful can cause problems and leak out into
 the blood. Because the liver is connected to the intestine by blood vessels the harmful
 bacteria can get to the liver and cause problems. These bacteria can cause the liver and the
 body to build up too much fat and might cause NAFLD and obesity. In this study, we will test
 the effects of a supplement (synbiotic) taken during the day, that contains a mixture of
 'good' healthy bacteria (probiotic) and a sugar (prebiotic) that is not broken down and
 absorbed into the blood. We will test whether the synbiotic supplement has beneficial effects
 on the NAFLD liver condition and on factors linked to too much body fat, diabetes and heart
 disease.
We will recruit people with NAFLD who have been diagnosed as part of their NHS (National
 Health Service) care with having this condition. At present there is no treatment for this
 condition.

 Purpose and design:

 We are asking the research question: "Does the modulation of gut microflora with a synbiotic
 improve non-alcoholic fatty liver disease and the related risk factors for heart disease and
 type 2 diabetes?"

 Presently there is no treatment for this liver condition. Research evidence suggests that a
 synbiotic supplement might be beneficial for this condition.

 To address this research question we want to undertake a randomised double blind placebo
 controlled trial recruiting people who have been diagnosed with NAFLD.
Inclusion Criteria:

 -  Both men and women

 -  Age > 18 years

 -  Liver fat diagnosed on normal clinical grounds including in most cases liver assessed
 by Kleiner scoring system to classify severity, with no known aetiological factors for
 underlying liver disease (e.g. exclusion of hepatitis A, B & C, primary biliary
 cirrhosis, autoimmune hepatitis, haemochromatosis). Last liver biopsy will be within 3
 years of recruitment to the study.

 -  Liver fat diagnosed by ultrasound, CT or magnetic resonance imaging (MRI) in patients
 who also have either diabetes and/or features of the metabolic syndrome, without
 evidence of known aetiological factors for underlying liver disease (e.g. exclusion of
 hepatitis A, B & C, primary biliary cirrhosis, autoimmune hepatitis,
 haemochromatosis).

 -  Alcohol consumption ≤ 14 units / week for women ≤ 21 units / week for men.

 Exclusion Criteria:

 -  Alcohol consumption > 15 units /week for women and > 22 units /week for men.

 -  Decompensated acute or chronic liver disease.

 -  A history of viral hepatitis, diarrhoea, diverticulosis, irritable bowel syndrome,
 inflammatory bowel diseases, coeliac disease (seropositivity for anti-endomysial
 immunoglobulin A antibodies; immunoglobulin A (IgA) EMA).

 -  Previous bariatric or other abdominal surgery.

 -  Continuous use of antibiotics that may change gut microflora, probiotics, or
 antisecretory drugs capable of causing achlorhydria within the 2 months preceding
 enrolment, or evidence of immunoglobulin A or immunoglobulin deficiency (both of which
 produce confounding effects during assessments of intestinal permeability and small
 intestinal bacterial overgrowth).