Please select the eligibility criteria that correspond to the clinical trial below.
Title: Prebiotic Fibre Supplementation and Gut Microbiota in Non-alcoholic Fatty Liver Disease
Brief Summary: Non-alcoholic fatty liver disease (NAFLD) is a condition where accumulation of fat in the liver leads to metabolic dysfunction. Currently there are no approved treatments for NAFLD. Part of the metabolic dysfunction may arise through changes in the gut microbiota. Prebiotic fibres have beneficial effects on glucose tolerance, body weight, and gut microbiota; therefore they may have potential as part of a dietary strategy for NAFLD treatment.


Options:
A: Inclusion Criteria:

1. NASH with NAS (NASH Activity Score) of \>4 evident on a biopsy performed within 6 months of enrollment.
2. Age 21 years or older.
3. BMI 25 or greater.
4. Ability to provide informed consent.

Exclusion Criteria:

1. Cirrhosis evident clinically or on biopsy.
2. Secondary forms of NASH such as that seen with bariatric surgery or medication induced from such medications as methotrexate, amiodarone, tamoxifen, corticosteroids.
3. Current or past history of diabetes or hyperlipidemia requiring specific drug therapy (see below).
4. Current use of a weight loss medicine, such as a 'fat-burner' or similar agent
5. Alcohol consumption \> 30 g/day, currently or for more than 3 consecutive months within 5 years.
6. Other liver disease (hepatitis C,B, Wilson's, autoimmune, ct-1-antitrypsin and hemochromatosis or HIV
7. Pregnancy or unwillingness to use an effective form of birth control for women of child bearing years.
8. Renal insufficiency (creatinine \> 2), symptomatic coronary, peripheral or neurovascular disease, symptomatic heart failure or advanced respiratory disease requiring oxygen therapy.
9. Inability to provide informed consent.
10. Any condition in the opinion of the primary investigator that would contraindicate the patient's participation.
B: Inclusion Criteria:

* age 6-19
* overweight or obesity
* ALT activity over 130% of upper limit norm
* hyperechogenicity of the liver on ultrasound

Exclusion Criteria:

* HCV, HBV infection
* cholestasis
* chronic/acute liver failure
* alpha-1-antitrypsin deficiency
* Wilson disease
* type 2 diabetes mellitus
* beta-oxidation defects
* alcohol consumption
* history of parenteral nutrition
* use of drugs
C: Inclusion Criteria:

* Adult subjects diagnosed with NAFLD on the basis of abnormal liver enzymes (ALT\>1.5x upper limit of normal) and ultrasonography
* Exclusion of other causes of liver disease including viral hepatitis and alcoholic liver disease
* Aspartate aminotransferase and alanine aminotransferase ≤10x upper limit of normal
* Patients with type 2 diabetes treated with diet and exercise alone or metformin

Exclusion Criteria:

* Cirrhosis of the liver (FibroScan \>17.5 kilopascal or FibroTest \>0.8) or clinical features of cirrhosis.
* Alcohol consumption \>20g/day (2 standard drinks) in women or \> 30g/d (3 drinks) in men
* Alternate (e.g. TPN) or concomitant etiology for abnormal liver enzymes.
* History of decompensated liver disease including ascites, encephalopathy or variceal bleeding
* Concomitant use of any weight loss medication, previous bariatric or other intestinal surgery
* Presence of active infection, pregnancy or lactation
* Regular use of a probiotic or prebiotic supplement within 3 months prior to enrollment
* Antibiotic use within 3 months prior to enrollment
* Weight loss \>3 kg within preceding 3 months to enrollment
* Uncontrolled cardiovascular or respiratory disease, active malignancy, or chronic infections
* Use of agents such as vitamin E, omega-3 fatty acids or medications with evidence for effects on NAFLD (pioglitazone, Glucagon-like peptide-1 analogues, dipeptidyl peptidase IV inhibitors, ursodeoxycholic acid)
* Patients with type 2 diabetes where HbA1c is \>9%
D: Inclusion Criteria:

* Diagnosis of definite NASH
* Patients with diabetes taking stable doses of anti-diabetic agents are eligible
* No significant concomitant medical illness

Exclusion Criteria:

* Diagnosis of cirrhosis.
* Serum ALT \> 300 U/L
* Use of drugs associated with steatohepatitis
* Use of the following anit-NASH agents:

  1. Vitamin E \> 60 IU per day
  2. Omega-3-acid ethyl esters or omega-3-polyunsaturated fatty acid (PUFA)-containing supplements \> 200 mg per day
  3. Thiazolidinediones (e.g. pioglitazone)
* Use of non-stable doses of the following anti-NASH agents: HMGCoA reductase inhibitors (statins), fibrates, probucol, ezetimibe, ursodiol (UDCA), taurine, betaine, N-acetylcysteine, s-adenosylmethionine (SAM-E), milk thistle, anti-TNF therapies, or probiotics.
* Other liver disease

Answer: C