Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised, Double-blind, Placebo-controlled, Phase II, Single-centre Study to Assess the Safety and Efficacy of Silymarin 700 mg Capsules TID for the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD)
Brief Summary: This is a randomised study to examine whether high dose Sillymarin will be able to help improve fat-induced liver damage in the liver. The study hypothesis is that high dose Sillymarin will be able to reduce steato-hepatitis (fat-related liver inflammation) better than placebo.


Options:
A: Inclusion Criteria:

* Age 18 to 70 years
* Fatty liver identified by imaging studies including ultrasound, computer tomography or magnetic resonance imaging
* Elevated alanine aminotransferase (ALT) according to Prati's criteria (\>30 IU/l in men and \>19 IU/l in women)18
* Written informed consent obtained

Exclusion Criteria:

* Positive hepatitis B surface antigen, anti-hepatitis C virus antibody, or anti-nuclear antibody titer above 1/160
* Alcohol consumption above 30 g per week in men or 20 g per week in women
* ALT above 10 times the upper limit of normal
* Liver decompensation, as evidenced by bilirubin above 50 µmol/l, platelet count below 100 × 109/l, prothrombin time above 1.3 times the upper limit of normal, albumin below 35 g/l, presence of ascites or varices
* Use of systemic corticosteroids and methotrexate in the last 6 months
* Evidence of hepatocellular carcinoma
* Terminal illness or cancer, unless in complete remission for more than 5 years
B: Inclusion Criteria:

* Male or female 18 years of age or older.
* Diagnosed with NASH (refer to Section 5.2)
* AST and/or ALT greater than 40 IU/L.
* Must agree to adhere to alcohol consumption guideline.
* Weight gain//loss of no more than 10% between biopsy and screening or within 30 days of screening if the biopsy is performed during the screening period.
* No change in diabetic and/or lipid medications between biopsy and screening or within 30 days of screening if the biopsy is performed during the screening period

Exclusion Criteria:

* Use of silymarin or other milk thistle preparations for a period of 90 consecutive days or longer between biopsy and initial screening, or within 30 days prior to screening if the biopsy is performed during the screening period.

  * Use of other antioxidants or non-prescribed complementary alternative medications for a period of 90 consecutive days or longer between biopsy and initial screening, or within 30 days prior to screening if the biopsy is performed during the screening period.
  * Use of warfarin, metronidazole, or acetaminophen (greater than 2 grams per day) between screening and randomization.
  * Use of oral steroids for more than 14 days of screening or prior to randomization.
  * BMI ≥ 35 kg/m2 between screening and randomization.
  * Poorly-controlled diabetes (HbA1c \> 8 %) between screening and randomization
  * Diabetes mellitus treated with oral agents other than the secretagogues or metformin between screening and randomization. Sitagliptin is allowed.
  * For patients using anti-hyperlipidemic agents or accepted anti-diabetic agents, any change of agent or dose between screening and randomization.
  * Radiologic imaging consistent with cirrhosis or portal hypertension.
  * Evidence of decompensated liver disease
  * Platelet count \< 130 x 109 /L at screening.
  * History of bariatric surgery, or undergoing evaluation for bariatric surgery.
  * Known allergy/sensitivity to milk thistle or its preparations.
  * History of immunologically mediated disease
  * History of thyroid disease poorly controlled on prescribed medications.
  * History of solid organ or bone marrow transplantation.
  * Primary hepatic malignancy.
  * Secondary hepatic malignancy or extrahepatic malignancy.
  * Serum Creatinine of 176 μmol/L or greater or creatinine clearance (calculated according to Cockcroft-Gault) 60 mL/min or less, or on dialysis, at screening.
  * Severe illness or any other conditions that would make the patient, in the opinion of the investigator, unsuitable for the study.
  * Women with ongoing pregnancy or breast feeding, or contemplating pregnancy.
  * Women of childbearing potential who are not practicing an acceptable form of birth control.
  * Participation in a research drug trial within 30 days of screening.
  * Inability or unwillingness to give informed consent or abide by the study protocol.
C: Inclusion Criteria:

* AST or ALT level \> 50 IU/L

Exclusion Criteria:

* Viral hepatitis
* Alcoholic hepatitis
* Autoimmune hepatitis
* Pancreatitis
* Hemochromatosis
* Wilson's disease
* Drug induced liver injury
* Cancer
D: 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).

Answer: B