Please select the eligibility criteria that correspond to the clinical trial below.
Title: N/A
Brief Summary: The purpose of this study is to investigate the effects of coffee main constituents (caffeine and chlorogenic acid) supplements on inflammatory, metabolic factors, hepatic steatosis and fibrosis in none- alcoholic fatty liver patients with type 2 diabetes. Two hundred patients with fatty liver and type 2 diabetes will be randomly assigned to one of four groups: group 1, caffeine (200 mg/d) plus chlorogenic acid (200 mg/d); group 2, caffeine (200 mg/d) plus placebo; group 3, chlorogenic acid (200 mg/d) plus placebo; group 4, placebo plus placebo. Supplementation will be daily and will supervise for 6 months.


Options:
A: Inclusion Criteria:

* Liver biopsy consistent with diagnosis of NASH (liver biopsy performed in 3-6 months before enrollment)
* Hyperechogenicity of liver at ultrasound examination
* ALT levels range between normal and \< 10 UNL
* INR \< 1.3
* Albumin \> 3 gr/dl.
* Total bilirubin \< 2.5 mg/dl
* normal renal function
* normal cells blood count
* exclusion of other causes of chronic hepatopathies in children
* Written informed consent to participate in the Protocol by their parents or legal guardians of patients

Exclusion Criteria:

* alcohols or drugs abuse
* use of drugs known to induce steatosis or to affect body weight or carbohydrate metabolism
* autoimmune liver diseases, Wilson's disease, alpha-1-antitripsin deficiency, metabolic liver disease
* every clinical or psychiatric diseases interfering with experimentation according to investigator's evaluation
* finding of active liver disease due to other causes
B: 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.
C: Inclusion Criteria:

* Patient diagnosed with type 2 diabetes based on American Diabetes Association (ADA) definition or who only take oral antidiabetic drug.
* CAPscore \>263

Exclusion Criteria:

* Criteria:

  * Taking any kind of antibiotics two weeks before recruitment;
  * History of alcohol consumption ;
  * pregnancy or lactation;
  * Professional athletes;
  * Other liver disease (viral/etc);
  * High dose synthetic estrogens, methotrexate , amiodarone, steroids, chloroquine, immunosuppressive drugs;
  * A history of Cardiovascular disease;
  * Renal disease, Celiac disease, Cirrhosis;
  * History of Upper Gastrointestinal surgery ;
  * A history of hypothyroidism or Cushing's syndrome;
  * History of drug dependence;
  * Body mass index (BMI) ≥35 kg/m2;
  * A restrictive diet or weight change ≥ 5 kg during the 3 months prior to study;
  * Any change in treatment with oral hypoglycemic; anti hypertensive and antilipid agents during the study;
  * Use of weight loss medications
D: 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.

Answer: C