Please select the eligibility criteria that correspond to the clinical trial below.
Title: VENS is a Multicenter, Randomized, Double-masked, Placebo Parallel Controlled Trial to Evaluate the Efficacy and Safety of Treatment With Vitamin E Softgel in Non Diabetic Adults With NASH Compared to Treatment With Placebo in China
Brief Summary: VENS is a multicenter, randomized, double-masked, placebo parallel controlled trial to evaluate the efficacy and safety of treatment with vitamin E softgel in non diabetic adults with NASH compared to treatment with placebo in China.


Options:
A: 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
B: Inclusion Criteria:

* Confirmed NAFLD/NASH
* 18 years \< Age \< 67 years
* BMI \> 30 kg/ m2

Exclusion Criteria:

* Hepatotoxic Medication, Concomitant Liver Disease
* Decompensated Diabetes Mellitus
* Dysthyroidism, hypopituitarism, Cushing syndrome / disease
* Alcohol abuse or drug addiction
* Clinically or biochemically recognized systemic diseases
* Pregnancy test, lactation
* Vegan or lacto- and ovo-lacto- vegetarianism
* Psychiatric or mental disorder
* Recent loss in body weight or current diet
* Any use of antioxidant-phytochemical rich supplement, anti-, pre- or pro-biotics within 3 months pre-intervention
* Changes in drug treatment for e.g. hypertension, diabetes mellitus, 3 months prior or during the 6month intervention
* Antibiotic treatment during and 2 months prior to screening
C: Inclusion Criteria:

* Adult patients (age \>18 years)
* Have type 2 diabetes mellitus with good control of blood sugar (hemoglobin A1c \[HbA1c\] \<7.5%) and will have been on a stable regimen of anti-diabetic agents for more than 4 months.
* NASH established on liver biopsy done within 6 months prior to inclusion in the study as determined by established histologic criteria

Exclusion Criteria:

* Cirrhosis of the liver
* End stage target organ damage in diabetes mellitus: advanced renal failure (serum creatinine \> 2.0 mg/dl) with or without dialysis, severe neuropathy, or advanced peripheral vascular disease.
* Any organ dysfunction with anticipated life expectancy of less than 2 years
* Co-existent etiologies for liver disease
* Significant alcohol consumption, defined as more than 30 g per day in men and more than 20 g per day in women.
D: Inclusion Criteria:

1. Age: 18 -75, no limitation for ethnic and gender
2. Body Mass Index(BMI) \< 35 kg/m2
3. Patients with nonalcoholic steatohepatitis (NASH) based on liver biopsy obtained within 6 months before randomization. The histological evidence of NASH was defined as Non - alcoholic fatty liver disease activity score（NAS）≥ 4 (according to Nonalcoholic Steatohepatitis Clinical Research Network, NASH CRN) with a minimum 1 score for steatosis, lobular inflammation, and hepatocyte ballooning respectively.
4. Fibrosis stage 0-3 according to nonalcoholic steatohepatitis clinical research network（NASH CRN).
5. Without history of significant alcohol consumption for a period of more than 3 months within 5 years (\<10 g/day for female and \< 20 g/day for male).
6. The lab test results should meet the requirements:

   ① Alanine aminotransferase （ALT） \< 5 times of normal upper limit

   ② Creatinine (Cr)\< normal upper limit

   ③ Albumin （ALB）\> 3.5g/L

   ④ International normalized ratio（INR）= 0.8-1.3

   ⑤ Fasting plasma glucose(FPG) \< 126mg/dL（7mmol/L） and/or 2h postprandial plasma glucose (PPG) \< 200mg/dL（11.1mmol/L）and/ or HbA1C \< 6.5 %
7. If a participant with hypertension, he/she was required a stable antihypertensive drug(s) to keep blood pressure stable.(blood pressure \< 140/90 mmHg) 3 months prior to randomization.
8. If a participant using a statin or fibrate, he/she was required on a stable dose to keep lipid stable (triglyceride(TG) \< 1.7 mmol/L, total cholesterol (TC) \< 5.72 mmol/L, LDL-c \< 3.64 mmol/L) 3 months prior to randomization.
9. Women of childbearing potential: negative pregnancy test during screening or at randomization or willingness to use an effective form of birth control during the trial(at least include one barrier contraceptive method) and not breast feeding
10. Men must agree to use an effective form of birth control during the trial(at least include one barrier contraceptive method)
11. All participants are needed to sign the informed consent form.

Exclusion Criteria:

1. Evidence of other form of acute or chronic liver disease. (Virus hepatitis, Hereditary hemochromatosis, Hepatolenticular degeneration, Alcoholic liver disease, Drug-induced hepatopathy).
2. History of diabetic mellitus or use of antidiabetic drugs.
3. Known heart failure of New York Heart Association class 2, 3, or 4.
4. Wear of cardiac pacemaker.
5. Hypothyroidism (TSH \> 2 times of upper normal limit).
6. History of disease affecting drug absorption, distribution, metabolism (inflammatory bowel disease, gastrointestinal surgery, chronic pancreatitis, gluten allergy, vagotomy).
7. Use of anti-NASH drugs within 3 months before randomization (metformin, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitor, glucagon-like peptide-1(GLP-1), sodium glucose contransporter2(SGLT2), S-adenosylmethionine -e(SAM-e), polyene phosphatidyl choline, glycyrrhizin, bicyclol, reduced glutathione, betaine, fish oil, silymarin,oberbic acid/ursodeoxycholic acid (OCA/UDCA), phosphodiesterase (PDE)-inhibitor, gemfibrozil, vitamin E, long term antibiotic (\>1 week).
8. Positivity of antibody to Human Immunodeficiency Virus.
9. Inability to safely obtain liver biopsy.
10. Known intolerance to vitamin E
11. Inability to fill out diary card, to manage diet and exercise, poor compliance.
12. Dependence or abuse of alcohol and/or drugs.
13. Any other condition which in the opinion of investigator would impede compliance or hinder completion of the study.

Answer: D