Please select the eligibility criteria that correspond to the clinical trial below.
Title: Combined Intensive and Conventional Exercise Intervention of Nonalcoholic Fatty Liver Disease
Brief Summary: The prevalence of NAFLD is 50-70% in obese people. A decrease of calorie intake and increase of physical activity are recommended as an effective approach for the prevention and treatment of NAFLD. However, the exercise model for NAFLD intervention is understudied. In the present study we aim to compare the effect of intensive and conventional exercise interventions on NAFLD.


Options:
A: 1. Subjects with NAFLD determined by MRS ;
2. Age 40-65 years old;
3. Waist circumference\> 90cm for men and \> 85cm for women.
B: 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.
C: 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.
D: 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%

Answer: A