Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Controlled Trial of Omega-3 Fatty Acids in the Treatment of Non-Alcoholic Steatohepatitis in Patients With Type 2 Diabetes Mellitus
Brief Summary: Non-alcoholic steatohepatitis (NASH), the most severe form of liver injury in the spectrum of non-alcoholic fatty liver disease (NAFLD), has emerged as the major cause of chronic liver disease in developed countries. Among adults in the United States, the prevalence is between 5.7% and 17%. These rates are expected to increase concurrent with the epidemics of obesity and type 2 diabetes mellitus, which are the major risk factors for NAFLD and NASH. In addition to its high prevalence, NASH is also a progressive fibrotic disease that advances to cirrhosis and liver related death in 20% and 12% of patients, respectively. Among NASH patients with cirrhosis, 40% have liver related death. Diabetics are particularly prone to experience these poor outcomes. No therapy has been proven effective for patients with NASH.

The purpose of this study is to find out whether treatment with polyunsaturated fatty acids (eicosapentaenoic acid \[EPA\] combined with docosahexaenoic acid \[DHA\] called Opti-EPA) improves NASH compared to treatment with placebo pills. The placebo pills will contain corn oil and will be contained in a capsule, but have no medical effect on the body. The investigators will determine improvement in NASH from microscopic changes in the subject's liver tissue during 48 weeks of treatment. This means that the subject will need to have a liver biopsy before and after the treatment.

Omega-3 fatty acids are a form of polyunsaturated fats, one of the four basic types of fat that the body gets from food. (Cholesterol, saturated fat, and monounsaturated fat are the others.) One's body does not make this type of fat; it comes from food sources. These fats are found in foods like cold water fish (tuna, salmon, and mackerel), and vegetable products like flaxseed oil and walnuts.

Research shows that polyunsaturated fats are good for people. Studies have shown that it is good for heart health by playing a role in keeping blood cholesterol levels low, keeping irregular heart rhythms stable, and reducing blood pressure.

The drug being studied, Opti-EPA, is a nutritional supplement. They do not have to be reviewed by the Food and Drug Administration (FDA) like medicines do. Opti-EPA is considered experimental in this study. This means that the United States Food and Drug Administration (FDA) has not approved it for use in people with nonalcoholic fatty liver disease.


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:

* persistently elevated serum aminotransferase levels
* diffusely echogenic liver on imaging studies suggestive of fatty liver
* biopsy consistent with the diagnosis of NAFLD

Exclusion Criteria:

* hepatic virus infections (HCV RNA-PCR negative)
* Hepatitis A, B, C, D, E and G
* cytomegalovirus and Epstein-Barr virus
* alcohol consumption
* history of parenteral nutrition
* use of drugs known to induce steatosis or to affect body weight and carbohydrate metabolism
* autoimmune liver disease, metabolic liver disease, Wilson's disease, and a-1-antitrypsin-associated liver disease were ruled out using standard clinical, laboratory and histological criteria
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:

* 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.

Answer: D