Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II Double-Blind, Placebo-Controlled Study of Two Doses of EPA-E in Patients With NASH
Brief Summary: This is a controlled study to determine the effectiveness and safety of ethyl icosapentate (EPA-E) in the treatment of adult patients with non-alcoholic steatohepatitis (NASH).


Options:
A: Inclusion Criteria:

* Multiple risk factors:

  * diabetes,
  * age =\> 65 years,
  * male sex,
  * hypertension,
  * hypercholesterolemia,
  * smoking,
  * obesity,
  * family history of premature cardiovascular disease;
* Previous manifestations of atherosclerotic disease (ischemic stoke, transient ischemic attack \[TIA\], peripheral artery disease, previous arterial revascularisation procedures, angina pectoris)

Exclusion Criteria:

* Contraindications (known allergies to n-3 PUFA) or indications (previous myocardial infarction) for the treatment with n-3 PUFA
* Serious comorbidity with an unfavourable prognosis over the short term
* Expected non compliance over a long period of time
* Pregnancy
B: Inclusion Criteria:

A patient may be included if he/she;

* Is aged between 18 and 55 years (both included).
* Has multiple sclerosis according to the McDonald criteria (McDonald 2001)
* Has a stable disease during the last month period prior to inclusion, and a disability equivalent to EDSS of 5.5 or less (Kurtzke 1983).
* Has shown disease activity defined as at least one relapse or at least one new MRI lesion (T1 enhancing or T2 lesion - ref. McDonald criteria) during the year prior to inclusion.
* Is prepared to and considered able to follow the protocol and to attend the planned visits during the whole study period.
* Is using adequate contraceptive methods and has negative pregnancy test results (female of childbearing potential must).
* Has given written informed consent.

Exclusion Criteria:

A patient has to be excluded if he/she;

* Has received continuous for more than one-week treatment with unsaturated fatty acids (omega-3) within 3 months prior to inclusion in the study.
* Has an active RRMS disease that would strongly be recommended for standard immunomodulatory treatment by the treating neurologist.
* Has received treatment with interferon-beta or glatiramer acetate within 6 months prior to inclusion in the study.
* Has received treatment with lymphoid irradiation, mitoxantrone, cyclophosphamide or long-term glucocorticoids.
* Has received treatment with azathioprine, cyclosporine or other immunosuppressive agents within the year prior to inclusion in the study.
* Has received treatment with glucocorticoids or ACTH within two month prior to inclusion in the study.
* Has experienced a relapse within one month prior to the inclusion in the study.
* Has converted to secondary progressive MS.
* Has suffered from major depression or any other psychiatric disorder that would preclude safe participation in the protocol.
* Has diabetes mellitus.
* Has alcohol or drug abuse.
* Has cardiac insufficiency, cardiomyopathy, significant cardiac dysrhythmia, unstable or advanced ischemic heart disease (NYHA III or IV), or malignant hypertension.
* Has renal insufficiency.
* Has ASAT or ALAT \> 2,5 x normal upper limit.
* Has leukopenia \< 2500 leukocytes per µl or thrombocytopenia \<100 000 thrombocytes per µl.
* Has any systemic disease, which can influence his/her safety and compliance, or the evaluation of the disability.
* Has thromboembolic disease that needs anticoagulative treatment.
* Have formerly shown severe reactions against study drug, interferon-beta or gadolinium (MRI contrast).
* Is breastfeeding or is pregnant.
C: Inclusion Criteria:

* Diagnosis of definite NASH
* Patients with diabetes taking stable doses of anti-diabetic agents are eligible
* No significant concomitant medical illness

Exclusion Criteria:

* Diagnosis of cirrhosis.
* Serum ALT \> 300 U/L
* Use of drugs associated with steatohepatitis
* Use of the following anit-NASH agents:

  1. Vitamin E \> 60 IU per day
  2. Omega-3-acid ethyl esters or omega-3-polyunsaturated fatty acid (PUFA)-containing supplements \> 200 mg per day
  3. Thiazolidinediones (e.g. pioglitazone)
* Use of non-stable doses of the following anti-NASH agents: HMGCoA reductase inhibitors (statins), fibrates, probucol, ezetimibe, ursodiol (UDCA), taurine, betaine, N-acetylcysteine, s-adenosylmethionine (SAM-E), milk thistle, anti-TNF therapies, or probiotics.
* Other liver disease
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: C