Please select the eligibility criteria that correspond to the clinical trial below.
Title: 48-week Phase II, Randomised, Double Blinded Placebo Controlled Multicentre Trial on Liraglutide's Safety, Efficacy and Action on Liver Histology and Metabolism in Overweight Patients With NASH +/- Type II Diabetes
Brief Summary: The purpose of this study is to investigate whether 48 weeks treatment with once-daily injections of liraglutide improves liver disease (liver fat, inflammation and scarring) and related metabolic parameters in overweight patients with nonalcoholic steatohepatitis, enough to warrant further investigation.


Options:
A: Inclusion Criteria:

1. Subjects must be willing to give written informed consent
2. Diagnosis of steatohepatitis Grade \>= 1 (Brunt et al. criteria - Am J Gastroenterology 1999;94(9)2467-74) on biopsy within 6 months prior to entry into protocol
3. No histologic evidence of cirrhosis
4. Persistent ALT elevation (\> 1.5 the upper limit normal) over 6 months prior to entry into study
5. Adult subjects 18-65 years of age of any race or gender
6. Compensated liver disease with the following hematologic, biochemical, and serological criteria on entry into protocol:

   * Hemoglobin \> 11 gm/dL for females and \> 12 gm/dL for males
   * White blood cell (WBC) \> 2.5 K/UL
   * Neutrophil count \> 1.5 K/UL
   * Platelets \> 100 K/UL
   * Direct bilirubin, within normal limits
   * Indirect bilirubin within normal limits (unless non-hepatitis factors such as Gilbert's disease explain indirect bilirubin rise. In such cases total bilirubin must be \< 3.0 mg/dL)
   * Albumin \> 3.2 g/dL
   * Serum creatinine within normal limits
7. Hemoglobin A1c (HgbA1c) \< 7%
8. Antinuclear antibodies (ANA) \< 1:160
9. Anti-smooth muscle Ab negative
10. Serum hepatitis B surface antigen (HepBsAg) negative
11. Serum hepatitis C antibody (HepC Ab) negative
12. Iron/total iron binding capacity (TIBC) ratio (transferrin saturation) \< 45%
13. Alpha-1-antitrypsin level within normal limits
14. Ceruloplasmin level within normal limits
15. Negative pregnancy test (females)
16. Concomitant use of lipid lowering agents at study entry will not exclude patients from the study.

Exclusion Criteria:

1. Evidence of decompensated cirrhosis
2. Active gastrointestinal (GI) bleeding
3. Renal failure (creatinine clearance \< 80 mL/min)
4. Active alcohol or drug abuse
5. Uncontrolled diabetes (HgbA1c \> 7)
6. Current treatment with anti-diabetic medications such as thiazolidinediones or metformin (stable doses of sulfonylureas are acceptable)
7. Current treatment with anti-TNF alpha medication (i.e. Remicade or Enbrel)
8. Current treatment with vitamin E
9. Alcohol consumption \< 20 g/day (males) or \< 10 g/day (females) - assessed by one physician and confirmed with one family member.
10. HIV positive status
11. Any history of cerebral and/or retinal hemorrhage
12. Prior intolerance of pentoxifylline or any other methylxanthine (i.e. caffeine, theophylline, or theobromine)
13. Current use of theophylline
14. Known diagnosis of malignancy
15. Any other conditions which the investigator feels would make the subject unsuitable for enrollment, or could interfere with the subject completing the protocol
B: Inclusion Criteria:

* NASH on liver biopsy (within 6 months of screening visit).
* NAFLD Activity Score (NAS) ≥ 3, comprising of a minimum of 1 point from each of the individual steatosis, lobular inflammation and hepatocyte ballooning scores
* Body Mass Index (BMI) ≥ 25 at randomisation
* Type 2 Diabetes Mellitus/impaired glucose tolerance or normal glucose tolerance

Exclusion Criteria (brief):

* Insulin dependent diabetes
* Glycosylated Haemoglobin (HbA1c) \> 9.0%
* treatment with dipeptidyl peptidase 4 (DPP-IV) inhibitors, Glucagon-like Peptides (GLP) 1 analogues, thiazolidinediones (TZDs)
* Past Medical History of Acute (or chronic) pancreatitis/pancreatic carcinoma, weight loss surgery, liver transplantation, Medullary thyroid cancer, hepatocellular carcinoma (HCC), Multiple Endocrine Neoplasia (MEN) syndrome, malignancy (within last 3 years, exception of treated skin malignancy)
* Other liver aetiologies (i.e. drug-induced, viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, haemochromatosis, alpha 1 anti-trypsin deficiency, Wilsons disease)
* concomitant or recent use of orlistat, prednisolone,
* Refusal or lacks capacity to give informed consent to participate in the trial
* Participation in any clinical trial of an investigational therapy or agent within 3 months of randomisation
* Patient (or carer) deemed not competent at using the correct site and technique for subcutaneous injection of the trial treatment (containing dummy drug on practice) at visit 2
* NAS\<3
* Child's B or C cirrhosis
* Abnormal clinical examination of thyroid (i.e. unexplained goitre or palpable nodules)
* Liver enzymes \> 10 x upper limit of normal
* Average alcohol consumption per week \> 21 units (210g) male, \>14 units (140g) female within the last 5 years.
* \>5% weight loss since the diagnostic liver biopsy was obtained.
* Recent or concomitant use of steroids (oral), methotrexate, amiodarone, Orlistat
* Addition or significant change (as judged by the chief investigator) in dose of the following drugs; Angiotensin converting enzymes (ACE)-inhibitors, Angiotensin receptor blockers (ARBs) and/or Multi-vitamins (containing Vitamin E)
* Known positivity for antibody to Human Immunodeficiency virus (HIV)
* Serum creatinine \> 150 μmol/L or currently being treated with renal replacement therapy
* Past medical history of multiple drug allergies (defined as anaphylactoid drug reactions in \>2 drug groups)
* Presence of any acute/chronic infections or illness that at the discretion of the chief investigator might compromise the patient's health and safety in the trial
* Pregnancy or breastfeeding
* Women, of child-bearing age, who are not willing to practise effective contraception (i.e. barrier, oral contraceptive pill, implanon or history hysterectomy) for the 48 week duration of the trial and for one-month after the last administration of the drug.
* Men, sexually active with women of child-bearing age, who are not willing to practise effective contraception for the 48 week duration of the trial and for one-month after the last administration of the drug.
C: Inclusion Criteria:

* Adult patients, 35-65 years of age
* Hepatic steatosis assessed by magnetic resonance spectroscopy (MRS) with liver fat \>5.56% at screening
* Body mass index (BMI) \>27 kg/m2 at screening
* Insulin resistance assessed by homeostatic model assessment-insulin resistance (HOMA-IR) \> 2.5 at screening
* Agreement to maintain prior diet and exercise habits during the full course of study

Exclusion Criteria:

* History of diabetes mellitus based on World Health Organization (WHO) criteria
* Known polycystic ovary syndrome
* Other liver disease e.g. chronic viral hepatitis, alcoholic liver disease, hemachromatosis, cirrhosis
* Known autoimmune disease or chronic inflammatory disease
* Myocardial infarction or stroke within 6 months prior to screening
* Patients taking any anti-diabetic and/or weight-lowering medication currently or within the previous 3 months before screening
D: * Histologic evidence of NASH based on a liver biopsy obtained within 6 months of randomization.
* Age 18 years or older

Answer: B