Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Effect of Pentoxifylline on Nonalcoholic Steatohepatitis (NASH)
Brief Summary: The purpose of this study is to explore the potential benefit of the medication, pentoxifylline, for the treatment of NASH.


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: * Histologic evidence of NASH based on a liver biopsy obtained within 6 months of randomization.
* Age 18 years or older
D: Inclusion Criteria:

* Males or females (females must be either of non-child bearing potential or using an efficient double contraception). For male participants, contraceptive measures must be taken during the study, either by the male participant or his female partner.
* Body Mass Index ≤ 45 kg/m².
* Patients agree to have one liver biopsy during the screening period for diagnostic purpose (if no historical biopsy within 6 months before randomization is available) and one at the end of the treatment period for assessment of the treatment effects.
* For hypertensive patients, hypertension must be controlled by stable dose of anti-hypertensive medication for at least 2 months prior to screening (and the stable dose can be maintained throughout the study).
* Patients treated with vitamin E (\>400IU/d), or Polyunsaturated fatty acids (\>2g/day)or Ursodeoxycholic acid can be included if drugs are stopped at least 3 months prior to diagnostic liver biopsy and up to the end of the study.
* Histological confirmation of steatohepatitis on a diagnostic liver biopsy. Histological diagnostic is confirmed by central reading of the slides (steatosis \> 5% + lobular inflammation, any grade + ballooning, any amount).
* For patients with Type 2 Diabetes, glycemia must be controlled (Glycosylated Haemoglobin A1c ≤8.5%). If glycemia is controlled by anti-diabetic drugs, qualitative change is not permitted within 6 months prior to randomization and should be avoided during the study. Treatments with metformin, Dipeptidyl Peptidase 4 inhibitors, Glucagon-like peptide-1 agonists, sulfamides, insulin are authorized. Sulfamides and insulin are permitted if glycemia is self-monitored by the patient.

Exclusion Criteria:

* Known heart failure (Grade I to IV of New York Heart Association classification).
* Weight loss of more than 5% within 6 months prior to randomization.
* History of bariatric surgery.
* Uncontrolled Blood Pressure.
* Type 1 diabetes patients.
* Patients who had an acute cardiovascular episode within the 6 months prior to screening, or with a history of coronary angioplasty, history of stroke, Transient Ischemic Attack, Coronary Heart Disease.
* Compensated and uncompensated cirrhosis. Notably, NASH patients with fibrosis stage = 4 according to the NASH CRN fibrosis staging system are excluded.
* Known alcohol and/or any other drug abuse or dependence in the last five years.
* Pregnant or lactating females.
* Other well documented causes of chronic liver disease
* Known intolerance or contra-indication to the list of excipients of GFT505.
* Evidence of any other unstable or, untreated clinically significant immunological, neoplastic, endocrine, haematological, gastrointestinal, neurological or psychiatric disorder.
* Positive HBsAg (Hepatitis B Surface Antigen), Positive anti-HIV, positive HCV-RNA (Hepatitis C Virus).
* Uncontrolled hypothyroidism defined as Thyroid Stimulating Hormone \> 2X the upper limit of normal (ULN). Thyroid dysfunction controlled for at least 6 months prior to screening is permitted.
* Significant renal disease, including nephritic syndrome, chronic renal failure (defined as creatinine clearance \< 60 mL/mn and serum creatinine \>180 μmol/L).
* Unexplained serum creatine phosphokinase (CPK) \> 3X the upper limit of normal (ULN). Patients with a reason for CPK elevation may have the measurement repeated prior to randomization; a CPK retest \> 3X ULN leads to exclusion.

Answer: A