Please select the eligibility criteria that correspond to the clinical trial below.
Title: Orlistat (Xenical) in the Treatment of Overweight Patients With Nonalcoholic Steatohepatitis (NASH)
Brief Summary: The purpose of this study is to determine if orlistat (Xenical) therapy in overweight patients with NASH leads to enhanced weight loss over time, with subsequent improvement in the underlying necroinflammatory and fibrotic changes that are typical of NASH.


Options:
A: 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.
B: Inclusion Criteria:

* Liver biopsy obtained no more than 24 months before randomization with a pathology report confirming that the histological diagnosis is consistent with NASH
* Compensated liver disease with the following laboratory parameters at the entry visit:

  * Hemoglobin values of greater than or equal to 12 gm/dl for females or 13 gm/dl for males
  * WBC count \> 3,000/mm3
  * Neutrophil count \> 1,500/mm3
  * Platelets \> 70,000/mm3
  * Albumin \>3.0 g/dl
* Serum creatinine \<1.4mg/dl
* Ability to give informed consent
* Alanine aminotransferase (ALT) greater than or equal to 40 U/L
* BMI \> or equal to 27 kg/m2
* Patients who receive orlistat must agree to participate in Xenicare, a free dietary counseling program provided by Roche (sponsor)

Exclusion Criteria:

* Any cause for chronic liver disease other than NASH
* Evidence of decompensated liver disease such as a history of or presence of ascites, bleeding varices, or spontaneous encephalopathy
* History of alcohol consumption of greater than 20 grams per day in the past 2 years
* Prior surgical procedures to include gastroplasty, jejunoileal or jejunocolic bypass
* TPN within the past 6 months
* History of prior organ transplantation
* Concurrent enrollment in other experimental treatment protocols
* Use of ursodeoxycholic acid, rosiglitazone, pioglitazone, or metformin within the 6-month period before enrollment
* Women who are pregnant or breast-feeding
C: Inclusion Criteria:

- Being enrolled in Golestan Cohort Study

Exclusion Criteria:

* Debilitating disease causing inability to comply
* Contraindications to any of the components of PolyPill
* Not consenting to the study
D: * Histologic evidence of NASH based on a liver biopsy obtained within 6 months of randomization.
* Age 18 years or older

Answer: B