BREATHID Octanoate Breath Test With or Without Methacetin Breath Test for Correlation With Biopsy in NASH

Inclusion Criteria

• Adult men or women (≥18 years of age)
• Liver biopsy, indicating NAFLD/NASH, performed within 6 months prior to both breath tests OR undergoing liver biopsy to rule-out or confrim NAFLD/NASH. NOTE:The samples obtained meet defined quality criteria. (In Appendix II of protocol)
• Any elevation of liver enzymes above the upper limit of normal (any or all of the following: AST, ALT, GGT, Alkaline phosphatase) for at least 3 months
• No other known co-existent liver disease, excluded by appropriate serologic / other testing
• Imaging - US / CT / MRI (if available) with the typical image of Fatty Liver or suggestive of NASH.
• Patient (or legal guardian) able and willing to sign an Informed Consent Form
• Can tolerate an overnight (8-hour) fast

Exclusion Criteria

• Positive studies for any of the following within three years prior to biopsy:
• Anti HCV positive
• Anti HB core antibody positive
• Iron saturation > 60% + gene test for hereditary hemochromatosis or iron overload as defined by presence of 3+ or 4+ stainable iron on liver biopsy
• Antinuclear antibody at a titer > 1: 160 along with hypergammaglobulinemia and 5 times ALT normal levels
• Alpha-1-antitrypsin level below lower limit of normal ( 20 gm/day (0.71 oz/day) for women and > 30 gm/day (1.06 oz/day) for men
• Drugs that may interfere with octanoate metabolism or can also cause NAFLD independent of the metabolic syndrome, including: corticosteroids, amiodarone, tetracycline, valproic acid, methotrexate, stavudine, zidovudine
• When MBT is performed subject should not have taken any of the following at least 48 hours prior to the breath test: Acyclovir , allopurinol, carbamazepine, cimetidine, ciprofloxacin, daidzein, (herbal) disulfiram, echinacea, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, montelukast, norfloxacin, phenylpropanolamine, phenytoin, propafenone, rifampin, terbinafine, ticlopidine, thiabendazole, verapamil, zileuton or any medication that might interfere with Methacetin metabolism or might affect CYP 1A2
• Patients that have had more than 10% weight change between biopsy and enrollment.
• Hypersensitivity to any of the study substrates; i.e. Octanoate or Methacetin respectively
• Known extra-hepatic diseases including but not limited to: severe congestive heart failure (NIHA>2), known severe pulmonary hypertension (>35 mmHg), history of chronic obstructive pulmonary disease or uncontrolled symptomatic bronchial asthma or uncontrolled diabetes mellitus (HA1c>9.5%)
• Previous surgical GI bypass surgery
• Extensive small bowel resection (>100 cm)
• Known uncontrolled malabsorption or diarrhea
• Concurrent total parenteral nutrition
• Any organ transplant
• Patients receiving any anti-viral treatment or any other liver directed therapy, procedure or surgery between the time of the biopsy and the breath test
• Pregnant or breast feeding
• Patients and/or legal guardian unable or refusing to sign informed consent
• Patients that, based on the opinion of the investigator, should not be enrolled into this study due to safety / adherence reasons.
• Patients participating in other clinical trials and already receiving experimental treatments or procedures
• Patients with suspected or documented hepatocellular carcinoma by ultra-sound or other imaging modality
• Patients diagnosed with partial / complete portal venous occlusion, hepatic venous occlusion, previous PHT surgery, or placement of a transjugular intrahepatic portosystemic shunt (TIPS) according to initial imaging studies.