BREATHID Octanoate Breath Test With or Without Methacetin Breath Test for Correlation With Biopsy in NASH
Condition: Non-Alcoholic Steatohepatitis
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease
Intervention: Suspected NASH BreathID test with 13C-Octanoate; Suspected NASH Breath test with 13C Methacetin
Intervention description: Subject will have breath measured before and after ingestion of solution of 100 mg 13C Octanoate dissolved in 150 cc of water; Subject will have breath measured before and after ingestion of solution of 75 mg 13C Methacetin dissolved in 150 cc of water
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 140.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study's aim is to develop an algorithm for the ¹³C-Octanoate Breath Test with or without
      the ¹³C-Methacetin Breath Test (OBT and MBT respectively) for correlation with histological
      findings associated with of Non-Alcoholic Steatohepatitis (NASH) and other liver diseases
      using the BreathID® System
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult men or women (≥18 years of age)

          2. 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)

          3. 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

          4. No other known co-existent liver disease, excluded by appropriate serologic / other
             testing

          5. Imaging - US / CT / MRI (if available) with the typical image of Fatty Liver or
             suggestive of NASH.

          6. Patient (or legal guardian) able and willing to sign an Informed Consent Form

          7. Can tolerate an overnight (8-hour) fast

        Exclusion Criteria:

          1. Positive studies for any of the following within three years prior to biopsy:

               1. Anti HCV positive

               2. Anti HB core antibody positive

               3. Iron saturation > 60% + gene test for hereditary hemochromatosis or iron overload
                  as defined by presence of 3+ or 4+ stainable iron on liver biopsy

               4. Antinuclear antibody at a titer > 1: 160 along with hypergammaglobulinemia and 5
                  times ALT normal levels

               5. Alpha-1-antitrypsin level below lower limit of normal (< 150 mg/dl) or no PAS
                  diastase resistant globules on biopsy.

               6. Primary biliary cirrhosis as defined by elevation of alkaline phosphatase greater
                  than upper limit of normal and anti-mitochondrial antibody (AMA) of greater than
                  1:80 and consistent liver histology

               7. Low level of ceruloplasmin

               8. Drug-induced liver disease as defined on the basis of typical exposure and
                  history

          2. Patients known to have chronic liver disease other than NAFLD as routinely diagnosed
             by the investigator

          3. Concurrent acute hepatic condition other than NAFLD

          4. Alcohol consumption > 20 gm/day (0.71 oz/day) for women and > 30 gm/day (1.06 oz/day)
             for men

          5. 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

          6. 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

          7. Patients that have had more than 10% weight change between biopsy and enrollment.

          8. Hypersensitivity to any of the study substrates; i.e. Octanoate or Methacetin
             respectively

          9. 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%)

         10. Previous surgical GI bypass surgery

         11. Extensive small bowel resection (>100 cm)

         12. Known uncontrolled malabsorption or diarrhea

         13. Concurrent total parenteral nutrition

         14. Any organ transplant

         15. 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

         16. Pregnant or breast feeding

         17. Patients and/or legal guardian unable or refusing to sign informed consent

         18. Patients that, based on the opinion of the investigator, should not be enrolled into
             this study due to safety / adherence reasons.

         19. Patients participating in other clinical trials and already receiving experimental
             treatments or procedures

         20. Patients with suspected or documented hepatocellular carcinoma by ultra-sound or other
             imaging modality

         21. 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.