Prediction of Severity of Liver Disease by a 13C Octanoate Breath Test (OBT)
Prediction of Severity of Liver Disease by a 13C Octanoate Breath Test (OBT)
The purpose of the study is to demonstrate that the ¹³C-Octanoate Breath Test (OBT) can be
 used as an aid, in conjunction with other clinical information and medical history, for
 evaluating disease severity and detecting NASH with a high probability.
The OBT was chosen to assess, along with other parameters, liver health in subjects suspected
 of NAFLD (non alcoholic fatty liver disease).

 Octanoate is absorbed promptly from the intestinal lumen and transported rapidly to the liver
 through the portal venous system, enters the hepatic mitochondria independently of the
 carnitine transport system and undergoes hepatic mitochondrial beta-oxidation which produces
 acetyl coenzyme A (CoA). Finally, acetyl CoA enters the Krebs cycle and is oxidized by carbon
 dioxide (CO2). This is a non invasive test that can be performed routinely at every visit to
 assess disease severity. The subject is connected to a breath analyzer via a nasal cannula
 for approximately 1 hour, that measures baseline breath and changes in delta over baseline
 due to metabolization of Octanoate.
Inclusion Criteria:

 -  Adult men or women (>18 years of age)

 -  • Liver -biopsy ( at least 1.7 cm and 4 portal tracts) performed within 6 months of
 breath test or planned within the next 6 weeks, providing no treatment for liver
 disease was given between the biopsy and the OBT Any elevation of liver enzymes above
 the upper limit of normal (any or all of the following: AST,ALT, GGT, Alkaline
 phosphatase)

 -  At least one of the features of the metabolic syndrome

 -  waist circumference > 100 cm for men, 88 cm for women

 -  triglycerides > 150 mg/dl

 -  fasting blood sugar > 110 mg/dl

 -  HDL cholesterol < 40 mg/dl

 -  blood pressure > 130/85 mm Hg

 -  No other known co-existent liver disease, excluded by appropriate serologic testing

 Exclusion Criteria:

 -  Positive studies for any of the following:

 -  hepatitis C (PCR)

 -  hepatitis B (surface antigen or DNA)

 -  iron saturation > 60% + gene test for hereditary hemochromatosis

 -  antinuclear antibody at a titer > 1: 160 along with hypergammaglobulinemia and ALT
 levels>250 U/L

 -  Patient has Alpha-1-antitrypsin level below lower limit of normal (< 150 mg/dl)

 -  Patient has alcohol consumption > 20 gm/day for women and > 30 gm/day for men

 -  Patient is pregnant

 -  Patient has been taking known hepatotoxic drugs e.g. (e.g.acebutolol,
 indomethacin,phenylbutazone,allopurinol,isoniazid,phenytoin,atenolol,ketoconazole
 ,piroxicam,carbamazepine,labetalol,probenecid,cimetidine,maprotiline,pyrazinamide
 ,dantrolene, metoprolol,quinidine,diclofenac, mianserin)• Patients that have had
 more than 10% reduction in body weight since biopsy

 -  Patient with known severe congestive heart failure (LVEF on echocardiogram < 20%)

 -  Patient with known severe pulmonary hypertension (By echocardiogram, PAS >45
 mmHg)

 -  Patient with uncontrolled diabetes mellitus (HA1c>10)

 -  Patient with previous surgical bypass surgery

 -  Patient with extensive short bowel syndrome(>100 cm)

 -  Patient currently receiving total parenteral nutrition

 -  Patient is a recipients of any organ transplant

 -  Patients that received any anti-viral treatment or any other liver therapy
 between the time of the biopsy and the breath test.

 -  Women who are pregnant

 -  Patients with an acute current exacerbation of chronic obstructive pulmonary
 disease or bronchial asthma.

 -  Patient has taken drugs that can interfere with octanoate metabolism or can also
 cause NAFLD independent of the metabolic syndrome, including: corticosteroids,
 amiodarone, tetracycline, valproic acid, methotrexate, stavudine, zidovudine.

 -  Patients unable or refuse to sign informed consent

 -  Patients that based on the opinion of the investigator should not be enrolled
 into this study

 -  Patients that are participating in other clinical trials evaluating experimental
 treatments or procedures