Prediction of Severity of Liver Disease by a 13C Octanoate Breath Test (OBT)

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