Prediction of Severity of Liver Disease in Patients With Suspected Nonalcoholic Fatty Liver Disease (NAFLD) by 13C Octanoate Breath Test (OBT)
Overview
- Phase
- Phase 2
- Intervention
- Sodium Octanoate Breath Test
- Conditions
- Metabolic Syndrome
- Sponsor
- Virginia Commonwealth University
- Enrollment
- 61
- Locations
- 2
- Primary Endpoint
- The Peak Value of the PDR (Percentage Dose Recovery of 13C) of OBT (Octanoate Breath Test)
- Status
- Terminated
- Last Updated
- 10 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
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%)
Arms & Interventions
Sodium Octanoate Breath Test
Only subjects with metabolic syndrome and suspected non alcoholic fatty liver disease will undergo breath test. They must not have any other liver disease.
Intervention: Sodium Octanoate Breath Test
Outcomes
Primary Outcomes
The Peak Value of the PDR (Percentage Dose Recovery of 13C) of OBT (Octanoate Breath Test)
Time Frame: 1 hour
To assess the ability of the OBT to assess disease severity in patients with suspected NAFLD (non alcoholic fatty liver disease) compared to NAS (Non-alcoholic-steatohepatitis (NASH) Activity Score) scoring system, where steatosis is scaled from 0-3, lobular inflammation is scaled from 0-3 and hepatocellular ballooning is scaled from 0-2. NAS score greater or equal to 5 indicates NASH. The higher the PDR peak, the better the liver health and function.PDR units are percent per hour of 13C dose recovery and describes rate of metabolism. The PDR peak is the highest rate of metabolism the liver reaches.The total range of NAS is 0-8.
Secondary Outcomes
- Histology -NAS Scoring of Liver Biopsy(Up to 6 months)