Method of Detection of Fatty Liver Diseases by Breath Analysis

Abstract

Analysis of a breath sample is a noninvasive point-of-care tool with ever increasing clinical applicability. Herein we describe a method to analyze the content of low-level, trace volatile organic compounds from alveolar breath captured as a breath sample from a patient suspected of having a fatty liver disease. The breath sample is then analyzed using a gas phase analysis methodology, such as gas chromatography-mass spectroscopy (“GCMS”), to generate an analysis result, such as a GCMS spectrum. A computer system is then used to develop a fingerprint pattern from the analysis result. The fingerprint pattern is then used to determine a patient status for the patient. The fingerprint pattern is typically a grouping of 75 to 450 compounds of known concentration which are indicative of a particular fatty liver disease.

Claims

1. A method comprising: collecting a breath sample from a patient in a sterile sampling vessel; analyzing the breath sample using at least one gas phase analysis methodology to generate an analysis result; and using a computer system: resolving a fingerprint pattern from the analysis result; and determining a patient status related to a fatty liver disease for the patient based on the fingerprint pattern.

2. The method of claim 1, wherein the sterile sampling vessel contains a carbon dioxide sensor.

3. The method of claim 1, wherein the sterile sampling vessel is a commercially available breath sampler.

4. The method of claim 1, wherein the sterile sampling vessel includes an absorbent material selected from the group consisting of solid-state adsorbent and thin film adsorbent media.

5. The method of claim 4, further comprising using thermal desorption techniques to release the breath sample from the absorbent material.

6. The method of claim 1, wherein the at least one gas phase analysis methodology is selected from the group consisting of gas chromatography, mass spectrometry, and gas chromatography-mass spectrometry.

7. The method of claim 1, wherein the fingerprint pattern is a chromatographic pattern specific to a particular fatty liver disease.

8. The method of claim 1, wherein the fingerprint pattern is a spectrographic pattern specific to a particular fatty liver disease.

9. The method of claim 1, wherein the fingerprint pattern contains at least one marker compound.

10. The method of claim 9, wherein the marker compound is a compound specific to a particular fatty liver disease.

11. The method of claim 1, wherein the patient status is selected from the group consisting of inflammatory status, disease state, disease severity, disease progression, therapy efficacy, and changes in patient status over time.

12. The method of claim 1, wherein the fatty liver disease is selected from the group consisting of non-alcoholic fatty liver disease and alcoholic fatty liver disease.

13. The method of claim 12, wherein the non-alcoholic fatty liver disease is selected from the group consisting of non-alcoholic fatty liver and non-alcoholic steatohepatitis.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0013] FIG. 1 provides a general overview of the method herein described.

DETAILED DESCRIPTION OF EMBODIMENTS

[0014] In the following description, for purposes of explanation and not limitation, details and descriptions are set forth in order to provide a thorough understanding of the present invention. However, it will be apparent to those skilled in the art that the present invention may be practiced in other embodiments that depart from these details and descriptions without departing from the spirit and scope of the invention.

[0015] For the purpose of this disclosure, patient status includes diagnosis of inflammatory status, disease state, disease severity, disease progression, therapy efficacy, and changes in patient status over time. Other patient statuses are contemplated.

[0016] For the purpose of definition, fatty liver disease is one or more of non-alcoholic fatty liver, non-alcoholic steatohepatitis, and alcoholic fatty liver disease.

[0017] In an illustrative embodiment of the invention, as summarized in FIG. 1, the method may be summarized in the following four steps: i) collecting a breath sample from a patient in a sterile sampling vessel; ii) analyzing the breath sample using a gas phase analysis methodology to generate an analysis result; using a computer system configured to iii) resolving a fingerprint pattern from the analysis result; and iv) determining a patient status for the patient related to a fatty liver disease based on the fingerprint pattern. Typically, the fingerprint pattern will be 75 to 450 different compounds within the analysis result. It is understood, however, that smaller or larger combinations may be used as a fingerprint pattern.

[0018] In a further embodiment, the sterile sampling vessel may contain a carbon dioxide sensor. This sensor could be used to determine when the patient has reached alveolar breath. This would ensure that the breath sample contains low-level VOCs. There are a number of commercially available BVOC collection samplers available which are suitable for the present invention. Many BVOC collection samplers contain a solid-state adsorbent or thin film adsorbent media to adsorb low-level VOCs thus ensuring capture. If a solid-state adsorbent or thin film adsorbent media is used in the breath sampler, thermal desorption or thin film adsorbent media techniques are used to release the low-level VOCs from the solid-state adsorbent prior to analysis with the gas phase analysis methodology.

[0019] In a further embodiment, the gas phase analysis methodology could be gas chromatography, mass spectrometry, or gas chromatography-mass spectrometry. Other gas phase analysis methods are contemplated.

[0020] In another embodiment, the fingerprint pattern is a spectrographic or chromatographic pattern within the analysis result that is specific to a particular fatty liver disease. The fingerprint pattern is typically a group of marker compounds between 75 and 450 unique compounds in predetermined concentrations for each specific fatty liver disease. It is contemplated, however, that a single or fewer than 75 marker compound(s) could be used to identify a particular fatty liver disease.

[0021] In an additional embodiment, patient status can be inflammatory status, disease state, disease severity, disease progression, efficacy of a particular therapy, or changes in patient status over time. Other patient statuses are contemplated.

[0022] In a further embodiment, a fatty liver disease is one or more of non-alcoholic fatty liver disease and alcoholic fatty liver disease. Non-alcoholic fatty liver disease includes non-alcoholic fatty liver and non-alcoholic steatohepatitis. Other fatty liver diseases are contemplated.

[0023] The present invention address many of the issues with currently available NAFLD screening and detection by offering a noninvasive, highly accurate, inexpensive, and widely available method for the detection of steatosis, NASH, and fibrosis for both pediatric and adult patients differentiating between the three disease states. Being non-invasive and without radiological exposures is a significant improvement over the currently used modalities and will allow for frequent testing in a physician's office for both pediatric and adult subjects. Additionally, the present invention removes the interobserver error frequently found with pathology studies and some imaging modalities.