The analysis of volatile organic compounds in exhaled breath may provide a noninvasive and accurate test for diagnosing nonalcoholic steatohepatitis, according to results from a pilot study published in March.
This test could reduce the number of unnecessary liver biopsies and missed diagnoses associated with assessing plasma transaminase levels, reported Dr. Froukje J. Verdam of Maastricht (the Netherlands) University Medical Center and her associates (J. Hepatol. 2013;58:543-8).
Researchers evaluated breath samples with gas chromatography–mass spectrometry from 65 consecutive overweight or obese patients before they underwent laparoscopic abdominal surgery, between October 2007 and May 2011. These results were compared with histologic analysis of liver biopsies taken intraoperatively and assessments of plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Overall, liver biopsies showed that 39 patients (60%) had nonalcoholic steatohepatitis (NASH), defined as "showing signs of steatosis and inflammation." Additionally, ALT and AST levels were significantly higher in patients with the disease than without. However, "parameters such as gender, age, BMI, and HbA1c did not differ significantly," reported the study authors.
The analysis of three volatile organic compounds (VOCs) – n-tridecane, 3-methylbutanonitrile, and 1-propanol – enabled investigators to distinguish between patients with and without NASH, with a sensitivity of 90%, a specificity of 69%, and an area under the receiver operating characteristic (ROC) curve of 0.77 plus or minus 0.07. The positive predictive value of using VOC analysis for NASH was 81%, while the negative predictive value was 82%.
In comparison, in 61 patients from whom plasma was available, the sensitivity of measuring ALT was 19%, while the specificity was 96%. The positive and negative predictive values of ALT were 88% and 43%, respectively.
Further evaluation of the AST/ALT ratio found that it was 32% sensitive and 79% specific, while positive and negative predictive values were 70% and 43%, respectively.
"It can be concluded that the diagnostic value of VOC is much higher than that of plasma transaminases, resulting in less misdiagnosed patients," wrote the study authors. Prediction of NASH using VOC, ALT, and the AST/ALT ratio did not reflect liver biopsy results in 18%, 51%, and 49% of subjects, respectively.
Using VOC evaluation rather than histologic testing has several other advantages, according to the researchers. "The analysis of exhaled breath can identify NASH presence at an early stage, and early identification in a mild stage is pivotal to enhance the chances of cure," they wrote. "Furthermore, whereas a small part of the liver is considered in the evaluation of biopsies, the breath test used in this study noninvasively reflects total liver function."
Funding for this pilot study was provided by grants from the Dutch SenterNovem Innovation Oriented Research Program on Genomics and the Transnational University Limburg, Belgium. The study authors reported no conflicts of interest.
