The Breathprints in Patients With Liver Disease Identify Novel Breath Biomarkers in Alcoholic Hepatitis

Abstract

Background & Aims Selected-ion flow-tube mass spectrometry (SIFT-MS) can precisely identify trace gases in the human breath, in the parts-per-billion range. We investigated whether concentrations of volatile compounds in breath samples correlate with the diagnosis of alcoholic hepatitis (AH) and the severity of liver disease in patients with AH. Methods We recruited patients with liver disease from a single tertiary care center. The study population was divided those with AH with cirrhosis (n=40) and those with cirrhosis with acute decompensation from etiologies other than alcohol (n=40); individuals without liver disease served as controls (n=43). We used SIFT-MS to identify and measure 14 volatile compounds in breath samples from fasted subjects. We used various statistical analyses to compare clinical characteristics and breath levels of compounds among groups, and test the correlation between levels of compounds and severity of liver disease. Logistic regression analysis was performed to build a predictive model for AH. Results We identified 6 compounds (2-propanol, acetaldehyde, acetone, ethanol, pentane and trimethylamine [TMA]) whose levels were increased in patients with liver disease compared with controls. Mean concentrations of TMA, acetone, and pentane were particularly high in breath samples from patients with AH, compared to those with acute decompensation or controls (for both, P<.001). Using receiver operating characteristic curve analysis, we developed a model for the diagnosis of AH based on breath levels of TMA, acetone, and pentane (TAP). TAP scores of 36 or higher identified the patients with AH (AUC=0.92), with 90% sensitivity and 80% specificity. The levels of exhaled TMA had a low level of correlation with the severity of AH based on model for end-stage liver disease score (r=0.38; 95% confidence interval, 0.07–0.69; P=.018]. Conclusion Based on levels of volatile compounds in breath samples, we can identify patients with AH vs patients with acute decompensation or individuals without liver disease. Levels of exhaled TMA moderately correlate with the severity of AH. These findings might be used in diagnosis of AH or in determining patient prognosis.

Metabolomics studies identify novel diagnostic and prognostic indicators in patients with alcoholic hepatitis

“…Figure 3 shows the sensitivity and specificity of citrulline and betaine for diagnosis and acute decompensation from non-alcohol-related etiologies. Alcohol consumption in patients with alcoholic liver disease results in bacterial overgrowth and increases gut permeability and translocation of bacteria-derived lipopolysaccharides from the gut to the liver [1] . This could explain the altered levels of amino acids in these patients.…”

“…The diagnosis of AH is usually a clinical one, based on severe liver dysfunction in the context of excessive alcohol consumption, excluding other causes of acute and chronic liver disease (CLD) [1] . However, this method of diagnosis is not steadfast, as some studies that have included a liver biopsy in all patients with clinically suspected AH have shown histologic confirmation in only 70%-80% of patients [1] . Thus, liver biopsy remains the gold standard in diagnosing AH patients; however it is invasive, expensive, and burdensome for the patient.…”

“…Therefore, it behooves practitioners to utilize alternative non-invasive tools to diagnose AH. Hanouneh et al [1] have shown promise in the possibility of analyzing volatile compounds in breath samples as a useful diagnostic test in patients with AH. Consequently, a rapid, non-invasive, accurate, and precise test would greatly benefit AH diagnosis.…”

“…Liver biopsy is considered an expensive and invasive procedure, and 1%-5% of patients require postprocedural hospitalization [1] . In addition, sampling error and inter-observer variability contribute to the limitations of liver biopsy as a procedure [1] . Therefore, it behooves practitioners to utilize alternative non-invasive tools to diagnose AH.…”

Toxicology and the biological role of methanol and ethanol: Current view

“…The metabolic syndrome alone is another possible consequence of heavy alcohol consumption even though the mechanism of onset of the syndrome remains unclear 139,140 . The association between liver diseases and alcoholism is also known 141 and in alcohol liver diseases the activation of ethanol to acetaldehyde and alcohol induced fibrosis and inflammation takes place resulting in hepatitis manifestation after a period of heavy drinking [142][143][144] .…”