Fatty liver disease

There is a need for more robust non-invasive screening of Non-Alcoholic Fatty Liver Disease

Non-Invasive Distinction of Non-Alcoholic Fatty Liver Disease using Urinary Volatile Organic Compound Analysis: Early Results

Ramesh P. Arasaradnam, Michael McFarlane, Emma Daulton, Erik Westenbrink, Nicola O’Connell, Subiatu Wurie, Chuka U. Nwokolo, Karna D. Bardhan, Richard S. Savage, James A. Covington

Non-alcoholic fatty liver disease (NAFLD) occurs when fat is deposited in the liver (steatosis) due to causes other than excessive alcohol use. NAFLD is currently the most common cause of chronic liver disease in the developed world, and is set to overtake the health burden of hepatitis C worldwide. The increasing prevalence of NAFLD is due to factors including the rise in obesity, more sedentary lifestyles, insulin resistance and type-2 diabetes.

A growing body of evidence suggests that there is a relationship between altered gut microbiota and instances of NAFLD.  Gut microbiota have been shown to affect the regulation of energy homeostasis and ectopic fat deposition, hence their implication in metabolic diseases. The alteration in metabolic and fat profiling can lead to abnormal fat deposition in the liver promoting steatohepatitis. Unique gut fermentation patterns are detectable by analysis of volatile organic compounds (VOCs) in urine, breath and feces. This pilot study used Owlstone Medical's Lonestar VOC analyzer to determine if progressive fatty liver disease (specifically NAFLD and Non-Alcoholic Steatohepatitis (NASH)) produced an altered urinary VOC pattern.

Lonestar uses field asymmetric ion mobility spectrometry (FAIMS) to measure VOCs in clinical samples. FAIMS spectra were collected from the headspace of urine samples provided by 34 patients; 8 with histologically confirmed cirrhosis, NASH-C, 7 with non-cirrhotic NASH (NASH confirmed by use of Fibroscan), 4 with NAFLD (confirmed on liver ultrasound) and 15 healthy controls. A Random Forest algorithm used to analyze the data showed that urinary VOCs were able to distinguish samples of patients with liver disease (NASH, NASH-C or NAFLD) from the healthy control samples with 0.58 (0.33 – 0.88) sensitivity but specificity of 0.93 (0.698 – 1.00) and Area Under the Receiver Operating Curve, AUROC 0.73 (0.55 – 0.90).

NAFLD ROC
AUC of liver disease vs controls: 0.73 (95% CI: 0.55-0.90).

FAIMS was also able to separate NASH (both NASH with and without cirrhosis) from NAFLD with sensitivity of 0.73 (0.45 - 0.92), specificity of 0.79 (0.54 - 0.94) and AUROC of 0.79 (0.64 - 0.95). Urinary VOCs’ smell prints were also able to distinguish NAFLD from controls as well as separating NASH-C from NASH alone (without cirrhosis).

Arasaradnam NAFLD ROC
AUC of NASH (including cirrhosis) vs NAFLD: 0.79 (0.64 - 0.95)

The VOC ‘fingerprint’ pattern produced by the different disease states investigated in this study suggests there is potential for urinary VOCs as a non-invasive diagnostic tool for NAFLD, NASH and NASH-C. It also provides evidence that detection of urinary VOCs is a potential alternative approach to the diagnosis and monitoring of fatty liver disease, specially in cases where patients are unwilling to undergo liver biopsy or those in whom liver biopsy is deemed unsuitable.

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