Use of Liver Breath Tests to Assess Severity of Nonalcoholic Fatty Liver Disease

As the prevalence of obesity and insulin-resistance continues to increase in the general population, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions, thus becoming one of the leading causes of chronic liver disease worldwide. It may present as simple steatosis (NAFL) or steatohepatitis (NASH), which in turn may develop fibrosis and ultimately cirrhosis. Conventional biochemical liver test and radiological investigations are not able to provide reliable information on liver functional reserve, and liver biopsy remains the gold standard to stage NAFLD, differentiate simple steatosis from NASH, and grade fibrosis. However, liver biopsy has some limitations, and is not preferred by patients due to its invasiveness. Thus, non-invasive assessment of disease stage by using liver breath tests – which are based on hepatic clearance of non-radioactive stable 13C-labelled drugs – may be of interest to stage disease and assess patients prognosis due to good accuracy and repeatability. These substrates are orally administered and are cleaved by enzymes specifically located in the liver thus reflecting either the microsomal, cytosolic, or mitochondrial functions. 13C-Breath Tests have been initially oriented to differentiate broad categories of patients and more recently to refine stage differentiation in patients with early stages of liver disease. In NAFLD patients, 13C-BTs were able to distinguish simple steatosis from NASH and had good correlation with both histological fibrosis stage and biochemical markers of fibrogenesis. Although promising results have been achieved in this field, their use in clinical practice is still restricted to a specialized niche. However, concordant data from literature conferred to 13C-Breath Tests a potential role in providing punctual and longitudinal evaluation of patients, identifying those patients where liver biopsy may selectively be performed to stage disease, monitoring and predicting therapeutic response.