Liver breath tests non-invasively predict higher stages of non-alcoholic steatohepatitis

Abstract

Effectively assessing subtle hepatic metabolic functions by novel non-invasive tests might be of clinical utility in scoring NAFLD (non-alcoholic fatty liver disease) and in identifying altered metabolic pathways. The present study was conducted on 39 (20 lean and 19 obese) hypertransaminasemic patients with histologically proven NAFLD {ranging from simple steatosis to severe steatohepatitis [NASH (non-alcoholic steatohepatitis)] and fibrosis} and 28 (20 lean and eight overweight) healthy controls, who underwent stable isotope breath testing ([(13)C]methacetin and [(13)C]ketoisocaproate) for microsomal and mitochondrial liver function in relation to histology, serum hyaluronate, as a marker of liver fibrosis, and body size. Compared with healthy subjects and patients with simple steatosis, NASH patients had enhanced methacetin demethylation (P=0.001), but decreased (P=0.001) and delayed (P=0.006) ketoisocaproate decarboxylation, which was inversely related (P=0.001) to the degree of histological fibrosis (r=-0.701), serum hyaluronate (r=-0.644) and body size (r=-0.485). Ketoisocaproate decarboxylation was impaired further in obese patients with NASH, but not in patients with simple steatosis and in overweight controls. NASH and insulin resistance were independently associated with an abnormal ketoisocaproate breath test (P=0.001). The cut-off value of 9.6% cumulative expired (13)CO(2) for ketoisocaproate at 60 min was associated with the highest prediction (positive predictive value, 0.90; negative predictive value, 0.73) for NASH, yielding an overall sensitivity of 68% and specificity of 94%. In conclusion, both microsomal and mitochondrial functions are disturbed in NASH. Therefore stable isotope breath tests may usefully contribute to a better and non-invasive characterization of patients with NAFLD.

Biochemical mechanisms in drug-induced liver injury: Certainties and doubts

“…In fact, some herbal components are converted to toxic metabolites by P-450 enzymes; this is the case of aristolochis acid, which generates the highly reactive cyclic nitrenium ions [42] . Upregulation of specific P-450 enzymes has been described during rifampicin treatment [43] in experimental models of obesity and fatty liver [44] and in humans with nonalcoholic fatty liver disease (NAFLD) [45] . Mitochondria are often a major target of drug toxicity, and therefore mitochondrial dysfunction represents a major determinant of hepatotoxicity [46,47] ( Figure 3).…”

Could quantitative liver function tests gain wide acceptance among hepatologists?

“…Further large-scale studies are needed to verify its reliability [20] . A previous study that tested 13C-M and 13 C-ketoisocaproate for microsomal and mitochondrial liver function has demonstrated its usefulness for better and noninvasive characterization of patients with NAFLD [21] . It is worth stressing that every breath test can be affected badly by severe restrictive lung disease, and in elderly patients with chronic heart failure [22] .…”

13C-methacetin breath test reproducibility study reveals persistent CYP1A2 stimulation on repeat examinations

“…A number of features support its usefulness as a functional liver probe: a fast metabolism to acetaminophen and 13 CO2 by cytochrome P450 1A2 (CYP 1A2), safety at low doses applied for a breath test, and a low cost [1][2][3][4] . Accordingly very promising results on its diagnostic usefulness were obtained in patients with chronic hepatitis C virus infection [5,6] , primary biliary cirrhosis [7,8] , non-alcoholic steatohepatitis [9] , and various stages of liver cirrhosis [10][11][12][13][14] , including those awaiting a liver transplantation [15] . A vital asset of any measurement or diagnostic method used in medical practice is an ability to provide reproducible results.…”