Potential use of metabolic breath tests to assess liver disease and prognosis: has the time arrived for routine use in the clinic?

Abstract

The progression of liver disease may be unique among organ system diseases in that progressive fibrosis compromises not only the sufficiency of hepatocyte mass but also impairs blood flow to the liver, resulting in porto-systemic shunting. Although liver biopsy as an assessment of fibrosis has become the key biomarker of and target for new therapies, it is invasive and subject to sampling error, and cannot quantify metabolic function or porto-systemic shunting. Measurement of the hepatic venous pressure gradient accommodates some of the deficiencies of biopsy but requires expertise not widely available and misses minor changes in hepatocellular mass and thereby information about metabolic function. Thus, an unmet need in clinical hepatology remains unfulfilled: a noninvasive biomarker which quantitates both the hepatocellular insufficiency and porto-systemic shunting inherent in progressive hepatic fibrosis. Ideally, such a biomarker should correlate with clinical endpoints including liver-related survival and cirrhotic complications, be performed at the point-of-care, and be affordable and easy to use. This review, an expert opinion, summarizes background and recent data suggesting that metabolic breath tests may now meet these requirements and have a valid place in clinical hepatology to supplant the time-honoured assessment of hepatic fibrosis. K E Y W O R D Sbreath tests, fibrosis, liver function, methacetin

Autofluorescence‐based optical biopsy: An effective diagnostic tool in hepatology

“…The in situ, sensitive optical detection of free fatty acids, lipofuscin‐like lipopigments and collagen in the absence of exogenous dyes is expected to improve the understanding of mechanisms of oxidative stress damages, steatosis and disease progression, the diagnosis and grading of liver disease or support pharmacological investigations. The response to the need for rapid, safe, minimally invasive or non‐invasive tests on liver metabolism and disease has been so far explored by non‐optical–based breathing tests and biochemical marker serum panels, and expectations for new insights are raised by recent optical studies on the blood …”

“…Another non‐invasive procedure supporting the assessment and follow‐up of liver disease progression is based on ultra‐high‐field magnetic resonance spectroscopy . This approach, however, requires the administration of radioactive biomarkers, a problem which also applies to the measurement of breath metabolites . A safer analysis of volatile breath compounds by an e‐nose has also been proposed but still requires a refinement of breath‐prints specific to the stages of hepatocellular failure and the impact of comorbidities .…”

“…137 This approach, however, requires the administration of radioactive biomarkers, a problem which also applies to the measurement of breath metabolites. 138 A safer analysis of volatile breath compounds by an e-nose has also been proposed but still requires a refinement of breath-prints specific to the stages of hepatocellular failure and the impact of comorbidities. 139 Serum biomarkers are promising non-invasive diagnostic resources, for profiling and monitoring pathophysiological changes in liver disease.…”

“…The liver was the historical model for AF-based optical biopsy in- and disease has been so far explored by non-optical-based breathing tests 138,139 and biochemical marker serum panels, and 140,141 expectations for new insights are raised by recent optical studies on the blood. 142,145 Besides numerous studies using animal models, we may recall the validation of the diagnostic significance of various EFs in tissue sections from normal, fatty or fibrotic human livers, 63,107,109 fully motivating recent proposals regarding forthcoming technologies for the automated characterization of the biometabolic features of liver biopsies.…”

Breath test using 13C methacetin does not seem to be useful in the assessment of liver function in girls with anorexia nervosa: a case control study

“…Substances such as 13 C methacetin are metabolized after oral administration by the cytochrome P450. During their decomposition 13 CO 2 is formed and the rate of its excretion indicates the microsomal function of the liver [ 14 ]. While biochemical parameters show only hepatocyte injury and provide indirectly information about the organ function, the breath test results allow to estimate the degree of organ damage and also determine quantitatively the functional mass of the organ.…”