Use of the methacetin breath test to classify the risk of cirrhotic complications and mortality in patients evaluated/listed for liver transplantation

Stravitz, R. Todd; Reuben, Adrian; Mizrahi, Meir; Lalazar, Gadi; Brown, Kimberly; Gordon, Stuart C.; Ilan, Yaron; Sanyal, Arun J.

doi:10.1016/j.jhep.2015.07.021

Cited by 21 publications

(26 citation statements)

References 25 publications

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“…After an overnight fast, subjects were given 10 mg/kg of [1‐ 13 C] palmitic acid (PA; Cambridge Isotope Laboratories) in a standardized heated liquid meal (Ensure ® ; Abbott Laboratories), to be consumed within 5 minutes. The appearance of 13 C in expired CO 2 was assayed by the BreathID (Exalenz Bioscience) molecular correlation spectrometer device . Subjects wore a nasal cannula connected to the device and the expired 13 CO 2 / 12 CO 2 ratio was measured continuously.…”

Section: Methodsmentioning

confidence: 99%

“…The appearance of 13 C in expired CO 2 was assayed by the BreathID (Exalenz Bioscience) molecular correlation spectrometer device. 4,5 Subjects wore a nasal cannula connected to the device and the expired 13 CO 2 / 12 CO 2 ratio was measured continuously. After measurement of baseline levels, subjects ingested the test meal and measurements continued for 6 hours after that.…”

Section: Palmitate Breath Testmentioning

confidence: 99%

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Dietary fatty acid oxidation is decreased in non‐alcoholic fatty liver disease: A palmitate breath test study

Naguib

Morris

Yang

et al. 2019

Liver International

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Background & Aim Hepatic fat excess in non‐alcoholic fatty liver disease (NAFLD) reflects an imbalance between fat accumulation and disposal. Conflicting data exist for the role of fatty acid oxidation (FAO), one of the disposal pathways, and have mostly come from the studies delivering fatty acids (FAs) intravenously. Whether FAO of orally provided FAs is affected in NAFLD is unknown. Methods We performed a breath test study to measure FAO in subjects with NAFLD and healthy controls. Subjects ingested [1‐13C] palmitic acid (PA, 10 mg/kg) in a liquid meal and the rate of 13CO2 appearance in expired air was measured over 6 hours by a BreathID device (Exalenz) to obtain the cumulative percent dose recovered (CPDR), the total amount of ingested 13C recovered. CPDR was corrected by the results of a [1‐13C] acetate breath test, performed 1‐4 weeks later, to calculate the rate of PA β‐oxidation. Results Palmitic acid oxidation was 27% lower in 43 subjects with NAFLD compared to 11 controls (CPDR 9.5 ± 2.4% vs 13.1 ± 3.7%, P = .0001) and this persisted after correcting for acetate (29.3 ± 10.5 vs 36.6 ± 13.9, P = .03). The decrease in FAO was not because of the delayed transit as the time to peak 13C detection did not differ between groups (4.9 ± 1.2 hours vs 4.7 ± 0.8 hours, P = .7). Rates of PA oxidation were not correlated with obesity, hepatic or adipose insulin resistance, alanine aminotransferase, liver fat content and NAFLD histology. Conclusion Fatty acid oxidation of orally delivered FA is decreased in NAFLD compared to healthy controls, likely reflecting decreased β‐oxidation. The use of a breath test offers non‐invasive dynamic assessment of FAO.

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Section: Methodsmentioning

confidence: 99%

Section: Palmitate Breath Testmentioning

confidence: 99%

Dietary fatty acid oxidation is decreased in non‐alcoholic fatty liver disease: A palmitate breath test study

Naguib

Morris

Yang

et al. 2019

Liver International

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“…In a recent study of 165 patients with cirrhosis, the MBT was found to be superior to MELD in predicting liver‐related death at 1 year, and was particularly useful in patient with low MELD scores. MBT also predicted the risk of liver‐related complications, particularly the risk of development/exacerbation of ascites, which was not achieved by MELD …”

Section: The Use Of Metabolic Tests In Assessing the Severity Of Livementioning

confidence: 99%

“…Patients with high‐risk MBT (defined as ≤than the median CPDR 20 for the entire population of 0.55%) were significantly more likely to experience liver‐related death during the 1 year follow‐up period than those with low risk MBT (>0.55%). (Adapted from reference)…”

Section: The Use Of Metabolic Tests In Assessing the Severity Of Livementioning

confidence: 99%

“…MBT also predicted the risk of liver-related complications, particularly the risk of development/exacerbation of ascites, which was not achieved by MELD. 80 Another recent study assessed the ability of MBT to predict survival and hepatic decompensation in 184 patients with cirrhosis of various etiologies. 81 MBT parameters accurately predicted survival after 1-13 months of follow-up.…”

Section: Chronic Liver Diseasementioning

confidence: 99%

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

Stravitz

Ilan

2016

Liver International

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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

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Prognostic Value of the 13C‐Methacetin Breath Test in Adults with Acute Liver Failure and Non‐acetaminophen Acute Liver Injury

et al. 2021

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BaCKgRoUND aND aIMS:The 13 C-methacetin breath test (MBT) is a noninvasive, quantitative hepatic metabolic function test. The aim of this prospective, multicenter study was to determine the utility of initial and serial 13 C-MBT in predicting 21-day outcomes in adults with acute liver failure (ALF) and non-acetaminophen acute liver injury (ALI). appRoaCH aND ReSUltS: The 13 C-MBT BreathID device (Exalenz Biosciences, Ltd.) provided the percent dose recovery (PDR) for a duration of 60 minutes after administration of 13 C-methacetin solution as the change in exhaled 13 CO 2 / 12 CO 2 compared with pre-ingestion ratio on study days 1, 2, 3, 5, and 7. Results were correlated with 21-day transplant-free survival and other prognostic indices. A total of 280 subjects were screened for enrollment between May 2016 and August 2019. Median age of the 62 enrolled patients with adequate data was 43 years, 79% were Caucasian, 76% had ALF with the remaining 24% having ALI. The mean PDR peak on day 1 or day 2 was significantly lower in nonsurvivors compared with transplant-free survivors (2.3%/ hour vs. 9.1%/hour; P < 0.0001). In addition, serial PDR peaks were consistently lower in nonsurvivors versus survivors (P < 0.0001). The area under the receiver operating characteristic curve (AUROC) of the 13 C-MBT in the combined cohort was 0.88 (95% CI: 0.79-0.97) and higher than that provided by King's College (AUROC = 0.70) and Model for End-Stage Liver Disease scores (AUROC = 0.83). The 13 C-MBT was well tolerated with only two gastrointestinal adverse events reported. CoNClUSIoNS:The 13 C-MBT is a promising tool to estimate the likelihood of hepatic recovery in patients with ALF and ALI. Use of the PDR peak data from the 13 C-MBT point-of-care test may assist with medical decision making and help avoid unnecessary transplantation in critically ill patients with ALF and ALI. (Hepatology 2021;74:961-972).A cute liver failure (ALF) is a rare but potentially devastating syndrome defined by the sudden onset of coagulopathy (i.e., an international normalized ratio [INR] of ≥ 1.5) and hepatic encephalopathy in a patient without known pre-existing liver disease. (1) Although a multitude of disease processes can lead to severe acute liver injury (ALI) and ALF, there are only about 3,000 cases of

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Use of the methacetin breath test to classify the risk of cirrhotic complications and mortality in patients evaluated/listed for liver transplantation

Cited by 21 publications

References 25 publications

Dietary fatty acid oxidation is decreased in non‐alcoholic fatty liver disease: A palmitate breath test study

Dietary fatty acid oxidation is decreased in non‐alcoholic fatty liver disease: A palmitate breath test study

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

Prognostic Value of the 13C‐Methacetin Breath Test in Adults with Acute Liver Failure and Non‐acetaminophen Acute Liver Injury

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