BOSTON -- A simple breath test gives a good overall measure of liver function in patients with chronic viral hepatitis and could help in evaluating potential liver transplant candidates, a researcher said here.
The test, which measures exhaled carbon dioxide following an oral dose of isotopically labeled methacetin, accurately predicted survival of 395 patients with chronic viral hepatitis during a median of five months of follow-up, reported Gadi Lalazar, MD, of Hadassah Hebrew University in Jerusalem.
The test predicted death with a sensitivity of 82% and specificity of 89% in the prospective study, Lalazar told attendees at the American Association for the Study of Liver Diseases meeting.
Although the findings still need additional validation, Lalazar said, it also appeared that the test could improve survival predictions for patients within specific ranges of Model of End-Stage Liver Disease (MELD) scores.
MELD is now the basis for allocating liver transplants, but is known to be an imperfect predictor of survival, Lalazar explained.
The breath test, tradenamed Breath ID, is based on the fact that methacetin is metabolized in the liver to produce acetaminophen and carbon dioxide. The speed of that reaction declines with impaired hepatic function.
The test uses methacetin containing 13C carbon atoms, such that the exhaled carbon dioxide is also labeled with this isotope. Therefore, Lalazar said, the amount of 13C-labeled carbon dioxide in breath correlates closely with hepatic function.
The technology, being developed by an Israeli company called Exalenz, translates the carbon dioxide measurement into a hepatic impairment score (HIS). For purposes of the study, scores were grouped into tertiles reflecting low, medium, and high risk.
Patients in the study had mean MELD scores of 8.2, with about 80% having scores below 10, indicating relatively mild liver disease. Close to 90% had hepatitis C virus infection; the remainder had hepatitis B. About 30% had cirrhosis.
Eleven patients died during follow-up, which ranged from two to 24 months.
Nine of the deaths occurred in patients with high-risk HIS values; the other two occurred in the medium-risk group.
Lalazar said the risk of death increased by 34% with each log10 unit increase in the HIS (P<0.0001).
The accuracy remained strong in patients with normal levels of alanine aminotransferase (ALT), he said.
Six of the deaths occurred in patients with normal ALT but who were determined to be at high risk on the basis of breath-test results. Two deaths occurred in medium-risk patients with normal ALT, and none in the low-risk patients.
Four patients with MELD scores under 15 died during the study; three of them were identified as high-risk on the basis of HIS scores.
Lalazar said only one death was recorded among 10 patients with MELD scores of 15 or higher whose HIS results indicated low risk.
He said that breath test results were associated with mortality risk, even among patients in a relatively narrow two-point range in MELD scores.
John Hoefs, MD, of the University of California Irvine, commented that quantitative tests of liver health such as this appear to be more accurate than the usual clinical measures.
"Quantitative liver function tests trump fibrosis and other measures in predicting clinical outcomes," he said.
Hoefs, who was not involved in the study, was part of a group that had reported here on a separate trial involving a panel of other quantitative tests, such as choline and antipyrine clearance and perfused hepatic mass. It also accurately predicted outcomes in patients with chronic viral hepatitis.
"We think this [methacetin breath test research] supports that effort," he said.
Lalazar noted that the study was limited by the low proportion of cirrhotic patients and the small number of deaths. "A validation study is required," he said.
The study was funded by Exalenz, developer of the methacetin breath test.
Lalazar reported no potential conflicts of interest other than the research funding. One co-author reported relationships with Alcobra, Immuron, Enzo Biochem, and ChiasmaPharma.
Hoefs reported relationships with Roche and Gilead.
- Reviewed by Dori F. Zaleznik, MD Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner