DDW 2009: Novel Breath Test Identifies Severity of Liver Disease

Martha Kerr

June 03, 2009

June 3, 2009 (Chicago, Illinois) — A new assessment tool that measures levels of (13)Carbon methacetin in exhaled breath accurately shows functional reserve in the liver, Swiss and Israeli researchers announced here at Digestive Disease Week 2009.

The test tags and measures a metabolite that is specific to the healthy liver. The breath test is accurate in both chronic and acute liver disease, Gadi Lalazar, MD, from the Liver Unit at the Hadassah Hebrew University Medical School in Jerusalem, told meeting attendees.

Dr. Lalazar's team assessed the value of the (13)C methacetin breath test (MBT) in 614 patients with liver disease as a measurement of fibrosis, liver function, and prognosis.

In 575 patients with chronic liver disease, MBT predicted the risk for death during a 24-month period, with a hazard ratio of 0.657 (< .0001).

Cirrhotic patients and their MBT survival scores were divided into low-, medium-, and high-risk groups according to Model for End-Stage Liver Disease (MELD) score (<10, 10–20, and >20, respectively).

The death rate in the high-risk group was 50% according to the MBT survival model, compared with 41% for MELD score.

Prognosis was excellent (99%) in the low-risk group, 90% in the medium-risk group, and 73% in the high-risk group at 24 months, Dr. Lalazar reported. Survival rates were 97% in the low-risk group, 85% in the medium-risk group, and 70% in the high-risk group at 24 months.

In 19 cirrhotic patients with hepatocellular carcinoma undergoing transarterial chemoembolization, MBT accurately predicted decompensation. "While patient age, preprocedure albumin, MELD, and Child classification did not differ significantly between the [17] patients who survived and the 2 who died, MBT parameters differed significantly between the 2 groups (P < .0001)," the research team found.

Of 278 patients with chronic hepatitis C virus infection, MBT predicted the stage of fibrosis with an area under the curve of 0.81 (95% confidence interval, 0.68 - 0.93), a sensitivity of 78%, and a negative predictive value of 83%. Biopsies could have been avoided in 67% of those performed.

In 20 patients with acute severe liver disease, evidence of consistent improvement began 4 to 7 days earlier for MBT parameters than for blood tests.

"In the 2 patients who died, MBT parameters remained low despite fluctuating laboratory values," Dr. Lalazar and colleagues found.

Two patients with drug-induced fulminant hepatic failure had MELD scores of 34 and 44 and Sequential Organ Failure Assessment (SOFA) scores of 12 and 15, indicating a very poor prognosis, but both recovered without transplantation after showing early improvement in their MBT scores.

"MBT shows decompensation early, before the MELD score changes. It offers a noninvasive, continuous way to assess liver function," Dr. Lalazar told Medscape Gastroenterology.

"With confirmation and more data, we may be able to prioritize patients according to liver function. . . . We don't know how to measure this well yet," he said, "and we need to get a better idea of its sensitivity and the false-positive rate."

"The MBT can be easily adopted into clinical practice. It will have all-around utility — in the office, at the bedside — and it requires no effort on the part of the patient. It is noninvasive and it will be relatively inexpensive," predicted session moderator Brent Tetri, MD, professor of internal medicine at St. Louis University in Missouri, in an interview with Medscape Gastroenterology.

"At the moment, there is no good test for liver function," Dr. Tetri commented. "Since (13)C methacetin is solely produced by healthy hepatocytes, this will be a very specific test. . . . However, there may be a problem in those patients who have shunting around the liver. Blood must get to the liver in order for this test to work."

"The test correlates with the portal gradient," Dr. Lalazar explained. "If the blood is shunted away, it shows the liver is not working."

The study was not commercially funded. Dr. Lalazar and Dr. Tetri have disclosed no relevant financial relationships.

Digestive Disease Week (DDW) 2009: Abstract 747. Presented June 1, 2009.