Liver biopsy remains the "gold standard" for assessing liver disease progression, but since the procedure is expensive, uncomfortable, and carries a small risk of complications, researchers have explored various non-invasive methods.

Several of these methods employ various blood biomarkers. Liver function tests that measure alanine aminotransferase (ALT) and aspartate aminotransferase (AST) indicate liver inflammation and may be a sign of progressive liver damage, but as many as one-third of hepatitis C patients with significant liver disease have persistently normal ALT.

As reported in the October 2008 Journal of Viral Hepatitis, G. Lalazar from Hadassah Hebrew University Medical Center in Jerusalem and colleagues evaluated the effectiveness of the "BreathID" continuous online (13)C-methacetin breath test for identifying liver inflammation and fibrosis in hepatitis C patients with normal ALT.

As background, the authors noted that the test reflects hepatic microsomal function and has been shown to correlate with liver fibrosis. Such tests work on the principle that a damaged liver is unable to efficiently metabolize various substances, which can be measured in the expelled breath.

The investigators tested 100 patients with untreated chronic HCV infection along with 100 healthy HCV negative age- and sex-matched volunteers. The (13)C-methacetin breath test was administered following ingestion of 75 mg methacetin. All participants had undergone a liver biopsy within 12 months of receiving the breath test.

Patients with a necroinflammatory grade <4 (based on Ishak score) were defined as having low-level inflammation, while those with a grade > 4 were defined as having high-level inflammation. Individuals with a histological activity fibrosis stage < 2 were defined as having non-significant fibrosis, while those > 2 were defined as having significant fibrosis.

Results

• A proprietary algorithm used to differentiate liver inflammation in chronic hepatitis C patients with normal ALT achieved an area under the curve (AUC) of 0.90.

• Setting a threshold on the point of best agreement, at 83%, resulted in 82% sensitivity and 84% specificity.

• Applying another proprietary algorithm to differentiate patients with non-significant or significant fibrosis, 67% of liver biopsies could have been avoided by using the breath test.

• This algorithm achieved an AUC of 0.92, with a sensitivity of 91% and a specificity of 88%.

" There was no correlation between body mass index and breath test scores for patients with the same histological score.

"The continuous BreathID (13)C-methacetin breath test is an accurate tool for measuring the degree of inflammation and fibrosis in patients with chronic HCV infection and normal ALT," the study authors concluded. "As such, it may prove to be a powerful, noninvasive alternative to liver biopsy in the management of this patient population."

10/24/08

Reference
G Lalazar, O Pappo, T Hershcovici, and others. A continuous (13)C methacetin breath test for noninvasive assessment of intrahepatic inflammation and fibrosis in patients with chronic HCV infection and normal ALT. Journal of Viral Hepatitis 15(10): 716-728. October 2008.