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A continuous (13)C methacetin breath test for noninvasive assessment of intrahepatic inflammation and fibrosis in patients with chronic HCV infection and normal ALT

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J Viral Hepat. 2008 Jul 10. [Epub ahead of print]

A continuous (13)C methacetin breath test for noninvasive assessment of

intrahepatic inflammation and fibrosis in patients with chronic HCV infection

and normal ALT.

Lalazar G, Pappo O, Hershcovici T, Hadjaj T, Shubi M, Ohana H, Hemed N, Ilan Y.

Liver Unit, Department of Medicine, Hadassah Hebrew University Medical Center,

Jerusalem, Israel.

Up to 30% of patients with hepatitis C virus (HCV) infection and normal serum

alanine aminotransferase (NALT) have significant liver disease. Currently, many

of these patients undergo a liver biopsy to guide therapeutic decisions. The

BreathID(®) continuous online (13)C-methacetin breath test (MBT) reflects

hepatic microsomal function and correlates with hepatic fibrosis. To assess its

role in identifying intrahepatic inflammation and fibrosis in NALT patients, we

tested 100 patients with untreated chronic HCV infection, and 100 age- and

sex-matched healthy volunteers using (13)C MBT following ingestion of 75 mg

methacetin. All HCV patients had undergone a liver biopsy within 12 months of

performing the MBT. Patients with a necroinflammatory grade 4, based on Ishak

(modified HAI) score, HAIa + HAIb + HAIc + HAId, were defined as having low or

high inflammation, respectively. Patients with a histological activity fibrosis

stage 2, were defined as having nonsignificant or significant fibrosis,

respectively. A proprietary algorithm to differentiate intrahepatic inflammation

within chronic HCV patients with NALT achieved an area under the curve (AUC) of

0.90. Setting a threshold on the point of best agreement (at 83%) results in 82%

sensitivity and 84% specificity. With application of another proprietary

algorithm to differentiate patients with nonsignificant or significant fibrosis,

67% of liver biopsies performed in the patient group could have been avoided.

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 (BMI) and

MBT scores for patients with the same histological score. The continuous

BreathID(®) (13)C MBT is an accurate tool for measuring the degree of

inflammation and fibrosis in patients with chronic HCV infection and NALT. As

such, it may prove to be a powerful, noninvasive alternative to liver biopsy in

the management of this patient population.

PMID: 18638013 [PubMed - as supplied by publisher]

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