title: A continuous 13C methacetin breath test for noninvasive assessment of intrahepatic inflammation and fibrosis in patients with chronic HCV infection and normal ALT.
abstract: 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 <or=4 or >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 <or=2 or >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.
authors.affiliation: Department of Medicine, Liver Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Lalazar
authors.forename: O
authors.initials: O
authors.lastname: Pappo
authors.forename: T
authors.initials: T
authors.lastname: Hershcovici
authors.forename: T
authors.initials: T
authors.lastname: Hadjaj
authors.forename: M
authors.initials: M
authors.lastname: Shubi
authors.forename: H
authors.initials: H
authors.lastname: Ohana
authors.forename: N
authors.initials: N
authors.lastname: Hemed
authors.forename: Y
authors.initials: Y
authors.lastname: Ilan
mesh_terms: D000081:Acetamides; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D000465:Algorithms; D001944:Breath Tests / Q000379:methods*; D002247:Carbon Isotopes; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D008099:Liver / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity
chemical_list: D000081:Acetamides; D002247:Carbon Isotopes; C035495:methacetin; D000410:Alanine Transaminase