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

[Guest guest]

http://www3.interscience.wiley.com/journal/120755731/abstract

Journal of Viral Hepatitis

Volume 15 Issue 10, Pages 716 - 728

Published Online: 11 Jul 2008

A continuous 13C methacetin breath test for noninvasive assessment of

intrahepatic inflammation and fibrosis in patients with chronic HCV infection

and normal ALT

G. Lalazar 1 , O. Pappo 2 , T. Hershcovici 1 , T. Hadjaj 1 , M. Shubi 1 , H.

Ohana 1 , N. Hemed 1 and Y. Ilan 1

1 Liver Unit, Department of Medicine ; and 2 Department of Pathology,

Hadassah Hebrew University Medical Center, Jerusalem, Israel

Correspondence to Yaron Ilan, Gastroenterology and Liver Units, Department of

Medicine, Hadassah-Hebrew University Medical Center, Ein-Kerem, IL91120, POB

12000, Jerusalem, Israel. E-mail: ilan@...

ABSTRACT

Summary. 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¢ç continuous online 13C-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 13C 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 ¡Â4 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 ¡Â2 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¢ç13C 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.

--------------------------------------------------------------------------------

Received October 2007; accepted for publication February 2008

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1365-2893.2008.01007.x

[Guest guest]

http://www3.interscience.wiley.com/journal/120755731/abstract

Journal of Viral Hepatitis

Volume 15 Issue 10, Pages 716 - 728

Published Online: 11 Jul 2008

A continuous 13C methacetin breath test for noninvasive assessment of

intrahepatic inflammation and fibrosis in patients with chronic HCV infection

and normal ALT

G. Lalazar 1 , O. Pappo 2 , T. Hershcovici 1 , T. Hadjaj 1 , M. Shubi 1 , H.

Ohana 1 , N. Hemed 1 and Y. Ilan 1

1 Liver Unit, Department of Medicine ; and 2 Department of Pathology,

Hadassah Hebrew University Medical Center, Jerusalem, Israel

Correspondence to Yaron Ilan, Gastroenterology and Liver Units, Department of

Medicine, Hadassah-Hebrew University Medical Center, Ein-Kerem, IL91120, POB

12000, Jerusalem, Israel. E-mail: ilan@...

ABSTRACT

Summary. 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¢ç continuous online 13C-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 13C 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 ¡Â4 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 ¡Â2 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¢ç13C 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.

--------------------------------------------------------------------------------

Received October 2007; accepted for publication February 2008

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1365-2893.2008.01007.x

[Guest guest]

http://www3.interscience.wiley.com/journal/120755731/abstract

Journal of Viral Hepatitis

Volume 15 Issue 10, Pages 716 - 728

Published Online: 11 Jul 2008

A continuous 13C methacetin breath test for noninvasive assessment of

intrahepatic inflammation and fibrosis in patients with chronic HCV infection

and normal ALT

G. Lalazar 1 , O. Pappo 2 , T. Hershcovici 1 , T. Hadjaj 1 , M. Shubi 1 , H.

Ohana 1 , N. Hemed 1 and Y. Ilan 1

1 Liver Unit, Department of Medicine ; and 2 Department of Pathology,

Hadassah Hebrew University Medical Center, Jerusalem, Israel

Correspondence to Yaron Ilan, Gastroenterology and Liver Units, Department of

Medicine, Hadassah-Hebrew University Medical Center, Ein-Kerem, IL91120, POB

12000, Jerusalem, Israel. E-mail: ilan@...

ABSTRACT

Summary. 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¢ç continuous online 13C-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 13C 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 ¡Â4 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 ¡Â2 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¢ç13C 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.

--------------------------------------------------------------------------------

Received October 2007; accepted for publication February 2008

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1365-2893.2008.01007.x

[Guest guest]

http://www3.interscience.wiley.com/journal/120755731/abstract

Journal of Viral Hepatitis

Volume 15 Issue 10, Pages 716 - 728

Published Online: 11 Jul 2008

A continuous 13C methacetin breath test for noninvasive assessment of

intrahepatic inflammation and fibrosis in patients with chronic HCV infection

and normal ALT

G. Lalazar 1 , O. Pappo 2 , T. Hershcovici 1 , T. Hadjaj 1 , M. Shubi 1 , H.

Ohana 1 , N. Hemed 1 and Y. Ilan 1

1 Liver Unit, Department of Medicine ; and 2 Department of Pathology,

Hadassah Hebrew University Medical Center, Jerusalem, Israel

Correspondence to Yaron Ilan, Gastroenterology and Liver Units, Department of

Medicine, Hadassah-Hebrew University Medical Center, Ein-Kerem, IL91120, POB

12000, Jerusalem, Israel. E-mail: ilan@...

ABSTRACT

Summary. 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¢ç continuous online 13C-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 13C 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 ¡Â4 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 ¡Â2 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¢ç13C 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.

--------------------------------------------------------------------------------

Received October 2007; accepted for publication February 2008

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1365-2893.2008.01007.x