Chronic Hepatitis C in Patients With Persistently Normal Alanine Transaminase Le

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Volume 4, Issue 5, Pages 645-652 (May 2006)

Chronic Hepatitis C in Patients With Persistently Normal Alanine

Transaminase Levels

L. Shiffman & #8270;, Moisés Diago‡, Albert Tran§1,

Pockros & #8214;2, Reindollar¶3, e Prati# & #8270; & #8270;,

Rodríguez–‡‡, Pilar Lardelli§§4, Blotner & #8741; & #8741;4, Stefan

Zeuzem¶¶5

published online 14 March 2006.

Background & Aims: Many patients with chronic hepatitis C virus (HCV) have

persistently normal serum alanine transaminase (ALT) levels. We compared

characteristics of chronic hepatitis C patients with patients with normal

and elevated ALT levels using data from 3 randomized phase III trials of

peginterferon alfa-2a (40 kDa). Methods: The characteristics of 480 patients

with normal ALT values (on & #8805;3 occasions without any increases in ALT

level over a 6- to 18-month period) and 1993 patients with elevated ALT

levels were compared. Sixty-eight of the 480 patients with normal ALT levels

were randomized to no treatment and monitored for 72 weeks. Results: More

patients with normal ALT levels than patients with elevated ALT levels were

women (59% vs 32%; P < .01). The serum HCV RNA titer was significantly lower

in patients with normal ALT levels (P < .01 vs in patients with elevated ALT

levels). Patients with normal ALT levels had significantly lower

inflammation and fibrosis scores on liver biopsy examination than patients

with elevated ALT levels, but almost two-thirds had portal fibrosis and 10%

had bridging fibrosis. No correlation between baseline ALT activity, HCV RNA

level, and liver histology was observed in patients with normal ALT levels.

During the 72-week follow-up period, ALT activity elevated above the upper

limit of normal in 53% of the untreated patients with normal levels of ALT.

None became HCV RNA undetectable. Conclusions: Chronic hepatitis C patients

with normal ALT levels should be evaluated in a similar manner as patients

with elevated ALT levels because they are at risk for developing significant

liver disease. The decision to treat with peginterferon alfa and ribavirin

should be based on multiple factors, rather than on ALT levels alone.

Abbreviations used in this paper: ALT, alanine transaminase, HAI, Histologic

Activity Index, HCV, chronic hepatitis C virus, ULN, upper limit of normal

Abbreviations used in this paper: ALT, alanine transaminase, HAI, Histologic

Activity Index, HCV, chronic hepatitis C virus, ULN, upper limit of normal

& #8270; Virginia Commonwealth University Medical Center, Richmond, Virginia

‡ Hospital General de Valencia, Valencia, Spain

§ Hôpital de L’Archet, Nice, France

& #8214; The Scripps Clinic, La Jolla, California

¶ Carolinas Center for Liver Disease, Charlotte, North Carolina

# IRCCS Ospedale Maggiore, Milan, Italy

& #8270; & #8270; Ospedale ‘A. Manzoni’, Lecco, Italy

‡‡ Fundación de Investigación de Diego, Santurce, Puerto Rico

§§ Roche, Basel, Switzerland

& #8741; & #8741; Roche, Nutley, New Jersey

¶¶ Saarland University Hospital, Homburg/Saar, Germany

Address requests for reprints to: L. Shiffman, MD, Hepatology

Section, Virginia Commonwealth University Medical Center, Box 980341,

Richmond, Virginia 23298; fax: (804) 828-4945.

Supported by Roche (Basel, Switzerland).

1 Dr Tran was an Investigator for the study.

2 Dr Pockros received research grants, was involved with CME programs, is a

Consultant for, and is on the Speaker’s Bureau for Roche.

3 Dr Reindollar has associations with Hoffmann LaRoche, Shering-Plough,

Intermune, and Vertex.

4 Drs Lardelli and Blotner are employees of Hoffmann LaRoche.

5 Dr Zeuzem is a Consultant for, is on the Speaker’s Bureau, and is a

Clinical Investigator for Shering-Plough and Hoffmann LaRoche.

PII: S1542-3565(06)00142-X

doi:10.1016/j.cgh.2006.02.002

© 2006 American Gastroenterological Association Institute. Published by

Elsevier Inc. All rights reserved.

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Volume 4, Issue 5, Pages 645-652 (May 2006)

Chronic Hepatitis C in Patients With Persistently Normal Alanine

Transaminase Levels

L. Shiffman & #8270;, Moisés Diago‡, Albert Tran§1,

Pockros & #8214;2, Reindollar¶3, e Prati# & #8270; & #8270;,

Rodríguez–‡‡, Pilar Lardelli§§4, Blotner & #8741; & #8741;4, Stefan

Zeuzem¶¶5

published online 14 March 2006.

Background & Aims: Many patients with chronic hepatitis C virus (HCV) have

persistently normal serum alanine transaminase (ALT) levels. We compared

characteristics of chronic hepatitis C patients with patients with normal

and elevated ALT levels using data from 3 randomized phase III trials of

peginterferon alfa-2a (40 kDa). Methods: The characteristics of 480 patients

with normal ALT values (on & #8805;3 occasions without any increases in ALT

level over a 6- to 18-month period) and 1993 patients with elevated ALT

levels were compared. Sixty-eight of the 480 patients with normal ALT levels

were randomized to no treatment and monitored for 72 weeks. Results: More

patients with normal ALT levels than patients with elevated ALT levels were

women (59% vs 32%; P < .01). The serum HCV RNA titer was significantly lower

in patients with normal ALT levels (P < .01 vs in patients with elevated ALT

levels). Patients with normal ALT levels had significantly lower

inflammation and fibrosis scores on liver biopsy examination than patients

with elevated ALT levels, but almost two-thirds had portal fibrosis and 10%

had bridging fibrosis. No correlation between baseline ALT activity, HCV RNA

level, and liver histology was observed in patients with normal ALT levels.

During the 72-week follow-up period, ALT activity elevated above the upper

limit of normal in 53% of the untreated patients with normal levels of ALT.

None became HCV RNA undetectable. Conclusions: Chronic hepatitis C patients

with normal ALT levels should be evaluated in a similar manner as patients

with elevated ALT levels because they are at risk for developing significant

liver disease. The decision to treat with peginterferon alfa and ribavirin

should be based on multiple factors, rather than on ALT levels alone.

Abbreviations used in this paper: ALT, alanine transaminase, HAI, Histologic

Activity Index, HCV, chronic hepatitis C virus, ULN, upper limit of normal

Abbreviations used in this paper: ALT, alanine transaminase, HAI, Histologic

Activity Index, HCV, chronic hepatitis C virus, ULN, upper limit of normal

& #8270; Virginia Commonwealth University Medical Center, Richmond, Virginia

‡ Hospital General de Valencia, Valencia, Spain

§ Hôpital de L’Archet, Nice, France

& #8214; The Scripps Clinic, La Jolla, California

¶ Carolinas Center for Liver Disease, Charlotte, North Carolina

# IRCCS Ospedale Maggiore, Milan, Italy

& #8270; & #8270; Ospedale ‘A. Manzoni’, Lecco, Italy

‡‡ Fundación de Investigación de Diego, Santurce, Puerto Rico

§§ Roche, Basel, Switzerland

& #8741; & #8741; Roche, Nutley, New Jersey

¶¶ Saarland University Hospital, Homburg/Saar, Germany

Address requests for reprints to: L. Shiffman, MD, Hepatology

Section, Virginia Commonwealth University Medical Center, Box 980341,

Richmond, Virginia 23298; fax: (804) 828-4945.

Supported by Roche (Basel, Switzerland).

1 Dr Tran was an Investigator for the study.

2 Dr Pockros received research grants, was involved with CME programs, is a

Consultant for, and is on the Speaker’s Bureau for Roche.

3 Dr Reindollar has associations with Hoffmann LaRoche, Shering-Plough,

Intermune, and Vertex.

4 Drs Lardelli and Blotner are employees of Hoffmann LaRoche.

5 Dr Zeuzem is a Consultant for, is on the Speaker’s Bureau, and is a

Clinical Investigator for Shering-Plough and Hoffmann LaRoche.

PII: S1542-3565(06)00142-X

doi:10.1016/j.cgh.2006.02.002

© 2006 American Gastroenterological Association Institute. Published by

Elsevier Inc. All rights reserved.

http://www.docguide.com/news/content.nsf/PaperFrameSet?OpenForm & refid=1361 & speci\

d=41 & id=061C33FC2A7F39888525689900589BFE & newsid=852571020057CCF68525716A006649AC\

& prevpage=0 & u=GOTO//www.cghjournal.org/article/PIIS154235650600142X/abstract & ref\

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_________________________________________________________________

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Volume 4, Issue 5, Pages 645-652 (May 2006)

Chronic Hepatitis C in Patients With Persistently Normal Alanine

Transaminase Levels

L. Shiffman & #8270;, Moisés Diago‡, Albert Tran§1,

Pockros & #8214;2, Reindollar¶3, e Prati# & #8270; & #8270;,

Rodríguez–‡‡, Pilar Lardelli§§4, Blotner & #8741; & #8741;4, Stefan

Zeuzem¶¶5

published online 14 March 2006.

Background & Aims: Many patients with chronic hepatitis C virus (HCV) have

persistently normal serum alanine transaminase (ALT) levels. We compared

characteristics of chronic hepatitis C patients with patients with normal

and elevated ALT levels using data from 3 randomized phase III trials of

peginterferon alfa-2a (40 kDa). Methods: The characteristics of 480 patients

with normal ALT values (on & #8805;3 occasions without any increases in ALT

level over a 6- to 18-month period) and 1993 patients with elevated ALT

levels were compared. Sixty-eight of the 480 patients with normal ALT levels

were randomized to no treatment and monitored for 72 weeks. Results: More

patients with normal ALT levels than patients with elevated ALT levels were

women (59% vs 32%; P < .01). The serum HCV RNA titer was significantly lower

in patients with normal ALT levels (P < .01 vs in patients with elevated ALT

levels). Patients with normal ALT levels had significantly lower

inflammation and fibrosis scores on liver biopsy examination than patients

with elevated ALT levels, but almost two-thirds had portal fibrosis and 10%

had bridging fibrosis. No correlation between baseline ALT activity, HCV RNA

level, and liver histology was observed in patients with normal ALT levels.

During the 72-week follow-up period, ALT activity elevated above the upper

limit of normal in 53% of the untreated patients with normal levels of ALT.

None became HCV RNA undetectable. Conclusions: Chronic hepatitis C patients

with normal ALT levels should be evaluated in a similar manner as patients

with elevated ALT levels because they are at risk for developing significant

liver disease. The decision to treat with peginterferon alfa and ribavirin

should be based on multiple factors, rather than on ALT levels alone.

Abbreviations used in this paper: ALT, alanine transaminase, HAI, Histologic

Activity Index, HCV, chronic hepatitis C virus, ULN, upper limit of normal

Abbreviations used in this paper: ALT, alanine transaminase, HAI, Histologic

Activity Index, HCV, chronic hepatitis C virus, ULN, upper limit of normal

& #8270; Virginia Commonwealth University Medical Center, Richmond, Virginia

‡ Hospital General de Valencia, Valencia, Spain

§ Hôpital de L’Archet, Nice, France

& #8214; The Scripps Clinic, La Jolla, California

¶ Carolinas Center for Liver Disease, Charlotte, North Carolina

# IRCCS Ospedale Maggiore, Milan, Italy

& #8270; & #8270; Ospedale ‘A. Manzoni’, Lecco, Italy

‡‡ Fundación de Investigación de Diego, Santurce, Puerto Rico

§§ Roche, Basel, Switzerland

& #8741; & #8741; Roche, Nutley, New Jersey

¶¶ Saarland University Hospital, Homburg/Saar, Germany

Address requests for reprints to: L. Shiffman, MD, Hepatology

Section, Virginia Commonwealth University Medical Center, Box 980341,

Richmond, Virginia 23298; fax: (804) 828-4945.

Supported by Roche (Basel, Switzerland).

1 Dr Tran was an Investigator for the study.

2 Dr Pockros received research grants, was involved with CME programs, is a

Consultant for, and is on the Speaker’s Bureau for Roche.

3 Dr Reindollar has associations with Hoffmann LaRoche, Shering-Plough,

Intermune, and Vertex.

4 Drs Lardelli and Blotner are employees of Hoffmann LaRoche.

5 Dr Zeuzem is a Consultant for, is on the Speaker’s Bureau, and is a

Clinical Investigator for Shering-Plough and Hoffmann LaRoche.

PII: S1542-3565(06)00142-X

doi:10.1016/j.cgh.2006.02.002

© 2006 American Gastroenterological Association Institute. Published by

Elsevier Inc. All rights reserved.

http://www.docguide.com/news/content.nsf/PaperFrameSet?OpenForm & refid=1361 & speci\

d=41 & id=061C33FC2A7F39888525689900589BFE & newsid=852571020057CCF68525716A006649AC\

& prevpage=0 & u=GOTO//www.cghjournal.org/article/PIIS154235650600142X/abstract & ref\

=

_________________________________________________________________

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[Guest guest]

Volume 4, Issue 5, Pages 645-652 (May 2006)

Chronic Hepatitis C in Patients With Persistently Normal Alanine

Transaminase Levels

L. Shiffman & #8270;, Moisés Diago‡, Albert Tran§1,

Pockros & #8214;2, Reindollar¶3, e Prati# & #8270; & #8270;,

Rodríguez–‡‡, Pilar Lardelli§§4, Blotner & #8741; & #8741;4, Stefan

Zeuzem¶¶5

published online 14 March 2006.

Background & Aims: Many patients with chronic hepatitis C virus (HCV) have

persistently normal serum alanine transaminase (ALT) levels. We compared

characteristics of chronic hepatitis C patients with patients with normal

and elevated ALT levels using data from 3 randomized phase III trials of

peginterferon alfa-2a (40 kDa). Methods: The characteristics of 480 patients

with normal ALT values (on & #8805;3 occasions without any increases in ALT

level over a 6- to 18-month period) and 1993 patients with elevated ALT

levels were compared. Sixty-eight of the 480 patients with normal ALT levels

were randomized to no treatment and monitored for 72 weeks. Results: More

patients with normal ALT levels than patients with elevated ALT levels were

women (59% vs 32%; P < .01). The serum HCV RNA titer was significantly lower

in patients with normal ALT levels (P < .01 vs in patients with elevated ALT

levels). Patients with normal ALT levels had significantly lower

inflammation and fibrosis scores on liver biopsy examination than patients

with elevated ALT levels, but almost two-thirds had portal fibrosis and 10%

had bridging fibrosis. No correlation between baseline ALT activity, HCV RNA

level, and liver histology was observed in patients with normal ALT levels.

During the 72-week follow-up period, ALT activity elevated above the upper

limit of normal in 53% of the untreated patients with normal levels of ALT.

None became HCV RNA undetectable. Conclusions: Chronic hepatitis C patients

with normal ALT levels should be evaluated in a similar manner as patients

with elevated ALT levels because they are at risk for developing significant

liver disease. The decision to treat with peginterferon alfa and ribavirin

should be based on multiple factors, rather than on ALT levels alone.

Abbreviations used in this paper: ALT, alanine transaminase, HAI, Histologic

Activity Index, HCV, chronic hepatitis C virus, ULN, upper limit of normal

Abbreviations used in this paper: ALT, alanine transaminase, HAI, Histologic

Activity Index, HCV, chronic hepatitis C virus, ULN, upper limit of normal

& #8270; Virginia Commonwealth University Medical Center, Richmond, Virginia

‡ Hospital General de Valencia, Valencia, Spain

§ Hôpital de L’Archet, Nice, France

& #8214; The Scripps Clinic, La Jolla, California

¶ Carolinas Center for Liver Disease, Charlotte, North Carolina

# IRCCS Ospedale Maggiore, Milan, Italy

& #8270; & #8270; Ospedale ‘A. Manzoni’, Lecco, Italy

‡‡ Fundación de Investigación de Diego, Santurce, Puerto Rico

§§ Roche, Basel, Switzerland

& #8741; & #8741; Roche, Nutley, New Jersey

¶¶ Saarland University Hospital, Homburg/Saar, Germany

Address requests for reprints to: L. Shiffman, MD, Hepatology

Section, Virginia Commonwealth University Medical Center, Box 980341,

Richmond, Virginia 23298; fax: (804) 828-4945.

Supported by Roche (Basel, Switzerland).

1 Dr Tran was an Investigator for the study.

2 Dr Pockros received research grants, was involved with CME programs, is a

Consultant for, and is on the Speaker’s Bureau for Roche.

3 Dr Reindollar has associations with Hoffmann LaRoche, Shering-Plough,

Intermune, and Vertex.

4 Drs Lardelli and Blotner are employees of Hoffmann LaRoche.

5 Dr Zeuzem is a Consultant for, is on the Speaker’s Bureau, and is a

Clinical Investigator for Shering-Plough and Hoffmann LaRoche.

PII: S1542-3565(06)00142-X

doi:10.1016/j.cgh.2006.02.002

© 2006 American Gastroenterological Association Institute. Published by

Elsevier Inc. All rights reserved.

http://www.docguide.com/news/content.nsf/PaperFrameSet?OpenForm & refid=1361 & speci\

d=41 & id=061C33FC2A7F39888525689900589BFE & newsid=852571020057CCF68525716A006649AC\

& prevpage=0 & u=GOTO//www.cghjournal.org/article/PIIS154235650600142X/abstract & ref\

=

_________________________________________________________________

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