Maintenance Peginterferon Therapy and Other Factors Associated With Hepatocellular Carcinoma in Patients With Advanced Hepatitis C

[Guest guest]

http://www.gastrojournal.org/article/PIIS0016508510017403/abstract?rss=yes

Gastroenterology

Volume 140, Issue 3 , Pages 840-849.e1, March 2011

Maintenance Peginterferon Therapy and Other Factors Associated With

Hepatocellular Carcinoma in Patients With Advanced Hepatitis C

S. Lok

Affiliations

Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor,

Michigan

Reprint requests Address requests for reprints to: S. Lok, MD, Division of

Gastroenterology, University of Michigan Health System, 3912 Taubman Center, SPC

5362, Ann Arbor, Michigan 48109. fax: (734) 936-7392,

E. Everhart

Affiliations

Division of Digestive Diseases and Nutrition, National Institute of Diabetes and

Digestive and Kidney Diseases, National Institutes of Health, Department of

Health and Human Services, Bethesda, land,

C.

Affiliations

Office of the Director, National Institute of Diabetes and Digestive and Kidney

Diseases, National Institutes of Health, Department of Health and Human

Services, Bethesda, land,

M. Di Bisceglie

Affiliations

Division of Gastroenterology and Hepatology, Saint Louis University School of

Medicine, St Louis, Missouri,

Hae¨CYoung Kim

Affiliations

New England Research Institutes, Watertown, Massachusetts,

K. Sterling

Affiliations

Hepatology Section, Virginia Commonwealth University Medical Center, Richmond,

Virginia,

T. Everson

Affiliations

Section of Hepatology, Division of Gastroenterology and Hepatology, University

of Colorado Denver School of Medicine, Aurora, Colorado,

L.

Affiliations

Division of Gastrointestinal and Liver Diseases, Keck School of Medicine,

University of Southern California, Los Angeles, California,

M. Lee

Affiliations

Division of Digestive and Liver Diseases, University of Texas Southwestern

Medical Center, Dallas, Texas,

Herbert L. Bonkovsky

Affiliations

Department of Medicine, University of Connecticut Health Center, Farmington,

Connecticut

Carolinas Medical Center, Charlotte, North Carolina,

Jules L. Dienstag

Affiliations

Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts

Department of Medicine, Harvard Medical School, Boston, Massachusetts,

Marc G. Ghany

Affiliations

Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney

Diseases, National Institutes of Health, Department of Health and Human

Services, Bethesda, land,

Chihiro Morishima

Affiliations

Division of Virology, Department of Laboratory Medicine, University of

Washington, Seattle, Washington,

R.

Affiliations

Division of Gastroenterology, University of California-Irvine, Irvine,

California

Gastroenterology Service, VA Long Beach Healthcare System, Long Beach,

California,

HALT-C Trial Group

Received 29 July 2010; accepted 16 November 2010. published online 03 December

2010.

Abstract

Full Text

PDF

Images

References

Background & Aims

Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC)

in patients with chronic hepatitis C. The Hepatitis C Antiviral Long-term

Treatment against Cirrhosis (HALT-C) Trial showed that 4 years of maintenance

therapy with pegylated interferon (peginterferon) does not reduce liver disease

progression. We investigated whether peginterferon decreases the incidence of

HCC in the HALT-C cohort over a longer posttreatment follow-up period.

Methods

The study included 1048 patients with chronic hepatitis C (Ishak fibrosis scores

¡Ý3) who did not have a sustained virologic response (SVR) to therapy. They were

randomly assigned to groups given a half-dose of peginterferon or no treatment

(controls) for 3.5 years and followed up for a median of 6.1 (maximum, 8.7)

years.

Results

Eighty-eight patients developed HCC (68 definite, 20 presumed): 37 of 515 who

were given peginterferon (7.2%) and 51 of 533 controls (9.6%; P = .24). There

was a significantly lower incidence of HCC among patients given peginterferon

therapy who had cirrhosis, but not fibrosis, based on analysis of baseline

biopsy samples. After 7 years, the cumulative incidences of HCC in treated and

control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio

---

, 0.45; 95% confidence interval [CI], 0.24¨C0.83); in treated and control

patients with fibrosis, incidences were 8.3% and 6.8%, respectively (HR, 1.44;

95% CI, 0.77¨C2.69). Treated patients with a ¡Ý2-point decrease in the

histologic activity index, based on a follow-up biopsy, had a lower incidence of

HCC than those with unchanged or increased scores (2.9% vs 9.4%; P = .03).

Conclusions

Extended analysis of the HALT-C cohort showed that long-term peginterferon

therapy does not reduce the incidence of HCC among patients with advanced

hepatitis C who did not achieve SVRs. Patients with cirrhosis who received

peginterferon treatment had a lower risk of HCC than controls.

[Guest guest]

http://www.gastrojournal.org/article/PIIS0016508510017403/abstract?rss=yes

Gastroenterology

Volume 140, Issue 3 , Pages 840-849.e1, March 2011

Maintenance Peginterferon Therapy and Other Factors Associated With

Hepatocellular Carcinoma in Patients With Advanced Hepatitis C

S. Lok

Affiliations

Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor,

Michigan

Reprint requests Address requests for reprints to: S. Lok, MD, Division of

Gastroenterology, University of Michigan Health System, 3912 Taubman Center, SPC

5362, Ann Arbor, Michigan 48109. fax: (734) 936-7392,

E. Everhart

Affiliations

Division of Digestive Diseases and Nutrition, National Institute of Diabetes and

Digestive and Kidney Diseases, National Institutes of Health, Department of

Health and Human Services, Bethesda, land,

C.

Affiliations

Office of the Director, National Institute of Diabetes and Digestive and Kidney

Diseases, National Institutes of Health, Department of Health and Human

Services, Bethesda, land,

M. Di Bisceglie

Affiliations

Division of Gastroenterology and Hepatology, Saint Louis University School of

Medicine, St Louis, Missouri,

Hae¨CYoung Kim

Affiliations

New England Research Institutes, Watertown, Massachusetts,

K. Sterling

Affiliations

Hepatology Section, Virginia Commonwealth University Medical Center, Richmond,

Virginia,

T. Everson

Affiliations

Section of Hepatology, Division of Gastroenterology and Hepatology, University

of Colorado Denver School of Medicine, Aurora, Colorado,

L.

Affiliations

Division of Gastrointestinal and Liver Diseases, Keck School of Medicine,

University of Southern California, Los Angeles, California,

M. Lee

Affiliations

Division of Digestive and Liver Diseases, University of Texas Southwestern

Medical Center, Dallas, Texas,

Herbert L. Bonkovsky

Affiliations

Department of Medicine, University of Connecticut Health Center, Farmington,

Connecticut

Carolinas Medical Center, Charlotte, North Carolina,

Jules L. Dienstag

Affiliations

Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts

Department of Medicine, Harvard Medical School, Boston, Massachusetts,

Marc G. Ghany

Affiliations

Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney

Diseases, National Institutes of Health, Department of Health and Human

Services, Bethesda, land,

Chihiro Morishima

Affiliations

Division of Virology, Department of Laboratory Medicine, University of

Washington, Seattle, Washington,

R.

Affiliations

Division of Gastroenterology, University of California-Irvine, Irvine,

California

Gastroenterology Service, VA Long Beach Healthcare System, Long Beach,

California,

HALT-C Trial Group

Received 29 July 2010; accepted 16 November 2010. published online 03 December

2010.

Abstract

Full Text

PDF

Images

References

Background & Aims

Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC)

in patients with chronic hepatitis C. The Hepatitis C Antiviral Long-term

Treatment against Cirrhosis (HALT-C) Trial showed that 4 years of maintenance

therapy with pegylated interferon (peginterferon) does not reduce liver disease

progression. We investigated whether peginterferon decreases the incidence of

HCC in the HALT-C cohort over a longer posttreatment follow-up period.

Methods

The study included 1048 patients with chronic hepatitis C (Ishak fibrosis scores

¡Ý3) who did not have a sustained virologic response (SVR) to therapy. They were

randomly assigned to groups given a half-dose of peginterferon or no treatment

(controls) for 3.5 years and followed up for a median of 6.1 (maximum, 8.7)

years.

Results

Eighty-eight patients developed HCC (68 definite, 20 presumed): 37 of 515 who

were given peginterferon (7.2%) and 51 of 533 controls (9.6%; P = .24). There

was a significantly lower incidence of HCC among patients given peginterferon

therapy who had cirrhosis, but not fibrosis, based on analysis of baseline

biopsy samples. After 7 years, the cumulative incidences of HCC in treated and

control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio

---

, 0.45; 95% confidence interval [CI], 0.24¨C0.83); in treated and control

patients with fibrosis, incidences were 8.3% and 6.8%, respectively (HR, 1.44;

95% CI, 0.77¨C2.69). Treated patients with a ¡Ý2-point decrease in the

histologic activity index, based on a follow-up biopsy, had a lower incidence of

HCC than those with unchanged or increased scores (2.9% vs 9.4%; P = .03).

Conclusions

Extended analysis of the HALT-C cohort showed that long-term peginterferon

therapy does not reduce the incidence of HCC among patients with advanced

hepatitis C who did not achieve SVRs. Patients with cirrhosis who received

peginterferon treatment had a lower risk of HCC than controls.

[Guest guest]

http://www.gastrojournal.org/article/PIIS0016508510017403/abstract?rss=yes

Gastroenterology

Volume 140, Issue 3 , Pages 840-849.e1, March 2011

Maintenance Peginterferon Therapy and Other Factors Associated With

Hepatocellular Carcinoma in Patients With Advanced Hepatitis C

S. Lok

Affiliations

Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor,

Michigan

Reprint requests Address requests for reprints to: S. Lok, MD, Division of

Gastroenterology, University of Michigan Health System, 3912 Taubman Center, SPC

5362, Ann Arbor, Michigan 48109. fax: (734) 936-7392,

E. Everhart

Affiliations

Division of Digestive Diseases and Nutrition, National Institute of Diabetes and

Digestive and Kidney Diseases, National Institutes of Health, Department of

Health and Human Services, Bethesda, land,

C.

Affiliations

Office of the Director, National Institute of Diabetes and Digestive and Kidney

Diseases, National Institutes of Health, Department of Health and Human

Services, Bethesda, land,

M. Di Bisceglie

Affiliations

Division of Gastroenterology and Hepatology, Saint Louis University School of

Medicine, St Louis, Missouri,

Hae¨CYoung Kim

Affiliations

New England Research Institutes, Watertown, Massachusetts,

K. Sterling

Affiliations

Hepatology Section, Virginia Commonwealth University Medical Center, Richmond,

Virginia,

T. Everson

Affiliations

Section of Hepatology, Division of Gastroenterology and Hepatology, University

of Colorado Denver School of Medicine, Aurora, Colorado,

L.

Affiliations

Division of Gastrointestinal and Liver Diseases, Keck School of Medicine,

University of Southern California, Los Angeles, California,

M. Lee

Affiliations

Division of Digestive and Liver Diseases, University of Texas Southwestern

Medical Center, Dallas, Texas,

Herbert L. Bonkovsky

Affiliations

Department of Medicine, University of Connecticut Health Center, Farmington,

Connecticut

Carolinas Medical Center, Charlotte, North Carolina,

Jules L. Dienstag

Affiliations

Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts

Department of Medicine, Harvard Medical School, Boston, Massachusetts,

Marc G. Ghany

Affiliations

Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney

Diseases, National Institutes of Health, Department of Health and Human

Services, Bethesda, land,

Chihiro Morishima

Affiliations

Division of Virology, Department of Laboratory Medicine, University of

Washington, Seattle, Washington,

R.

Affiliations

Division of Gastroenterology, University of California-Irvine, Irvine,

California

Gastroenterology Service, VA Long Beach Healthcare System, Long Beach,

California,

HALT-C Trial Group

Received 29 July 2010; accepted 16 November 2010. published online 03 December

2010.

Abstract

Full Text

PDF

Images

References

Background & Aims

Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC)

in patients with chronic hepatitis C. The Hepatitis C Antiviral Long-term

Treatment against Cirrhosis (HALT-C) Trial showed that 4 years of maintenance

therapy with pegylated interferon (peginterferon) does not reduce liver disease

progression. We investigated whether peginterferon decreases the incidence of

HCC in the HALT-C cohort over a longer posttreatment follow-up period.

Methods

The study included 1048 patients with chronic hepatitis C (Ishak fibrosis scores

¡Ý3) who did not have a sustained virologic response (SVR) to therapy. They were

randomly assigned to groups given a half-dose of peginterferon or no treatment

(controls) for 3.5 years and followed up for a median of 6.1 (maximum, 8.7)

years.

Results

Eighty-eight patients developed HCC (68 definite, 20 presumed): 37 of 515 who

were given peginterferon (7.2%) and 51 of 533 controls (9.6%; P = .24). There

was a significantly lower incidence of HCC among patients given peginterferon

therapy who had cirrhosis, but not fibrosis, based on analysis of baseline

biopsy samples. After 7 years, the cumulative incidences of HCC in treated and

control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio

---

, 0.45; 95% confidence interval [CI], 0.24¨C0.83); in treated and control

patients with fibrosis, incidences were 8.3% and 6.8%, respectively (HR, 1.44;

95% CI, 0.77¨C2.69). Treated patients with a ¡Ý2-point decrease in the

histologic activity index, based on a follow-up biopsy, had a lower incidence of

HCC than those with unchanged or increased scores (2.9% vs 9.4%; P = .03).

Conclusions

Extended analysis of the HALT-C cohort showed that long-term peginterferon

therapy does not reduce the incidence of HCC among patients with advanced

hepatitis C who did not achieve SVRs. Patients with cirrhosis who received

peginterferon treatment had a lower risk of HCC than controls.

[Guest guest]

http://www.gastrojournal.org/article/PIIS0016508510017403/abstract?rss=yes

Gastroenterology

Volume 140, Issue 3 , Pages 840-849.e1, March 2011

Maintenance Peginterferon Therapy and Other Factors Associated With

Hepatocellular Carcinoma in Patients With Advanced Hepatitis C

S. Lok

Affiliations

Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor,

Michigan

Reprint requests Address requests for reprints to: S. Lok, MD, Division of

Gastroenterology, University of Michigan Health System, 3912 Taubman Center, SPC

5362, Ann Arbor, Michigan 48109. fax: (734) 936-7392,

E. Everhart

Affiliations

Division of Digestive Diseases and Nutrition, National Institute of Diabetes and

Digestive and Kidney Diseases, National Institutes of Health, Department of

Health and Human Services, Bethesda, land,

C.

Affiliations

Office of the Director, National Institute of Diabetes and Digestive and Kidney

Diseases, National Institutes of Health, Department of Health and Human

Services, Bethesda, land,

M. Di Bisceglie

Affiliations

Division of Gastroenterology and Hepatology, Saint Louis University School of

Medicine, St Louis, Missouri,

Hae¨CYoung Kim

Affiliations

New England Research Institutes, Watertown, Massachusetts,

K. Sterling

Affiliations

Hepatology Section, Virginia Commonwealth University Medical Center, Richmond,

Virginia,

T. Everson

Affiliations

Section of Hepatology, Division of Gastroenterology and Hepatology, University

of Colorado Denver School of Medicine, Aurora, Colorado,

L.

Affiliations

Division of Gastrointestinal and Liver Diseases, Keck School of Medicine,

University of Southern California, Los Angeles, California,

M. Lee

Affiliations

Division of Digestive and Liver Diseases, University of Texas Southwestern

Medical Center, Dallas, Texas,

Herbert L. Bonkovsky

Affiliations

Department of Medicine, University of Connecticut Health Center, Farmington,

Connecticut

Carolinas Medical Center, Charlotte, North Carolina,

Jules L. Dienstag

Affiliations

Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts

Department of Medicine, Harvard Medical School, Boston, Massachusetts,

Marc G. Ghany

Affiliations

Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney

Diseases, National Institutes of Health, Department of Health and Human

Services, Bethesda, land,

Chihiro Morishima

Affiliations

Division of Virology, Department of Laboratory Medicine, University of

Washington, Seattle, Washington,

R.

Affiliations

Division of Gastroenterology, University of California-Irvine, Irvine,

California

Gastroenterology Service, VA Long Beach Healthcare System, Long Beach,

California,

HALT-C Trial Group

Received 29 July 2010; accepted 16 November 2010. published online 03 December

2010.

Abstract

Full Text

PDF

Images

References

Background & Aims

Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC)

in patients with chronic hepatitis C. The Hepatitis C Antiviral Long-term

Treatment against Cirrhosis (HALT-C) Trial showed that 4 years of maintenance

therapy with pegylated interferon (peginterferon) does not reduce liver disease

progression. We investigated whether peginterferon decreases the incidence of

HCC in the HALT-C cohort over a longer posttreatment follow-up period.

Methods

The study included 1048 patients with chronic hepatitis C (Ishak fibrosis scores

¡Ý3) who did not have a sustained virologic response (SVR) to therapy. They were

randomly assigned to groups given a half-dose of peginterferon or no treatment

(controls) for 3.5 years and followed up for a median of 6.1 (maximum, 8.7)

years.

Results

Eighty-eight patients developed HCC (68 definite, 20 presumed): 37 of 515 who

were given peginterferon (7.2%) and 51 of 533 controls (9.6%; P = .24). There

was a significantly lower incidence of HCC among patients given peginterferon

therapy who had cirrhosis, but not fibrosis, based on analysis of baseline

biopsy samples. After 7 years, the cumulative incidences of HCC in treated and

control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio

---

, 0.45; 95% confidence interval [CI], 0.24¨C0.83); in treated and control

patients with fibrosis, incidences were 8.3% and 6.8%, respectively (HR, 1.44;

95% CI, 0.77¨C2.69). Treated patients with a ¡Ý2-point decrease in the

histologic activity index, based on a follow-up biopsy, had a lower incidence of

HCC than those with unchanged or increased scores (2.9% vs 9.4%; P = .03).

Conclusions

Extended analysis of the HALT-C cohort showed that long-term peginterferon

therapy does not reduce the incidence of HCC among patients with advanced

hepatitis C who did not achieve SVRs. Patients with cirrhosis who received

peginterferon treatment had a lower risk of HCC than controls.