Silymarin use and liver disease progression in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2010.04503.x/abstract

Silymarin use and liver disease progression in the Hepatitis C Antiviral

Long-Term Treatment against Cirrhosis trial

N. D. Freedman1, T. M. Curto2, C. Morishima3, L. B. Seeff4, Z. D. Goodman5, E.

C. 6, R. Sinha1, J. E. Everhart7, the HALT-C Trial Group1Article first

published online: 2 NOV 2010

DOI: 10.1111/j.1365-2036.2010.04503.x

Published 2010. This article is a US Government work and is in the public domain

in the USA.

Issue

Alimentary Pharmacology & Therapeutics

Early View (Articles online in advance of print)

Freedman, N. D., Curto, T. M., Morishima, C., Seeff, L. B., Goodman, Z. D.,

, E. C., Sinha, R., Everhart, J. E. and the HALT-C Trial Group , Silymarin

use and liver disease progression in the Hepatitis C Antiviral Long-Term

Treatment against Cirrhosis trial. Alimentary Pharmacology & Therapeutics, no.

doi: 10.1111/j.1365-2036.2010.04503.x

Author Information

1Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics,

National Cancer Institute, National Institutes of Health, Department of Health

and Human Services, Rockville, MD, USA.

2New England Research Institutes, Watertown, MA, USA.

3Division of Virology, Department of Laboratory Medicine, University of

Washington, Seattle, WA, USA.

4Division of Digestive Diseases and Nutrition, and Liver Diseases Branch,

National Institutes of Diabetes and Digestive and Kidney Diseases, National

Institutes of Health, Department of Health and Human Services, Bethesda, MD,

USA.

5Division of Hepatic Pathology, Armed Forces Institute of Pathology, Washington,

DC, USA.

6Office of the Director, National Institute of Diabetes and Digestive and Kidney

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

Services, Bethesda, MD, USA.

7Division 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, MD, USA.

*Correspondence: Dr N. D. Freedman, Nutritional Epidemiology Branch, Division of

Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive

Blvd, EPS/320, MSC 7232, Rockville, MD 20852, USA. E-mail:

freedmanne@...

Publication History

Article first published online: 2 NOV 2010

Publication data Submitted 12 July 2010 First decision 31 July 2010 Resubmitted

7 October 2010 Accepted 11 October 2010

Summary

Background  Silymarin is the most commonly used herbal product for chronic

liver disease; yet, whether silymarin protects against liver disease progression

remains unclear.

Aim  To assess the effects of silymarin use on subsequent liver disease

progression in 1049 patients of the Hepatitis C Antiviral Long-Term Treatment

against Cirrhosis (HALT-C) trial who had advanced fibrosis or cirrhosis and had

failed prior peginterferon plus ribavirin treatment.

Methods  Patients recorded their use of silymarin at baseline and were

followed up for liver disease progression (two point increase in Ishak fibrosis

score across baseline, year 1.5, and year 3.5 biopsies) and over 8.65 years for

clinical outcomes.

Results  At baseline, 34% of patients had used silymarin, half of whom were

current users. Use of silymarin was associated (P < 0.05) with male gender;

oesophageal varices; higher ALT and albumin; and lower AST/ALT ratio, among

other features. Baseline users had less hepatic collagen content on study

biopsies and had less histological progression (HR: 0.57, 95% CI: 0.33–1.00;

P-trend for longer duration of use=0.026). No effect was seen for clinical

outcomes.

Conclusions  Silymarin use among patients with advanced hepatitis C-related

liver disease is associated with reduced progression from fibrosis to cirrhosis,

but has no impact on clinical outcomes (Clinicaltrials.gov #NCT00006164).

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2010.04503.x/abstract

Silymarin use and liver disease progression in the Hepatitis C Antiviral

Long-Term Treatment against Cirrhosis trial

N. D. Freedman1, T. M. Curto2, C. Morishima3, L. B. Seeff4, Z. D. Goodman5, E.

C. 6, R. Sinha1, J. E. Everhart7, the HALT-C Trial Group1Article first

published online: 2 NOV 2010

DOI: 10.1111/j.1365-2036.2010.04503.x

Published 2010. This article is a US Government work and is in the public domain

in the USA.

Issue

Alimentary Pharmacology & Therapeutics

Early View (Articles online in advance of print)

Freedman, N. D., Curto, T. M., Morishima, C., Seeff, L. B., Goodman, Z. D.,

, E. C., Sinha, R., Everhart, J. E. and the HALT-C Trial Group , Silymarin

use and liver disease progression in the Hepatitis C Antiviral Long-Term

Treatment against Cirrhosis trial. Alimentary Pharmacology & Therapeutics, no.

doi: 10.1111/j.1365-2036.2010.04503.x

Author Information

1Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics,

National Cancer Institute, National Institutes of Health, Department of Health

and Human Services, Rockville, MD, USA.

2New England Research Institutes, Watertown, MA, USA.

3Division of Virology, Department of Laboratory Medicine, University of

Washington, Seattle, WA, USA.

4Division of Digestive Diseases and Nutrition, and Liver Diseases Branch,

National Institutes of Diabetes and Digestive and Kidney Diseases, National

Institutes of Health, Department of Health and Human Services, Bethesda, MD,

USA.

5Division of Hepatic Pathology, Armed Forces Institute of Pathology, Washington,

DC, USA.

6Office of the Director, National Institute of Diabetes and Digestive and Kidney

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

Services, Bethesda, MD, USA.

7Division 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, MD, USA.

*Correspondence: Dr N. D. Freedman, Nutritional Epidemiology Branch, Division of

Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive

Blvd, EPS/320, MSC 7232, Rockville, MD 20852, USA. E-mail:

freedmanne@...

Publication History

Article first published online: 2 NOV 2010

Publication data Submitted 12 July 2010 First decision 31 July 2010 Resubmitted

7 October 2010 Accepted 11 October 2010

Summary

Background  Silymarin is the most commonly used herbal product for chronic

liver disease; yet, whether silymarin protects against liver disease progression

remains unclear.

Aim  To assess the effects of silymarin use on subsequent liver disease

progression in 1049 patients of the Hepatitis C Antiviral Long-Term Treatment

against Cirrhosis (HALT-C) trial who had advanced fibrosis or cirrhosis and had

failed prior peginterferon plus ribavirin treatment.

Methods  Patients recorded their use of silymarin at baseline and were

followed up for liver disease progression (two point increase in Ishak fibrosis

score across baseline, year 1.5, and year 3.5 biopsies) and over 8.65 years for

clinical outcomes.

Results  At baseline, 34% of patients had used silymarin, half of whom were

current users. Use of silymarin was associated (P < 0.05) with male gender;

oesophageal varices; higher ALT and albumin; and lower AST/ALT ratio, among

other features. Baseline users had less hepatic collagen content on study

biopsies and had less histological progression (HR: 0.57, 95% CI: 0.33–1.00;

P-trend for longer duration of use=0.026). No effect was seen for clinical

outcomes.

Conclusions  Silymarin use among patients with advanced hepatitis C-related

liver disease is associated with reduced progression from fibrosis to cirrhosis,

but has no impact on clinical outcomes (Clinicaltrials.gov #NCT00006164).