Serum Fibrosis Marker Levels Decrease After Successful Antiviral Treatment in Chronic Hepatitis C Patients With Advanced Fibrosis

published online 11 November 2008.

Background & Aims

Serum fibrosis marker levels during the lead-in treatment phase of patients enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial were determined.

Methods

Week 0, 24, 48, and 72 serum samples were analyzed for YKL-40, tissue inhibitor of matrix metalloproteinase-1, amino-terminal peptide of type III procollagen (PIIINP), and hyaluronic acid (HA) levels. All 456 chronic hepatitis C (CHC) patients received peginterferon alfa 2a and ribavirin for 24 to 48 weeks.

Results

Mean age was 49.2 years, 71% were male, and 39% had cirrhosis. Lower pretreatment serum YKL-40, tissue inhibitor of matrix metalloproteinase-1, PIIINP, and HA levels were associated significantly with week-20 virologic response (P < .0001). In multivariate analysis, non-1 CHC genotype, non-black race, prior interferon monotherapy, and lower baseline serum aspartate aminotransferase/alanine aminotransferase levels and log10YKL-40 levels were associated independently with week-20 virologic response. Statistically significant declines in all marker levels were observed at week 72 compared with baseline in the 81 patients with a sustained virologic response, but not in the 72 patients with breakthrough or relapse. At weeks 24 and 48, significant increases were observed in serum PIIINP and HA levels compared with baseline in virologic responders and nonresponders (P < .0001).

Conclusions

Pretreatment YKL-40 levels are an independent predictor of initial virologic response to peginterferon and ribavirin treatment. Levels of all 4 serum fibrosis markers decreased significantly in the SVR patients, consistent with reduced hepatic fibrogenesis. Measuring serum fibrosis marker levels before and after antiviral therapy may provide important prognostic information in CHC patients.

⁎ Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan

‡ Departments of Medicine and Molecular & Structural Biology and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, Connecticut

§ New England Research Institutes, Watertown, Massachusetts

∥ Gastrointestinal Unit, Medical Services, Massachusetts General Hospital, Boston, Massachusetts

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

# Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, Virginia

⁎⁎ Gastroenterology Section, Ann Arbor Veterans Administration Health Systems, Ann Arbor, Michigan

Address requests for reprints to: Robert J. Fontana, MD, Department of Internal Medicine, University of Michigan Medical Center, 3912 Taubman Center, Ann Arbor, Michigan 48109-0362. fax: (734) 936-7392

In addition to the authors of this manuscript, the following individuals were instrumental in the planning, conduct, and/or care of patients enrolled in this study at each of the participating institutions as follows: University of Massachusetts Medical Center, Worcester, MA (contract N01-DK-9-2326): Gyongyi Szabo, MD, Maureen Cormier, RN, and Donna Giansiracusa, RN; University of Connecticut Health Center, Farmington, CT (grant M01RR-06192): Gloria Borders, RN; Massachusetts General Hospital, Boston, MA (contract N01-DK-9-2319 and grant M01RR-01066): Raymond T. Chung, MD, Andrea E. Reid, MD, Atul K. Bhan, MD, and Wallis A. Molchen; University of Michigan Medical Center, Ann Arbor, MI (contract N01-DK-9-2323 and grant M01RR-00042): Pamela A. Richtmyer, LPN, CCRC, R. Tess Bonham, BS, Mita Ghosh, Leslie Giudotti, and Emily Anderson; Virginia Commonwealth University Health System, Richmond, VA (contract N01-DK-9-2322 and grant M01RR-00065): Mitchell L. Shiffman, MD, Charlotte Hofmann, RN, and Paula Smith, RN; Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD: James E. Everhart, MD, MPH, Jay H. Hoofnagle, MD, Leonard B. Seeff, MD, and Elizabeth C. Wright, PhD; New England Research Institutes, Watertown, MA (contract N01-DK-9-2328): Kristin K. Snow, MSc, ScD, Linda Massey, and Teresa M. Curto, MSW, MPH; Armed Forces Institute of Pathology, Washington, DC: Zachary D. Goodman, MD; Data and Safety Monitoring Board Members: Gary L. Davis, MD (Chair), Guadalupe Garcia-Tsao, MD, Michael Kutner, PhD, Stanley M. Lemon, MD, and Robert P. Perrillo, MD.

Dr Bonkovsky's current address is Department of Internal Medicine Carolinas Medical Center, Charlotte, NC.

This is publication #36 from the HALT-C Trial Group.

The authors disclose the following: This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed later). Additional support was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities, and by General Clinical Research Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed later). Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement with the National Institutes of Health. The financial relationships of the authors with Hoffmann-La Roche, Inc., are as follows: R. J. Fontana is on the speaker's bureau; H. L. Bonkovsky receives research support; R. K. Sterling is a consultant, receives research support, and is on the speaker's bureau; and A. S. Lok is a consultant.

J. L. Dienstag, D. Naishadham, and G. L. Su disclose no conflicts.

PII: S1542-3565(08)01120-8

doi:10.1016/j.cgh.2008.10.034

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