Fibrosis progression in chronic hepatitis C: Morphometric image analysis in the HALT-C trial
Goodman, Zachary D.; Stoddard, Anne M.; Bonkovsky, Herbert L.; Fontana, Robert John; Ghany, Marc G.; Morgan, Timothy R.; Wright, Elizabeth C.; Brunt, Elizabeth M.; Kleiner, David E.; Shiffman, Mitchell L.; Everson, Gregory T.; Lindsay, Karen L.; Dienstag, Jules L.; Morishima, Chihiro
2009-12
Citation
Goodman, Zachary D.; Stoddard, Anne M.; Bonkovsky, Herbert L.; Fontana, Robert J.; Ghany, Marc G.; Morgan, Timothy R.; Wright, Elizabeth C.; Brunt, Elizabeth M.; Kleiner, David E.; Shiffman, Mitchell L.; Everson, Gregory T.; Lindsay, Karen L.; Dienstag, Jules L.; Morishima, Chihiro (2009). "Fibrosis progression in chronic hepatitis C: Morphometric image analysis in the HALT-C trial The opinions and assertions expressed in this study are the private views of the authors and do not represent the views of the National Center for Research Resources, the National Institutes of Health, the Department of the Army, or the Department of Defense. Potential conflict of interest: Dr. Goodman received grants from Schering-Plough, Novartis, and Pharmasset. Dr. Bonkovskyi is a consultant for and advises Boehringer-Ingelheim and Novartis. He also advises and is on the speakers' bureau of Lunbeck Pharma. He received grants from Hoffmann-LaRoche, Merck, and Vertex. Dr. Fontana is on the speakers' bureau of Roche. Dr. Lindsay received grants from Schering-Plough, Valeant, Vertex, and Wyeth. She is also a consultant for and advises Bristol-Myers Squibb, Clinical Care Options, Kendle International, King, Peregrine, Roche Diagnostics, Valeant, Zymogenetics. She received grants from, is a consultant for, and advises, Hoffmann-LaRoche, Human Genome Sciences, and Idenix Pharmaceuticals. Dr. Morgan is a consultant for, is on the speakers' bureau of, and received grants from Roche. He advises and received grants from Vertex. He received grants from Schering-Plough and March. Dr. Shiffman advises and received grants from Biolex, Conatus, Human Genome Sciences, Romark, Valeant, Vertex, and Zymogenetics. He advises Bristol-Myers Squibb, Anadys and Novartis. He received grants from GlaxoSmithKline, Globeimmune, Idenix, Johnson and Johnson, and Wyeth. He is a consultant for, advises, is on the speakers' bureau of, and received grants from Roche. He also advises, is on the speakers' bureau of, and received grants from Schering-Plough. Dr. Stoddard owns stock in Elan Corp., Johnson and Johnson, Stryker, Proctor and Gamble, and Bristol-Myers Squibb. Additional support was provided by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement with the National Institutes of Health. (See Appendix for contract and grant details.) ." Hepatology 50(6): 1738-1749. <http://hdl.handle.net/2027.42/64551>
Abstract
Computer-assisted morphometry can provide precise measurement of hepatic fibrosis on a continuous scale. Previous morphometric studies of large cohorts of patients with treatment refractory chronic hepatitis C have shown a mean increase in fibrosis of 30% to 58% in 1 year. The aim of the present study was to quantify fibrosis progression in biopsy specimens obtained over 1.5 to 5 years from three groups of patients with baseline bridging fibrosis or cirrhosis (Ishak stages 3-6) enrolled in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial. The main group of 346 lead-in nonresponders (viremic after 24 weeks of peginterferon-ribavirin therapy) had a mean fibrosis increase of 61% over pretreatment baseline after 2 years and 80% after 4 years. In contrast, the 78 breakthrough/relapse patients (undetectable serum hepatitis C virus RNA after 24 weeks of peginterferon-ribavirin and receiving antiviral therapy for 48 weeks) showed a mean increase in fibrosis of 48% when biopsied 36 months from pretreatment baseline but no further increase at 60 months. Finally, the 111 express patients with baseline biopsies following unsuccessful peginterferon-ribavirin outside the trial had significantly more baseline fibrosis than the others but an increase of only 21% after 21 months and a slight decrease at 45 months. Maintenance therapy with low-dose peginterferon had no effect on fibrosis changes in any of the groups. Conclusion: Morphometry demonstrated complex, nonlinear changes in fibrosis over time in this heterogeneous cohort of patients with interferon-refractory chronic hepatitis C. (H EPATOLOGY 2009.)Publisher
Wiley Subscription Services, Inc., A Wiley Company
ISSN
0270-9139 1527-3350
Other DOIs
PMID
19824074
Types
Article
URI
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=19824074&dopt=citationMetadata
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