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Long-Term Histologic Improvement and Loss of Detectable Intrahepatic HCV RNA in Patients with Chronic Hepatitis C and Sustained Response to Interferon-α Therapy

Patrick Marcellin, MD; Nathalie Boyer, MD; Anne Gervais, MD; Michele Martinot, BS; Michele Pouteau, MD; Corinne Castelnau, MD; Afef Kilani, MD; Jorge Areias, MD; Anne Auperin, MD; Jean Pierre Benhamou, MD; Claude Degott, MD; and Serge Erlinger, MD
[+] Article and Author Information

From Hopital Beaujon, Clichy, France. Acknowledgments: The authors thank Drs. C. Lemonnier and C. Langlois (Schering-Plough Corp.) for their support. Grant Support: In part by a grant from the Association pour la Recherche contre le Cancer. Requests for Reprints: Patrick Marcellin, MD, Service d'Hepatologie, Hopital Beaujon, 100 Boulevard du General Leclerc, 92118 Clichy, France. Current Author Addresses: Drs. Marcellin, Boyer, Gervais, Pouteau, Castelnau, Kilani, Areias, Auperin, Benhamou, and Erlinger and Ms. Martinot: Service d'Hepatologie and Unite de Recherches de Physiopathologie Hepatique (INSERM U24), Hopital Beaujon, 100 Boulevard du General Leclerc, 92118 Clichy, France.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1997;127(10):875-881. doi:10.7326/0003-4819-127-10-199711150-00003
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Background: Less than 20% of patients with chronic hepatitis C have a sustained response to interferon-α therapy. The long-term benefit of interferon-α with regard to hepatic viral clearance and histologic improvement remains unknown.

Objective: To determine the long-term biochemical, virologic, and histologic outcomes in patients with chronic hepatitis C who have a sustained response to interferon-α therapy.

Design: Prospective cohort study.

Setting: University hospital.

Patients: 80 patients who had chronic hepatitis C, had a sustained biochemical and virologic response to interferon-α therapy, and were followed for at least 12 months.

Measurements: Serum hepatitis C virus (HCV) RNA detected by polymerase chain reaction (PCR); HCV genotyping determined by line probe assay; liver histologic studies; liver HCV RNA detected by PCR on frozen liver tissue samples (in 27 patients); and repeated measurements of serum alanine aminotransferase (ALT) levels. Liver biopsy was done before treatment in all 80 patients, and at least one biopsy was done in 69 patients 1 to 6 years after treatment.

Results: The 80 patients had follow-up 1 to 7.6 years (mean ±SD, 4.0 ± 2.0 years) after interferon-α treatment. The follow-up period was 1, 2, 3, 4, 5, 6, and more than 6 years in 11, 13, 14, 18, 10, 12, and 2 patients, respectively, after the end of therapy. During the entire follow-up period, 93% (95% CI, 84% to 97%) of patients had persistently normal serum ALT levels. Serum HCV RNA remained undetectable in 96% (CI, 89% to 99%) of patients. A comparison of liver histologic findings before and 1 to 6.2 years after interferon-α treatment showed a clear improvement in 94% (CI, 83% to 99%) of patients. In 62% of patients, the last biopsy done showed normal or nearly normal histologic findings. Liver HCV RNA was detectable before treatment in all 13 patients tested and was undetectable 1 to 5 years after treatment in all 27 patients tested.

Conclusions: In patients with chronic hepatitis C who have persistently normal serum ALT levels and no detectable serum HCV RNA 6 months after interferon-α therapy, a long-term sustained biochemical and virologic response is generally seen. This response is associated with an absence of detectable intrahepatic HCV RNA and marked histologic improvement.

Figures

Grahic Jump Location
Figure 1.
Total Knodell score before, at the end of, and after interferon-α (IFN) therapy.

Liver biopsies were done during the first, second, or third year after therapy or later than the third year after therapy.

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Grahic Jump Location
Figure 2.
Knodell score for fibrosis (top left), portal inflammation (bottom left), periportal necrosis (top right), and lobular necrosis (bottom right) before, at the end of, and after interferon-α (IFN) therapy.

Liver biopsies were done during the first, second, or third year after therapy or later than the third year after therapy.

Grahic Jump Location

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