Histologic outcomes in hepatitis C-infected patients with varying degrees of virologic response to interferon-based treatments.

Paul J. Pockros, Fayez M. Hamzeh, Paul Martin, Ellen Lentz, Xiaolei Zhou, Sugantha Govindarajan, Anna S. Lok

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Patients with chronic hepatitis C with partial virologic response or nonresponse to interferon-based therapies can experience treatment-related improvements in liver histology. This retrospective analysis assessed the histologic response to treatment in patients with varying degrees of virologic response (sustained virologic response [SVR], breakthrough, relapse, or nonresponse), time to hepatitis C virus (HCV) RNA undetectability, and duration of viral suppression. Patients (HCV genotypes 1-6) with baseline and follow-up liver biopsies from eight phase 2 to phase 4 interferon-based trials were analyzed. Blinded biopsies were evaluated by a single pathologist. Improvements or worsening of METAVIR necroinflammatory activity and fibrosis were defined as increase or decrease of ≥1 grading category from baseline to 24 weeks after end of treatment. A majority of the 1571 patients with paired biopsy data were white, male, with HCV genotype 1/4, baseline HCV RNA levels >800,000 IU/mL, and baseline alanine aminotransferase levels ≤3 × upper limit of the normal range; mean baseline activity and fibrosis scores were 1.8 and 1.7, respectively. Overall, 80% of patients received peginterferon alfa-2a monotherapy or peginterferon alfa-2a/ribavirin combination therapy. Mean treatment duration was 46 weeks. There was a positive correlation between the degree of virologic response and improvements in METAVIR activity and fibrosis, and an inverse correlation with worsening activity and fibrosis (all comparisons, P < 0.0001). Patients with SVR had the greatest histologic benefit. As a combined group, relapsers and patients with breakthrough had significantly greater benefits than nonresponders (activity, P = 0.0001; fibrosis, P = 0.003). Consistent with these results, a better histologic response was correlated with a shorter time to undetectable HCV RNA and a longer duration of viral suppression (all comparisons, P < 0.0001). Conclusion: In patients with chronic hepatitis C who were treated with interferon-based therapies, histologic benefits may be observed even in the absence of an SVR.

Original languageEnglish
Pages (from-to)1193-1200
Number of pages8
JournalHepatology (Baltimore, Md.)
Volume52
Issue number4
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

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Hepatitis C
Interferons
Hepacivirus
Fibrosis
Chronic Hepatitis C
RNA
Therapeutics
Biopsy
Genotype
Ribavirin
Liver
Alanine Transaminase
Histology
Reference Values
Recurrence
Sustained Virologic Response

ASJC Scopus subject areas

  • Medicine(all)

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Histologic outcomes in hepatitis C-infected patients with varying degrees of virologic response to interferon-based treatments. / Pockros, Paul J.; Hamzeh, Fayez M.; Martin, Paul; Lentz, Ellen; Zhou, Xiaolei; Govindarajan, Sugantha; Lok, Anna S.

In: Hepatology (Baltimore, Md.), Vol. 52, No. 4, 01.10.2010, p. 1193-1200.

Research output: Contribution to journalArticle

Pockros, Paul J. ; Hamzeh, Fayez M. ; Martin, Paul ; Lentz, Ellen ; Zhou, Xiaolei ; Govindarajan, Sugantha ; Lok, Anna S. / Histologic outcomes in hepatitis C-infected patients with varying degrees of virologic response to interferon-based treatments. In: Hepatology (Baltimore, Md.). 2010 ; Vol. 52, No. 4. pp. 1193-1200.
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abstract = "Patients with chronic hepatitis C with partial virologic response or nonresponse to interferon-based therapies can experience treatment-related improvements in liver histology. This retrospective analysis assessed the histologic response to treatment in patients with varying degrees of virologic response (sustained virologic response [SVR], breakthrough, relapse, or nonresponse), time to hepatitis C virus (HCV) RNA undetectability, and duration of viral suppression. Patients (HCV genotypes 1-6) with baseline and follow-up liver biopsies from eight phase 2 to phase 4 interferon-based trials were analyzed. Blinded biopsies were evaluated by a single pathologist. Improvements or worsening of METAVIR necroinflammatory activity and fibrosis were defined as increase or decrease of ≥1 grading category from baseline to 24 weeks after end of treatment. A majority of the 1571 patients with paired biopsy data were white, male, with HCV genotype 1/4, baseline HCV RNA levels >800,000 IU/mL, and baseline alanine aminotransferase levels ≤3 × upper limit of the normal range; mean baseline activity and fibrosis scores were 1.8 and 1.7, respectively. Overall, 80{\%} of patients received peginterferon alfa-2a monotherapy or peginterferon alfa-2a/ribavirin combination therapy. Mean treatment duration was 46 weeks. There was a positive correlation between the degree of virologic response and improvements in METAVIR activity and fibrosis, and an inverse correlation with worsening activity and fibrosis (all comparisons, P < 0.0001). Patients with SVR had the greatest histologic benefit. As a combined group, relapsers and patients with breakthrough had significantly greater benefits than nonresponders (activity, P = 0.0001; fibrosis, P = 0.003). Consistent with these results, a better histologic response was correlated with a shorter time to undetectable HCV RNA and a longer duration of viral suppression (all comparisons, P < 0.0001). Conclusion: In patients with chronic hepatitis C who were treated with interferon-based therapies, histologic benefits may be observed even in the absence of an SVR.",
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