Liver
Fibrosis Progression Is Highly Variable in Non-responder
Hepatitis C Patients, with or without Pegylated Interferon
Maintenance
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| SUMMARY:
Liver fibrosis progression is non-linear,
or inconsistent over time, and varies widely
among individuals who did not achieve sustained
response to pegylated interferon plus ribavirin,
according to data from the HALT-C study
published in the December
2009 issue of Hepatology. Use
of pegylated interferon maintenance monotherapy
did not have a significant effect on disease
progression. |
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By
Liz Highleyman
Approximately
half of chronic hepatitis
C patients treated with interferon-based
therapy do not achieve sustained
virological response (SVR) after completing treatment,
leaving them at risk for progressive liver disease.
The
large HALT-C (Hepatitis C Antiviral Long-term Treatment
against Cirrhosis) trial aimed to determine whether
extended maintenance with pegylated
interferon alfa-2a (Pegasys) monotherapy could
prevent liver disease progression in non-responders
with severe fibrosis
or cirrhosis.
As
previously reported, although HCV viral load and
ALT levels declined in the maintenance therapy group,
treated patients were no less likely to progress to
decompensated cirrhosis, hepatocellular carcinoma
(HCC), or death over a follow-up period of 3.5 years.
In
the present analysis, HALT-C investigators used computer-assisted
morphometric analysis to quantify fibrosis progression
in liver biopsy specimens obtained over 1.5 to 5 years
from 3 groups of patients with bridging fibrosis or
cirrhosis (Ishak stages 3-6) at baseline:
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346
non-responders who had continued detectable HCV
RNA after a lead-in period of 24 weeks of pegylated
interferon plus ribavirin; |
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78
patients who had undetectable HCV RNA at week
24 of therapy and went on to receive 48 weeks
of treatment, but experienced viral breakthrough
while still on therapy or post-treatment relapse; |
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111
"express" patients who entered the monotherapy
maintenance phase directly after being treated
unsuccessful with pegylated interferon plus ribavirin
outside the HALT-C trial. |
Results
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The
346 non-responders after the lead-in period had
a mean 61% increase in fibrosis from the pretreatment
baseline level after 2 years, and an 80% increase
after 4 years. |
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In
contrast, the 78 breakthrough and relapse patients
had a mean 48% increase in fibrosis according
to a biopsy 36 months after starting treatment,
but no further increase at 60 months. |
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The
111 "express" patients who underwent
baseline biopsies had significantly more fibrosis
than the others at baseline, but experienced an
increase of just 21% after 21 months, and had
a slight decrease at 45 months. |
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Maintenance
therapy with low-dose pegylated interferon had
no effect on fibrosis progression in any of the
groups. |
Based
on these results, the study authors concluded, "Morphometry
demonstrated complex, nonlinear changes in fibrosis
over time in this heterogeneous cohort of patients
with interferon-refractory chronic hepatitis C."
These
findings suggest that it will be difficult, without
repeated biopsies, for clinicians to predict which
patients are likely to experience liver disease progression
and are therefore at the greatest risk for severe
complications such as decompensation or liver cancer.
Armed
Forces Institute of Pathology, Division of Hepatic
Pathology and Veterans Administration Special Reference
Laboratory for Pathology, Washington, DC; New England
Research Institutes, Watertown, MA; University of
Connecticut Health Center, Farmington, CT; University
of Michigan Medical Center, Ann Arbor, MI; Liver Diseases
Branch, National Institute of Diabetes and Digestive
and Kidney Diseases, Bethesda, MD; University of California
Irvine, Irvine, CA; VA Long Beach Healthcare System,
Long Beach, CA; Washington University, St. Louis,
MO; National Cancer Institute, Bethesda, MD; Virginia
Commonwealth University Medical Center, Richmond,
VA; University of Colorado Denver, Anschutz Medical
Campus, Aurora, CO; Keck School of Medicine, University
of Southern California, Los Angeles, CA; Massachusetts
General Hospital, Boston, MA; Harvard Medical School,
Boston, MA; University of Washington, Seattle, WA.
12/15/09
Reference
ZD
Goodman, AM Stoddard, HL Bonkovsky, and others. Fibrosis
progression in chronic hepatitis C: morphometric image
analysis in the HALT-C trial. Hepatology 50(6):
1738-1749 (Abstract).December
2009.
