Fibrosis progression in chronic hepatitis C: morphometric image analysis in the HALT-C trial.
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.


CONCLUSIONS
Morphometry demonstrated complex, nonlinear changes in fibrosis over time in this heterogeneous cohort of patients with interferon-refractory chronic hepatitis C.
Goodman
Zachary D
ZD
Armed Forces Institute of Pathology, Division of Hepatic Pathology and Veterans Administration Special Reference Laboratory for Pathology, Washington, DC, USA. zgoodman@aiplabloratories.com
Stoddard
Anne M
AM
Bonkovsky
Herbert L
HL
Fontana
Robert J
RJ
Ghany
Marc G
MG
Morgan
Timothy R
TR
Wright
Elizabeth C
EC
Brunt
Elizabeth M
EM
Kleiner
David E
DE
Shiffman
Mitchell L
ML
Everson
Gregory T
GT
Lindsay
Karen L
KL
Dienstag
Jules L
JL
Morishima
Chihiro
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003094:Collagen / Q000032:analysis; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged
D003094:Collagen