Histological changes but not virus eradication reflect biochemical improvement in chronic hepatitis C patients showing a long-term response to interferon alpha therapy.
OBJECTIVE
To assess the relationship between changes in liver histology and virological parameters of HCV infection in patients with a sustained biochemical response to alpha-interferon treatment for chronic hepatitis, with the aim of identifying the most reliable indicator of treatment efficacy.


METHODS
Quantitative serial testing of HCV-RNA in plasma samples collected on a monthly basis over the last period of post-treatment follow-up were tested in sixteen subjects with > or = 12 months aminotransferase normalisation following discontinuation of interferon therapy. The quantitative HCV-RNA determination in plasma was performed by a competitive reverse-transcription polymerase-chain reaction. Pretreatment and 12-month post-treatment liver histologies were blindly evaluated using a semi-quantitative scoring system. At these times a qualitative HCV-RNA analysis was also carried out.


RESULTS
The post-treatment histological grading score was significantly reduced. Nevertheless, all patients except one tested positive for HCV-RNA in plasma (mean 1.7 x 10(6) molecules/ml): nine were positive in all the serial determinations, while the remaining 6 were intermittently positive. No relationship between genotype, viral load, pattern of viremia (intermittent or continuous) and change in histological score was found.


CONCLUSIONS
Changes in liver histology are the most reliable indicator of the efficacy of interferon treatment in hepatitis C related liver disease. HCV-RNA clearance based on serial sampling does not appear to be a reliable indicator, even in the presence of a sustained biochemical response and histological improvement.
Bruno
S
S
Department of Medicine, University of Milan, Italy.
Manzin
A
A
Roncalli
M
M
Petroni
M L
ML
Rossi
S
S
Pedicino
M
M
Larghi
A
A
Crosignani
A
A
Podda
M
M
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000473:pathology / Q000628:therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors
D016898:Interferon-alpha; D012367:RNA, Viral