LONG-TERM HISTOLOGIC IMPROVEMENT AND LOSS OF DETECTABLE INTRAHEPATIC HCV RNA IN PATIENTS WITH CHRONIC HEPATITIS-C AND SUSTAINED RESPONSE TOINTERFERON-ALPHA THERAPY
P. Marcellin et al., LONG-TERM HISTOLOGIC IMPROVEMENT AND LOSS OF DETECTABLE INTRAHEPATIC HCV RNA IN PATIENTS WITH CHRONIC HEPATITIS-C AND SUSTAINED RESPONSE TOINTERFERON-ALPHA THERAPY, Annals of internal medicine, 127(10), 1997, pp. 875
Background: Less than 20% of patients with chronic hepatitis C have a
sustained response to interferon-alpha therapy. The long-term benefit
of interferon-alpha with regard to hepatic viral clearance and histolo
gic improvement remains unknown. Objective: To determine the long-term
biochemical, virologic, and histologic outcomes in patients with chro
nic hepatitis C who have a sustained response to interferon-alpha ther
apy. Design: Prospective cohort study. Setting: University hospital. P
atients: 80 patients who had chronic hepatitis C, had a sustained bioc
hemical and virologic response to interferon-alpha therapy, and were f
ollowed 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 RN
A 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 lea
st one biopsy was done in 69 patients 1 to 6 years after treatment. Re
sults: The 80 patients had follow-up 1 to 7.6 years (mean +/- SD, 4.0
+/- 2.0 years) after interferon-alpha 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 en
tire follow-up period, 93% (95% CI, 84% to 97%) of patients had persis
tently normal serum ALT levels. Serum HCV RNA remained undetectable in
96% (CI, 89% to 99%) of patients, A comparison of liver histologic fi
ndings before and 1 to 6.2 years after interferon-alpha treatment show
ed a clear improvement in 94% (CI, 83% to 99%) of patients, In 62% of
patients, the last biopsy done showed normal or nearly normal histolog
ic findings. Liver HCV RNA was detectable before treatment in all 13 p
atients tested and was undetectable 1 to 5 years after treatment in al
l 27 patients tested. Conclusions: In patients with chronic hepatitis
C who have persistently normal serum ALT levels and no detectable seru
m HCV RNA 6 months after interferon-alpha therapy, a long-term sustain
ed biochemical and virologic response is generally seen. This response
is associated with an absence of detectable intrahepatic HCV RNA and
marked histologic improvement.