Hepatocellular proliferation in patients with chronic hepatitis C and persistently
normal or abnormal aminotransferase levels.
J Hepatol 2000 Oct;33(4):640-7 Kronenberger
B, Ruster B, Lee JH, Sarrazin C, Roth WK, Herrmann G, Zeuzem S Medizinische
Klinik II, Klinikum der Johann Wolfgang Goethe-Universitat, Frankfurt
a M., Germany.
Background/Aims:
Some patients chronically infected with the hepatitis C virus (HCV)
have persistently normal alanine aminotransferase (ALT) levels while
progressive liver damage is observed histologically. In the present
study, we compared the rate of proliferation, apoptosis, and necrosis
in liver biopsy specimens of patients with persistently normal or
elevated ALT levels.
Methods:
Fourteen patients with persistently normal and 14 age- and sex-matched
patients with elevated ALT levels were enrolled. Proliferation was
detected using anti-Ki 67 in 10-microm liver biopsy specimens of the
patients. Apoptosis was measured by TUNEL-assay and by monoclonal
anti-M30 directed against caspase-cleaved cytokeratin 18 filaments.
Results:
The mean number of anti-Ki 67 positive hepatocytes was lower in patients
with persistently normal aminotransferases (3.1 +/- 2.8/10(3) vs 10.8
+/- 8.8/10(3) hepatocytes, p<0.0011) and was correlated with serum
ALT (r=0.86, p<0.01) and aspartate aminotransferase levels (r=0.83,
p<0.01). The rate of apoptosis detected by TUNEL assay was low and
not different between patients with persistently normal and elevated
aminotransferases. Staining with anti-M30 revealed a granular staining
pattern and showed a trend towards higher cell death rates in patients
with elevated aminotransferase levels (apoptotic hepatocytes with
>75% staining: 3.97 +/- 6.24/10(3) hepatocytes vs 13.65 +/- 19.41/10(3)
hepatocytes; p=0.08).
Conclusions:
Patients with chronic hepatitis C and normal aminotransferases have
significantly lower hepatocyte proliferation rates and show a trend
towards lower apoptosis rates compared with patients with elevated
amonitransferases. PMID: 11059870, UI: 20511677