Hepatocellular proliferation in patients with chronic hepatitis C and persistently normal or abnormal aminotransferase levels.
OBJECTIVE
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 aminotransferases.
Kronenberger
B
B
Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt a M., Germany.
Rüster
B
B
Lee
J H
JH
Sarrazin
C
C
Roth
W K
WK
Herrmann
G
G
Zeuzem
S
S
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D002455:Cell Division; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000201:enzymology / Q000473:pathology*; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis; D008099:Liver / Q000473:pathology*; D008297:Male; D009336:Necrosis; D012016:Reference Values; D012307:Risk Factors; D005723:gamma-Glutamyltransferase / Q000097:blood
D019394:Ki-67 Antigen; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase