Dynamics of apoptotic activity during antiviral treatment of patients with chronic hepatitis C.
BACKGROUND
Cell death during antiviral therapy of patients with chronic hepatitis C is not well understood.


METHODS
In the present study, apoptotic activity was monitored by quantification of apoptotic cytokeratin-18 neoepitopes in serum from patients with chronic hepatitis C before and 4, 12, 24 and 48 weeks after initiation of antiviral therapy with pegylated interferon-alpha2a and ribavirin and was compared with viral kinetic parameters.


RESULTS
After 4 weeks of treatment apoptotic activity decreased significantly compared with baseline. Later during treatment, however, apoptotic activity increased again to levels similar to baseline. Alanine aminotransferase (ALT) activity also showed a significant decrease at week 4 compared with baseline but, in contrast to apoptotic activity, ALT remained at a reduced level during the treatment period. Baseline apoptotic activity was inversely correlated with the infected cell loss while an increase of apoptotic activity within the first 4 treatment weeks compared with baseline was positively correlated with the infected cell loss.


CONCLUSIONS
Apoptosis appears to be an important form of cell death during interferon-alpha-based treatment and is associated with infected cell loss and underestimated by ALT activity.
Kronenberger
Bernd
B
Medizinische Klinik I, Klinikum der Johann Wolfgang Goethe-UniversitRt, Frankfurt/Main, Germany.
Zeuzem
Stefan
S
Sarrazin
Christoph
C
Mihm
Ulrike
U
von Wagner
Michael
M
Hofmann
W Peter
WP
Piiper
Albrecht
A
Herrmann
Eva
E
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D053538:Keratin-18 / Q000097:blood; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C488421:KRT18 protein, human; D053538:Keratin-18; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a