Effect of antiviral therapy on circulating cytokeratin-18 fragments in patients with chronic hepatitis C.
Hepatocellular apoptosis plays a major role in the pathogenesis of chronic hepatitis C. It can be measured noninvasively by determining the circulating levels of cytokeratin-18 fragments. We hypothesized that the effect of antiviral therapy on this parameter will be different in patients with a sustained virological response, relapse (REL) and nonresponse (NR). We quantified cytokeratin-18 fragments in plasma of patients participating in the Swiss Hepatitis C cohort, who received antiviral therapy without stopping because of sides effects. A total of 315 patients were included, 183 with a sustained response, 64 with NR and 68 who relapsed. Mean levels ±SD of circulating cytokeratin-18 fragments before therapy were 174 ± 172 U/L for responsders, 188 ± 145 for nonresponders and 269 ± 158 U/L for patients who relapsed. The values were significantly higher in the REL group (ANOVA P < 0.006). A sustained response was associated with a significant improvement of the plasma levels (94 ± 92 U/L, paired test P < 0.000001), whereas there was no improvement in the nonresponder group (183 ± 158 U/L) and in the relapser group (158 ± 148 U/L). There was a weak correlation between alanine aminotransferase (ALT) and cytokeratin-18 fragment levels (r² = 0.35, P < 0.000001) before therapy but not after therapy and none with hepatitis C virus (HCV) viremia. Successful antiviral therapy results in a significant decrease in circulating levels of cytokeratin-18 fragments arguing for a reduction in hepatocellular apoptosis after clearance of the HCV. Baseline cytokeratin-18 fragment levels are higher in relapsers. Correlations with ALT are weak, suggesting that these two tests measure different but related processes.
Sgier
C
C
Institute of Clinical Pharmacology and Visceral Research, University of Bern, Bern, Switzerland.
Müllhaupt
B
B
Gerlach
T
T
Moradpour
D
D
Negro
F
F
Malé
P J
PJ
Heim
M H
MH
Malinverni
R
R
Cerny
A
A
Dufour
J-F
JF
D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D017209:Apoptosis; D015331:Cohort Studies; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D013557:Switzerland; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects*; D014766:Viremia / Q000188:drug therapy / Q000821:virology
D000998:Antiviral Agents; D053538:Keratin-18; D012367:RNA, Viral; D000410:Alanine Transaminase