Inflammatory markers neopterin and alanine aminotransferase in HCV patients treated with HCV NS3.4A protease inhibitor telaprevir (VX-950) and/or peginterferon alfa-2a.
OBJECTIVE
Neopterin is a marker of monocyte/macrophage activity. Alanine aminotransferase (ALAT) is a marker of hepatocyte injury. The aim of this study was to determine changes in neopterin and ALAT levels, as markers of inflammation, in two ancillary studies during two-phase 1b trials of hepatitis C virus (HCV) NS3.4A protease inhibitor telaprevir (VX-950), with or without peginterferon alfa-2a (Peg-IFN).


METHODS
Fifty-four chronic hepatitis C patients (genotype 1) received placebo or telaprevir, with or without Peg-IFN, for 14 days in two multiple-dose studies.


RESULTS
During administration of telaprevir, every patient demonstrated a >2-log decrease in HCV RNA. Mean neopterin and ALAT levels decreased in all four groups receiving telaprevir alone. In contrast, mean neopterin levels increased and ALAT levels decreased in the Peg-IFN plus telaprevir and Peg-IFN plus placebo groups.


CONCLUSIONS
These data suggest that treatment of chronic hepatitis C patients with an HCV NS3.4A protease inhibitor ameliorates inflammation. The increase in neopterin levels and the decrease in ALAT levels during administration of Peg-IFN with or without telaprevir are in accordance with earlier observations showing that IFN reduces hepatocyte injury but increases monocyte/macrophage activity. The IFN-mediated immunomodulatory effects appear to remain intact when IFN is combined with telaprevir.
Gelderblom
Huub C
HC
Department of Gastroenterology and Hepatology, AMC Liver Center, Homburg/Saar, Germany.
Zeuzem
Stefan
S
Weegink
Christine J
CJ
Forestier
Nicole
N
Mcnair
Lindsay
L
Purdy
Susan
S
Dijkgraaf
Marcel G W
MG
Jansen
Peter L M
PL
Reesink
Henk W
HW
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000187:drug effects / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008111:Liver Function Tests; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D009842:Oligopeptides / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000410:Alanine Transaminase; D018836:Inflammation Mediators; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D019798:Neopterin; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C486464:telaprevir; C100416:peginterferon alfa-2a