Performance of two HCV RNA assays during protease inhibitor-based triple therapy in patients with advanced liver fibrosis and cirrhosis.
BACKGROUND
On-treatment HCV RNA measurements are crucial for the prediction of a sustained virological response (SVR) and to determine treatment futility during protease inhibitor-based triple therapies. In patients with advanced liver disease an accurate risk/benefit calculation based on reliable HCV RNA results can reduce the number of adverse events. However, the different available HCV RNA assays vary in their diagnostic performance.


OBJECTIVE
To investigate the clinical relevance of concordant and discordant results of two HCV RNA assays during triple therapy with boceprevir and telaprevir in patients with advanced liver fibrosis/cirrhosis.


METHODS
We collected on-treatment samples of 191 patients with advanced liver fibrosis/cirrhosis treated at four European centers for testing with the Abbott RealTime (ART) and COBAS AmpliPrep/COBAS TaqMan HCV v2.0 (CTM) assays.


RESULTS
Discordant test results for HCV RNA detectability were observed in 23% at week 4, 17% at week 8/12 and 9% at week 24 on-treatment. The ART detected HCV RNA in 41% of week 4 samples tested negative by the CTM. However, the positive predictive value of an undetectable week 4 result for SVR was similar for both assays (80% and 82%). Discordance was also found for application of stopping rules. In 27% of patients who met stopping rules by CTM the ART measured levels below the respective cut-offs of 100 and 1000 IU/ml, respectively, which would have resulted in treatment continuation. In contrast, in nine patients with negative HCV RNA by CTM at week 24 treatment would have been discontinued due to detectable residual HCV RNA by the ART assay. Importantly, only 4 of these patients failed to achieve SVR.


CONCLUSIONS
Application of stopping rules determined in approval studies by one assay to other HCV RNA assays in clinical practice may lead to over and undertreatment in a significant number of patients undergoing protease inhibitor-based triple therapy.
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover, Germany.
Benjamin
B
Maasoumy
Somogy County Kaposi Mor Teaching Hospital, Kaposvar, Hungary; University of Pecs, Pecs, Hungary.
Bela
B
Hunyady
Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
Vincenza
V
Calvaruso
Outpatient Clinic, Saint Laszlo Hospital, Budapest, Hungary.
Mihály
M
Makara
Department of Medicine 1, JW Goethe-University Hospital, Frankfurt am Main, Germany.
Johannes
J
Vermehren
Somogy County Kaposi Mor Teaching Hospital, Kaposvar, Hungary.
Attila
A
Haragh
Department of Medicine 1, JW Goethe-University Hospital, Frankfurt am Main, Germany.
Simone
S
Susser
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover, Germany.
Birgit
B
Bremer
Abbott Molecular, Des Plaines, Illinois, United States of America.
Gavin
G
Cloherty
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover, Germany.
Michael P
MP
Manns
Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
Antonio
A
Craxì
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover, Germany.
Heiner
H
Wedemeyer
Department of Medicine 1, JW Goethe-University Hospital, Frankfurt am Main, Germany.
Christoph
C
Sarrazin
D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D019411:Clinical Laboratory Techniques; D005060:Europe; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000821:virology; D009842:Oligopeptides / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis*; D015203:Reproducibility of Results; D016896:Treatment Outcome; D014766:Viremia
D044966:Anti-Retroviral Agents; D009842:Oligopeptides; D011480:Protease Inhibitors; D012367:RNA, Viral; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline