Yu M.-L.CHEN-HUA LIUHuang C.-F.TAI-CHUNG TSENGHuang J.-F.Dai C.-Y.Lin Z.-Y.Chen S.-C.Wang L.-Y.Juo S.-H.H.Chuang W.-L.JIA-HORNG KAO2021-09-042021-09-0420121932-6203https://www.scopus.com/inward/record.uri?eid=2-s2.0-84871355062&doi=10.1371%2fjournal.pone.0052048&partnerID=40&md5=3764c569ce8b011c911c3ce0fd97a66bhttps://scholars.lib.ntu.edu.tw/handle/123456789/582024Background: The current stopping rule for peginterferon/ribavirin therapy in hepatitis C virus genotype-1 (HCV-1) patients is based on an early virological response (EVR, defined as >2 log10 viral reduction at treatment week 12). We aimed to explore rapid stopping rules at week 4. Methods: We randomly allocated 528 HCV-1 patients into training and validation sets (at a 1:2 ratio). The interleukin-28B rs8099917 genotypes and on-treatment virological responses were evaluated to determine the negative predictive value (NPV) for achieving a sustained virological response (SVR, defined as undetectable HCV RNA 24 weeks after end-of-treatment). The study was approved by the ethics committees of the participating hospitals. All of the patients gave written informed consent before enrollment. Results: A poor week 4 response (W4R), defined as a HCV RNA reduction of <1 log10 IU/mL at week 4 or a week 4 HCV RNA>10,000 IU/mL with interleukin-28B non-TT genotype, had the highest NPV (95%). In the complete sample, poor W4R could identify 43.4% (59/136) of the non-responders, with an NPV of 95% and a false negative rate of only 0.8% (3/396). The multivariate analysis revealed that a poor W4R was the most important negative predictor (odds ratio/95% confidence intervals: 49.01/13.70-175.37), followed by the lack of an EVR. In addition to HCV RNA<1 log10 IU/mL reduction, using the criteria of HCV RNA>10,000 IU/mL/non-TT genotype helped identifying an additional one-third of non-SVR patients at W4.Using the strategy of sequential rapid stopping rule strategy could identify 53.7% (73/136) of the non-responders (43.4% at week 4 and an addition 11.3% at week 12), as compared to 40.4% for the classical week-12 early stopping rule. Conclusions: Sequential rapid stopping rules using on-treatment virological responses and interleukin-28B genotype can rapidly identify additional peginterferon/ribavirin non-responders. ? 2012 Yu et al.[SDGs]SDG3interleukin 28B; peginterferon alpha2a; peginterferon alpha2b; ribavirin; virus RNA; adult; age distribution; article; body weight; controlled study; drug response; drug treatment failure; drug withdrawal; early virological response; end of treatment virological response; false negative result; female; gender; genotype; hepatitis C; homozygote; human; major clinical study; male; poor week 4 response; predictive value; rapid virological response; stopping rule; sustained virological response; treatment duration; validation process; virus load; Adult; Female; Genotype; Hepacivirus; Hepatitis C; Humans; Interferon-alpha; Interleukins; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Ribavirin; Time Factors; Treatment Outcome; Viral Load; Hepatitis C virus; Hepatitis C virus genotype 1; Nucleopolyhedrovirusjournal article10.1371/journal.pone.0052048232848662-s2.0-84871355062