UNLABELLED: A substantial proportion of hepatitis C virus (HCV)-1b-infected patients still do not respond to interferon-based therapy. This study aims to explore a predictive marker for the ultimate virological response of HCV-1b-infected patients treated with pegylated interferon/ribavirin (PEG-IFN/RBV) combination therapy. Nonstructural protein 5A (NS5A) sequences of HCV in the pretreated sera of 45 patients infected with HCV-1b were analyzed. The mean number of mutations in the variable region 3 (V3) plus its upstream flanking region of NS5A (amino acid 2334-2379), referred to as IFN/RBV resistance-determining region (IRRDR), was significantly higher for HCV isolates obtained from patients who later achieved sustained virological response (SVR) by PEG-IFN/RBV than for those in patients undergoing non-SVR. The receiver operating characteristic curve analysis estimated six mutations in IRRDR as the optimal threshold for SVR prediction. Indeed, 16 (76%) of 21 SVR, but only 2 (8%) of 24 non-SVR, had HCV with six or more mutations in IRRDR (IRRDR > or = 6) (P < 0.0001). All of 18 patients infected with HCV of IRRDR of 6 or greater examined showed a significant (> or =1 log) reduction or disappearance of serum HCV core antigen titers within 24 hours after initial dose of PEG-IFN/RBV, whereas 10 (37%) of 27 patients with HCV of IRRDR of 5 or less did (P < 0.0001). The positive predictive value of IRRDR of 6 or greater for SVR was 89% (16/18; P = 0.0007), with its negative predictive value for non-SVR being 81% (22/27; P = 0.0008). CONCLUSION: A high degree (> or =6) of sequence variation in IRRDR would be a useful marker for predicting SVR, whereas a less diverse (< or =5) IRRDR sequence predicts non-SVR.
UNLABELLED: A substantial proportion of hepatitis C virus (HCV)-1b-infected patients still do not respond to interferon-based therapy. This study aims to explore a predictive marker for the ultimate virological response of HCV-1b-infected patients treated with pegylated interferon/ribavirin (PEG-IFN/RBV) combination therapy. Nonstructural protein 5A (NS5A) sequences of HCV in the pretreated sera of 45 patients infected with HCV-1b were analyzed. The mean number of mutations in the variable region 3 (V3) plus its upstream flanking region of NS5A (amino acid 2334-2379), referred to as IFN/RBV resistance-determining region (IRRDR), was significantly higher for HCV isolates obtained from patients who later achieved sustained virological response (SVR) by PEG-IFN/RBV than for those in patients undergoing non-SVR. The receiver operating characteristic curve analysis estimated six mutations in IRRDR as the optimal threshold for SVR prediction. Indeed, 16 (76%) of 21 SVR, but only 2 (8%) of 24 non-SVR, had HCV with six or more mutations in IRRDR (IRRDR > or = 6) (P < 0.0001). All of 18 patients infected with HCV of IRRDR of 6 or greater examined showed a significant (> or =1 log) reduction or disappearance of serum HCV core antigen titers within 24 hours after initial dose of PEG-IFN/RBV, whereas 10 (37%) of 27 patients with HCV of IRRDR of 5 or less did (P < 0.0001). The positive predictive value of IRRDR of 6 or greater for SVR was 89% (16/18; P = 0.0007), with its negative predictive value for non-SVR being 81% (22/27; P = 0.0008). CONCLUSION: A high degree (> or =6) of sequence variation in IRRDR would be a useful marker for predicting SVR, whereas a less diverse (< or =5) IRRDR sequence predicts non-SVR.
Authors: Hangfei Qi; Virginia Chu; Nicholas C Wu; Zugen Chen; Shawna Truong; Gurpreet Brar; Sheng-Yao Su; Yushen Du; Vaithilingaraja Arumugaswami; C Anders Olson; Shu-Hua Chen; Chung-Yen Lin; Ting-Ting Wu; Ren Sun Journal: Proc Natl Acad Sci U S A Date: 2017-02-03 Impact factor: 11.205
Authors: Mostafa K El Awady; Noha G Bader El Din; Ashraf Tabll; Yaser El Hosary; Ashraf O Abdel Aziz; Hesham El Khayat; Mohsen Salama; Tawfeek H Abdelhafez Journal: World J Gastroenterol Date: 2013-01-14 Impact factor: 5.742