BACKGROUND: Viral genomic mutations have become increasingly recognized as being associated with the outcome of chronic HBV infection. However, the role of viral mutations as a predictor of response to pegylated-interferon (PEG-IFN) therapy has so far remained unclear. STUDY DESIGN: Viral mutations in the enhancer II/basal core promoter (BCP)/precore and the pre-S regions were characterized by direct sequencing in pretreatment serum samples of 50 patients with chronic hepatitis B (33 HBeAg-positive and 17 HBeAg-negative), who were treated for 48 weeks with PEG-IFN alpha-2b. RESULTS: Sustained virological response at 48 weeks post treatment, defined as HBeAg seroconversion and HBV DNA<2000IU/mL for HBeAg-positive patients, and HBV DNA<200IU/mL for HBeAg-negative patients, was achieved in 12 (36.4%) and 6 (35.3%) of HBeAg-positive and HBeAg-negative patients, respectively. Response to PEG-IFN therapy correlated to low pretreatment HBsAg level but did not correlate with HBV genotype, pretreatment alanine transaminase and HBV DNA levels. In HBeAg-positive hepatitis, PEG-IFN response correlated with the appearance of double BCP mutations (A1762T/G1764A) at baseline (P=0.041). In the HBeAg-negative group, response to PEG-IFN therapy was associated with the presence of pre-S mutation/deletions (P=0.028). Multivariate analysis identified low pretreatment HBsAg level as an independent factor associated with SVR in both groups. CONCLUSIONS: Pretreatment quantitative HBsAg determination is useful for predicting response to PEG-IFN therapy. The presence of double BCP and pre-S mutation/deletions at entry may be associated with a high rate of antiviral response in HBeAg-positive and HBeAg-negative hepatitis, respectively.
BACKGROUND: Viral genomic mutations have become increasingly recognized as being associated with the outcome of chronic HBV infection. However, the role of viral mutations as a predictor of response to pegylated-interferon (PEG-IFN) therapy has so far remained unclear. STUDY DESIGN: Viral mutations in the enhancer II/basal core promoter (BCP)/precore and the pre-S regions were characterized by direct sequencing in pretreatment serum samples of 50 patients with chronic hepatitis B (33 HBeAg-positive and 17 HBeAg-negative), who were treated for 48 weeks with PEG-IFN alpha-2b. RESULTS: Sustained virological response at 48 weeks post treatment, defined as HBeAg seroconversion and HBV DNA<2000IU/mL for HBeAg-positive patients, and HBV DNA<200IU/mL for HBeAg-negative patients, was achieved in 12 (36.4%) and 6 (35.3%) of HBeAg-positive and HBeAg-negative patients, respectively. Response to PEG-IFN therapy correlated to low pretreatment HBsAg level but did not correlate with HBV genotype, pretreatment alanine transaminase and HBV DNA levels. In HBeAg-positive hepatitis, PEG-IFN response correlated with the appearance of double BCP mutations (A1762T/G1764A) at baseline (P=0.041). In the HBeAg-negative group, response to PEG-IFN therapy was associated with the presence of pre-S mutation/deletions (P=0.028). Multivariate analysis identified low pretreatment HBsAg level as an independent factor associated with SVR in both groups. CONCLUSIONS: Pretreatment quantitative HBsAg determination is useful for predicting response to PEG-IFN therapy. The presence of double BCP and pre-S mutation/deletions at entry may be associated with a high rate of antiviral response in HBeAg-positive and HBeAg-negative hepatitis, respectively.
Authors: S K Sarin; M Kumar; G K Lau; Z Abbas; H L Y Chan; C J Chen; D S Chen; H L Chen; P J Chen; R N Chien; A K Dokmeci; Ed Gane; J L Hou; W Jafri; J Jia; J H Kim; C L Lai; H C Lee; S G Lim; C J Liu; S Locarnini; M Al Mahtab; R Mohamed; M Omata; J Park; T Piratvisuth; B C Sharma; J Sollano; F S Wang; L Wei; M F Yuen; S S Zheng; J H Kao Journal: Hepatol Int Date: 2015-11-13 Impact factor: 6.047
Authors: Hamad I Al-Ashgar; Mohammed Q Khan; Abdulrahman Aljumah; Faisal M Sanai; Ayman A Abdo; Mutasim M Dafalla; Mosa A Fagih; Khalid I Bzeizi Journal: Hepatol Int Date: 2011-11-25 Impact factor: 6.047