The treatment efficacy of pegylated interferon plus ribavirin therapy in chronic hepatitis C patients with mixed genotype 1/2 infection

• Main Authors: Ching-I Huang, 黃駿逸
• Other Authors: Wan-Long Chuang
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/28513837707540501311

碩士 === 高雄醫學大學 === 臨床醫學研究所 === 102 === Background Pegylated interferon (peginterferon) and ribavirin combination therapy remains the standard-of-care for patients with chronic hepatitis C virus (HCV) infection in the vast majority of countries. HCV genotype has been suggested to be the most powerful pretreatment virological predictor of sustained virological response (SVR). The treatment efficacy of patients with mixed HCV genotype 1/genotype 2 (HCV 1+2) remains unknown and the impact of host interleukin 28B (IL-28B) genetic variants on the treatment outcome is to be elucidated. Aims To elucidate the clinical presentation and treatment efficacy of HCV1/2 patients by using response-guided therapy in well characterized Asian cohort and to explore the potential role of host IL-28B genetic variants in the treatment of HCV 1/2 infection. Methods HCV 1+2 patients treated with response-guided peginterferon/ribavirin therapy (RGT), defined as 24 weeks for patients with a rapid virological response (RVR; seronegative of HCV RNA at week 4 of treatment) and low baseline viral loads (&;lt;400,000 IU/mL), and 48 weeks for patients without a RVR or with a RVR but high baseline viral loads (>400,000 IU/mL) were allocated for evaluation from 2003 to 2007. Rs8099917 genotype was tested for the association with an SVR among patients. Results Sixty-six (60.0%) of the 110 patients were treated with an abbreviated 24-week regimen, whereas 44 (40.0%) patients were treated with a standard 48-week regimen. The mean baseline HCV RNA levels were 5.1 log IU/ml. Rs8099917 TT genotype accounted for 78.9% (60/76) of the population. The rates of RVR, early virological response (EVR, defined as more than 2 log IU/mL reduction of HCV RNA at week 12 of treatment ), end of treatment virological response (EOTVR, defined as seronegative of HCV RNA at the end of treatment) , SVR and relapse rate of the patients with RGT were 71.8% 79/110), 98.2%(108/110), 98.2% (108/110), 87.3%(96/110) and 11.1%(12/108), respectively. In univariate analysis, lower baseline HCV RNA levels and lower body weight were factors significantly associated with a RVR.. Stepwise logistic regression analysis revealed that lower baseline viral loads was the single factor predictive of a RVR with an odds ratio/95% confidence intervals (OR/CI) of 41.619/9.721–178.189, P&;lt;0.001. Patients with low body weight, low pretreatment HCV RNA levels, the achievement of an RVR, and with an abbreviated regimen were factors predictive of an SVR in univariate analysis. Logistic regression revealed that the achievement of RVR was the single best factor predictive of an SVR ([OR/CI]: 7.5 / 1.33 – 42.27, P＝0.022). Nevertheless, an abbreviated regimen became the single factor associated with an SVR ([OR/CI]: 11.0 /1.25–96.79, P=0.031) if treatment regimen was taken into consideration. The SVR rate was significantly higher (95.5% vs. 75.0 %, P=0.002) and the relapse rate was significantly lower (4.5 % vs. 21.4 %, P=0.01)in patients with an abbreviated regimen. There were no significantly different regarding both basic characteristics and treatment responses between patients with or without available IL-28B genotype data. Conclusion The outcome of patients with HCV 1/2 infection treated by response-guided therapy was satisfactory. The clinical utility of host IL-28B genetic variants in the management of the special population might be limited.