長效型干擾素合併雷巴威靈在基因型第一型及第二型混合感染之慢性C型肝炎患者的治療效果研究

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

黃駿逸(Ching-I Huang)

指導教授 ： 莊萬龍

高雄醫學大學/醫學院/臨床醫學研究所/碩士(2014年)

https://doi.org/10.6832/KMU.2014.00018

摘要

背景
長效型干擾素合併雷巴威靈治療仍然是絕大多數國家慢性C型肝炎病毒（HCV）感染患者的標準治療。C型肝炎病毒基因型是預測持續病毒反應（SVR）最有效的預測因子。HCV基因型第一型及第二型混合感染（HCV 1 +2）患者的治療效果和細胞白介素28B（IL-28B）的遺傳變異及對治療效果的影響仍是未知且待進一步研究。
目標
為了闡明以反應引導治療 (response-guided therapy) HCV1 / 2的亞洲患者的臨床表現和治療效果，並探索細胞白介素28B (IL-28B)遺傳變異的HCV1 / 2病患治療的潛在作用。
方法
在2003年至2007年間C型肝炎病毒1 +2治療患者以反應引導(response-guided therapy, RGT)長效型干擾素合併雷巴威靈治療，定義具有快速病毒學反應（RVR，治療4週時HCV RNA陰性）和低基礎病毒量（<400,000 IU / mL）患者治療24週療程，無RVR的患者或未達RVR但高基礎病毒量（> 400,000 IU / mL）病患治療48週療程。 病患的rs8099917基因型也與SVR的關聯性進行了測試。
結果
110例患者中的63位（60.0％）為24週的簡短療程，44例患者（40.0％）為標準的48週療程。平均基礎病毒量為5.1 log IU /mL。Rs8099917 TT基因型佔人數的78.9％（60/76）。RVR的達成率，早期病毒學反應（EVR，定義為在治療中12週的HCV RNA減少超過2 log IU /mL），結束治療的病毒學反應（EOTVR，定義為在治療結束時HCV RNA為陰性），SVR，復發率分別為71.8％(79/110），98.2％(108/110），98.2％(108/110），87.3％(96/110）和11.1％(12/108）。在單變數分析，較低的基礎HCV RNA和低體重是RVR的顯著相關因素。逐步邏輯迴歸分析顯示，低基礎病毒量是預測RVR的單一因素，odds ratio/95% confidence intervals (OR/CI) 為41.619/9.721-178.189，P <0.001。低體重，低治療前病毒量，RVR的達成，與24週簡短療程為病患SVR在單變數分析中的預測因素。邏輯回歸分析顯示，RVR的達成是預測SVR最好的一個因素（[OR / CI]：7.5 / 1.33 - 42.27，P = 0.022）。然而，一個24週簡短療程成為預測SVR最好的一個因素（[OR / CI]：11.0 / 1.25-96.79，P = 0.031），如果將治療療程加入分析。在一個簡短療程的患者，SVR達成率顯著較高（95.5％比75.0％，P = 0.002），復發率顯著降低（4.5％對21.4％，P = 0.01）。在有或沒有IL-28B基因型數據的患者之間， 兩者的基本特徵和治療反應沒有顯著不同的。
結論
以反應引導治療(response-guided therapy, RGT) HCV 1/2感染的患者，治療結果是令人滿意的。而以宿主IL-28B遺傳變異來預測特定群組的臨床應用可能會受到限制。

關鍵字

C型肝炎病毒混合感染 ； 治療 ； IL-28B

並列摘要

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 (<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<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.

並列關鍵字

HCV ； mixed infection ； treatment ； IL-28B

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