IL28B基因多形性對於慢性C型肝炎感染之再次治療結果的預測價值

Predictive Value of IL28B Gene Polymorphisms on Retreatment Outcome of Chronic Hepatitis C

陳明堯(Ming-Yao Chen)

指導教授 ： 劉俊人

共同指導教授 ： 高嘉宏(Jia-Horng Kao)

國立臺灣大學/醫學院/臨床醫學研究所/碩士(2012年)

https://doi.org/10.6342/NTU.2012.01932

摘要

慢性C型肝炎感染(chronic hepatitis C, CHC)是造成失償性肝硬化以及肝細胞癌的主要原因之一。為期48週的長效干擾素合併依體重調整的雷巴威林是亞太地區當今治療第一型慢性C型肝炎的標準治療，然而，約只有60-70%患者可以達成持續病毒學反應(SVR)。在從未治療過的患者中，IL28B附近的單一核苷酸多形性(SNP)與是否會自發性痊癒或者經治療而清除病毒有關。但是對於台灣人之慢性C型肝炎的復發者(relapser)而言，當今標準治療的效果以及IL28B SNP的影響均不明瞭。
在台灣，吾人從2009年收錄了103位慢性C型肝炎的復發者。吾人進行48週的長效干擾素及雷巴威林的合併治療，評估IL28B SNP以及治療過程中的病毒動力學變化以及生化反應。其中僅納入75位(73%)的第一基因型慢性C型肝炎患者進行分析研究。整體而言，治療中的病毒動力學變化針對快速病毒學反應(RVR)、治療結束病毒反應(EOT-VR)與SVR而論，分別為37%、73%與52%。復發率則為29%。若能達成RVR，則有較高的機率可以達成SVR (P<0.0001) 以及較低的復發率(P=0.0034)。與GT IL28B基因型相比，TT的患者有較高的RVR (P=0.0002)、EOT-VR (P=0.0001)以及 SVR (P<0.0001)的機會。若合併第四週病毒轉陰化(week 4 viral negativity，即RVR)與IL28B基因型，則判別SVR的陽性與陰性預測值(PPV, NPV)與第12週時的病毒轉陰化效果相當。
運用當今標準治療來醫治台灣的第一基因型慢性C型肝炎復發者，約有半數可以達成持續病毒學反應。IL28B SNP會影響再次治療中的病毒動力學變化，SVR以及復發率。將來若能依據IL28B SNP以及RVR的變化，或許可進行個人化的治療，甚至可以當成早期停藥的指標。

關鍵字

慢性C型肝炎 ； 長效型干擾素 ； IL28B ； 再治療

並列摘要

Chronic hepatitis C infection (CHC) is a leading cause of decompensated cirrhosis and hepatocellular carcinoma. Forty-eight-weekly pegylated interferon (PEG-IFN)plus weight-based ribavirin (RBV) has been the current standard of care (SOC) for CHC genotype 1 in Asia-Pacific region and can only achieve an overall sustained virologic response (SVR) of 60-70%.The single nucleotide polymorphism (SNP) near the interleukin-28B (IL28B) is associated with spontaneous or treatment-induced viral clearance in untreated patients. It remains unclear for the efficacy of current SOC and influence of IL28B SNP in re-treating Taiwan CHC relapsers.
In Taiwan, since November 2009, we consecutively enrolled 103 CHC relapsers into this study. We evaluated the IL28B SNPs, virologic kinetics, and biochemical responses of CHC patients receiving 48-weekPEG-IFN plus RBV. Only 75 CHC genotype 1 relapsers (73%) were included for analysis. The overall viral kinetics was 37%,73% and 52% in rapid virologic response (RVR), end-of-treatment viral response (EOT-VR) and SVR respectively. Relapse rate was 29%.Patient with TT IL28B had higher rate of RVR (P=0.0002), EOT-VR (P=0.0001) and SVR (P<0.0001) in comparison with GT. Achieving a RVR ensured a higher SVR rate (P<0.0001) and lower relapse rate (P=0.0034). In combination of week 4 viral negativity (i.e. RVR) with IL28B genotype, a high positive and negative predictive value of SVR achieved as equally good as week 12 viral negativity.
About half of the CHC relapsers in Taiwan would achieve SVR under current SOC. IL28B SNP would influence the on-treatment viral kinetics, SVR and relapse rate in retreatment. There might be the individualized therapy according to the IL28B SNP and RVR in the future, especially the early stopping rule.

並列關鍵字

chronic hepatitis C ； pegylated interferon ； IL28B ； retreatment

參考文獻

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