臺灣C型肝炎之治療現況

Treatment of Hepatitis C in Taiwan

肝炎是台灣的國病，B型肝炎與C型肝炎更是國人最大的健康威脅之一，根據國民健康署的統計，直到2012年以前國人十大癌症死因，肝癌都還排名第一。自1984年台灣實施新生兒B型肝炎疫苗接種之國家級B型肝炎防治計畫以來，全國B型肝炎的盛行率已從舊世代的15%大幅降至新世代的1%以下。但相較於B型肝炎，C型肝炎並無疫苗可以預防。據估計，全國C型肝炎盛行率約3.3%，在西南部部分鄉鎮甚至高達15%以上，估計約74萬人曾受C型肝炎病毒感染，其中55萬人發展成慢性C型肝炎。自1989年發現C型肝炎病毒以來，主要依賴以干擾素為基礎的治療，因為台灣C型肝炎病毒基因型主要為基因型1b型及基因型2型，所以自台灣健保開放長效型干擾素（peginterferon）合併雷巴威林（ribavirin）給付，成效在全世界數一數二，高達75%以上。然而因長效型干擾素/雷巴威林適合治療的範圍有一定限制，又有諸多副作用，所以10幾年以來，總感染人數中，也僅約13%病人接受治療，約10%成功治癒。全世界C型肝炎的防治也因此進度緩慢。所幸生技製藥科技迅速發展，自2013年第一個全口服之直接抗病毒藥物（DAA）療程問世以來，已有多種療程可以在12週之內，極少副作用的情形之下，成功治癒95%以上的C型肝炎病患，可謂是人類抗病毒聖戰過程中極大的進展，奠定撲滅C型肝炎終極目標之基礎。現在台灣已有多種無干擾素全口服直接抗病毒藥物療程可以使用，包括ombitasvir/paritaprevir/ritonavir單一劑量合併dasabuvir，daclatasvir合併asunaprevir，sofosbuvir合併雷巴威林，sofosbuvir/ledipasvir單一劑量，elbasvin/grazoprevir單一劑量等。目前台灣健保已開放前兩種療程及最後一種療程給付治療病毒基因型第一型且肝纖維化第3期及第4期患者，未來將有機會逐步開放更多藥物予所有C型肝炎患者使用，相信在2030年前可以達到世界衛生組織（WHO）撲滅病毒性肝炎防治的全球目標。

Hepatitis is a major disease burden in Taiwan. Both of hepatitis B virus (HBV) and hepatitis C virus (HCV) are endemic in Taiwan and are threatening the health of Taiwanese for years, including the end stage of liver diseases and hepatocellular carcinoma (HCC). After the introduction of nationwide mass HBV vaccination for newborn in 1975, the HBV prevalence has declined from 15% to less than 1%. However, HCV remains lack of vaccine for prevention of new HCV infection. The prevalence of antibodies to HCV (anti-HCV) is estimated to be 3.3% with an estimated anti-HCV population and HCV viremic population of 0.74 million and 0.55 million, respectively, in Taiwan. Since the discovery of HCV in 1989, interferon (IFN)-based therapy has been the only approved regimen in the treatment of HCV infection. With the combination of pegylated IFN (PegIFN) and ribavirin (RBV), the Taiwanese HCV patients could achieve high sustained virological response (SVR) rates of more than 75%, 70%-75% for HCV genotype 1b and 85%-90% for HCV genotype 2, the most prevalent HCV genotypes in Taiwan with distribution of 50% and 45%, respectively. Nevertheless, there are substantial contraindication and adverse events for PegIFN plus RBV. In addition, the rate of disease awareness, accessibility and recommendation as well as acceptance of anti-HCV therapy are lower in Taiwan. As a result, it is estimated that only 13% of HCV viremic patients in Taiwan had received anti-HCV therapy and 10% of HCV viremic population achieved an SVR. It is grateful that the first directly acting antivirals (DAA) was approved in 2011. Recently, the progress of DAA in HCV treatment is moving from IFN containing regimens to IFN-free regimens which are currently the standard-of-care for HCV infection. With a short duration of 12 to 24 weeks of easy dosing regimens, the current DAA IFN-free regimens could provide very high SVR rates of 90% to 98%, with high safety profiles, including ombitasvir/paritaprevir/ritonavir coformulation plus dasabuvir, daclatasvir plus asunaprevir, sofosbuvir plus RBV, sofosbuvir/ledipasvir fixed dose combination, and elbasvir/grazoprevir fixed dose combination. The Taiwan Health Insurance Administration approved the reimbursement of ombitasvir/paritaprevir/ritonavir coformulation plus dasabuvir and daclatasvir plus asunaprevir in the treatment of HCV genotype 1 and 1b, respectively in January 2017, and elbasvir/grazoprevir for HCV genotype 1or 4, if the patients have fibrosis score of 3 or 4. With the policy of stepwise broadening the reimbursement criteria and regimens, it is foreseeable that Taiwan will achieve the World Health Organization goal of HCV elimination by 2030.