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亚洲慢性丙型肝炎的治疗:当东方与西方相遇时。

Treatment of chronic hepatitis C in Asia: when East meets West.

作者信息

Yu Ming-Lung, Chuang Wan-Long

机构信息

Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

出版信息

J Gastroenterol Hepatol. 2009 Mar;24(3):336-45. doi: 10.1111/j.1440-1746.2009.05789.x.

DOI:10.1111/j.1440-1746.2009.05789.x
PMID:19335784
Abstract

The issue of best treatment for chronic hepatitis C virus (HCV) infection is in constant flux, not only in Western countries but also in Asia. Currently, pegylated-interferon plus ribavirin is the standard of care. Studies from Asia provide evidence to support the same broad treatment strategies for Asian patients as recommended in Western countries. Nevertheless, there is increasing evidence that Asians have a higher likelihood of achieving a sustained virological response (SVR) than their Caucasians counterparts when treated with the corresponding regimen. With the recommended 'standard dose and duration treatment regimens', SVR is achieved in Asia for around 70% of HCV genotype 1 (HCV-1) infected cases, approximately 90% of HCV-2/3, approximately 65% of HCV-4, and approximately 80% of HCV-6 patients. Difference of body weight in race might contribute the superior response in Asian patients. HCV genotype distribution in Asia also differs from North-America/Europe. HCV-6 and its variants, previously mistyped as HCV-1, needs accurate genotyping. Increasing data support the proposal that HCV genotype, baseline viral load and on-treatment virological response provide information for decision-making so that treatment can be individualized. Beyond the older recommendations, an abbreviated 24-week regimen could be suggested for HCV-1/4 patients with baseline viral loads < 400 000 IU/mL and a rapid virological response (RVR, HCV RNA undetectable at week 4), and an abbreviated 12-16 weeks of pegylated-interferon with weight-based doses of ribavirin could be suggested for HCV-2/3 patients with a RVR. Such tailored treatment regimens can reduce the costs of treatment and incidence of adverse events without compromising efficacy. Hepatitis C virus (HCV) infection is one of the most important causes of cirrhosis worldwide, and particularly in some countries of Asia (notably Japan) where it is now more prevalent than chronic hepatitis B virus infection. Hepatitis C virus infection can also lead to hepatocellular carcinoma (HCC). It is estimated that there are more than 170 million people chronically infected with HCV, and 3 to 4 million persons are newly infected each year. The risk for developing cirrhosis 20 years after initial HCV infection among those chronically infected varies between studies, but is estimated at around 10%-15% for men and 1-5% for women. Once cirrhosis is established, the rate of developing HCC is at 1%-4% per year. Approximately 280 000 deaths per year are related to HCV infection. Hepatitis C virus-related end-stage liver disease and HCC have become the leading cause for liver transplantation worldwide. In the Asia-Pacific area, the estimated prevalence of antibodies to HCV (anti-HCV) range from 0.3% in New Zealand to 5.6% in Thailand. In Japan, Middle East, Vietnam and Taiwan, several HCV hyper-endemic areas have been reported with an anti-HCV prevalence rate of 12% to as high as 58%. In addition to the well-known endemic status of HBV infection in most countries of the Asia-Pacific region, HCV infection presents another critical scenario of public health issue in this region, as outlined in Guidelines by the Asia-Pacific Association for Study of the Liver (APASL). Given the lack of an effective vaccine, optimal treatment of chronic HCV infection is now perceived as a 'must' in terms of public health strategies, as well as of the clinical setting for individual patients.

摘要

慢性丙型肝炎病毒(HCV)感染的最佳治疗方案问题一直在不断变化,不仅在西方国家如此,在亚洲也是如此。目前,聚乙二醇化干扰素联合利巴韦林是标准治疗方案。来自亚洲的研究提供了证据,支持对亚洲患者采用与西方国家推荐的相同的广泛治疗策略。然而,越来越多的证据表明,在接受相应治疗方案时,亚洲人比白种人更有可能实现持续病毒学应答(SVR)。采用推荐的“标准剂量和疗程治疗方案”,亚洲约70%的HCV 1型(HCV-1)感染病例、约90%的HCV-2/3、约65%的HCV-4和约80%的HCV-6患者可实现SVR。种族间体重差异可能是亚洲患者反应更好的原因之一。亚洲的HCV基因型分布也与北美/欧洲不同。HCV-6及其变体以前被误分类为HCV-1,需要进行准确的基因分型。越来越多的数据支持这样的提议,即HCV基因型、基线病毒载量和治疗期间的病毒学应答可为决策提供信息,从而实现个体化治疗。除了以前的建议外,对于基线病毒载量<40万IU/mL且有快速病毒学应答(RVR,第4周时HCV RNA检测不到)的HCV-1/4患者,可建议采用缩短至24周的疗程;对于有RVR的HCV-2/3患者,可建议采用缩短至12 - 16周的聚乙二醇化干扰素联合基于体重剂量的利巴韦林治疗。这种量身定制的治疗方案可以降低治疗成本和不良事件发生率,同时不影响疗效。丙型肝炎病毒(HCV)感染是全球肝硬化的最重要原因之一,在亚洲的一些国家(尤其是日本)尤其如此,在这些国家,HCV感染现在比慢性乙型肝炎病毒感染更为普遍。丙型肝炎病毒感染还可导致肝细胞癌(HCC)。据估计,全球有超过1.7亿人慢性感染HCV,每年有300万至400万人新感染。在初次感染HCV后20年,慢性感染者发生肝硬化的风险在不同研究中有所不同,但估计男性约为10% - 15%,女性约为1% - 5%。一旦形成肝硬化,每年发生HCC的比率为1% - 4%。每年约有28万人死于HCV感染。丙型肝炎病毒相关的终末期肝病和HCC已成为全球肝移植的主要原因。在亚太地区,HCV抗体(抗-HCV)的估计患病率从新西兰的0.3%到泰国的5.6%不等。在日本、中东、越南和台湾,已报告了几个HCV高流行地区,抗-HCV患病率为12%至高达58%。除了亚太地区大多数国家众所周知的HBV感染流行状况外,如亚太肝脏研究协会(APASL)指南所述,HCV感染在该地区呈现出另一个重要的公共卫生问题。鉴于缺乏有效的疫苗,从公共卫生策略以及个体患者的临床情况来看,慢性HCV感染的最佳治疗现在被视为“必须”。

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