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【medical-news】正在变化的乙型肝炎治疗
http://www.medscape.com/viewarticle/556300?src=mp
Part 1 The Changing Landscape in Hepatitis B
http://www.medscape.com/viewarticle/556300?src=mp
Part 1
Washington, DC; Wednesday, May 23, 2007 -- The management of chronic hepatitis B is rapidly evolving, and this is reflected in the plethora of treatment options available, including 6 US Food and Drug Administration approved therapies: standard interferon alfa-2b, lamivudine, adefovir, peginterferon alfa-2a, entecavir, and telbivudine. Clinical debate exists regarding every aspect of therapy: who, when, what, and for how long. Published guidelines are generally evidence-based. However, most clinical trails have only enrolled patients thought to be appropriate for therapy -- ie, those with elevated aminotransferases and elevated hepatitis B virus (HBV) DNA or patients who demonstrate significant disease on biopsy. This approach limits our evidence to a very specific population.
2007.05.23华盛顿报道：慢性乙型肝炎的治疗正在取得迅速的发展，表现在存在多种可选择的治疗方法，包括6种美国FDA批准的治疗方法：标准干扰素α -2b、拉米呋啶、阿的福韦、聚二乙醇化干扰素α-2a、恩替卡韦与汰比夫定。临床上在乙肝治疗的每一个方面都存在争论，如患者、治疗时间、选用药品以及治疗疗程。发布的指导原则一般遵循循证原则，然而，大多数试验仅仅招募了一些被认为是适合治疗的患者，如转氨酶升高、乙型肝炎病毒（HBV）DNA水平升高或组织活检证明为乙肝的患者，从而将循证基础限制于一个非常特殊的人群。
Ultimately, the goal is to initiate therapy at a time when the risk-benefit ratio is tipped in favor of therapy, before the development of significant fibrosis or malignancy. Thus, it would seem that the earlier that treatment is begun, the better. However, this decision must be weighed against issues in cost, compliance, and the potential development of drug resistance.
最终，治疗的目的是选择在肝脏发展至显著纤维化或恶性化之前，在危险/受益的天平向有利于治疗的方向倾斜的时候开始进行治疗。看起来是越早开始治疗越好，然而，决定治疗前必须仔细权衡治疗成本、患者依从性以及可能发生的药物耐受情况。
As we continue to gain insight into the benefits of effective treatment, a fundamental reappraisal of this disease is currently under way. This report highlights some of the key research in this area as presented during Digestive Disease Week (DDW) 2007.
由于我们不断探询有效治疗的受益，因而乙肝治疗的全面重新评价得以展开。该报告对该领域内2007消化系统疾病周（DDW）中所描述的一些主要研究加以阐明。
Identification of Patients at Risk for Disease Progression
疾病进展患者的确认
Previously it was thought that disease progression in chronic hepatitis B occurred if hepatitis B e antigen (HBeAg) was positive, serum HBV DNA levels were > 105 copies/mL, and if the alanine aminotransferase (ALT) level was greater than 2 times the upper limit of normal (ULN), and that disease progression did not occur in the healthy carrier -- patients with hepatitis B surface antigen (HBsAg) positivity and HBeAg loss, normal liver enzyme levels, and with negative HBV DNA as measured by an insensitive assay (with detection only above 105 copies/mL).[1-4] Although we now realize that this terminology is misleading, as "healthy carriers" can still develop disease progression, these patients continue to be viewed as relatively protected and are not traditionally offered therapy.
以前，人们认为慢性乙肝患者存在如下情况时疾病处于发展状态：乙肝e抗原阳性、血浆HBV DNA水平大于105拷贝/ml、谷丙转氨酶（ALT）水平超过正常水平上限2倍；而同时认为乙肝健康携带者的疾病处于不发展状态，所谓乙肝健康携带者是指那些乙肝表明抗原（HBsAg）阳性、HBeAg阴性、肝功酶水平正常、HBV DNA检测阴性的患者，事实上HBV DNA的检测并不灵敏，仅为105拷贝/ml水平。尽管我们现在意识到术语误导了人们，健康携带者同样可以处于疾病发展状态，但这些患者仍然被视为相对安全的，传统上不必接受治疗。
During this year's DDW meeting, Terrault and colleges[5] confirmed previous findings[6] suggesting that liver enzyme levels do not accurately reflect histology. Patients enrolled in phase 3 entecavir registration trials were categorized by ALT elevation. All had high viral load as defined by the study criteria. Among those patients with an ALT level less than 2 times ULN, more than two thirds demonstrated significant necroinflammation (Knodell necroinflammatory score: NI > 7), and a significant proportion also demonstrated advanced fibrosis. However, serum ALT level may still have some predictive value, as Chen and colleagues[7] demonstrated a strong correlation between serum ALT elevations over the disease course, high viral load, and the risk of developing hepatocellular carcinoma (HCC). Those individuals with persistently lower (< 45 U/L) serum ALT had the lowest risk for HCC development. In this study, a single-point viral load was best at capturing the eventual risk for ALT elevation as well as predicting future HCC risk. However, Akhtar and colleagues[8] presented a small case series of patients with significant necroinflammation and fibrosis with very low-level HBV DNA, emphasizing previous findings that suggested low viral load as a guarantee against disease progression.[9,10] All of these studies serve to highlight that no patient with hepatitis B remains immune to complications, and no parameter can be used to identify a subset of patients that does not need close clinical follow-up.
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作者:admin@医学,生命科学 2011-04-09 05:11
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