12月26號(hào)發(fā)表于《JAMA》雜志上的一項(xiàng)研究表明，在慢性丙型肝炎患者和肝纖維化患者中，基于干擾素療法的持續(xù)病毒學(xué)應(yīng)答能降低死亡率。

　　慢性丙型肝炎病毒（HCV）感染是肝硬化、肝細(xì)胞癌（HCC）及終末期肝病的重要風(fēng)險(xiǎn)因素。HCV相關(guān)的肝硬化及其并發(fā)癥的發(fā)病率在未來(lái)幾年預(yù)計(jì)將升高。根據(jù)文章的背景資料估計(jì)，目前慢性丙型肝炎發(fā)病率約為25%（350萬(wàn)人），并將在2030年增長(zhǎng)到45%.

　　持續(xù)病毒應(yīng)答是指停止所有抗病毒藥物后24周不發(fā)生病毒血癥。雖然SVR存在長(zhǎng)期穩(wěn)定性，但是支持其作為抗病毒治療的替代終點(diǎn)的生存改善有關(guān)的數(shù)據(jù)尚不全面。展示其直接臨床效果會(huì)更好的證明密集昂貴的抗病毒治療的使用效果。

　　研究者探討SVR的獲得與否與慢性丙肝患者和肝纖維化患者的生存率是否有關(guān)。這項(xiàng)研究由歐洲和加拿大的5家三級(jí)醫(yī)院完成，包括530位在1990年至2003年間接受干擾素治療的慢性丙肝患者，收集肝纖維化和肝硬化的組織學(xué)證據(jù)。隨訪(fǎng)時(shí)間為2010年1月至2011年10月。隨訪(fǎng)時(shí)間中位數(shù)為8.4年，患者年齡基線(xiàn)中位數(shù)為48歲，369例（70%）為男性。

　　其中，192例（36%）獲得SVR；13例獲得SVR和100例未獲得SVR的患者死亡。在進(jìn)一步分析中研究者發(fā)現(xiàn)，SVR與全因死亡及肝臟相關(guān)的死亡率和移植率降低有關(guān)。其他基線(xiàn)因素包括衰老、HCV基因3型感染、糖尿病、酗酒，均與全因死亡密切相關(guān)。在未獲得SVR的100例死亡患者中，70例患者死因與肝臟有關(guān)，15例與肝臟無(wú)關(guān)，15例未知。

　　肝臟相關(guān)的死亡或移植的10年累計(jì)發(fā)病率中，獲得SVR的為1.9%，未獲得的為27.4%.10年后，HCC的累計(jì)增長(zhǎng)率，獲得SVR的為5.1%，未獲得的為21.8%.10年累積肝功能衰竭率，獲得SVR的為2.1%，未獲得的為29.9%.

　　在國(guó)際化多中心長(zhǎng)期隨訪(fǎng)研究中，SVR與長(zhǎng)期總體生存率相關(guān)。獲得SVR與未獲得的患者相比，各種原因的死亡率低4倍。長(zhǎng)期隨訪(fǎng)研究表明，獲得SVR慢性丙肝、肝纖維化和肝硬化患者死亡率降低。此外，研究者能夠進(jìn)一步建立和量化SVR患者肝癌、肝功能刷街以及肝臟相關(guān)的死亡率和移植率。

　　Sustained virological response linked with improved survival for patients with chronic HCV infection

　　Among patients with chronic hepatitis C virus infection and advanced hepatic fibrosis (development of excess fibrous connective tissue), sustained virological response (SVR) to interferon-based treatment was associated with a lower risk of all-cause mortality compared with patients without SVR, according to a study in the December 26 issue of JAMA.

　　"Chronic hepatitis C virus (HCV) infection is a major cause of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease. The incidence of HCV-related cirrhosis and its complications is expected to increase in upcoming years. Davis et al estimated that currently 25 percent of the approximately 3.5 million U.S. patients with chronic HCV infection have cirrhosis and that the proportion of patients with cirrhosis is likely to increase up to 45 percent by 2030," according to background information in the article.

　　"Sustained virological response is defined as absence of viremia [the presence of a virus in the blood] 24 weeks after cessation of all antiviral medication. Although SVR has long-term durability, data on the relationship with improved survival to support its use as a surrogate end point of antiviral therapy is scarce. Demonstrating direct clinical benefits would better justify the use of intensive and costly antiviral therapy …" the authors write.

　　Adriaan J. van der Meer, M.D., of Erasmus MC University Medical Center, Rotterdam, the Netherlands and colleagues conducted a study to examine whether achievement of SVR vs. without SVR is associated with a prolonged overall survival in patients with chronic HCV infection and advanced hepatic fibrosis. The study, conducted at five tertiary care hospitals in Europe and Canada, included 530 patients with chronic HCV infection who started an interferon-based treatment regimen between 1990 and 2003, following histological proof of advanced hepatic fibrosis or cirrhosis. Complete follow-up ranged between January 2010 and October 2011. The patients were followed up for a median (midpoint) of 8.4 years. The baseline median age was 48 years and 369 patients (70 percent) were men.

　　There were 192 patients (36 percent) who achieved SVR; 13 patients with SVR and 100 without SVR died (10-year cumulative all-cause mortality rate, 8.9 percent with SVR and 26.0 percent without SVR). In further analysis, the researchers found that SVR was associated with a reduced risk of all-cause mortality and liver-related mortality or transplantation. Other baseline factors significantly associated with all-cause mortality included older age, HCV genotype 3 infection, presence of diabetes, and a history of severe alcohol use. Of the 100 deaths in patients without SVR, the cause was liver-related in 70 patients (70 percent), not liver-related in 15 percent of patients, and unknown in another 15 percent.

　　The 10-year cumulative incidence rate of liver-related mortality or transplantation was 1.9 percent with SVR and 27.4 percent without SVR. After 10 years, the cumulative occurrence of HCC was 5.1 percent in patients with SVR and 21.8 percent in patients without SVR. The 10-year cumulative liver failure rate was 2.1 percent in patients with SVR vs. 29.9 percent in patients without SVR.

　　"In our international, multicenter, long-term follow-up study, SVR was associated with prolonged overall survival. The risk of all-cause mortality was almost 4-fold lower in patients with SVR compared with patients without SVR. Our study with a long follow-up duration demonstrated a lower risk for all-cause mortality in patients with chronic HCV infection and advanced hepatic fibrosis who achieved SVR. In addition, we were able to further establish and quantify the risk reduction of HCC, liver failure, and liver-related mortality or liver transplantation in patients with SVR," the authors conclude.

　　(JAMA. 2012;308(24):2584-2593; Available pre-embargo to the media at http://media.jamanetwork.com)