JAMA：持续病毒学应答与丙型肝炎

据发表在12月26日出版的《美国医学会杂志》上的一项研究披露，在患有慢性丙型肝炎病毒感染及晚期肝纤维化（生长出过多的纤维结缔组织）的患者中，与那些没有持续病毒学应答（SVR）的患者相比，那些患者对以干扰素为基础的治疗作出的持续病毒学应答（SVR）与较低的全因死亡率有关。

根据文章的背景资料：“慢性丙型肝炎病毒（HCV）感染是肝硬化、肝细胞性肝癌（HCC）及终末期肝病的一个主要原因。HCV相关性肝硬化发病率及其并发症预计会在未来几年有所增加。Davis等人估计，在大约350万名美国的慢性HCV感染的患者中，目前有25%的人有肝硬化，而有肝硬化的病人比例可能会在2030年时增加至45%。”

荷兰鹿特丹伊拉斯谟大学医疗中心的Adriaan J. van der Meer, M.D.及其同事开展了一项研究，旨在检查有SVR vs.没有SVR是否与患有慢性HCV感染及晚期肝纤维化的患者的延长了的总体存活率有关。这项在欧洲和加拿大5家三级医院中开展的研究包括了530名患有慢性HCV感染的患者，他们在得到晚期肝纤维化或肝硬化的组织学证实之后在1990年至2003年间开始接受一项基于干扰素的治疗方案。完整的随访时间范围在2010年1月至2011年10月间。这些患者的随访中位数（中点）为8.4年。病人的基线中位数年龄为48岁，有369位患者（70%）为男性。

有192名患者（36%）有SVR；有13名有SVR的患者和100位无SVR的患者死亡（10-年累计全因死亡率在有SVR者中为8.9%，在无SVR者中为26.0%）。在进一步的分析中，研究人员发现，SVR与全因死亡率及肝脏相关性死亡率或移植风险下降有关。其它的与全因死亡率明显有关的基线因子包括年龄较大、HCV基因型3感染、存在糖尿病及有严重的酒精饮料使用历史。在无SVR的100名死亡的患者中，有70人（70%）的死因与肝脏有关，有15%的患者的死因与肝脏无关，另外15%的人的死因不明。

文章的作者得出结论：“在我们的国际性、多中心、长期的随访研究中，SVR与延长了的总体存活率有关。在有SVR的患者中，其全因死亡率的风险几乎比那些没有SVR的患者低了4倍。我们的这一有着长时间随访期的研究证明，那些达到SVR的慢性HCV感染的患者及晚期肝纤维化的患者有着较低的全因死亡率风险。此外，我们还能进一步确立并量化在SVR患者中的HCC、肝衰竭及肝脏相关性死亡率或肝移植风险的降低。”

与丙肝相关的拓展阅读：

• Liver Transpl：美国老年丙肝患者肝移植需求增多
• NEJM：Sofosbuvir用于慢性丙肝病毒感染初治安全有效
• Clin Infect Dis：血清标志物FIB-4或可用于慢性丙肝纤维化分期
• Hepatology：VitA缺乏——丙肝抗病毒治疗失败的“疑凶”
• Hepatology：丙肝肝硬化大多因酗酒导致
• PLoS One：IFN治疗丙肝对甲状腺功能影响报道不一
更多信息请点击：有关丙肝更多资讯

Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis.
CONTEXT
Chronic hepatitis C virus (HCV) infection outcomes include liver failure, hepatocellular carcinoma (HCC), and liver-related death.
OBJECTIVE
To assess the association between sustained virological response (SVR) and all-cause mortality in patients with chronic HCV infection and advanced hepatic fibrosis.
DESIGN, SETTING, AND PATIENTS
An international, multicenter, long-term follow-up study from 5 large tertiary care hospitals in Europe and Canada of 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 (Ishak score 4-6). Complete follow-up ranged between January 2010 and October 2011.
MAIN OUTCOME MEASURES
All-cause mortality. Secondary outcomes were liver failure, HCC, and liver-related mortality or liver transplantation.
RESULTS
The 530 study patients were followed up for a median (interquartile range [IQR]) of 8.4 (6.4-11.4) years. The baseline median (IQR) age was 48 (42-56) years and 369 patients (70%) were men. The Ishak fibrosis score was 4 in 143 patients (27%), 5 in 101 patients (19%), and 6 in 286 patients (54%). There were 192 patients (36%) who achieved SVR; 13 patients with SVR and 100 without SVR died (10-year cumulative all-cause mortality rate, 8.9% [95% CI, 3.3%-14.5%] with SVR and 26.0% [95% CI, 20.2%-28.4%] without SVR; P < .001). In time-dependent multivariate Cox regression analysis, SVR was associated with reduced risk of all-cause mortality (hazard ratio [HR], 0.26; 95% CI, 0.14-0.49; P < .001) and reduced risk of liver-related mortality or transplantation (HR, 0.06; 95% CI, 0.02-0.19; P < .001), the latter occurring in 3 patients with SVR and 103 without SVR. The 10-year cumulative incidence rate of liver-related mortality or transplantation was 1.9% (95% CI, 0.0%-4.1%) with SVR and 27.4% (95% CI, 22.0%-32.8%) without SVR (P < .001). There were 7 patients with SVR and 76 without SVR who developed HCC (10-year cumulative incidence rate, 5.1%; 95% CI, 1.3%-8.9%; vs 21.8%; 95% CI, 16.6%-27.0%; P < .001), and 4 patients with SVR and 111 without SVR experienced liver failure (10-year cumulative incidence rate, 2.1%; 95% CI, 0.0%-4.5%; vs 29.9%; 95% CI, 24.3%-35.5%; P < .001).
CONCLUSION
Among patients with chronic HCV infection and advanced hepatic fibrosis, sustained virological response to interferon-based treatment was associated with lower all-cause mortality.