慢性疾病管理计划可以改善肝硬化患者的预后?

StephenW

Can Chronic Disease Management Programs Improve Outcomes in Patients With Cirrhosis?

    Christian A. Mayorga
    ,
    Amit G. Singal

published online 23 September 2013.

Philip S. Schoenfeld, Section Editor, John Y. Kao, Section Editor



Wigg AJ, McCormick R, Wundke R, et al. Efficacy of a chronic disease management model for patients with chronic liver failure. Clin Gastroenterol Hepatol 2013;11:850–858.

Cirrhosis affects >5.5 million patients and costs nearly $4 billion annually. Furthermore, there are nearly 30,000 new diagnoses of cirrhosis per year (Hepatology 2002;36:227–242). The prevalence of cirrhosis is increasing owing to an aging population of patients with chronic hepatitis C virus infection and an increasing prevalence of nonalcoholic fatty liver disease. Unfortunately, our current episodic system of health care delivery is suboptimal for patients with chronic diseases, such as cirrhosis (Gastroenterology 2010;139:14–16 e1). Patients with cirrhosis are at high risk of hospitalization, including nearly one third of patients requiring readmission within 1 month (Clin Gastroenterol Hepatol 2013;11:1335–1141). In other chronic diseases, such as congestive heart failure, chronic disease management (CDM) models have significantly improved clinical outcomes, including disease-specific admission rates, all-cause admission rates, and overall survival (Eur J Heart Fail 2005;7:1133–1144). CDM improves outcomes through several components including delivery system design, decision support systems, coordination of care between providers, and self-management support systems (Milbank Q 1996;74:511–544). The authors of this study sought to determine the impact of a CDM intervention on patients with decompensated cirrhosis (Clin Gastroenterol Hepatol 2013;11:850–858).

In this single-center, randomized, controlled, pilot study, the authors enrolled 60 adult patients who had been admitted with any cirrhosis-related decompensation (ascites, encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatocellular carcinoma (HCC), hepatorenal syndrome, alcoholic hepatitis, or sepsis). Patients were randomized 2:1 to CDM (n = 40) or usual care (n = 20), respectively, and then followed for 12 months. The multifaceted CDM intervention was administered by hepatology nursing staff after hospital discharge and continued for the duration of the 12-month trial. The intervention included nurse case management, decision support tools, patient and caretaker education, and nurse-generated patient data sheets for providers. Specifically, delivery system design measures included multidisciplinary care in clinic, home visits by a nurse within 1 week of discharge, and rapid access to care pathways as needed. Nurses provided self-management support, including patient and caregiver education, to optimize care between visits. Finally, decision support tools, such as evidence-based protocols for cirrhosis complications, and clinical information systems, such as patient data sheets, were implemented.

Patients enrolled in the CDM group had a 30% higher attendance rate at planned outpatient appointments compared to the usual care group (incidence rate ratio [IRR], 1.3; 95% confidence interval [CI], 1.1–1.6). Several quality-of-care indicators were higher in the intervention group than the usual care group, including significant differences in rates of HCC screening, vaccination, and liver transplant assessments. However, there was no difference in the primary study endpoint of cirrhosis-related hospital days between the CDM and usual care groups (17.8 vs 11.0 days per person-year, respectively; IRR, 1.6; 95% CI, 0.5–4.8). Similarly, the authors found no difference in cirrhosis-related admission rates (IRR, 2.2; 95% CI, 1.0–4.5), all-cause admission rates (IRR, 1.7; 95% CI, 1.0–3.7), median length of hospitalization (hazard ratio 1.3; 95% CI, 0.9–1.9), or overall survival (hazard ratio, 0.6; 95% CI, 0.3–.5).

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Comment

CDM programs have been shown to improve clinical outcomes in several chronic diseases. In chronic obstructive pulmonary disease, for instance, CDM models resulted in a significant reduction in hospitalization rate (Arch Intern Med 2007;167:551–561). Similarly, for congestive heart failure, the use of CDM programs has been associated with significant reductions in both hospitalization and mortality rates (Eur J Heart Fail 2005;7:1133–1144). Although the upfront cost of these programs is not trivial, this cost may be offset by a substantial increase in quality-adjusted life-years and perhaps cost-savings with reduced downstream hospitalizations (Heart 2008;94:1601–1606). Cirrhosis is currently responsible for significant morbidity and health care costs and parallels other target populations of prior CDM efforts.

This pilot study is the first prospective, randomized trial assessing the impact of a CDM model in the management of chronic liver disease. In contrast with other chronic diseases in which CDM intervention significantly improves clinical outcomes, this study showed no difference in cirrhosis-related hospital days, all-cause admission rates, or median length of hospitalization. In fact, there was a nonsignificant trend toward worse outcomes in the intervention group, with more liver-related hospital days and higher all-cause admission rates.

The negative findings of this study may be related to intrinsic differences between patients with cirrhosis and those with other chronic diseases. The authors hypothesize that patients with cirrhosis may be more marginalized from health care services than other chronic diseases. It is also possible that acute exacerbations of cirrhosis are unpredictable and unavoidable, even in the setting of high-quality care. For example, hepatic encephalopathy can be a unique and challenging barrier to providing consistent outpatient care to patients with cirrhosis, including sudden exacerbations owing to a host of etiologies, including infection, medication noncompliance, and renal failure.

Alternatively, CDM interventions may be effective in patients with cirrhosis but simply not detected by this study owing to its limitations. First, this was a pilot study and was not powered a priori for all planned analyses (although the authors performed a post hoc power analysis). Furthermore, the small sample size led to imbalances in several measured (and likely unmeasured) confounders between the intervention group and usual care group. There were higher rates of reversible insults, such as spontaneous bacterial peritonitis and alcoholic hepatitis, in the usual care group. Similarly, there was a trend toward higher Model for End-stage Liver Disease scores and comorbidity index in the intervention group.

Furthermore, this study was conducted in a tertiary care center, with easy access to subspecialty care. This is a setting where CDM may be unnecessary, because rates of quality care were high among patients in the usual care group, with >80% of patients receiving HCC surveillance, variceal screening, and spontaneous bacterial peritonitis prophylaxis as needed. Prior studies have demonstrated that subspecialty consultation from a gastroenterologist results in shorter lengths of hospitalization and lower 30-day readmission rates among patients with cirrhosis (Hepatology 2001;34:1089–1095). Therefore, it is possible that CDM interventions may be more beneficial in a community hospital setting where expert consultation is scarcer or in a subgroup of high-risk patients.

Although the authors chose the components of their CDM intervention based on available evidence from other chronic diseases, it is possible that different components are necessary to improve outcomes in patients with cirrhosis. For example, a high proportion of admissions in the intervention group were for elective procedures, such as paracentesis, liver biopsy, or endoscopic procedures. Availability of an outpatient procedure facility could have prevented 48% of hospitalizations in the intervention group and should be included in future CDM intervention trials. Furthermore, several of the components of the CDM intervention in this study, such home visits and patient education, were directed to outpatient care, although the primary study outcomes were all inpatient based. Future studies are needed to characterize reasons for readmission and prolonged hospitalization among patients with cirrhosis to help develop an effective intervention strategy.

Interestingly, there was no difference in the primary and secondary outcomes of the study despite an improvement in several quality measures, such as HCC surveillance, vaccination, and liver transplant evaluation. Although process measures are more sensitive to differences in quality of care, outcomes are often of greater interest. It is possible that improvements in process measures would translate to improved outcomes with longer follow-up; however, it is also possible that there is a disconnect between these quality metrics and the outcomes of interest. Although a recent study from HALT-C helped to establish a link between HCC surveillance process measures and downstream outcomes (Am J Gastroenterol 2013;108:425–432), similar studies are needed for other cirrhosis quality metrics.

Despite not finding a difference in outcomes with CDM, this is an important proof-of-principle pilot study with several strengths. The study raises several interesting questions regarding the benefits of CDM among patients with decompensated cirrhosis. Future studies are needed to determine the optimal components of a CDM program as well as the most appropriate quality measures. Larger studies with longer follow-up are then needed to determine the effectiveness and cost-effectiveness of CDM interventions in improving outcomes among this patient population.

StephenW

Wigg AJ ，麦考密克ŗ ， Wundke等。慢性肝功能衰竭患者的一种慢性疾病管理模式的功效。临床胃肠肝脏病杂志2013 ; 11:850-858 。

肝硬化会影响550万患者和成本每年近400亿美元。此外，有近30,000个新的诊断肝硬化每年（ 2002年肝病; 36:227-242 ） 。肝硬化的患病率增加，由于患者的慢性丙型肝炎病毒感染和非酒精性脂肪肝疾病的患病率增加，人口老龄化。不幸的是，我们目前的情节系统的卫生保健服务的患者有慢性疾病，如肝硬化（消化内科2010 ， 139:14-16 E1 ）是最理想的。肝硬化患者在住院的风险高，包括近三分之一的患者需要再住院1个月内（临床胃肠肝脏病杂志2013 ; 11:1335-1141 ） 。在其他慢性疾病，如充血性心脏衰竭，慢性疾病管理（CDM ）模型显着改善临床结果，包括针对特定疾病的住院率，各种原因的住院率，和总生存期（欧元J心故障2005 7:1133 -1144 ） 。清洁发展机制的改善结果通过几部分组成，包括输送系统设计，决策支持系统，护理供应商之间的协调，以及自我管理支持系统（米尔班克1996年Q ; 74:511-544 ） 。这项研究的作者试图确定患者失代偿期肝硬化（临床胃肠病肝脏病杂志2013 ; 11:850-858 ）上的清洁发展机制干预的影响。

在这种单中心，随机，对照试验研究，招收60名成年患者已被送往任何相关肝硬化失代偿（腹水，肝性脑病，食管静脉曲张破裂出血，自发性细菌性腹膜炎，肝细胞肝癌（HCC） ，肝肾综合征，酒精性肝炎，败血症） 。患者随机2:1 CDM组（n = 40 ）或常规治疗组（n = 20 ） ，分别，然后随访12个月。多方面的CDM干预肝病护理人员出院后管理，并持续了12个月的审判的持续时间。干预包括护士的个案管理，决策支持工具，耐心和看守政府教育和护士生成的患者数据表提供商。具体来说，输送系统的设计措施包括多学科的临床护理，由护士家访放电，并在1周内快速访问需要护理途径。护士提供自我管理的支持，包括教育病人和照顾者之间的互访，优化护理。最后，决策支持工具，如肝硬化并发症，临床信息系统，如病人的数据表以证据为基础的协议，实施。

计划的预约门诊，就读于CDM组的患者有30％以上的出席率相比，常规治疗组（发病率比（IRR）为1.3; 95 ％信心区间[CI]为1.1-1.6 ） 。几个护理质量指标均高于干预组比常规治疗组，其中包括肝癌筛查，预防接种，和肝移植评估利率的显着差异。然而，在肝硬化相关的住院天数之间的清洁发展机制和常规护理组（ 17.8和11.0天每人每年分别IRR ， 1.6 ，95％ CI ， 0.5-4.8 ）主要研究终点无显着差异。同样，作者发现肝硬化相关的录取率（IRR ， 2.2 ，95％ CI ， 1.0-4.5 ） ，各种原因的住院率（IRR ， 1.7 ，95％ CI ， 1.0-3.7 ），中位住院时间无差异（危险比为1.3; 95％ CI ， 0.9-1.9 ） ，或总生存期（危险比为0.6 ，95％CI ， 0.3 - 0.5 ） 。

备份文章概要
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CDM项目已被证明在一些慢性疾病，提高临床疗效。慢性阻塞性肺疾病，例如， CDM模型在显着减少住院率（拱内科杂志2007 ; 167:551-561 ） 。同样，对于充血性心脏衰竭，使用CDM方案已显着减少，相关的住院率和死亡率（欧元J心失败2005 ， 7:1133-1144 ） 。虽然这些节目的前期成本是不平凡的，这可能会抵消成本大幅增加，质量调整生命年，也许是节省成本减少下游住院（心2008 ， 94:1601-1606 ） 。肝硬化是目前负责重大的发病率和医疗保健费用和其他相似之处之前CDM努力的目标人群。

这项试验的研究是第一个前瞻性，随机试验评估清洁发展机制在慢性肝病的管理模式的影响。对比其他慢性疾病，其中清洁发展机制的干预显着改善临床预后，这项研究表明肝硬化相关的住院天数无差异，各种原因住院率，住院中位数。事实上，有不显着趋向恶化的结果，干预组与肝脏相关的住院天数和更高的全导致录取率。

这项研究的阴性结果，可能与肝硬化和那些与其他慢性疾病的患者之间的内在差异。作者推测，从医疗保健服务比其他慢性疾病，肝硬化患者可能会更加边缘化。也有可能是肝硬化急性发作是不可预知的和不可避免的，即使是在高品质的护理的设置。例如，肝性脑病可以是一个独特的和富有挑战性的障碍，肝硬化，包括突然发作由于主机的病因，包括感染，不遵从服药，肾功能衰竭患者提供一致的门诊医疗。

另外， CDM干预可能是肝硬化患者有效，但根本就没有检测到这项研究中，由于它的局限性。首先，这是一个试验性研究，未通电的所有计划的分析（虽然作者进行事后功耗分析） 。此外，小样本几个干预组和常规护理组之间测量（可能不可测的）混杂因素导致的不平衡。有率较高的可逆的侮辱，如自发性细菌性腹膜炎和酒精性肝炎，在平时的护理组。同样，有更高的型号终末期肝病的分数和干预组的合并症指数的趋势。

此外，这项研究是在一家三级医疗中心进行，方便地访问专科护理。这是一个设置清洁发展机制可能是不必要的，因为优质护理服务率是高的患者在平时的护理组， > 80％的患者接受监视，静脉曲张筛查肝癌，自发性细菌性腹膜炎的预防需要。此前的研究已经证明，专科会诊，住院30天再入院率肝硬化患者之间（ 2001年肝病; 34:1089-1095 ）长度较短肠胃病结果。因此，它可能是清洁发展机制的干预措施可能更有利于在社区医院设置专家咨询稀少或在一个高风险的患者亚组。

尽管作者选择了他们的CDM干预的基础上提供的证据等慢性疾病的组件，它是可能的不同的元件是必要的改进结果肝硬化患者。例如，高比例的招生干预组选修的程序，如腹腔穿刺，肝穿刺活检，或内视镜手术。一个门诊手术设施的可用性可能会阻止48％的住院治疗，干预组和中应包括未来CDM干预试验。此外，一些清洁发展机制的干预，在这项研究中，这样的家访和患者教育的组成部分，门诊保健，虽然主要的研究结果为所有住院。肝硬化患者中，以帮助制定有效的干预策略，未来的研究需要表征入院和住院时间延长的原因。

有趣的是，在小学和中学的研究成果无显着差异，尽管改进质量的措施，如肝癌的监测，预防接种，肝移植评估。虽然工艺措施更加敏感，护理质量的差异，结果往往是更大的兴趣。这是可能的改进工艺措施将转化为较长的后续的改进的结果，但是，它也有可能是这些质量指标和感兴趣结局的之间存在脱节。虽然最近的一项研究从HALT -C有助于监测HCC工艺措施和下游的成果（上午胃肠病学杂志2013 ; 108:425-432 ）之间建立了联系，类似的研究是必要的其他肝硬化质量指标。

尽管没有找到一个差异与CDM的结果，这是一个重要的几个优势证明了原理试验研究。这项研究提出了几个有趣的问题，对失代偿期肝硬化患者中清洁发展机制的好处。未来的研究需要一个CDM方案，以及最合适的质量的措施，以确定最佳的元器件。具有较长的后续更大规模的研究，然后需要确定这个病人人口改善清洁发展机制的干预措施的有效性和成本效益。