https://orcid.org/0000-0001-7226-8821
Figures
Abstract
Background and objective
Liver cirrhosis represents a considerable health burden and causes 1.2 million deaths annually. Patients with decompensated liver cirrhosis have a poor prognosis and severely reduced health-related quality of life. Nurse-led outpatient care has proven safe and feasible for several chronic diseases and engaging nurses in the outpatient care of patients with liver cirrhosis has been recommended. At the decompensated stage, the treatment and nursing care are directed at specific complications, educational support, and guidance concerning preventive measures and signs of decompensation. This review aimed to assess the effects of nurse-assisted follow-up after admission with decompensation in patients with liver cirrhosis from all causes.
Method
A systematic search was conducted through February 2022. Studies were eligible for inclusion if i) they assessed adult patients diagnosed with liver cirrhosis that had been admitted with one or more complications to liver cirrhosis and ii) if nurse-assisted follow-up, including nurse-assisted multidisciplinary interventions, was described in the manuscript. Randomized clinical trials were prioritized, but controlled trials and prospective cohort studies with the intervention were also included. Primary outcomes were mortality and readmission, but secondary subjective outcomes were also assessed.
Results and conclusion
We included eleven controlled studies and five prospective studies with a historical control group comprising 1224 participants. Overall, the studies were of moderate to low quality, and heterogeneity across studies was substantial. In a descriptive summary, the 16 studies were divided into three main types of interventions: educational interventions, case management, and standardized hospital follow-up. We saw a significant improvement across all types of studies on several parameters, but currently, no data support a specific type of nurse-assisted, post-discharge intervention. Controlled trials with a predefined intervention evaluating clinically- and practice-relevant endpoints in a real-life, patient-oriented setting are highly warranted.
Citation: O’Connell MB, Bendtsen F, Nørholm V, Brødsgaard A, Kimer N (2023) Nurse-assisted and multidisciplinary outpatient follow-up among patients with decompensated liver cirrhosis: A systematic review. PLoS ONE 18(2): e0278545. https://doi.org/10.1371/journal.pone.0278545
Editor: Riccardo Nevola, University of Campania Luigi Vanvitelli: Universita degli Studi della Campania Luigi Vanvitelli, ITALY
Received: August 17, 2022; Accepted: November 18, 2022; Published: February 9, 2023
Copyright: © 2023 O’Connell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting information files.
Funding: The authors received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Nurse-led and nurse-assisted outpatient care programs have proven safe and feasible across several chronic diseases. They have shown equal or better outcomes regarding health-related quality of life, symptom burden, and disease-specific clinical outcomes compared to physician-led programs [1]. A recent meta-analysis of four studies found no advantage of self-management programs on the clinical impact in patients with liver cirrhosis [2]. Still, the effect of nurse-assisted post-discharge interventions, including nurse-assisted multidisciplinary interventions among patients with decompensated liver cirrhosis, has not been investigated thoroughly.
Worldwide, liver cirrhosis represents a considerable health burden and causes 1.2 million deaths annually. The distribution of aetiologies and frequency among regions differs. Globally, Hepatitis C infection (HCV) is the leading cause of liver disease-related death, followed by Hepatitis B infection (HBV). In the western world, alcohol-related liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the most frequent causes and are increasing in prevalence [3, 4]. Liver cirrhosis evolves from compensated cirrhosis without any apparent signs of liver disease and no significant health issues related to the liver disease to decompensated cirrhosis characterized by several complications [5, 6]. Patients with liver cirrhosis are often diagnosed at a late stage, where the patients are decompensated with complications such as infections, ascites, hepatic encephalopathy, and variceal bleeding, all of which indicate a poor prognosis and severely reduced health-related quality of life [7–9]. Studies have shown that 20–37% of patients with liver cirrhosis are readmitted fewer than 30 days after hospitalization for decompensation, with a higher 90-day mortality rate than those who are not readmitted [10–12].
It has been recommended to engage nurses in the outpatient care of patients with liver cirrhosis [5, 6, 13]. At the decompensated stage, the treatment and nursing care are directed at specific complications, educational support, and guidance concerning preventive measures and signs of decompensation [5, 6]. Lifestyle changes and self-care are essential to disease management. Still, low compliance with prevention and treatment recommendations and inadequate self-care among patients with liver cirrhosis often leads to worse outcomes [14–16].
This review aimed to assess the effects of nurse-assisted and multidisciplinary follow-up interventions after admission with decompensation in patients with liver cirrhosis from all causes.
Methods
A study protocol was registered at PROSPERO, the international prospective register of systematic reviews, and approved on May 15, 2019 (CRD42019128249). This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [17].
Search strategy
We searched the following databases Pubmed, Embase, Cinahl, Web of Science, and Cochrane Libraries. Clinicaltrials.gov and the International Clinical Trials Registry Platform were searched for ongoing trials. Conference proceedings, reference lists for the included studies, and bibliographies were searched manually. All studies were reviewed irrespective of publication status, and no data range was applied. The following search terms were applied in different combinations and adjusted according to the specific database: “Liver cirrhosis,”Cirrhosis,” “Nurs*,” “Outpatient,” “Aftercare,” “Rehabilitation,” “Intervention,” “Follow-up,” “Outpatient Care,” “Post-discharge,” “Post-admission,” “Post hospitalization.” The central search strategy is available in the S1 Appendix.
Eligibility criteria and study selection
Studies were eligible for inclusion if i) they assessed patients diagnosed with liver cirrhosis by liver biopsy or classical clinical signs in combination with biochemistry and ultrasound, CT scan, Liver elastography, or other relevant imaging techniques, and had been admitted with a one or more complications to liver cirrhosis, and ii) if a nurse-assisted follow-up intervention including nurse-assisted multidisciplinary intervention was tested in the trial. The primary outcomes stated in the PROSPERO record were mortality, readmissions, and quality of life. We further included the secondary outcomes of self-efficacy, disease knowledge, lifestyle, and cost-effectiveness. Randomized clinical trials were prioritized, but non-randomized controlled trials and prospective cohort studies were also included due to low numbers. Case studies, reviews, expert opinions, and retrospective and registry studies were excluded, as studies with no clinically relevant outcomes and studies assessing interventions without a nurse-assisted element. Excluded studies and the reason for exclusion are presented in supplementary S2 Appendix.
Data collection process
Two reviewers independently screened the searched titles, abstracts, full texts, and extracted data. All authors resolved disagreements regarding inclusion or exclusion or discrepancies in data extraction by consensus. The following data were extracted: study characteristics (author, country, year of publication, study design, funding source), patient demographics (age, sex, number of patients in each study arm, Child-Pugh score [18], and Model for End-stage Liver Disease (MELD) [19] scores, follow-up, type of intervention(s) and outcomes as defined by the authors of the studies.
Risk of bias
The risk of bias for randomized trials was assessed using the Cochrane Handbook for Systematic Reviews of Interventions [20, 21], assessing the following bias items: i) selection bias (randomization, allocation), ii) performance bias (blinding of participants, personnel), iii) detection bias (blinding of assessors and outcomes), iv) attrition bias (incomplete outcome data), and v) reporting bias (selection of the reported results). The risk of bias for prospective studies with no control group was assessed using the Methodological Index for Non-Randomized Studies (MINORS) [22].
Results
Literature search
Electronic searches were performed in May 2019 and updated in February 2022. We identified 2741 studies (Fig 1). Manual searches identified another five studies of relevance. After screening titles and abstracts and removing duplicates, 123 studies were assessed. Letters and studies irrelevant to the aim of our study were excluded, and 31 studies were further evaluated. Nine studies assessed interventions after hospital discharge with liver cirrhosis complications [23–31], and seven assessed interventions among stable outpatients [14, 32–37]. These 16 studies, comprising 1224 participants, were included in a descriptive summary.
Quality of evidence
A bias assessment of the randomized controlled trials is presented in Fig 2. In general, studies were open-label, and only one study performed blinding of outcome assessment [33]. One study conducted blinding of allocation [25]. One study had a 40% dropout rate after the intervention, and attrition bias was likely [23]. Non-randomized studies were evaluated by the Methodological Index for Non-Randomized Studies (MINORS) [22] (Fig 3). None of the comparative studies scored a maximum of 24 points, and none of the non-comparative studies scored a maximum of 16 points. All studies enrolled and collected data prospectively. None of the studies evaluated results blinded or carried out an unbiased assessment of study results. Only one trial reported prior sample size calculation [36]. Two studies had a loss to follow-up of 9% and 23% [14, 35]. Of note, one study was published as an abstract [30], and reporting bias was suspected. Based on the above, all studies were of low or moderate quality.
Guided by the Cochrane Handbook for Systematic Reviews of Interventions.
Guided by Methodological Index for Non-Randomized Studies.
Study characteristics
Study characteristics of the 16 included studies are presented in Table 1. The included studies were published between 2005 and 2019. Of the 16 studies included, six trials comprising 361 participants were open-label randomized controlled trials [23, 25, 32, 33] or consecutive allocated trials [26, 34]. Another five trials, with 529 participants, used a historical control group [24, 27, 28, 30, 31]. Five studies comprising 334 participants were prospective cohort studies with pre- and post-intervention but no control groups, and these were included in the descriptive summary of the outcomes [14, 29, 35–37]. Two studies targeted patients with alcoholic liver cirrhosis [23, 24], and four focused on complications such as hepatic encephalopathy and ascites [24, 26, 29, 30]. The follow-up period varied from 30 days to five years. In the 16 studies assessed, the number of participants ranged from 25 to 199. The mean age went from 40.0 to 65.3 years, with an age range of 20 to 79. Of the participants, 827 were male (67.6%); one study did not report age and sex [30]. Five studies were carried out in the USA, three in Iran, two in Italy, and one in Denmark, Spain, the United Kingdom, Slovenia, Australia, and China.
Descriptive summary of interventions
The 16 studies were divided into three main types of interventions: i) educational interventions, where an educational tool (video, booklet, educational classes, mindfulness or empowerment) was used to benefit the patient [14, 23, 29–37]; ii) case management studies characterized by a collaborative approach used to assess, plan, facilitate and coordinate care to meet patient and family health needs and intended to improve individual outcomes [24, 25]; and iii) standardized hospital follow-up where a structured protocol was implemented [26–28]. For each of the 16 studies, the intervention is shortly described in Table 1.
Educational studies.
Eleven studies assessed a variety of educational interventions and varied in both duration and design. Five studies used a single educational tool [14, 23, 32, 36, 37], while six used a multifaceted intervention with various tools [29–31, 33–35]. The educational tools included films, apps, booklets/pamphlets, individual education, and group classes. Three studies used mindfulness-, health empowerment- and self-efficacy theories as a basis for the patient education program [31, 33, 36]. Kumral et al. was the only study that divided participants into different educational groups depending on their academic level and time spent in the sessions [30]. Five studies included more than one session/visit [23, 29, 31, 33, 34]. In five studies, the patients were followed up or checked for adherence by telephone call [29–31, 34] or a combination of text messages and telephone calls [35]. Four studies involved caregivers chosen by the participant in the intervention [29–31, 36], but Bajaj et al. was the only study assessing caregiver-reported outcomes [36].
Case management.
Two studies were case management studies [24, 25], with specialized nurses as the primary care providers, combined with assistance from multidisciplinary teams comprising physicians, dieticians, and alcohol consultants. Both interventions included individual patient and caregiver education, home visits, and referral for alcohol treatment if needed. Both studies used individualized patient action plans. Andersen et al. planned the patient interventions according to the etiology of cirrhosis and the patient’s physical and social problems and needs [24]. Wigg et al. individualized the intervention to target the patient’s specific complications, conducted weekly telephone follow-ups, and offered telephone consultations for concerned patients [25].
Standardized hospital follow-up.
Three studies used a standardized hospital follow-up design [26–28]. In all three studies, the patients were followed by a multidisciplinary team consisting of nurses specializing in treating patients with liver diseases and hepatologists. Morando et al. designed a structured program consisting of an ultrasound of the liver, upper endoscopy, neurocognitive assessment, assessment of alcohol use, and updated medical and dietary treatments [26]. Morales et al. designed a program consisting of a seven-day follow-up, including a physical exam, one-on-one interviews to determine potential risk factors, adherence to treatment and diet recommendations, medicine adjustment, lab tests or diagnostics as needed, and a leaflet on warning signs of decompensation [28]. Majc et al. designed a structured follow-up with regular outpatient controls. The education was customized for each patient and included information about alcohol cessation, diet, and adjustment of diuretic treatment. Every patient was offered alcohol treatment, and family members were asked to assist in recovery [27]. In all three studies, follow-up visits were planned according to the severity of cirrhosis [26–28].
Intervention outcomes
Intervention endpoints, outcomes and measurements for the 16 individual studies are presented in Table 2.
In the following we will present the results from our primary endpoints, mortality, readmissions and quality of life, and our secondary outcomes of disease knowledge, self-efficacy, lifestyle, and cost-effectiveness.
Primary outcomes.
Mortality. Five studies comprising two randomized studies [25, 26] and three clinical trials with a historical control group [24, 27, 28] presented mortality as an intervention outcome. The three standardized hospital follow-up studies all showed significantly reduced mortality rates [26–28]. Morando et al. showed lower all-cause mortality in the intervention group (23.1%) compared to the control group (45.7%) (p = 0.025) [26]. Majc et al. showed a median survival time of 4.66 years in the intervention group compared to 2.9 years in the control group (p = 0.021) [27]. Morales et al. showed significantly lower mortality at 60 days follow-up (p = 0.016) but no differences in 30 days (p = 0.134) or 90 days follow-up (p = 0.655) [28]. Between the two standardized hospital follow-up studies, Wigg et al. showed no difference in risk of death between the two groups (p = 0.32) [25], and Andersen et al. demonstrated a significantly higher survival rate in the intervention group (p = 0.012) [24].
Readmissions. Nine studies comprising three randomized studies [25, 26, 32], four clinical trials with a historical control group [24, 27, 28, 30], and two prospective clinical trials [29, 35] presented readmissions as an intervention outcome. The three standardized hospital follow-up studies showed diverse readmission results [26–28]. The randomized clinical trial by Morando et al. showed significantly lower 30-day and 12 months readmission rates and fewer days of hospitalizations in the intervention group (15.4%) compared to the control group (42.4%) (p<0.01) [26]. The clinical trial with a historical control group by Majc et al. showed a non-significant reduction in hospitalizations over five years with a lower average number of hospitalizations in the intervention group (1.88) compared to the control group (2.07) (p = 0.612) [27]. Another clinical trial with a historical control group by Morales et al. showed a significant reduction in early admissions (<30 days) in the intervention group compared to the control group (95% CI 19–75) (p = 0.003), longer time from discharge to early readmission in the intervention group (p<0.001), and a shorter duration of admissions in the intervention group (p = 0.007). There was no significant difference between the groups in readmissions after 30 days (p = 0.278) [28]. The educational studies showed mixed results [29, 30, 32]. The clinical trial with a historical control group by Kumral et al. showed a significantly reduced 30-day readmission rate in the intervention group (25%) compared to the control group (62%) (p = 0.02) [30]. The randomized clinical trial by Garrido et al. showed possible prevention of admissions for hepatic encephalopathy, but the study was not equipped to assess this outcome [32]. The prospective clinical trial by Ganapathy et al. measured both 30-day readmissions and HE-related readmissions. They showed that 17 patients (42.5%) were readmitted within 30 days, but none due to hepatic encephalopathy, and eight potential HE-related readmission were prevented through app-generated alerts [29]. Another prospective clinical trial by Alavinejad et al. showed a decrease in days of hospitalization (p = 0.001) [35]. The two case management studies by Wigg et al. and Andersen et al. showed no significant difference in hospital admissions [24, 25].
Quality of life. Four studies comprising two randomized clinical trials [25, 34] and two prospective clinical trials [35, 36] presented quality of life as an intervention outcome. Three studies measured health-related quality of life by the disease-specific questionnaire to assess the quality of life in patients with chronic liver disease Chronic Liver Disease Questionnaire (CLDQ). The 29-item questionnaire incorporates disease-specific and physical- and mental health questions into six domains [38]. The randomized clinical educational study by Zandi et al. showed an increase in CLDQ in the intervention group (mean score 139 to 171.6) (p = 0.001) and a decrease in CLDQ in the control group (mean score 137 to 112.2) (p = 0.001) [34]. The randomized clinical case-management study by Wigg et al. showed improved health-related quality of life scores in the intervention group during the study period but no significant improvement compared to the control group at six months (p = 0.76) and 12 months (0.80) [25]. The prospective clinical educational study by Alavinejad et al. showed an increase in CLDQ in the intervention group (p<0.0001) [35]. Another prospective clinical, educational study by Bajaj et al. measured quality of life by the behaviourally based health status measure, The Sickness Impact Profile (SIP), which was designed to measure the extent to which health and illness affect daily life and functioning [36]. The results showed an improvement in the overall SIP score in the intervention group (p = 0.005) [36].
Secondary outcomes.
Disease knowledge. Six educational studies comprising two randomized clinical trials [23, 32], one clinical trial with historical control group [31], and three prospective clinical trials [14, 35, 37] presented disease knowledge as an intervention outcome. The randomized clinical trial by Sussman et al. measured knowledge in the intervention group using 19 forced-choice items concerning liver cirrhosis, including preventive measures and complications. The study showed significantly greater learning in the intervention group P<0.004 [23]. Another randomized clinical trial by Garrido et al. measured knowledge in the intervention group using the Questionnaire on the Awareness of Encephalopathy (QAE) [32]. The study showed a highly significantly increased knowledge in the intervention group concerning the management of hepatic encephalopathy from 5% (95% CI 1 to 24) to 80% (95% CI 58 to 92) p<0.001) [32]. The clinical trial with a historical control group by Zhang et al. measured knowledge by a health knowledge questionnaire for liver cirrhosis developed for the specific study with answer options “know” or “don’t know” [31]. The study showed significantly greater total awareness rates in the intervention group compared to the control group (p = <0.05) [31]. In the prospective clinical trial by Alavinejad et al., knowledge was measured by a liver cirrhosis knowledge questionnaire developed for the specific study with 20 questions with the answer options “know” or “don’t know.” The study showed that the knowledge scores improved significantly before (141.89 ± 20.40) and after (182.72 ± 10.27) the educational intervention (P < 0.0001) [35]. In another prospective clinical trial by Goldsworthy et al., knowledge was measured by a nine-item questionnaire concerning liver cirrhosis developed for this specific study. The study showed a baseline median questionnaire score of 25.0% (IQR 16.7–41.7%) which increased to 66.7% (IQR 50.0–75.0%) at follow-up, showing a significant improvement of 41.7% (p<0.001) [37]. The prospective clinical trial by Volk et al. measured knowledge using a 15-item survey covering topics such as diet, medications, and health maintenance activities. The study showed a significant median knowledge score improvement from 53% to 67% (p<0.001) [14].
Self-efficacy and Health-promoting lifestyle. One randomized educational study by Mansouri et al. measured self-reported self-efficacy by the 29-item Strategies Used by People to Promote Health (SUPPH) [33]. The study showed a significant increase in total self-efficacy scores after self-management training in the intervention group compared to the control group (p<0.05) [33]. One educational clinical trial with a historical control group by Zhang et al. measured health-promoting lifestyle by the health-promoting lifestyle profile II questionnaire (HPLP II) [31]. The study showed a significantly higher health-promoting lifestyle score in the intervention group compared with the control group at both discharge and two months after discharge [31].
Lifestyle. Four studies comprising two randomized clinical trials [23, 24] and two clinical trials with historical control groups [27, 31] presented lifestyle measures as an intervention outcome. The randomized controlled educational study by Sussman et al. measured lifestyle change using an 18 forced-choice questionnaire on diet, alcohol, smoking, drugs, exercise, and medication compliance. The study showed a more significant difference in average lifestyle score in the intervention group (P<0.05) [23]. The clinical educational trial with a historical control group by Zhang et al. measured health-promoting lifestyle using the 52-item Health-promoting lifestyle profile II questionnaire (HPLP II), including questions related to the six dimensions of health responsibility, exercise, nutrition, self-realization, interpersonal relationships, and stress management [31]. The study showed significantly higher HPLP II scores in the study group compared to the control group at discharge and two months after discharge (p<0.05) [31]. Two clinical trials with a historical control group presented results on alcohol consumption [24, 27]. The case management study by Andersen et al. showed reduced alcohol consumption in the intervention group in 17 out of 19 participants, and five participants stopped alcohol consumption altogether. Data for the control group was unreliable and not used for statistical analysis [24]. The standardized follow-up study by Majc et al. showed a significant decrease in alcohol consumption in the intervention group compared to the control group (p = 0.018) [27].
Cost-effectiveness. Two studies conducted a cost-effectiveness analysis [26, 28]. The randomized controlled, standardized hospital follow-up study by Morando et al. showed higher costs of the specialized caregiver model for the intervention group than the treatment in the control group. However, the costs of readmissions were higher in the control group causing significantly lower overall management costs in the intervention group compared to the control group (p<0.05) [26]. The case-management study by Andersen et al. showed that the median economic costs for subsequent hospital admissions were similar in the intervention and control group (p = 0.65) [24].
Discussion
Through a systematic approach to the search strategy and data quality assessment, this review summarises the best evidence available on mortality, readmissions, quality of life, self-efficacy, disease knowledge, lifestyle, and cost-effectiveness in cases of decompensated cirrhosis, where a nurse-assisted follow-up, including nurse-assisted multidisciplinary interventions, was administered. The results show three main types of interventions: educational interventions, case management studies, and standardized hospital follow-up. We saw significant improvement across all types of studies on several parameters, including objective outcomes such as mortality, readmissions and cost-effectiveness and subjective outcomes such as quality of life, self-efficacy, and patient knowledge. The three standardized hospital follow-up studies all showed significantly reduced mortality rates. We did though see mixed results concerning readmissions rates and quality of life across the different types of interventions, indicating that currently, no data support a specific type of nurse-assisted or multidisciplinary post-discharge intervention.
The present review shows that controlled trials with a predefined intervention evaluating clinically- and practice-relevant endpoints in a real-life, patient-oriented setting are highly warranted. As described in previous studies, there is a need for randomized clinical studies concerning standardized nursing care and chronic care models with multidisciplinary involvement in the treatment of liver cirrhosis [5, 39, 40], as the efficacy of such programs is widely shown in other major chronic diseases, including heart failure and chronic obstructive pulmonary disease [41, 42]. Future studies should focus on evaluating and validating nurse- and physician-driven clinics and programs of rehabilitation to secure personalized healthcare services for patients and their families and optimize the use of healthcare resources. The involvement of a patient’s family in health care has proven beneficial in other chronic diseases [43, 44]. In a recent review concerning nursing care of patients with liver cirrhosis, the involvement of caregivers or family members is stated as an essential part of both treatment and follow-up [5]. Several studies show the positive effect and importance of utilizing family nursing and involving families in health care for acute and chronically ill patients [44, 45].
In a multi-center randomized trial, patients with liver cirrhosis are offered standard care or participation in a nurse-led clinic in addition in addition to standard care [46]. The primary outcome will be the physical and mental health-related quality of life, while the secondary outcomes include readmissions and disease progress. Another mixed methods hybrid type I effectiveness-implementation study aims to demonstrate the effectiveness and implementation feasibility of using an order-set in routine patient care within eight hospital sites in Alberta [47]. And, in a large randomized multi-cite study a 28-day home-based multidisciplinary intensive liver optimization programme “LivR” aimed at improving 28-day mortality and reducing 30-day readmission will be tested compared to standard care [48]. These studies may provide substantial evidence about nurse-assisted personalized management of cirrhosis.
Limitations
All included randomized studies were classified as having a high risk of bias, and all non-randomized studies were assessed as having low certainty of the evidence. Given the nature of the interventions in question, blinding participants and personnel was neither feasible nor rational, partly explaining the high risk of performance bias in the randomized studies. Some studies may have moderated performance bias by objective outcomes such as hospital admission and mortality. Detection bias could be a potential source of bias in the individual studies in this review due to many subjective outcomes, such as self-efficacy, lifestyle improvements, and quality of life. A high attrition rate is reported in several studies in this review [14, 23, 25, 28, 36, 37], which is expected in studies with vulnerable and frail populations. A substantial loss to follow-up could lead to both overestimations of the treatment effects and underestimation due to attrition of the most fragile patients [49]. Studies were conducted in countries that vary in culture, religion, and etiology of cirrhosis; thus, comparing results from different healthcare settings should be considered. Lastly, concerning the multifaceted educational interventions, it should be considered which part of the educational program created the beneficial effects or if it was the combination of the educational program and closer contact with health care personnel that proved effective. Future studies with stratified outcomes may improve the evidence of using educational tools in post-discharge follow-up.
Initially, we planned to perform meta-analyses of mortality outcomes and the number of patients admitted to the hospital during the follow-up period. Due to the heterogeneity of the eight randomized studies concerning populations, interventions, controls, and outcomes, a meta-analysis was not found justified to perform [50].
Conclusion
In this review, we applied a systematic approach to nurse-assisted and multidisciplinary outpatient follow-up among patients with decompensated liver cirrhosis. Studies were found to be of low to moderate quality. We saw significant improvement across all types of studies on several parameters, including objective outcomes such as mortality, readmissions, and cost-effectiveness, and subjective outcomes such as quality of life, self-management, and patient knowledge, but currently, no data support a specific type of nurse-assisted, post-discharge intervention. Due to the low number of randomized studies included in this systematic review, divergent methodology, and high heterogeneity across interventions, the present review shows that controlled trials with a predefined intervention evaluating clinically- and practice-relevant endpoints in a real-life, patient-oriented setting are highly warranted.
Supporting information
S2 Appendix. Excluded studies and the reason for exclusion.
https://doi.org/10.1371/journal.pone.0278545.s002
(PDF)
Acknowledgments
The authors wish to thank their colleagues, Steve Sussman, Alan Wigg, Bojan Tepes, and Dejan Majc, for answering questions about their research and, where possible, providing additional data on outcomes. Special thanks to Frank V. Schiødt and Sarah Montagnese for providing individual patient data from their trials conducted in Denmark and Italy, respectively.
References
- 1. Chan RJ, Marx W, Bradford N, Gordon L, Bonner A, Douglas C, et al. Clinical and economic outcomes of nurse-led services in the ambulatory care setting: A systematic review. Int J Nurs Stud. 2018;81:61–80. pmid:29518623
- 2. Boudreault S, Chen J, Wu KY, Pluddemann A, Heneghan C. Self-management programmes for cirrhosis: A systematic review. J Clin Nurs. 2020;29(19–20):3625–37. pmid:32671877
- 3. Moon AM, Singal AG, Tapper EB. Contemporary Epidemiology of Chronic Liver Disease and Cirrhosis. Clin Gastroenterol Hepatol. 2020;18(12):2650–66. pmid:31401364
- 4. Rowe IA. Lessons from Epidemiology: The Burden of Liver Disease. Dig Dis. 2017;35(4):304–9. pmid:28468017
- 5. Fabrellas N, Carol M, Palacio E, Aban M, Lanzillotti T, Nicolao G, et al. Nursing care of patients with cirrhosis. Hepatology (Baltimore, Md). 2020:
- 6. Ginès P, Krag A, Abraldes JG, Solà E, Fabrellas N, Kamath PS. Liver cirrhosis. Lancet. 2021;398(10308):1359–76. pmid:34543610
- 7. Jepsen P, Ott P, Andersen PK, Sorensen HT, Vilstrup H. Clinical course of alcoholic liver cirrhosis: a Danish population-based cohort study. Hepatology (Baltimore, Md). 2010;51(5):1675–82. pmid:20186844
- 8. Galant LH, Forgiarini LA Junior, Dias AS, Marroni CA. Functional status, respiratory muscle strength, and quality of life in patients with cirrhosis. Revista brasileira de fisioterapia (Sao Carlos (Sao Paulo, Brazil)). 2012;16(1):30–4. pmid:22441225
- 9. Hansen L, Chang MF, Lee CS, Hiatt S, Firsick EJ, Dieckmann NF, et al. Physical and Mental Quality of Life in Patients With End-Stage Liver Disease and Their Informal Caregivers. Clin Gastroenterol Hepatol. 2021;19(1):155–61 e1. pmid:32289544
- 10. Volk ML, Tocco RS, Bazick J, Rakoski MO, Lok AS. Hospital readmissions among patients with decompensated cirrhosis. The American journal of gastroenterology. 2012;107(2):247–52. pmid:21931378
- 11. Morales BP, Planas R, Bartoli R, Morillas RM, Sala M, Cabré E, et al. Early hospital readmission in decompensated cirrhosis: Incidence, impact on mortality, and predictive factors. Dig Liver Dis. 2017;49(8):903–9. pmid:28410915
- 12. Berman K, Tandra S, Forssell K, Vuppalanchi R, Burton JR Jr., Nguyen J, et al. Incidence and predictors of 30-day readmission among patients hospitalized for advanced liver disease. Clin Gastroenterol Hepatol. 2011;9(3):254–9. pmid:21092762
- 13. Williams R, Ashton K, Aspinall R, Bellis MA, Bosanquet J, Cramp ME, et al. Implementation of the Lancet Standing Commission on Liver Disease in the UK. Lancet. 2015;386(10008):2098–111. pmid:26700394
- 14. Volk ML, Fisher N, Fontana RJ. Patient knowledge about disease self-management in cirrhosis. The American journal of gastroenterology. 2013;108(3):302–5. pmid:23459041
- 15. Burnham B, Wallington S, Jillson IA, Trandafili H, Shetty K, Wang J, et al. Knowledge, attitudes, and beliefs of patients with chronic liver disease. Am J Health Behav. 2014;38(5):737–44. pmid:24933143
- 16. Saleh ZM, Bloom PP, Grzyb K, Tapper EB. How Do Patients With Cirrhosis and Their Caregivers Learn About and Manage Their Health? A Review and Qualitative Study. Hepatol Commun. 2021;5(2):168–76. pmid:33553967
- 17. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS medicine. 2009;6(7):e1000097. pmid:19621072
- 18. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60(8):646–9. pmid:4541913
- 19. Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33(2):464–70. pmid:11172350
- 20.
Higgins JPT TJ, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane Handbook for Systematic Reviews of Interventions version 6.0 www.training.cochrane.org/handbook.: Cochrane; 2019
- 21.
Schünemann HB, Jan; Guyatt, Gordon; Oxman, Andrew. Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach https://gdt.gradepro.org/app/handbook/handbook.html#h.52ccy41iwbon2013 [
- 22. Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ journal of surgery. 2003;73(9):712–6. pmid:12956787
- 23. Sussman S, Runyon BA, Hernandez R, Magallanes M, Mendler M, Yuan JM, et al. A pilot study of an alcoholic liver disease recurrence prevention education program in hospitalized patients with advanced liver disease. Addict Behav. 2005;30(3):465–73. pmid:15718064
- 24. Andersen MM, Aunt S, Jensen NM, Homann C, Manniche J, Svendsen S, et al. Rehabilitation for cirrhotic patients discharged after hepatic encephalopathy improves survival. Dan Med J. 2013;60(8):A4683. pmid:23905568
- 25. Wigg AJ, McCormick R, Wundke R, Woodman RJ. Efficacy of a chronic disease management model for patients with chronic liver failure. Clin Gastroenterol Hepatol. 2013;11(7):850–8.e1-4. pmid:23375997
- 26. Morando F, Maresio G, Piano S, Fasolato S, Cavallin M, Romano A, et al. How to improve care in outpatients with cirrhosis and ascites: a new model of care coordination by consultant hepatologists. J Hepatol. 2013;59(2):257–64. pmid:23523582
- 27. Majc D, Tepes B. The Impact of Outpatient Clinical Care on the Survival and Hospitalisation Rate in Patients with Alcoholic Liver Cirrhosis. Radiology and oncology. 2018;52(1):75–82. pmid:29520208
- 28. Morales BP, Planas R, Bartoli R, Morillas RM, Sala M, Casas I, et al. HEPACONTROL. A program that reduces early readmissions, mortality at 60 days, and healthcare costs in decompensated cirrhosis. Dig Liver Dis. 2018;50(1):76–83. pmid:28870446
- 29. Ganapathy D, Acharya C, Lachar J, Patidar K, Sterling RK, White MB, et al. The patient buddy app can potentially prevent hepatic encephalopathy-related readmissions. Liver Int. 2017;37(12):1843–51. pmid:28618192
- 30. Kumral D, Crothers MW, Caldwell SH, Henry Z. A simple educational tool for reducing 30-day hospital readmissions in patients with decompensated cirrhosis. Hepatology (Baltimore, Md). 2015;62:214A.
- 31. Zhang X, Xi W, Liu L, Wang L. Improvement in Quality of Life and Activities of Daily Living in Patients with Liver Cirrhosis with the Use of Health Education and Patient Health Empowerment. Med Sci Monit. 2019;25:4602–8. pmid:31223134
- 32. Garrido M, Turco M, Formentin C, Corrias M, De Rui M, Montagnese S, et al. An educational tool for the prophylaxis of hepatic encephalopathy. BMJ open gastroenterology. 2017;4(1):e000161. pmid:28944074
- 33. Mansouri PM, Ghadami MM, Najafi SSM, Yektatalab SP. The effect of Self-Management Training on Self-Efficacy of Cirrhotic Patients Referring to Transplantation Center of Nemazee Hospital: A Randomized Controlled Clinical Trial. Int J Community Based Nurs Midwifery. 2017;5(3):256–63. pmid:28698885
- 34. Zandi M, Adib-Hajbagheri M, Memarian R, Nejhad AK, Alavian SM. Effects of a self-care program on quality of life of cirrhotic patients referring to Tehran Hepatitis Center. Health and quality of life outcomes. 2005;3:35. pmid:15904528
- 35. Alavinejad P, Hajiani E, Danyaee B, Morvaridi M. The effect of nutritional education and continuous monitoring on clinical symptoms, knowledge, and quality of life in patients with cirrhosis. Gastroenterology & Hepatology from Bed to Bench. 2019;12(1):17–24. pmid:30949315
- 36. Bajaj JS, Ellwood M, Ainger T, Burroughs T, Fagan A, Gavis EA, et al. Mindfulness-Based Stress Reduction Therapy Improves Patient and Caregiver-Reported Outcomes in Cirrhosis. Clin Transl Gastroenterol. 2017;8(7):e108. pmid:28749453
- 37. Goldsworthy MA, Fateen W, Thygesen H, Aldersley MA, Rowe IA, Jones RL. Patient understanding of liver cirrhosis and improvement using multimedia education. Frontline gastroenterology. 2017;8(3):214–9. pmid:28706622
- 38. Younossi ZM, Guyatt G, Kiwi M, Boparai N, King D. Development of a disease specific questionnaire to measure health related quality of life in patients with chronic liver disease. Gut. 1999;45(2):295–300. pmid:10403745
- 39. Mellinger JL, Volk ML. Multidisciplinary management of patients with cirrhosis: a need for care coordination. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association. 2013;11(3):217–23. pmid:23142204
- 40. Thomson MJ, Lok AS, Tapper EB. Optimizing medication management for patients with cirrhosis: Evidence-based strategies and their outcomes. Liver international: official journal of the International Association for the Study of the Liver. 2018;38(11):1882–90. pmid:29845749
- 41. Guell R, Casan P, Belda J, Sangenis M, Morante F, Guyatt GH, et al. Long-term effects of outpatient rehabilitation of COPD: A randomized trial. Chest. 2000;117(4):976–83. pmid:10767227
- 42. Sadeghi M, Salehi-Abargouei A, Kasaei Z, Sajjadieh-Khajooie H, Heidari R, Roohafza H. Effect of cardiac rehabilitation on metabolic syndrome and its components: A systematic review and meta-analysis. J Res Med Sci. 2016;21:18. pmid:27904564
- 43. Halldórsdóttir BS, Svavarsdóttir EK. Purposeful Therapeutic Conversations: Are They Effective for Families of Individuals with COPD: A Quasi-Experimental Study. Vård i Norden. 2012;32(1):48–51.
- 44. Svavarsdottir EK, Sigurdardottir AO. Benefits of a brief therapeutic conversation intervention for families of children and adolescents in active cancer treatment. Oncol Nurs Forum. 2013;40(5):E346–57. pmid:23989027
- 45. Halldórsdóttir BS, Svavarsdóttir EK. Purposeful Therapeutic Conversations: Are They Effective for Families of Individuals with COPD: A Quasi-Experimental Study. Vård i Norden. 2012;32(1):48–51.
- 46. Hjorth M, Sjöberg D, Svanberg A, Kaminsky E, Langenskiöld S, Rorsman F. Nurse-led clinic for patients with liver cirrhosis-effects on health-related quality of life: study protocol of a pragmatic multicentre randomised controlled trial. BMJ Open. 2018;8(10):e023064. pmid:30337316
- 47. Carbonneau M, Eboreime EA, Hyde A, Campbell-Scherer D, Faris P, Gramlich L, et al. The cirrhosis care Alberta (CCAB) protocol: implementing an evidence-based best practice order set for the management of liver cirrhosis—a hybrid type I effectiveness-implementation trial. BMC Health Serv Res. 2020;20(1):558. pmid:32552833
- 48. Ngu NL, Saxby E, Worland T, Anderson P, Stothers L, Figredo A, et al. A home-based, multidisciplinary liver optimisation programme for the first 28 days after an admission for acute-on-chronic liver failure (LivR well): a study protocol for a randomised controlled trial. Trials. 2022;23(1):744. pmid:36064596
- 49. Akl EA, Briel M, You JJ, Sun X, Johnston BC, Busse JW, et al. Potential impact on estimated treatment effects of information lost to follow-up in randomised controlled trials (LOST-IT): systematic review. BMJ. 2012;344:e2809. pmid:22611167
- 50. Egger M, Smith GD, Sterne JA. Uses and abuses of meta-analysis. Clin Med (Lond). 2001;1(6):478–84. pmid:11792089