A randomized multicenter trial of a chronic disease management intervention for decompensated cirrhosis. The Australian Liver Failure (ALFIE) trial.

BACKGROUND AND AIMS: Improving the care of decompensated cirrhosis is a significant clinical challenge. The primary aim of this trial was to assess the efficacy of a chronic disease management (CDM) model to reduce liver-related emergency admissions (LREA). The secondary aims were to assess model effects on quality-of-care and patient-reported outcomes. APPROACH AND RESULTS: The study design was a 2-year, multicenter, randomized controlled study with 1:1 allocation of a CDM model versus usual care. The study setting involved both tertiary and community care. Participants were randomly allocated following a decompensated cirrhosis admission. The intervention was a multifaceted CDM model coordinated by a liver nurse. A total of 147 participants (intervention=75, control=71) were recruited with a median Model for End-Stage Liver Disease score of 19. For the primary outcome, there was no difference in the overall LREA rate for the intervention group versus the control group (incident rate ratio 0.89; 95% CI: 0.53-1.50, p=0.666) or in actuarial survival (HR=1.14; 95% CI: 0.66-1.96, p=0.646). However, there was a reduced risk of LREA due to encephalopathy in the intervention versus control group (HR=1.87; 95% CI: 1.18-2.96, p=0.007). Significant improvement in quality-of-care measures was seen for the performance of bone density (p<0.001), vitamin D testing (p<0.001), and HCC surveillance adherence (p=0.050). For assessable participants (44/74 intervention, 32/71 controls) significant improvements in patient-reported outcomes at 3 months were seen in self-management ability and quality of life as assessed by visual analog scale (p=0.044). CONCLUSIONS: This CDM intervention did not reduce overall LREA events and may not be effective in decompensated cirrhosis for this end point.

Validation of Knowledge Questionnaire for Patients With Liver Cirrhosis.

BACKGROUND & AIMS: There is no validated questionnaire to assess disease knowledge and self-management in patients with liver cirrhosis. We developed and validated a Cirrhosis Knowledge Questionnaire (CKQ). METHODS: We created a preliminary CKQ comprising 10 questions relevant to self-management of cirrhosis, based on publications and clinical experiences. The CKQ was given to a pilot sample of 17 patients with decompensated cirrhosis to assess its face validity. In consultation with experts, we developed a second version of CKQ, comprising 14 multiple choice questions, and administered it to 116 patients with cirrhosis participating in a Chronic Liver Failure Program. The dimensionality of the construct was assessed using exploratory factor analysis and internal consistency was assessed with Cronbach's alpha. Known-group validity of the resulting instrument was assessed by comparing the performance of the CKQ in 69 patients with decompensated cirrhosis (mean age, 62 ± 13 years; 109 responses), with (n = 42) vs without (n = 67) case management. RESULTS: A 3-factor model with 7 questions related to variceal bleeding, ascites, and hepatic encephalopathy was considered the optimal dimensionality with excellent internal consistency (Cronbach's alpha = 0.82). The mean knowledge score was higher in patients with case management (5.6 ± 1.1) than in patients without case management (4.3 ± 2.1) (P = .002). CONCLUSIONS: We developed and validated a questionnaire with 7 questions on ascites, variceal bleeding, and hepatic encephalopathy to assess knowledge and self-management in patients with liver cirrhosis. Studies are needed to confirm its dimensionality and assess association of scores with patient outcomes.

Very early-onset of Cryptococcus neoformans disease following liver transplantation: Report of two cases and a review of the literature.

Cryptococcosis is the third most common invasive fungal infection following solid organ transplantation, and mortality is high. Most cases occur late and are due to reactivation of latent infection; however, very early reactivation and donor-derived transmission can occur. Routine screening pre-transplant and antifungal prophylaxis for cryptococcosis post-transplant in solid organ transplantation are not standard practice. We present two cases of very early-onset Cryptococcus neoformans disease following liver transplantation to highlight the need to consider individualized pre-transplant screening and be aware that reactivation of Cryptococcosis neoformans can occur in the immediate post-transplant period.

Outcomes for children after second liver transplantations are similar to those after first transplantations: a binational registry analysis.

OBJECTIVE: To assess long term graft and patient survival after donor liver retransplantation in children in Australia and New Zealand during 1986-2017; to determine the factors that influence survival. DESIGN: Retrospective cohort analysis (registry data). SETTING, PARTICIPANTS: Australia and New Zealand Liver Transplant Registry data for all liver retransplantations in children (under 18 years of age), 1986-2017, in all four paediatric and six adult liver transplantation centres in the two countries. MAIN OUTCOME MEASURES: Graft and patient survival at one, 5, 10 and 15 years. RESULTS: 142 liver retransplantations were undertaken in children (59 during 1986-2000, 83 during 2001-2017). Kaplan-Meier survival analysis indicated that survival was significantly greater during 2001-2017 than 1986-2000 (P < 0.001). During 2001-2017, graft survival one year after retransplantation was 84%, at 5 years 75%, at 10 years 70%, and at 15 years 54%; patient survival was 89% at one year, 87% at 5 years, 87% at 10 years, and 71% at 15 years. Median time between transplantations was 0.2 years (IQR, 0.03-1.4 years) during 1986-2000, and 1.8 years (IQR, 0.1-6.8 years) during 2001-2017 (P = 0.002). The proportion of graft failures that involved split grafts was larger during 2001-2017 (35 of 83, 42%) than 1986-2000 (10 of 59, 17%). Graft type, cause of graft failure, and number of transplants did not influence survival following retransplantation. CONCLUSION: Survival for children following retransplantation is excellent. Graft survival is similar for split and whole grafts. Children on the liver waiting list requiring retransplantation should have the same access to donor grafts as children requiring a first transplant.

Efficacy of High-Dose, Rapid, Hepatitis A and B Vaccination Schedules in Patients With Cirrhosis.

Patients with cirrhosis have increased morbidity from hepatitis A virus (HAV) and hepatitis B virus (HBV) infections, and vaccination against these infections is an important standard of care.1,2 However, vaccination in patients with cirrhosis is hindered by immune dysfunction and there is limited high-quality literature available. The aim of this work therefore was to compare immune responses of standard dose (SD) with high-dose accelerated (HDA) vaccination in cirrhotic patients.

High rates of indeterminate interferon-gamma release assays for the diagnosis of latent tuberculosis infection in liver transplantation candidates.

BACKGROUND AND AIMS: Screening for latent tuberculosis infection (LTBI) is recommended prior to solid organ transplantation. Interferon-gamma release assays (IGRAs) are the most widely used test for LTBI screening; however, assessment of IGRA performance in patients with end-stage liver disease is limited. The purpose of this study was to evaluate the prevalence and predictors of indeterminate (INDT) IGRA results in liver transplantation candidates. METHODS: Between March 2011 and May 2018, we retrospectively analyzed 155 patients undergoing liver transplantation assessment, who underwent IGRA testing (Quantiferon-TB Gold, QFT-G) to exclude LTBI. Characteristics of patients, including age, gender, etiology of liver disease, MELD score, and absolute lymphocyte counts, were compared by QFT-G result (determinate vs INDT). RESULTS: Of the 155 patients screened, the rate of positive, negative, and INDT results were 5.2%, 69.8%, and 25%, respectively. The only variable independently associated with an indeterminate test on multivariate analysis was MELD score (odds ratio = 1.07, 95% CI = 1.01-1.14 per unit increase; P = 0.014). In 95% of INDT tests, both TB antigen tube and the positive control tube were negative and repeat testing gave the same indeterminate result, suggestive of anergy rather than laboratory error. CONCLUSIONS: Our study suggests a high rate of INDT IGRA results during screening of liver transplant candidates for LTBI, associated with severity of liver disease and anergy. Because of the high rate of INDT QFT-G testing in this setting, individualized risk assessment is required including a thorough assessment of clinical risk factors and knowledge of local TB prevalence.

Early palliative care referral in patients with end stage liver disease is associated with reduced resource utilisation.

BACKGROUND AND AIMS: Palliative care referral for end stage liver disease (ESLD) is uncommon and usually occurs late. We aimed to review the rate of early palliative care referral (EPCR) in ESLD patients, its associations, and its impacts on resource utilisation and survival. METHODS: A retrospective review of all patients with ESLD admitted to a single hepatology unit between 2013 and 2016. Inclusion criteria for study entry were at least two admissions for decompensated liver disease within a six month period and not eligible for liver transplantation. The EPCR group was defined as those patients who received palliative care referral at least 30 days prior to mortality. RESULTS: 74 patients were included in the study. EPCR rate was 19%. On multivariate analysis EPCR was associated with hepatocellular carcinoma (OR 4.47, 95% CI 1.02-19.5, p=0.047), and negatively associated with alcoholic liver disease (OR 0.16, 95% CI 0.032-0.88 p=0.035). There was no difference in survival based on EPCR status. Hospitalization costs were lower in the EPCR group (p=0.027). There was also a significantly lower number of endoscopies (p=0.009), and blood transfusions (p=0.001) in the EPCR group. EPCR was also associated with higher rates of outpatient palliative care and advanced care planning. CONCLUSIONS: EPCR in ESLD was uncommon and associated with hepatocellular carcinoma and lack of alcoholic liver disease. EPCR was associated with decreased resource utilisation and further high quality studies are required to confirm the benefits of EPCR in ESLD.

Coordinated care for patients with cirrhosis: fewer liver-related emergency admissions and improved survival.

OBJECTIVES: To compare the incidence of liver-related emergency admissions and survival of patients after hospitalisation for decompensated cirrhosis at two major hospitals, one applying a coordinated chronic disease management model (U1), the other standard care (U2); to examine predictors of mortality for these patients. DESIGN: Retrospective observational cohort study. SETTING: Two major tertiary hospitals in an Australian capital city. PARTICIPANTS: Patients admitted with a diagnosis of decompensated cirrhosis during October 2013 - October 2014, identified on the basis of International Classification of Diseases (ICD-10) codes. MAIN OUTCOME MEASURES: Incident rates of liver-related emergency admissions; survival (to 3 years). RESULTS: Sixty-nine patients from U1 and 54 from U2 were eligible for inclusion; the median follow-up time was 530 days (range, 21-1105 days). The incidence of liver-related emergency admissions was lower for U1 (mean, 1.14 admissions per person-year; 95% CI, 0.95-1.36) than for U2 (mean, 1.55 admissions per person-year; 95% CI, 1.28-1.85; adjusted incidence rate ratio [U1 v U2], 0.52; 95% CI, 0.28-0.98; P = 0.042). The adjusted probabilities of transplantation-free survival at 3 years were 67.7% (U1) and 37.2% (U2) (P = 0.009). Independent predictors of reduced transplantation-free free survival were Charlson comorbidity index score (per point: hazard ratio [HR], 1.27; 95% CI, 1.05-1.54, P = 0.014), liver-related emergency admissions within 90 days of discharge (HR, 3.60; 95% CI, 1.87-6.92; P < 0.001), and unit (U2 v U1: HR, 2.54, 95% CI, 1.26-5.09; P = 0.009). CONCLUSIONS: A coordinated care model for managing patients with decompensated cirrhosis was associated with improved survival and fewer liver-related emergency admissions than standard care.

Cost-effectiveness of a chronic disease management model for cirrhosis: Analysis of a randomized controlled trial.

BACKGROUND AND AIMS: In this follow-up study to a randomized controlled trial of a chronic disease management (CDM) model in cirrhosis, our aim was to assess the relative cost-effectiveness of this model compared with usual care during the 12-month study period, using incremental costs per death avoided as the primary outcome. METHODS: Mean differences in hospitalization costs, deaths avoided, and change in Chronic Liver Disease Questionnaire (CLDQ) total scores were presented with 95% non-parametric bootstrapped confidence intervals. Results were also presented using a cost-effectiveness plane (CEP) and cost-effectiveness acceptability curve. RESULTS: The CDM intervention was more expensive, by 18 521 AUD per participant, but more effective (% of deaths at 12 months: 10% vs 15% and 0.67 units increase per patient in CLDQ total scores). The resultant incremental cost-effectiveness ratios were 370 425 AUD per death avoided (95% confidence interval: -14 564 AUD to 2 059 373 AUD) and 27 547 AUD per unit improvement in the CLDQ total score (95% CI: 7455 AUD to 143 874 AUD). The CEPs demonstrated some uncertainty around cost-effectiveness. The cost-effectiveness acceptability curves demonstrated that at willingness to pay values of 400 000 AUD per additional death avoided and 40 000 AUD per unit improvement in the CLDQ, there was at least a 70% probability of CDM being more cost-effective than usual care. At 24 months, CDM was much more effective (12% less deaths but now also cheaper by 985 AUD per patient). CONCLUSIONS: The analysis of data from a randomized controlled trial suggests that the CDM intervention used is likely to be cost-effective, relative to usual care, due to fewer patient deaths.

Hepatitis B screening before rituximab therapy: a multicentre South Australian study of adherence.

BACKGROUND: International guidelines recommend screening for hepatitis B virus (HBV) infection prior to administration of rituximab, due to high risk of HBV reactivation in at-risk patients. AIMS: To determine: (i) adherence to the South Australian (SA) protocol for HBV screening; (ii) HBV prevalence in patients receiving rituximab; and (iii) outcomes of patients at risk of HBV reactivation. METHODS: All patients commenced on rituximab at the six major SA public hospitals during a 12-month period were included in the study. Adherence was assessed by documentation of both hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) prior to initiation of rituximab. Patients were observed for a minimum of 6 months following rituximab initiation. RESULTS: Four hundred and thirty eight patients were included in the study. The main indication for rituximab therapy was haematological malignancy (76.0%). Two hundred and nine (47.7%) failed to receive appropriate HBV screening, 86 (19.6%) had neither HBsAg nor HBcAb performed, and 119 (27.2%) had only HBsAg performed. The identified prevalence of at-risk cases (either HBsAg- or HBcAb-positive) within the study population was 4.6% (20/438 cases). One case of HBV reactivation was identified, but none led to acute liver failure, transplantation or death. CONCLUSIONS: Poor adherence to HBV screening protocols suggests the need for targeted clinician education and system redesign. While the rate of reactivation was low, the prevalence of at-risk patients in this population was high and justifies further initiatives to increase adherence rates to HBV screening pre-rituximab.

Assessing the clinical and economic impact of increasing treatment uptake in chronic hepatitis B infection using a Markov model.

Treatment uptake in chronic hepatitis B virus (HBV) infection is low in South Australia, and the cost-effectiveness of increasing treatment uptake rates in this population has not been assessed. AIMS AND METHODS: Using a cohort Markov model, cost-effectiveness was assessed for three different treatment uptake scenarios: 2.9% (current level-scenario 1), 10% (scenario 2), and 15% (scenario 3). The initial HBV population included 2550 treatment eligible patients who transitioned between six different health states over a 10-year period. Treatment transition probabilities were based on tenofovir therapy, while those not assigned to treatment followed the natural history transition probabilities. We estimated the incremental cost per quality adjusted life year gained using the prevented number of deaths, hepatocellular carcinoma, and liver transplants. RESULTS: Scenario 3 was associated with the lowest mean cost/person over 10 years (AU$60 133), compared with scenario 2 (AU$61 964) and scenario 1 (AU$64 597). Scenario 3 was also associated with the highest quality adjusted life year gained (8.196) compared with scenario 2 (7.985) and scenario 1 (7.684). Scenario 3 would result in 50% reduction in hepatocellular carcinoma and 30% reduction in HBV-related mortality compared with scenario 1, over a 10-year period. Higher treatment uptake was found to be cost-effective with at least 2 years of treatment at either 10% or 15% of the target population. CONCLUSION: Maximizing the treatment uptake in the existing HBV population from 2.9% to 15% was cost-effective for periods of 2 years or more. This was due to a reduction in the number of expected clinical events.

Outcomes and predictors of harmful relapse following liver transplantation for alcoholic liver disease in an Australian population.

BACKGROUND: Limited studies of patient survival and alcoholic relapse following transplantation for alcoholic liver disease have been described in Australian populations. AIM: To describe these outcomes in an Australian population, to determine the association between harmful alcoholic relapse and patient survival, and to examine pre-transplant variables associated with harmful relapse. METHODS: Single centre, retrospective review of consecutive patients transplanted at the South Australian Liver Transplant Unit. Relapse was identified by an independent investigator using case note review and confidential patient questionnaire. RESULTS: A total of 87 patients (median age 52 years, 84% male, median Model for End-Stage Liver Disease (MELD) score 18) was included in the study with a median follow-up time of 50 months. The 1-, 3- and 5-year survival of patients was 93.1, 87.4 and 82.0% respectively. Two deaths were directly attributable to graft failure due to alcohol. Fourteen (16%) patients fulfilled criteria for harmful relapse and 18 (21%) patients experienced any form of relapse to alcohol. Harmful relapse was associated with increased mortality (hazard ratio (HR) 3.2, 95% confidence interval (CI) 1.1-9.7, P = 0.041). Only two factors were independently associated with harmful relapse on multivariate analysis; prior alcohol rehabilitation (HR 8.4, 95% CI 2.5-28.4, P = 0.001) and single versus married status (HR 0.09, 95% CI 0.02-1.2, P = 0.019). CONCLUSION: Good patient survival outcomes were seen for this South Australian population. Harmful alcohol relapse occurs in a minority of patients and rarely results in direct graft loss. Modifiable pre-transplant factors that predict harmful relapse were not identified.

Percutaneous thermal ablation for primary hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND AND AIM: Percutaneous thermal ablation using radiofrequency ablation (RFA) and microwave ablation (MWA) are both widely available curative treatments for hepatocellular carcinoma. Despite significant advances, it remains unclear which modality results in better outcomes. This meta-analysis of randomized controlled trials (RCT) and observational studies was undertaken to compare the techniques in terms of effectiveness and safety. METHODS: Electronic reference databases (Medline, EMBASE and Cochrane Central) were searched between January 1980 and May 2014 for human studies comparing RFA and MWA. The primary outcome was the risk of local tumor progression (LTP). Secondary outcomes were complete ablation (CA), overall survival, and major adverse events (AE). The ORs were combined across studies using the random-effects model. RESULTS: Ten studies (two prospective and eight retrospective) were included, and the overall LTP rate was 13.6% (176/1298). There was no difference in LTP rates between RFA and MWA [OR (95% CI): 1.01(0.67-1.50), P = 0.9]. The CA rate, 1- and 3-year overall survival and major AE were similar between the two modalities (P > 0.05 for all). In subgroup analysis, there was no difference in LTP rates according to study quality, but LTP rates were lower with MWA for treatment of larger tumors [1.88(1.10-3.23), P = 0.02]. There was no significant publication bias or inter-study heterogeneity (I(2) < 50% and P > 0.1) observed in any of the measured outcomes. CONCLUSION: Overall, both RFA and MWA are equally effective and safe, but MWA may be more effective compared to RFA in preventing LTP when treating larger tumors. Well-designed, larger, multicentre RCTs are required to confirm these findings.

Additive impact of pre-liver transplant metabolic factors on survival post-liver transplant.

BACKGROUND AND AIM: Diabetes at time of liver transplantation is associated with reduced post-transplant survival. We aimed to assess whether additional metabolic conditions such as obesity or hypertension had additive prognostic impact on post-transplantation survival. METHODS: A multi-center cohort study of 617 adult subjects undergoing liver transplantation between 2003 and 2009 has been used. Dry body mass index was calculated following adjustment for ascites. RESULTS: After a median follow-up of 5.8 years (range 0-10.5), 112 (18.2%) patients died. Diabetes was associated with reduced post-transplant survival (hazard ratio 1.89, 95% confidence interval [CI] 1.25-2.86, P = 0.003), whereas obesity, hypertension, dyslipidemia, and the metabolic syndrome itself were not (P > 0.3 for all). Patients with concomitant diabetes and obesity had lower survival (adjusted Hazard Ratio [aHR] 2.40, 95%CI 1.32-4.38, P = 0.004), whereas obese non-diabetic patients or diabetic non-obese patients had similar survival compared with non-diabetic, non-obese individuals. The presence of hypertension or dyslipidemia did not impact on survival in patients with diabetes (P > 0.1 for both). Obese diabetic patients had longer intensive care and hospital stays than non-obese diabetic or obese, non-diabetic patients (P < 0.05). The impact of concomitant obesity and diabetes on survival was greater in subjects aged 50+ years (52.6% 5-year survival, aHR 3.04, 95% CI 1.54-5.98) or those transplanted with hepatocellular carcinoma (34.1% 5-year survival, aHR 3.35, 95% CI 1.31-5.57). Diabetes without obesity was not associated with an increased mortality rate in these sub-groups. CONCLUSIONS: Concomitant diabetes and obesity but not each condition in the absence of the other is associated with reduced post-liver transplant survival. The impact of diabetes and obesity is greater in older patients and those with hepatocellular carcinoma.

Good outcomes of liver transplantation for hepatitis C at a low volume centre.

BACKGROUND AND AIMS: Concerns exist about outcomes of liver transplantation (LT) from low volume centres, especially for hepatitis C (HCV) patients. The aim of the study was to assess patient outcomes as well as their predictors post LT for HCV in a small volume Australian unit (< 25 LTs/year), comparing these with the average outcomes obtained from national and international transplant registries. Patients transplanted for HCV at the South Australian Liver Transplant Unit between 1992 and 2012 were studied. Outcomes assessed were patient and graft survival at 1,3, and 5 years. Factors independently associated with the outcomes were assessed using Cox regression model. RESULTS: 1, 3, and 5-year patient survival for HCV patients was 95.2, 82.9, and 78.2%, graft survival were 93.7, 80.1, and 75.5% respectively. The total follow-up time observed was 299.9 years amongst 61 patients in which there were 16 deaths. The expected number of deaths was 40.4 and the standardized mortality ratio 0.40 (95% CI = 0.24, 0.65). These results compared favourably to those obtained from the SRTR registry. Variables independently associated with lower patient survival: donor age (HR = 1.06, 95% CI 1.02 - 1.11; P = 0.003), and post LT cytomegalovirus (CMV) disease requiring treatment (HR = 4.03, 95% CI 1.48 - 10.92;P = 0.06). CONCLUSION: In conclusion, high rates of patient and graft survival for HCV liver transplantation can be obtained in a small volume unit. Young donor age and lack of CMV disease post-transplant were associated with better outcomes. Institutional factors may be influential determinants of outcomes.

Liver transplantation outcomes for Australian Aboriginal and Torres Strait Islanders.

An increased liver disease burden has been reported for Aboriginal and Torres Strait Islanders (ATSIs) in Australia; however, few proceed to liver transplantation (LT). We aimed to compare overall survival and graft survival after LT between ATSI and non-ATSI populations, assess the factors influencing survival within ATSIs, and finally examine the proportion of ATSIs undergoing LT. This study was a retrospective review of the Australia and New Zealand Liver Transplant Registry from 1985 to 2012 and examined consecutive primary LT performed in Australia. Overall and graft survival were compared between ATSI and non-ATSI groups. The Accessibility/Remoteness Index of Australia (ARIA) was used to calculate the remoteness of individuals. There were 3493 primary LT performed, and 45 patients (1.3%; 14 children and 31 adults) were ATSIs. The median (range) ages of the ATSI children and adults at the time of LT were 9.6 (0.2-15.3) years and 44.5 (19.5-65.5) years, respectively. There were 10 deaths in the ATSI cohort. The median (range) overall survival was similar for ATSI and non-ATSI children [6.5 (0.1-23.5) years versus 9.0 (0-28.2) years, P = 0.9] and adults [7.1 (0.1-15.7) years versus 6.3 0-26.7) years, P = 0.8]. The cumulative graft survival was similar for ATSI and non-ATSI children (P = 0.8) and adults (P = 0.8). High ARIA scores [hazard ratio (HR) = 1.2, 95% confidence interval (CI) = 1.01-1.53, P = 0.03] in children and blood group O (HR = 3.8, 95% CI = 1.1-12.7, P = 0.03) in adults predicted worse outcomes for ATSIs. Although ATSIs accounted for 4.7% and 1.8% of the Australian pediatric and adult populations, respectively, they represented only 2.2% of pediatric LT recipients (χ(2) = 8.2, P = 0.004) and 1.1% of adult LT recipients (χ(2) = 7.9, P = 0.005). In conclusion, overall survival and graft survival after LT are comparable in ATSIs and non-ATSIs. There is a trend toward increased death/retransplantation in ATSIs from remote areas. ATSI children and adults appear to be underrepresented in the Australian LT population.

Efficacy of a chronic disease management model for patients with chronic liver failure.

BACKGROUND & AIMS: Despite the economic impacts of chronic liver failure (CLF) and the success of chronic disease management (CDM) programs in routine clinical practice, there have been no randomized controlled trials of CDM for CLF. We investigated the efficacy of CDM programs for CLF patients in a prospective, controlled trial. METHODS: Sixty consecutive patients with cirrhosis and complications from CLF were assigned randomly to groups given intervention (n = 40) or usual care (n = 20), from 2009 to 2010. The 12-month intervention comprised 4 CDM components: delivery system redesign, self-management support, decision support, and clinical information systems. The primary outcome was the number of days spent in a hospital bed for liver-related reasons. Secondary outcomes were rates of other hospital use measures, rate of attendance at planned outpatient care, disease severity, quality of life, and quality of care. RESULTS: The intervention did not reduce the number of days patients spent in hospital beds for liver-related reasons, compared with usual care (17.8 vs 11.0 bed days/person/y, respectively; incidence rate ratio, 1.6; 95% confidence interval, 0.5-4.8; P = .39), or affect other measures of hospitalization. Patients given the intervention had a 30% higher rate of attendance at outpatient care (incidence rate ratio, 1.3; 95% confidence interval, 1.1-1.5; P = .004) and significant increases in quality of care, based on adherence to hepatoma screening, osteoporosis and vaccination guidelines, and referral to transplant centers (P < .05 for all). CONCLUSIONS: In a pilot study to determine the efficacy of CDM for patients with CLF, patients receiving CDM had significant increases in attendance at outpatient centers and quality of care, compared with patients who did not receive CDM. However, CDM did not appear to reduce hospital admission rates or disease severity or improve patient quality of life. Larger trials with longer follow-up periods are required to confirm these findings and assess cost effectiveness.

Integrating smart phone applications in the management of cirrhotic patients: A scoping review.

Background and Aim: Chronic liver disease and cirrhosis is a significant cause of healthcare utilization and patient morbidity and mortality worldwide. Smartphone applications have high uptake in most communities and therefore have great potential to provide remote support solutions to this patient population. The aim of this scoping review was therefore to provide a comprehensive overview using narrative synthesis on the use of smartphone-application-based digital interventions in cirrhotic populations. Materials and Methods: PRISMA guidelines were followed, with two independent researchers identifying 10 relevant studies. Patients studied were predominantly those with decompensated cirrhosis, and hepatic encephalopathy was the most common complication studied. Results: Smartphones were the most common platform used, but training periods, prior to commencement of the study, were rarely offered. Patient engagement rates with the technology were reported only in three studies, but all reported high (>50%) rates of engagement. Only one study examined the clinical effects of their digital intervention, with a 38% reduction in readmission rate reported. Conclusion: Overall, the use of smartphone apps in cirrhosis is in an early phase of development and evaluation but preliminary studies suggest significant potential as an adjunct to routine medical care. Further high-quality studies of well-designed digital interventions are needed to advance this promising early experience.

Association of physiological reserve measures with adverse outcomes following liver transplantation.

BACKGROUND AND AIM: The comparative utility of physiological reserve measures in predicting important clinical outcomes following liver transplantation (LT) requires further study. The aim of this work was therefore to compare the utility of physiological reserve measures in predicting early adverse clinical outcomes post-LT. METHODS: A single-center, retrospective cohort study of LT patients consecutively recruited between 1 January 2015, and 31 August 2020. Outcomes measured were sepsis and death within 12 months of LT, hospital length of stay (LOS), and intensive care LOS. Physiological reserve measures were handgrip strength, mid-arm muscle circumference, and cardiopulmonary exercise testing (CPET) measures. Analysis was performed using univariate and multivariate logistic regression for sepsis and death, and univariate and multivariate Cox regression for hospital and intensive care LOS. RESULTS: Data were obtained for 109 subjects. Patients were predominantly (64%) male with a median (interquartile range [IQR]) age of 57 (49-63) and median (IQR) Model for End-Stage Liver Disease score of 16 (11-21). In multivariate analysis, the odds of sepsis were lower in patients in the highest versus lowest tertile (odds ratio = 0.004; 95% confidence interval [CI] 0.00-0.13; P = 0.002). Hospital LOS was linearly associated with handgrip strength (hazard ratio [HR] = 1.03; 95% CI 1.00-1.06; P = 0.03) in multivariate analysis. Intensive care LOS was associated with peak VO2 (HR 1.83; 95% CI 1.06-3.16; P = 0.03) and VE/VCO2 slope (HR 0.71; 95% CI 0.58-0.88; P = 0.002) in multivariate analysis. CONCLUSION: Handgrip strength and CPET both identify candidates at high risk of adverse outcomes after LT.