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.

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.

Hepatocellular carcinoma amongst Aboriginal and Torres Strait Islander peoples of Australia.

BACKGROUND: Liver disease and hepatocellular carcinoma (HCC) are important contributors to the mortality gap between Indigenous and non-Indigenous Australians. However, there is a lack of population based high quality data assessing the differences in HCC epidemiology and outcomes according to Indigenous status. The aim of this study was therefore to perform a large epidemiological study of HCC investigating differences between Indigenous and non-Indigenous Australians with HCC. METHODS: Study design was a retrospective cohort study. Data linkage methodology was used to link data from cancer registries with hospital separation summaries across three Australian jurisdictions during 2000-2017. Cumulative survival (Kaplan-Meier) and the differences in survival (Multivariable Cox-regression) by Indigenous status were assessed. FINDINGS: A total of 229 Indigenous and 3587 non-Indigenous HCC cases were included in the analyses. Significant epidemiological differences identified for Indigenous HCC cases included younger age at onset, higher proportion of females, higher rurality, lower socioeconomic status, and higher comorbidity burden (all p < 0.001). The distribution of cofactors was also significantly different for Indigenous Australians including higher prevalence of alcohol misuse, hepatitis B, and diabetes and more frequent presence of multiple HCC cofactors (all p < 0.001). Indigenous Australians received curative HCC therapies less frequently (6.6% vs. 14.5%, p < 0.001) and had poorer 5-year survival (10.0% vs. 17.3%, p < 0.001; unadjusted hazard ratio (HR) =1.42 96%CI 1.21-1.65) compared to non-Indigenous Australians. The strength of the association between indigenous status and survival was weaker and statistically non-significant after adjusting for rurality, comorbidity burden and lack of curative therapy (adjusted-HR=1.20 95%CI 0.97-1.47). INTERPRETATION: Such data provide a call to action to help design and implement health literacy, liver management and HCC surveillance programs for Indigenous people to help close the liver cancer mortality gap.

Outcomes of transjugular intrahepatic portosystemic shunt procedures: a 10-year experience.

INTRODUCTION: Transjugular intrahepatic portosystemic shunt (TIPSS) is an effective modality in reducing portal pressure, and its current main indications are for the management of recurrent ascites and variceal bleeding. The demand and indications for TIPSS are growing. However, it is a complicated and technically demanding procedure with poorer outcomes associated with low volume centres. The aim of this study was, therefore, to review the outcomes of TIPSS at a 'low volume' single centre. Outcomes assessed included indications, safety, efficacy and survival. METHODS: A retrospective study was undertaken of all patients who underwent a TIPSS procedure over 10 years at tertiary referral centre for complex liver disease and transplantation. Kaplan-Meier method was used to calculate actuarial survival and log-rank analysis was used to determine significant differences in survival. RESULTS: Thirty-eight patients underwent the TIPSS procedure between January 2008 and December 2018. Technical, haemodynamic and clinical success were 95%, 92% and 92% respectively. Cumulative survival at one month, one year and five years were 86.8%, 72% and 44.7% respectively. Results achieved standards published in practice parameters to evaluate TIPSS safety and efficacy. CONCLUSION: At a low volume centre, TIPSS usage was associated with high rates of technical, haemodynamic (HPVG reduction) and clinical success. Low volume should not be a contraindication to providing a TIPSS service; however, auditing outcomes and understanding specific institutional factors that influence quality are important requirements for low volume centres.

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.

Cost effectiveness of treatment models of care for hepatitis C: the South Australian state-wide experience.

AIM: The objective was to study the long-term (lifetime) cost effectiveness of four different hepatitis C virus (HCV) treatment models of care (MOC) with directly acting antiviral drugs. METHODS: A cohort Markov model-based probabilistic cost-effectiveness analysis (CEA) was undertaken extrapolating to up to 30 years from cost and outcome data collected from a primary study involving a real-life Australian cohort. In this study, noncirrhotic patients treated for HCV from 1 March 2016 to 28 February 2017 at four major public hospitals and liaising sites in South Australia were studied retrospectively. The MOC were classified depending on the person providing patient workup, treatment and monitoring into MOC1 (specialist), MOC2 (mixed specialist and hepatitis nurse), MOC3 (hepatitis nurse) and MOC4 (general practitioner, GP). Incremental costs were estimated from the Medicare perspective. Incremental outcomes were estimated based on the quality-adjusted life years (QALY) gained by achieving a sustained virological response. A cost-effectiveness threshold of Australian dollar 50 000 per QALY gained, the implicit criterion used for assessing the cost-effectiveness of new pharmaceuticals and medical services in Australia was assumed. Net monetary benefit (NMB) estimates based on this threshold were calculated. RESULTS: A total of 1373 patients, 64% males, mean age 50 (SD ±11) years, were studied. In the CEA, MOC4 and MOC2 clearly dominated MOC1 over 30 years with lower costs and higher QALYs. Similarly, NMB was the highest in MOC4, followed by MOC2. CONCLUSION: Decentralized care using GP and mixed consultant nurse models were cost-effective ways of promoting HCV treatment uptake in the setting of unrestricted access to new antivirals.

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.

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.

Stereotactic body radiation therapy for early hepatocellular carcinoma: a retrospective analysis of the South Australian experience.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for liver tumours unsuitable for established curative treatment such as ablation or surgery. The aim of the study is to evaluate the efficacy and safety of SBRT in the treatment of small hepatocellular carcinoma (HCC) in South Australia. METHODS: From 2014 to 2018, 13 HCC patients were treated with SBRT. Eligibility criteria for SBRT included: unsuitable for standard curative therapies (resection or percutaneous ablation), lack of complete response to prior transarterial chemoembolization, Child-Pugh classification ≤B7, tumours ≤5 cm and minimum of up to 6 months follow-up post-SBRT. The prescribed radiation dose was determined by liver function with doses ranging from 40 to 45 Gy in three or five fractions. Records for all patients were reviewed, and treatment response was scored according to the modified response evaluation criteria in solid tumours. Toxicity was graded according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median follow-up time was 22.7 months, and the median tumour size was 40 mm. The 1 year local control was 92.3%, recurrence-free survival was 67.7% and overall survival was 86.4% at end of study. Three patients underwent liver transplant. No grade ≥3 non-haematological toxicities were observed. One patient experienced acute grade ≥3 haematological toxicity. CONCLUSION: SBRT is a safe, effective and non-invasive alternative treatment option for patients with small HCCs, unsuitable for standard, evidence-based therapies and lacking complete response to transarterial chemoembolization. Randomized controlled trials are required to further investigate the role of SBRT in HCC.

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.

Improved Survival of Hepatocellular Carcinoma Patients Diagnosed with a Dedicated Screening Programme-a Propensity Score Adjusted Analysis.

AIM: To assess the overall survival (OS) in those with hepatocellular carcinoma (HCC) diagnosed within a programmatic, centrally co-ordinated, regional screening programme. METHODS: A retrospective cohort analysis of consecutive HCC patients diagnosed between 2004 and 2013. Patients were followed up till death or end of study period (30 April 2015). A dedicated screening programme was commenced in 2009 to screen high-risk patients for HCC. Primary objective is to compare the OS between HCC patients diagnosed within the screening group versus those diagnosed outside this group. Other objectives were to compare tumour stage at diagnosis and the proportion having curative treatments in the two groups. Propensity score adjustments were performed to assess the survival benefit. RESULTS: HCC was diagnosed in 130 subjects during the study period (82.3% males, median [IQR] age 62 [± 19] years and median [IQR] follow-up of 11.3 (± 23.5) months). Ninety-six patients (73.8%) died during the follow-up, and the median (95%CI) OS was 15.7 (9.7-21.8) months. HCC diagnosed within the screening programme had a better OS compared to those diagnosed outside this programme (26.8 vs 11.5 months, p = 0.01). Further, those diagnosed within the programme had an earlier stage HCC ([58.3% vs 23.6%], Ó¼2 = 11.3, p = 0.001), and a significant proportion were treated with curative intent ([62.5% vs 31.1%], Ó¼2 = 8.3, p = 0.004). Propensity score adjustment showed a 58% reduction in mortality for HCC diagnosed within the screening programme (HR [95%CI] 0.42 [0.20-0.89], p = 0.02). CONCLUSION: A programmatic, regional HCC screening programme improved the OS and detected tumours at an earlier stage enabling more patients to have curative therapies.

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.

NGM282 for Treatment of Patients With Primary Biliary Cholangitis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Patients with primary biliary cholangitis (PBC) who had an inadequate response to ursodiol have few treatment options. Alkaline phosphatase (ALP) and bilirubin levels correlate with the risk of liver transplant or death in PBC patients. Fibroblast growth factor (FGF) 19 is a hormone that acts directly in the liver to regulate bile acid synthesis. We evaluated NGM282, an engineered analogue of FGF19, for the treatment of PBC. In this 28-day, double-blind, placebo-controlled phase 2 trial, 45 PBC patients who had an inadequate response to ursodiol were randomly assigned 1:1:1 to receive subcutaneous daily doses of either NGM282 at 0.3 mg (n = 14), 3 mg (n = 16), or placebo (n = 15). The primary endpoint was a change in ALP from baseline after 28 days of treatment. At day 28, ALP was significantly reduced with NGM282 treatment at both 0.3 mg (least-squares mean -51.0 IU/L [standard error (SE) 15.4]) and 3 mg (-66.0 IU/L [SE 16.0]) versus placebo (3.3 IU/L [SE 14.8]), with least-squares mean differences of -54.3 IU/L (95% confidence interval -104.2 to -4.5; P = 0.0149) and -69.3 IU/L (95% confidence interval -120.5 to -18.3; P = 0.0030), respectively. Fifty percent (7 of 14) of patients receiving NGM282 0.3 mg and 46% (6 of 13) of those receiving NGM282 3mg achieved 15% or greater reduction in ALP levels from baseline, compared with 7% (1 of 15) of patients receiving placebo. NGM282 also significantly reduced serum concentrations of transaminases and immunoglobulins. Most adverse events were grade 1 (mild) to grade 2 (moderate) in severity, with gastrointestinal disorders more frequent in the NGM282 treatment groups. No worsening of pruritus was observed with NGM282 treatment. Conclusion: NGM282 administered for 28 days resulted in significant improvements in ALP and transaminase levels compared with placebo, with an acceptable safety profile in patients with PBC. (Hepatology Communications 2018; 00:000-000).

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.

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.