James Orr

Health related quality of life in people with advanced chronic liver disease

Cirrhosis has a long natural history with considerable symptomatic impacts, particularly in advancing disease. Measuring health related quality of life (HRQOL) in liver disease provides detail about the nature and extent of its effects on individuals. Understanding the drivers of impaired HRQOL can help identify targets for improvement through new treatments or health systems service delivery. Evaluation of novel therapies which target symptomatic improvement, should be done with suitable outcome measures, including HRQOL assessment. In this article, we provide an overview of HRQOL in advanced liver disease for the clinician. A clear description of the important HRQOL tools is given alongside a discussion of the factors, which are known to contribute to impaired HRQOL in advanced liver disease.

The impact on hospital resource utilisation of treatment of hepatic encephalopathy with rifaximin-α.

Rifaximin‐α reduces the risk of recurrence of overt hepatic encephalopathy. However, there remain concerns regarding the financial cost of the drug. We aimed to study the impact of treatment with rifaximin‐α on healthcare resource utilisation using data from seven UK liver treatment centres.

Predictors of quality of life in patients evaluated for liver transplantation

Health‐related quality of life (HRQOL) is severely impaired in advanced liver disease. The purpose of this study was to evaluate the impact of actual liver function and disease‐specific factors on HRQOL of patients evaluated for liver transplantation.

Natural History of Patients Taking Rifaximin-α for Recurrent Hepatic Encephalopathy and Risk of Future Overt Episodes and Mortality: A Post-hoc Analysis of Clinical Trials Data

PURPOSE Hepatic encephalopathy (HE) is a complication of cirrhosis signaling decompensation and is associated with mortality. There has been little characterization of HE once an incident episode has occurred and of what effect the transition to overt HE might have on outcomes. We characterized the relationships between the number of previous HE episodes and risk of subsequent episodes and mortality to better understand the natural history of HE. METHODS Data on 321 patients from a 24-month, open-label, nonrandomized trial evaluating the long-term safety profile and tolerability of twice-daily rifaximin-α 550 mg were analyzed. Patients were followed for a mean of 1.5 years (total follow-up of 467 years). FINDINGS There were a total of 334 HE episodes and 75 deaths, corresponding to unadjusted event rates of 715 HE episodes and 161 deaths per 1000 years. There was a direct association between rate of subsequent HE episodes and number of prior HE episodes; the risk of subsequent HE episodes was elevated for each additional HE episode (hazard ratio = 1.23; 95% CI, 1.19-1.29). There was a nonlinear, nonmonotonic relationship between risk of death and number of prior HE episodes; risk initially increased, then decreased, and finally plateaued as the number of prior HE episodes increased. IMPLICATIONS Patients with a larger number of previous, overt HE episodes had a greater risk for subsequent episodes. However, mortality risk decreased after the third episode of HE. A plausible hypothesis to explain this finding is that risk of mortality may be reduced in patients receiving long-term rifaximin-α therapy.

How can primary care enhance end-of-life care for liver disease? Qualitative study of general practitioners’ perceptions and experiences

Background Liver disease is the third most common cause of premature death in the UK. The symptoms of terminal liver disease are often difficult to treat, but very few patients see a palliative care specialist and a high proportion die in hospital. Primary care has been identified as a setting where knowledge and awareness of liver disease is poor. Little is known about general practitioners’ (GPs) perceptions of their role in managing end-stage liver disease. Objective To explore GPs’ experiences and perceptions of how primary care can enhance end-of-life care for patients with liver disease. Design Qualitative interview study, thematic analysis. Participants Purposive sample of 25 GPs from five regions of England. Results GPs expressed a desire to be more closely involved in end-of-life care for patients with liver disease but identified a number of factors that constrained their ability to contribute. These fell into three main areas; those relating directly to the condition, (symptom management and the need to combine a palliative care approach with ongoing medical interventions); issues arising from patients’ social circumstances (stigma, social isolation and the social consequences of liver disease) and deficiencies in the organisation and delivery of services. Collaborative working with support from specialist hospital clinicians was regarded as essential, with GPs acknowledging their lack of experience and expertise in this area. Conclusions End-of-life care for patients with liver disease merits attention from both primary and secondary care services. Development of care pathways and equitable access to symptom relief should be a priority.

Liver transplantation for acute liver failure caused by macrophage activation syndrome

Macrophage activation syndrome (MAS) is a rare, potentially fatal condition, which most frequently complicates rheumatological conditions and is often associated with liver dysfunction. In this case report of a patient with MAS, acute liver failure developed despite conventional immunosuppressive therapy. Liver transplantation resulted in rapid recovery and the patient has remained well for six years. A recent diagnosis of Adult Onset Stills Disease (AOSD) provides additional supporting evidence that the initial presentation was caused by MAS. While transplantation in the context of systemic disease remains controversial, this first reported case of successful adult liver transplantation for acute liver failure caused by MAS raises an interesting clinical dilemma.

PTU-112 Rifaximin for Hepatic Encephalopathy is Cost Effective at Reducing Emergency Hospital Admission

Introduction Overt Hepatic Encephalopathy (HE) frequently results in emergency admission to hospital. Treatment with the non-absorbable antibiotic rifaximin is effective at preventing recurrence of overt HE but there are concerns about the high cost of the drug. The aim of this study was to evaluate the cost-effectiveness of rifaximin at reducing emergency admission to hospital. Methods All patients commenced on rifaximin for HE from 1st January to 31st December 2011 were identified from the records of the pharmacy department at Freeman Hospital. The number and length of emergency hospital admissions for the period 1 year prior to starting rifaximin was compared to 1 year after starting the drug. Cost effectiveness was calculated using the standard British National Formulary (BNF) tariff for rifaximin and the estimated cost per day for acute inpatient admission to the Newcastle upon Tyne Hospitals Trust. Results 64 patients (75% male, 53% ALD) were identified, 40 (63%) were on concomitant lactulose. In 8 patients rifaximin was discontinued (5 after transplant and 3 when HE excluded). 23 (36%) patients died within 1 year (median survival 62 days (range 2–364) and 33 (52%) were alive at 1 year and remained on rifaximin. Mean MELD of survivors was significantly lower than non-survivors (13.0 vs. 19.0 P < 0.05) and scores predicted 28 day mortality (median MELD 29 (range 4–37)). Complete data were available for 25 of the survivors and showed a significant reduction in the number of emergency admissions from a mean of 2.8 to 1.7 admissions per patient per year with rifaximin (P < 0.05). Duration of inpatient admission decreased significantly from a mean of 30.2 to 9.8 bed days per patient per year (P < 0.05). Taking into account the cost of one year’s treatment with rifaximin (£3,687GBP) the reduction in the number of emergency admissions represents an annual saving of £3,468GBP per patient. Conclusion Treatment with rifaximin for secondary prevention of hepatic encephalopathy appears to be cost effective at reducing emergency admission to hospital. Disclosure of Interest None Declared

Development and validation of diagnostic triage criteria for liver disease from a minimum data set enabling the ‘intelligent LFT’ pathway for the automated assessment of deranged liver enzymes

Background Liver function tests (LFTs) are commonly abnormal; most patients with ‘incidental’ abnormal LFTs are not investigated appropriately and for those who are, current care pathways are geared to find an explanation for the abnormality by a lengthy process of investigation and exclusion, with costs to the patient and to the health service. Objective To validate an intelligent automatable analysis tool (iLFT) for abnormal liver enzymes, which diagnoses common liver conditions, provides fibrosis stage and recommends management Design A retrospective case note review from three tertiary referral liver centres, with application of the iLFT algorithm and comparison with the clinician’s final opinion as gold standard. Results The iLFT algorithm in 91.3% of cases would have correctly recommended referral or management in primary care. In the majority of the rest of the cases, iLFT failed safe and recommended referral even when the final clinical diagnosis could have been managed in primary care. Diagnostic accuracy was achieved in 82.4% of cases, consistent with the fail-safe design of the algorithm. Two cases would have remained in primary care as per the algorithm outcome, however on clinical review had features of advanced fibrosis. Conclusion iLFT analysis of abnormal liver enzymes offers a safe and robust method of risk stratifying patients to the most appropriate care pathway as well as providing reliable diagnostic information based on a single blood draw, without repeated contacts with health services. Offers the possibility of high quality investigation and diagnosis to all patients rather than a tiny minority.

Where are we going? Translational research in hepatic encephalopathy

Translational medicine, rather than being a unidirectional clinical utilization of basic research discoveries, should be a bidirectional process of cross-fertilization between basic science, medical knowledge and clinical utilization. While steps and processes differ across these branches of research, clear language and proper definitions are prerequisites for effective interaction of researchers to facilitate knowledge development. With respect to Hepatic Encephalopathy, at first glance the areas which require development are around prevention, both to reduce the risk of relapse following an episode of overt HE and to reduce the risk of the first episode of HE. In addition, shortening the duration of episodes of overt HE may also be relevant. Comparisons of treatments and combinations of treatments, acting by different but potentially synergistic mechanisms, are reasonable targets for both basic and applied research.

PTU-127 Resource Use Associated With Hepatic Encephalopathy In Patients With Severe Liver Disease

Introduction Overt hepatic encephalopathy (HE) is associated with frequent hospitalisations which are expensive to manage and result in poor quality of life. The aim was to estimate the resource use associated with HE and hospitalisation in the UK. Methods The Clinical Practice Research Datalink (CPRD) with linked hospital data from Health Episode Statistics (HES) was used to identify patients with a first diagnosis of liver disease between 1998 and 2012 and examine their all-cause hospitalisations. HE patients were matched to controls at a ratio of 1:1 by age, gender, year of diagnosis, duration and severity of liver disease. Hospital admission data (frequency and length of stay) were characterised from HES. Admissions associated with the index diagnosis of HE were excluded. Results 17,030 patients were identified with an incident diagnosis of liver disease, of whom 551 (3.2%) had a recorded diagnosis of HE. 389 patients (70.6%) could be matched to non-HE controls. Total number of primarily liver-related admissions was greater in the HE group with a crude admission ratio of 3.588 (95% CI 3.085–4.173; p < 0.001). In the HE group, a significantly greater proportion of liver-related admissions were through AandE (62.1% vs. 50.0%, p < 0.001) and mean length of stay was 8.0 days (sd 11.6) vs 6.8 days (sd 9.5) (p = 0.148) in the non-HE group. Following first HE event, patients had 18.2 primary care contacts per patient year compared with 8.7 for non-HE controls (p < 0.001). Conclusion HE was associated with increased risk of liver-related hospital admissions and increased GP attendances. Disclosure of Interest J. Orr: None Declared, C. Morgan Consultant for: Norgine;, M. Hudson: None Declared, S. Jenkins-Jones Consultant for: Norgine, P. Conway Employee of: Norgine, A. Radwan Employee of: Norgine, C. Currie Consultant for: Norgine.