We present the results of a multicenter clinical trial using Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) generated from EBV-seropositive blood donors to treat patients with EBVpositive posttransplantation lymphoproliferative disease (PTLD) on the basis of the best HLA match and specific in vitro cytotoxicity. Thirty-three PTLD patients who had failed on conventional therapy were enrolled. No adverse effects of CTL infusions were observed and the response rate (complete or partial) in 33 patients was 64% at 5 weeks and 52% at 6 months. Fourteen patients achieved a complete remission, 3 showed a partial response, and 16 had no response at 6 months (5 died before completing treatment). At 5 weeks, there was a significant trend toward better responses with higher numbers of CD4 ؉ cells in infused CTL lines (P ‫؍‬ .001) that were maintained at 6 months (P ‫؍‬ .001). Patients receiving CTLs with closer HLA matching responded better at 6 months (P ‫؍‬ .048). Female patients responded better than male patients, but the differences were not statistically significant. Our results show that allogeneic CTLs are a safe and rapid therapy for PTLD, bypassing the need to grow CTLs for individual patients. The response rate in this poor prognosis patient group is encouraging. (Blood.

No abstract

Cytomegalovirus infection (CMV) in solid organ transplant recipients is a major clinical problem. The aim of this study was to evaluate the incidence of CMV infection and its association with mortality during the first year after transplantation in a large solid organ transplant cohort at the Royal Infirmary of Edinburgh between January 2006 and April 2009. Data including the use of CMV prophylaxis, nature of CMV disease, treatment and deceased date (when appropriate) was collected retrospectively using hospital databases and patient notes for all transplanted patients with detectable CMV viraemia. The outcomes between recipients of kidney and liver transplants in the four CMV donor/recipient serostatus categories (D+R+, D-R-, D+R-, D-R+) were compared. A total of 428 individuals were included. Despite the administration of valganciclovir prophylaxis, CMV disease (syndrome or end-organ involvement) was diagnosed within the year of transplantation in the D+R--group in 31.3% of liver and 19.2% of kidney recipients. All D+R- transplant recipients that received CMV-prophylaxis presented with late-onset CMV disease. Furthermore, the rate of CMV disease in the D+R+-group was markedly higher in renal graft recipients compared to liver recipients (22% vs. 5%). The highest mortality was observed among the D+R+ liver and kidney graft recipients with CMV infection. The high incidence of late-onset CMV disease in D+R- transplant recipients receiving CMV prophylaxis demonstrates that CMV disease remains an important problem after organ transplantation. Furthermore, the surprisingly high mortality in the D+R+-transplant patients with CMV viraemia highlights the need for proactive monitoring of this group.

This final report of the Lancet Commission into Liver Disease in the UK stresses the continuing increase in disease burden of liver disease from excess alcohol consumption and obesity, with high levels of hospital admissions and a worsening in deprived areas. It concludes that only with comprehensive food and alcohol strategies based on fiscal and regulatory measures including the Minimum Unit Price (MUP) for alcohol and the alcohol duty escalator, as well as an extension of the sugar levy on food content which has been proven by previous experience in this country, can the disease burden be curtailed. Further evidence of the value of MUP is shown by initial published results (1) of its introduction in Scotland showing an overall 3% reduction in consumption, with the major effect as predicted on heavy drinkers of low-cost alcohol products The major contribution of obesity and alcohol to the high rates of the ten most common cancers is also discussed. The measures outlined by the departing Chief Medical Officer, Dame Sally Davies, to combat rising levels of obesitythe highest of any country in the Westare described along with the estimated health costs. The latest audit analysis of unacceptable levels of mortality for severely ill patients with liver disease in District General Hospitals (DGHs)(2) indicates the need for developing a masterplan for improving hospital care and such a plan is proposed in this report based around specialist hospital centres linked to DGHs by Operational Delivery Networks (ODNs). It has received strong backing from the British Association for Study of the Liver (BASL) and British Society of Gastroenterology (BSG) but is held up at NHS England (NHSE). The value of day-case care bundles to reduce high hospital readmission rates with greater care in the community is described, along with examples of locally derived schemes for the early detection of disease and in particular schemes to allow general practitioners (GPs) to refer patients directly for elastography assessment. New funding arrangements for GPs will be required if these are to be taken up more widely around the country, as is recommended. A new ComRes poll, to be published in autumn 2019, shows an appalling lack of understanding of harm to health from lifestyle causes, with a poor knowledge of alcohol consumption and dietary guidelines. The Commission has serious doubts as to whether the initiatives described in the Prevention Green Paper(3), with the onus placed on the individual based on the use of information technology and the latest in behavioural science will be effective. The final section of the report raises questions of meaningful survival in paediatric liver disease where despite excellent overall survival results, there are high levels of cognitive impairment. In the Conclusion, a strong plea is made for greater coordination between the various official and non-official bodies that have expressed views on the unacceptable disease burden from liver disease in this country in presenting a single, strong voice to the ...

Background:Liver disease is an increasing cause of death worldwide but palliative care is largely absent for these patients.Aim:We conducted a feasibility trial of a complex intervention delivered by a supportive care liver nurse specialist to improve care coordination, anticipatory care planning and quality of life for people with advanced liver disease and their carers.Design:Patients received a 6-month intervention (alongside usual care) from a specially trained liver nurse specialist. The nurse supported patients/carers to live as well as possible with the condition and acted as a resource to facilitate care by community professionals. A mixed-method evaluation was conducted. Case note analysis and questionnaires examined resource use, care planning processes and quality-of-life outcomes over time. Interviews with patients, carers and professionals explored acceptability, effectiveness, feasibility and the intervention.Setting/participants:Patients with advanced liver disease who had an unplanned hospital admission with decompensated cirrhosis were recruited from an inpatient liver unit. The intervention was delivered to patients once they had returned home.Results:We recruited 47 patients, 27 family carers and 13 case-linked professionals. The intervention was acceptable to all participants. They welcomed access to additional expert advice, support and continuity of care. The intervention greatly increased the number of electronic summary care plans shared by primary care and hospitals. The Palliative care Outcome Scale and EuroQol-5D-5L questionnaire were suitable outcome measurement tools.Conclusion:This nurse-led intervention proved acceptable and feasible. We have refined the recruitment processes and outcome measures for a future randomised controlled trial.