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Biomedical subjects

James Neuberger

Publications and source records attributed to James Neuberger.

At least 37 records · Page 2Linked to original sources
PubMed2003

Living liver donation: a survey of the attitudes of the public in Great Britain.

BACKGROUND: Living liver donation (LLD) is becoming an accepted way of increasing the donor pool for liver transplantation. The procedure is associated with major ethical difficulties because there is a significant risk of death to the healthy donor. METHODS: We therefore conducted two surveys of the Great Britain population to determine their attitudes to LLD. RESULTS: Approximately three quarters of the population of 1734 adults aged more than 15 years were supportive of LLD. Those in favor were more likely to be men, better educated, and younger. Seventy-four percent were supportive of the donor being reimbursed for costs incurred in donation, and 19% agreed that the donor should be paid for donation, although there was great variation in the amount suggested. Forty-two percent of the population believed that a risk of 1:200 or less was acceptable when donating to a family member, and only 14% believed that this risk was acceptable when donating to a friend. CONCLUSIONS: Most adults in Great Britain are in favor of LLD, although more than half believe that a donor risk of mortality of 1:200 is acceptable.

Adolescent↗
PubMed2003

Does a betaretrovirus infection trigger primary biliary cirrhosis?

Patients with primary biliary cirrhosis develop progressive ductopenia associated with the production of antimitochondrial antibodies that react with a protein aberrantly expressed on biliary epithelial cells and peri-hepatic lymph nodes. Although no specific microbe has been identified, it is thought that an infectious agent triggers this autoimmune liver disease in genetically predisposed individuals. Previous serologic studies have provided evidence to suggest a viral association with primary biliary cirrhosis. Here we describe the identification of viral particles in biliary epithelium by electron microscopy and the cloning of exogenous retroviral nucleotide sequences from patients with primary biliary cirrhosis. The putative agent is referred to as the human betaretrovirus because it shares close homology with the murine mammary tumor virus and a human retrovirus cloned from breast cancer tissue. In vivo, we have found that the majority of patients with primary biliary cirrhosis have both RT-PCR and immunohistochemistry evidence of human betaretrovirus infection in lymph nodes. Moreover, the viral proteins colocalize to cells demonstrating aberrant autoantigen expression. In vitro, we have found that lymph node homogenates from patients with primary biliary cirrhosis can induce autoantigen expression in normal biliary epithelial cells in coculture. Normal biliary epithelial cells also develop the phenotypic manifestation of primary biliary cirrhosis when cocultivated in serial passage with supernatants containing the human betaretrovirus or the murine mammary tumor virus, providing a model to test Koch's postulates in vitro.

Autoantigens↗
PubMed2003

Colorectal cancer in patients with inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis.

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) may have an increased risk of developing colorectal cancer (CRC) after liver transplantation (LT). We evaluated our patients with PSC after LT to identify risk factors for CRC and its impact on survival. PATIENTS AND METHODS: A total of 152 patients (108 men, 100 with IBD) with PSC who underwent 173 LTs between 1986 and May 2000 were analyzed in three groups: (1) PSC without IBD (n=52); (2) PSC with colectomy (pre-LT and at LT) (n=17, colectomy pre-LT in 13 and simultaneous colectomy at LT in four); and (3) PSC with IBD and an intact colon (n=83). The following factors were studied: age, gender, liver, and renal biochemistry, international normalized ratio, Child-Pugh stage, operative time, blood use, hospital stay, immunosuppression, risk of CRC, retransplantation rate, and mortality. RESULTS: The incidence of CRC after LT was 5.3% (8/152) compared with 0.6% (7/1,184) in non-PSC cases (P<0.001). All CRCs in the PSC group were in patients with IBD and an intact colon. The cumulative risk of developing CRC in the 83 patients with an intact colon and IBD was 14% and 17% after 5 and 10 years, respectively (PSC non-IBD group 0% risk after 10 years, P<0.06). The multivariate analysis showed three significant variables related to the risk of developing CRC: colonic dysplasia after LT (P<0.0003), duration of colitis more than 10 years (P<0.002), and pancolitis (P<0.004). The cause of death in patients with CRC was cancer related in 75% of cases with a reduced 5-year survival of 55% versus 75% without CRC (not significant). CONCLUSION: Patients with PSC undergoing LT with a long history of ulcerative colitis and pancolitis have an increased risk of developing CRC with reduced survival. We advocate long-term aggressive colonic surveillance and colectomy in selected high-risk patients with longstanding severe colitis.

Adolescent↗
PubMed2003

Liver Transplantation for Cholestatic Liver Disease.

Liver transplantation is an effective form of therapy for patients with end-stage cholestatic disease that improves both survival and quality of life. Liver transplantation is very effective for the treatment of intractable pruritus but less effective for the treatment of lethargy. Survival rates are good (more than 70% at 5 years); these patients are at greater risk of developing acute and chronic rejection and are more likely to require long-term immunosuppression. Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) recur in the graft. Recurrent PSC may be difficult to differentiate from secondary sclerosing cholangitis, but it recurs in up to 60% of patients at 5 years and may reduce graft survival. PBC recurrence, noted in up to 40% of patients at 10 years, has little effect on graft survival with respect to cancers. Patients with PSC are at greater risk of both colonic cancer (which may be reduced by ursodeoxycholic acid) and cholangiocarcinoma. Diagnosis of cholangiocarcinoma before transplantation usually contraindicates transplantation. The main challenges facing liver transplantation are the need to expand the donor pool and the need to find immunosuppressive regimens with fewer long-term toxicities.

Journal Article↗
PubMed2003

Midterm cost-effectiveness of the liver transplantation program of England and Wales for three disease groups.

Liver transplantation has never been the subject of a randomized controlled trial, and there remains uncertainty about the magnitude of benefit and cost-effectiveness for specific patient groups. This article reports the results of an economic evaluation of adult liver transplantation in England and Wales. Patients placed on the waiting list for a liver transplant were observed over 27 months. The costs and health benefits of a comparison group, representing experience in the absence of liver transplantation, were estimated using a combination of observed data from patients waiting for a transplant and published prognostic models. The analysis focuses on three disease groups, for each of which prognostic models were available: primary biliary cirrhosis (PBC), alcoholic liver disease (ALD), and primary sclerosing cholangitis (PSC). A higher proportion of patients with ALD were assessed for a transplant but not placed on the waiting list. The estimated gain in quality-adjusted life-years from transplantation was positive for each of the disease groups. The mean incremental cost per quality-adjusted life-year (95% bootstrap confidence intervals) from time of listing to 27 months for patients with PBC, ALD, and PSC are pound 29,000 (pounds 1,000 to pounds 59,000), pounds 48,000 (pounds 12,000 to pounds 83,000) and pounds 21,000 (-pounds 23,000 to pounds 60,000), respectively. In conclusion, liver transplantation increases the survival and health-related quality of life of patients with each of three end-stage liver diseases. However, the extent of this increase differs between different disease groups. Cost-effectiveness estimates were poorer for patients with ALD over the 27-month period than for patients with PBC or PSC. This in part reflects the costs of the higher number of ALD patients assessed for each transplant.

Adolescent↗
PubMed2003

Liver transplantation for primary biliary cirrhosis.

Liver transplantation is the accepted treatment for patients with end-stage liver disease or intractable symptoms secondary to primary biliary cirrhosis (PBC), and has proven survival benefit. Indications for transplantation are an unacceptable quality of life or anticipated death in less than 1 year. Although there are a number of prognostic models, serum bilirubin provides the simplest guide to transplantation timing. Those grafted for PBC are at greater risk of developing chronic rejection, and are less likely to be successfully weaned from immunosuppression than those grafted for other indications. Following transplantation, antimitochondrial antibodies persist and histological features of recurrent PBC may be seen in the allograft in up to 50% by 10 years; however, at least in the medium-term, this rarely causes clinical problems.

Europe↗
PubMed2003

Liver transplantation for primary biliary cirrhosis.

Liver transplantation is now the accepted treatment for patients with end-stage disease or intractable symptoms. The success rate is high. Those grafted for PBC are at greater risk of developing acute and chronic rejection and are less likely to be weaned from immunosuppression. Following transplantation, AMA persist and histological features of PBC may be seen in the allograft, in up to 50% by 10 years.

Autoantibodies↗
PubMed2003

Alternative medicines and the liver.

Complementary and Alternative Medicine (CAM) is a heterogeneous group of theories and practices that are becoming increasingly popular in the West - between 20% and 65% of patients use CAM on a regular basis. In the UK, CAM is provided by over a third of general practitioners as well as by hospitals. The subject of much debate in both the lay and medical press, CAM is subject to increasing scrutiny from clinical research. In this review, we discuss the available evidence for herbal medicines, including that for silymarin, glycyrrhizin, Chinese herbal medicines and other herbal mixtures. We also review evidence regarding the safety of herbal medicines, both in terms of hepatotoxicity and drug interactions. We conclude that although CAM may be of benefit in the treatment of liver disease, the available evidence is insufficient to recommend any of the available therapies. CAM has not yet been well studied in liver disease and rigorous evaluation with well-designed double-blind randomised controlled trails is required. Doctors need to be aware of the widespread use of CAM, ask their patients specifically regarding their use of CAM and be aware of the potential for hepatotoxicity and interactions.

Animals↗
PubMed2003

Recurrent primary biliary cirrhosis.

Liver transplantation remains the only effective treatment for end-stage primary biliary cirrhosis (PBC). It appears now well accepted that the disease recurs in the allograft. The diagnosis of recurrent PBC is made on the basis of a consistent history and demonstrating the histologic features of PBC on liver biopsy and exclusion of other causes of bile duct damage.

Autoantibodies↗
PubMed2003

Carriage of methicillin-resistant Staphylococcus aureus is associated with an increased risk of infection after liver transplantation.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of sepsis in patients with cirrhosis and after liver transplantation. The association between nasal carriage of MRSA and sepsis in these patients is unclear. The goal of this study was to investigate the relationship between MRSA carriage before liver transplantation and subsequent sepsis after transplantation. This was a retrospective study of 374 consecutive adults who underwent orthotopic liver transplantation between 1998 and 2001 and for whom full data were available. Of these, 157 had been screened for MRSA as part of a study assessing the prevalence of MRSA infection. All MRSA carriers were treated with nasal mupirocin and chlorhexidine baths. The records of MRSA carriers and noncarriers were analyzed for Child and Model for End-Stage Liver Disease (MELD) score, posttransplantation MRSA, and other infections and mortality. Of the 157 patients who had an MRSA screen, 35 patients were MRSA nasal carriers. These carriers had significantly greater MELD score (mean, 16.2 compared with 13.1; P =.02) and Child scores (mean, 10 versus 9; P =.001) than noncarriers. The incidence of posttransplantation MRSA infection was significantly higher in MRSA carriers (31% versus 9%; P =.002). The incidence of other posttransplantation infection was not significantly different in the two groups. There was no significant difference in survival between the two groups (1-year patient survival, 74% and 82%, respectively). Patients carrying MRSA are predisposed to an increased risk of sepsis after liver transplantation with a trend to increased mortality. Screening for MRSA should be considered in high-risk patients being assessed for liver transplantation.

Adolescent↗
PubMed2003

First report of a psychosocial intervention for patients with alcohol-related liver disease undergoing liver transplantation.

Performing transplantations in patients with alcoholic liver disease raises great concerns for both clinicians and lay people, not least because of the fear that relapse back to drinking after the procedure may lead to poor outcomes. Therefore it is important to develop and evaluate new strategies for assessing and supporting such patients. A program of psychosocial intervention was developed to assist patients undergoing transplantation for alcoholic liver disease in coping with their alcohol problems. We describe a feasibility study of its implementation in a group of 20 such patients. This report shows that it is feasible to deliver a time-limited psychological intervention to patients undergoing assessment for liver transplantation. The intervention was readily integrated into the usual transplantation process and was acceptable to both patients and staff. Further research is required to clarify its impact on longer-term outcome measures.

Adult↗
PubMed2003

Treatment of hepatitis C virus infection in the allograft.

1. Recurrence of hepatitis C virus (HCV) in the graft is associated with a reduced quality of life and worse graft survival. 2. Pretransplantation, the severity of HCV recurrence may be reduced by reducing the pretransplantation load, by avoiding the use of organs from older donors, and by reducing the ischemic times. The effect of split livers on recurrence rates is uncertain. 3. The optimal immunosuppression regime has not been established but a heavy induction regime and treatment for acute rejection are associated with more viral replication and more graft damage. 4. Presently, there is no convincing evidence for preemptive treatment of HCV. 5. There are many studies on the effect of interferon with and without ribavirin for the treatment of HCV hepatitis. However, few are prospective, randomized, and controlled. 6. The current best treatment is with pegylated interferon and ribavirin; the dose and duration of treatment need to be established. Side-effects of treatment are common and reduction/withdrawal is frequent, but the regime is cost-effective. 7. The role of newer treatments remains to be established.

Antiviral Agents↗
PubMed2002

Risk factors for recurrence of primary sclerosing cholangitis of liver allograft.

Primary sclerosing cholangitis (PSC) is a disease of unknown cause that effects the biliary tree and is closely associated with inflammatory bowel disease. We did a retrospective analysis of the risk factors associated with recurrence of PSC in an allograft after liver transplantation. Recurrence of disease, assessed by liver histology or imaging the biliary tree, occurred in 56 of 152 patients (37%) at a median of 36 months (range 1.4-120 months). Multivariate analysis showed that being male (relative risk 1.2, 95% CI 0.73-2.15) and an intact colon before transplantation (8.7, 1.19-64.48) were associated with recurrence. These observations could help elucidate the pathogenesis of the disease.

Cholangitis, Sclerosing↗
PubMed2002

Cardiovascular morbidity and mortality after orthotopic liver transplantation.

BACKGROUND: Hyperlipidemia and hypertension have been reported in liver allograft recipients and contribute to an increased risk of ischemic heart disease (IHD) after orthotopic liver transplantation (OLT). The aims of the study were (1) to determine the prevalence of risk factors for IHD in these patients and (2) to compare the observed incidence of cardiovascular events and related mortality in allograft recipients with a matched population. METHODS: One hundred ten consecutive adults (50 male) who attended for review after OLT (median follow-up 3.9 years; range 0.1-17.9) were assessed for cardiovascular risk factors using current blood pressure, diabetic status, and smoking history and measurements of total cholesterol, high-density lipoprotein cholesterol, and triglyceride concentrations. Cardiovascular events and cardiovascular mortality data were collected from the prospective database of all adult liver allograft recipients and compared to matched data from myocardial infarction registries and Office for National Statistics data, respectively. RESULTS: Raised serum cholesterol (>5.0 mmol/L) was found in 48 (44%) patients (18 male), and systolic hypertension (>140 mmHg) was found in 69 (63%) patients (27 male). The relative risk of ischemic cardiac events was 3.07 (95% [confidence interval] CI, 1.98-4.53) and the relative risk for cardiovascular deaths was 2.56 (95% CI, 1.52-4.05) in allograft recipients compared to an age-matched population without transplants. CONCLUSIONS: Liver allograft recipients have a greater risk of cardiovascular deaths and ischemic events than an age- and sex-matched population. The prevalence of raised cholesterol concentrations in patients after OLT is similar to those in previous reports. Moderate hypertension and hyperlipidemia may be more detrimental in patients after OLT compared to non-transplant patients without these risk factors.

Adolescent↗