No abstract

No abstract

After nearly 18 years of research, the association between human leukocyte antigens A1-B8-DR3 and autoimmune chronic active hepatitis still provokes debate. The principal reasons for this are disease heterogeneity and racial variation in the distribution of human leukocyte antigens between populations. The aim of the present study was to reexamine the relationship between these antigens and autoimmune chronic active hepatitis in a well-characterized series of patients. Ninety-six outpatients with autoimmune chronic active hepatitis and an additional 14 referred for liver transplantation with end-stage autoimmune chronic active hepatitis were studied. Human leukocyte antigen frequencies were compared with those of 100 racially and geographically matched controls. The A1-B8-DR3 haplotype was present in 38% of patients compared with 11% of controls (chi 2 = 20.6, p less than 0.0005). When all the DR3-positive patients were eliminated, there was a striking secondary association with DR4; 35 (80%) of 44 remaining patients were DR4 positive compared with 31 (39%) of 79 DR3-negative controls (Fisher's exact probability test p = 0.000031, pc = 0.0013). In addition patients with A1-B8-DR3 are seen at a significantly younger age than those without (39.75 yr vs. 48.21 yr, p less than 0.025), relapse more frequently (52% of patients with A1-B8-DR3 relapsed on one or more occasions compared with 34% of patients without this haplotype) and are more frequently referred for liver transplantation. These data indicate for the first time that two genes within the major histocompatibility complex closely linked to the DR3 and DR4 genes independently confer susceptibility to autoimmune chronic active hepatitis.

A prospective study of bacterial and fungal infections after liver transplantation in 284 adults was undertaken. One hundred seventy-five (62%) became infected; bacterial or fungal infections occurred in 159 (56%) and 36 (13%) patients, respectively. Gram-positive cocci, in particular Staphylococcus aureus and Enterococcus faecium, were the commonest bacterial pathogens, and bacteremia and wound infection were the most frequent bacterial infections. Acute rejection and prolonged admission were independent risk factors for bacterial infection; pretransplantation antibacterials had a protective effect. Fungal infection most frequently involved the urinary tract and chest; Candida albicans was the most common pathogen. Four independent variables predicted fungal infection: low pretransplantation hemoglobin, high pretransplantation bilirubin, return to surgery, and prolonged therapy with ciprofloxacin. Patients with acute liver failure were more prone to bacterial, but not fungal, infection. No associations were found between infections and duration of surgery. Bacterial, and to a lesser extent, fungal infections are important complications of liver transplantation. However, liver transplantation surgery per se may not be the major determinant of infection.

No abstract

Previous studies based on serological HLA phenotyping have implicated genes in the HLA class II region in susceptibility to and protection from primary sclerosing cholangitis. In a recent report, the HLA DRw52a antigen was present in all 29 patients who had been referred for liver transplantation. In this study, HLA DRB, DQA and DQB genotypes were studied using gene amplification and sequence-specific oligonucleotide probing in 71 patients with primary sclerosing cholangitis and 68 healthy controls to determine the frequency among the patients of the DRB3*0101 allele that encodes DRw52a and whether other class II alleles are involved in susceptibility or protection. DRB3*0101 was the most strongly associated allele, being present in 55% of the patients and 22% of the controls. Survival among the DRB3*0101-positive patients was reduced compared with the DRB3*0101-negative patients. Both DRB3*0101 and DRB5*0101, a possible second DRB susceptibility allele, encode a leucine residue at position 38 of the DR beta molecule. The DRB4*0101 allele, which encodes DRw53 and may be protective, encodes an alanine residue at this position. Susceptibility to and protection from primary sclerosing cholangitis may result from amino acid substitutions at position 38 of the DR beta molecule because maximum relative risk was conferred by two leucine-38-containing DR beta molecules, whereas minimum relative risk was conferred by two alanine-38-containing molecules.

The value of coagulation factor V and VIIIIV levels as prognostic indicators was assessed in 27 patients with fulminant hepatic failure and compared with other predictive indices. Admission factor V levels were significantly reduced in 22 patients with paracetamol induced hepatic failure compared with a healthy control group (median 9*5% v 103%, respectively; p<0001) and with lower values in non-A non-B hepatitis (median 2.7%).Values in the seven patients who died after paracetamol overdose, considered together with the four who underwent liver transplantation (group median 5-1%), were significantly lower than in the 11 who survived (median 11-8%; p<001). Median admission factor VIII was higher in those who died or received a transplant than in those who survived (298% v 162%; p<005), with both results higher than in healthy volunteers (median 104%; p<001) but lower than in non-A non-B hepatitis (median 340%). The ratio of factor VIIIIV on admission was <30 in all patients who survived paracetamol overdose (median 17) with corresponding values >30 in 10 of 11 of those who died (median 39). A factor V result -10% on admission predicted an adverse outcome in 10 of 11 fatal cases, a 91% sensitivity which was greater than for the previously defined indicator of an arterial blood pH <7*30 on admission (sensitivity 82%). Prothrombin time at admission or on day 4 did not usefully predict outcome in our series. Predictive accuracy was 73% and 82% for factor V and admission acidosis respectively and 95% for factor V in conjunction with admission coma grade III or IV and factor VIII (ratio >30). These criteria may be useful in selecting patients with paracetamol induced fulminant hepatic failure for transplantation.Institute of Liver Studies,

Abstractyears, predominantly as a result of improved respiratory care. 2 3 Death, however, continues Background -The treatment for endstage cystic fibrosis is, where appropriate, to be due, in most cases, to respiratory failure associated with cor pulmonale and pulmonary double-lung, heart-lung or, occasionally, heart-lung-liver transplantation. Op-hypertension. 3Transplantation (double-lung, heart-lung or, timising the timing of transplantation depends upon an accurate prediction of occasionally, heart-lung-liver) remains the cornerstone of treatment in the terminal phase of survival, but while current criteria give some guidance to this, they are not based the disease. 4 Results have been encouraging in both adults 5 and children 6 and include enupon statistically derived prognostic models.hanced survival and improvement in lung function. Methods -Data collected prospectively on 403 patients with cystic fibrosis, recruitedTo optimise the timing and results of transplantation, particularly in the presence of a between 1969 and 1987 (cohort A), were analysed by log rank and univariate Cox donor shortage, there is a need for an accurate prediction of patient survival. Current reregression analysis to determine variables that accurately predict survival. The sig-commendations for transplantation include those patients whose quality of life is severely nificant variables were then subject to time dependent multivariate Cox regression impaired and whose life expectancy is less than two years. 7 Current criteria suggested for reanalysis to generate a prognostic model. The model was validated, within the study commending transplantation include percentage predicted forced expiratory volume in population, using split sample testing, and was subsequently validated in a further one second (FEV 1 ) <30% and significant carbon dioxide retention.