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Biomedical subjects

B K Gunson

Publications and source records attributed to B K Gunson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Bile duct splintage in liver transplantation: is it necessary?

The choledochochole-dochal (duct-duct, D-D) anastomosis in orthotopic liver transplantation (OLT) is usually splinted by a T-tube to facilitate easy cholangiography, monitor bile quality and allow biliary decompression. T-tubes, however, are a focus for sepsis and sludge deposition, and their removal may result in bile leakage. From January 1993 to December 1994, 199 consecutive adult OLTs in 183 patients (median age 50 years, range 16-69 years, 118 females) with a D-D anastomosis were studied prospectively with a median follow-up of 16 (3-27) months. Of the 199 OLTs, 110 had an 8 Fr T-tube (group 1) and 89 had no T-tube (group 2). The two groups were similar for indication, preservation solution, median cold and warm ischaemia times and early graft function parameters. Biliary complications developed in 26/110 patients, including 10 with bile leaks on T-tube removal in group 1 compared to 10/89 biliary complications in group 2 (P = 0.024). The use of T-tubes is associated with increased morbidity and their routine use should be discontinued.

Adolescent↗
PubMed1996

Effect of pre-reperfusion portal venous blood flush on early liver transplant function.

Portal venous blood for rinsing out the University of Wisconsin solution (UWs) has the advantages of being a physiological fluid, removing acidotic mesenteric venous blood and perhaps resulting in more stable haemodynamic parameters during reperfusion. A group of 209 consecutive adult OLTs carried out between July 1993 and February 1995 were studied prospectively. The UWs was flushed out with 500 ml portal blood in 95 OLTs (group 1) and with 1.0 L 0.5% dextrose at 37 degrees C in 114 OLTs (group 2). The median day 1 and peak day 1-5 AST levels were significantly elevated in the 5% dextrose group: median 755 (118-11090) vs. 546 (121-6150) IU/I (P = 0.007, Wilcoxon); and median 1095 (159-11090) vs. 744 (157-7870) IU/l (p = 0.008, Wilcoxon), respectively. A median of 5 (0-27) units of blood were transfused in group 1 compared to 4 (0-54) units in group 2 (n.s.). There was no difference in peak bilirubin, lowest day 1-5 PT levels, primary nonfunction, median ITU stay, total inpatient stay and 1-month graft survival between the two groups (89% vs. 88%). Pre-reperfusion blood flush may be associated with less hepatocellular damage, without significant additional blood usage.

Adolescent↗
PubMed1996

Clinical significance of serum hepatocyte growth factor in orthotopic liver transplantation.

BACKGROUND: Hepatocyte growth factor (HGF) plays a key role in the regulation of liver regeneration after hepatocyte damage. Changes in HGF production reflect the status of the regeneration process. METHODS: Serum concentrations of HGF and energy substrates were measured during and after liver transplantation in 30 recipients. RESULTS: In the patients with compromised grafts (group A) HGF concentrations were persistently high after reperfusion, whereas in the patients with well-functioning grafts (group B), HGF concentrations decreased rapidly and remained low 4 hours after reperfusion. The patients in group A who died had persistently high concentrations of HGF. The surviving patients with reversible primary graft dysfunction in group A exhibited low concentrations 48 hours after reperfusion. The decrease in HGF concentration preceded the decrease in aspartate aminotransferase concentration. The metabolic parameters that reflect carbohydrate metabolism by the graft paralleled the changes in HGF. CONCLUSIONS: HGF may be more sensitive and specific in predicting early graft function than prothrombin time, ratio, aspartate aminotransferase, or arterial ketone body ratio. The determination of HGF levels after liver transplantation may yield valuable information for evaluating early graft function and making an early decision to repeat a graft procedure in an acutely ill patient.

Adolescent↗
PubMed1996

Liver transplantation in Birmingham: indications, results, and changes.

The improvements in survival following liver grafting during the last five years reflect refinements in technique and in immunosuppressive regimens. Cirrhosis due to Hepatitis C and alcohol have become more common indications in this center. Efforts are being made to overcome the problems of donor organ shortage by using 'marginal' donors and by splitting liver grafts.

Adult↗
PubMed1995

Timing, significance, and prognosis of late acute liver allograft rejection.

Liver allograft rejection is usually divided into acute (cellular) rejection and chronic (ductopenic) rejection. Most cases of acute rejection occur within four weeks of transplantation. There is a paucity of published literature on late acute rejection (LAR) in liver allografts and little is known about factors affecting its occurrence and outcome. To study the predisposing factors, clinical presentation, and prognosis of LAR, data prospectively collected on consecutive adult patients who underwent liver transplantation between 1982 and 1994, were analyzed. LAR was defined as histologically confirmed acute cellular rejection occurring 30 or more days after liver transplantation. Of the 717 patients, 59 (7.5%) had 71 episodes of LAR. Fifty-seven episodes were seen during the first year after transplantation, the remaining occurring between 1 and 6 years. Age, sex, pretransplant diagnosis, donor match of HLA, and blood groups was not associated with risk of LAR. Twenty-seven (38%) episodes were preceded by subtherapeutic blood levels of cyclosporine/FK506 (< 100 ng/ml and < 5 ng/ml, respectively) while an additional 6 (8%) had marginally low blood levels (< 150 ng/ml and < 10 ng/ml, respectively). Treatment with high-dose prednisolone resulted in complete resolution of rejection in 36 (51%) episodes, partial response in 21, and no response in 14 patients. Sixteen patients (27%) developed chronic rejection and graft loss. Development of chronic rejection was not affected by age or sex of the patient, timing of LAR, or histological severity of AR. Delayed response to therapy during an earlier episode of AR, and histological findings of centrilobular necrosis or bile duct loss at the time of diagnosis of LAR were associated with high risk of progression to chronic rejection and graft loss.

Adolescent↗
PubMed1995

Sex mismatch as a risk factor for chronic rejection of liver allografts.

Chronic irreversible rejection is a major cause of graft loss and retransplantation after orthotopic liver allotransplantation. To identify risk factors we retrospectively analysed 423 adult consecutive primary liver allograft recipients. The endpoint of the study was graft failure due to chronic rejection leading either to retransplantation or death. Chronic rejection developed in 22 (5.2%) patients. Pretransplant diagnosis of primary biliary cirrhosis or autoimmune hepatitis, recipient age less than 30 years, 1 or more episodes of acute cellular rejection, and transplantation of an organ from cytomegalovirus (CMV). IgG positive donor to an IgG negative recipient were identified as risk factors for chronic rejection. Transplantation of a liver from a male donor into a female recipient was also associated with an increased probability of chronic rejection. By logistic regression analysis, the probability of chronic rejection was predicted by: sex and cytomegalovirus match of donor and recipient, the presence of acute rejection, recipient age, transplantation for autoimmune hepatitis or primary biliary cirrhosis, and recipients receiving no azathioprine during the third month after transplantation. Sensitisation to antigens expressed by bile-duct epithelium as in primary biliary cirrhosis or exposure to donor bile-duct minor histocompatibility antigens, such as the male sex related H-Y antigen, may provide an explanation. More selective allocation of donor organs may allow a reduction in the incidence of ductopaenic rejection and graft loss.

ABO Blood-Group System↗
PubMed1995

Inflammatory bowel disease in primary sclerosing cholangitis: an analysis of patients undergoing liver transplantation.

Fifty-five patients undergoing orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) were reviewed retrospectively. After OLT there were significantly more episodes of acute rejection in 31 patients with a previous history of inflammatory bowel disease (IBD) than in 24 without such a history. Patients who had severe acute rejection were significantly younger at diagnosis of IBD. Five patients with histological features suggestive of recurrent PSC after OLT were significantly younger at the time of transplantation than those who did not develop recurrence. Patients with poor control of IBD after OLT had a significantly lower age at diagnosis of bowel inflammation. The presence of IBD did not affect the outcome after OLT, but was associated with a higher rate of acute rejection. Younger patients had a greater risk of developing severe rejection, recurrent PSC and poor control of IBD after liver transplantation.

Adolescent↗
PubMed1994

Policies in Europe on "marginal quality" donor livers.

Shortage of donor livers has led several liver transplant centres to widen their definition of liver donor suitability. We have assessed the function of liver grafts from "marginal" donors and attitudes to use of such organs. Over an 18-month period, livers used in 30 of 213 consecutive liver transplantations in Birmingham, UK, came from marginal donors (history of alcoholism, abnormal liver function test results, drug overdose that included paracetamol, advanced cardiovascular disease, sepsis, lengthy hypotension [systolic blood pressure < 80 mm Hg for > 1 h], high-dose inotropic drug use). 16 of these donors had been refused by other UK liver transplant centres, 11 on medical grounds. The controls were grafts retrieved from "good" donors (n = 183) during the same period. All 30 grafts showed satisfactory early function but had greater day 1 (p = 0.004) and peak serum aspartate aminotransferase (p = 0.0008) values than control grafts. Graft and patient survival at 1 year in the two groups was similar (72% vs 73% and 80% vs 82%, respectively). To assess attitudes to marginal donor livers, a questionnaire outlining the details of these 30 donors was sent to the 80 centres in the European Liver Transplant Group, and 60 replied. Median immediate refusal rate of the marginal donors was 7/30 (range 0-18) and median outright acceptance rate was only 11/30 (1-26). Larger centres were less selective, with a significantly lower refusal rate (p = 0.03). These results indicate that, because of existing liver donor criteria within Europe, usable donor livers are being unnecessarily refused on medical grounds.

Adolescent↗
PubMed1994

Extended preservation of the liver with UW solution--is it justifiable?

The outcome of 228 liver grafts in 208 elective adult recipients was assessed to identify any adverse effects of extending the length of cold preservation with UW solution beyond 12 hr. A total of 114 grafts had been preserved < 12 hr--median 9.5 (group I) and 114 > 12 hr--median 14.5 (group II). Intraoperative blood and blood product usage, graft function, hospital stay, and graft and patient survival were identical in the two groups. Biliary strictures occurred in 5.7% of grafts (8 anastomotic (3 group I, 5 group II; 5 hilar/nonanastomotic: 3 group I, 2 group II). There was no graft or patient loss due to the hilar strictures but 1 patient died following reconstruction of an anastomotic stricture (0.4%). It is concluded that extending the cold preservation to approximately 15 hr does not adversely affect outcome after liver transplantation.

Adenosine↗
PubMed1994

Steroid withdrawal 3 months after liver transplantation--does FK 506 confer any advantage over cyclosporin?

Eighty-one liver recipients were randomised to FK 506 or cyclosporin (CyA) and azathioprine (AzA), both in combination with steroids. Twenty-seven FK 506 and 29 CyA/AzA patients continued in the trial 3 months after transplantation. Steroids were ceased in 23 (85%) FK 506 patients and in 27 (93%) CyA patients. After steroid withdrawal, 2 FK 506 and 4 CyA patients were excluded from the study, all for reasons other than rejection. The median follow-up was 16 months for the FK 506, and 19 months for CyA group. There were no acute rejection episodes or graft losses in the FK 506 group. None of the CyA patients lost their graft but three (13%) had episodes of acute rejection requiring steroids to be recommenced in two cases. There was no evidence of chronic rejection in any of the annual review biopsies in either group. Our results suggested no advantage of FK 506 over CyA in its steroid-sparing effect.

Adolescent↗
PubMed1994

Viral hepatitis in Nigeria--sickle-cell disease and commercial blood donors.

Hepatitis virus infection is a major cause of morbidity and mortality in sub-Saharan Africa. The high prevalence of hepatitis B virus (HBV) infection in this region is thought to be due to horizontal transmission during childhood. Hepatitis C virus (HCV) infection is also quite prevalent in Africa, but the epidemiology of this infection has yet to be defined. We examined the prevalence of HBV and HCV serological markers in 220 patients attending sickle-cell anaemia clinics in Benin City, Nigeria, in 228 healthy locals, and in 104 local commercial blood donors, to test the hypothesis that patients requiring blood transfusion from unscreened commercial blood donors (in this area of high prevalence for viral hepatitis) are at great risk for the acquisition of post-transfusion hepatitis. Overall, the frequency of hepatitis viraemia in blood donors was high (14% of donors were either HbsAg or anti-HCV positive). Evidence of previous exposure to HBV was common in all three study groups. Risk of HBV infection for sickle-cell patients was not clearly increased by blood transfusion. HCV exposure, however, appears related to transfusion requirement, and all Western-blot-confirmed anti-HCV-positive sicklers had a history of blood transfusion. Screening of blood products in sub-Saharan Africa is unlikely to reduce prevalence of HBV, but may minimize the risks of HCV transmission.

Adolescent↗
PubMed1993

Acute liver allograft rejection--is treatment always necessary?

A group of 195 consecutive adult patients who received a primary orthotopic liver allograft were reviewed retrospectively to analyze the incidence of rejection, the response to antirejection therapy, and the impact of acute rejection on the development of ductopenic rejection. The diagnosis of acute rejection (AR) was based on a combination of clinical and histological criteria, and 69.7% of the patients had at least one episode of acute rejection. Only 6.7% of the patients failed to respond to steroids and were treated with OKT3. Four (2.3%) patients developed acute vanishing bile duct syndrome (within 60 days) and 6 (3.5%) patients developed chronic rejection. Eight patients who spontaneously recovered from AR without additional immunosuppression are described in detail. In addition to histological damage, all developed significant hepatic dysfunction. Except for one patient who died from disseminated fungal infection, the 7 remaining patients are alive with excellent graft function 7 to 21 months posttransplant. While severe AR and recurrent AR should be treated without delay, some patients with mild-to-moderate rejection and hepatic dysfunction may resolve without additional immunosuppression.

Acute Disease↗
PubMed1993

Steroid withdrawal from long-term immunosuppression in liver allograft recipients.

Corticosteroids were withdrawn from the immunosuppressive regimen of 168/197 (85%) of liver transplant patients who survived for more than three months. In 14, steroids were restarted for reasons other than rejection. The remaining 154 patients were evaluated for the occurrence of rejection and graft loss. Risk factors for the development of rejection after steroid withdrawal were assessed. There were 13 episodes of rejection in 12 (7.8%) grafts; 7 (4.5%) experienced acute cellular rejection, and 6 (3.9%) developed chronic ductopenic rejection. All cases of acute rejection resolved with high-dose steroids. Graft and patient loss due to chronic rejection was 3 (1.9%) and 2 (1.3%), respectively. Chronic rejection resolved in 1 patient, 1 was successfully retransplanted, and in the other 2 the principal cause of death was recurrent tumor. None of the risk factors examined (primary indication for transplant, severity of previous acute rejection, use of OKT3, retransplantation, ABO blood group donor/recipient match, CMV infection, and CsA mono versus CsA and AZA double therapy) were associated with the development of chronic rejection poststeroid withdrawal. The prevalence of side effects, after steroid withdrawal, was low; 66% of patients never required antihypertensive medication; 14% experienced a significant septic episode, and only 4 died with sepsis as the major factor. There were no fungal sepsis and no new cases of diabetes. Withdrawal of corticosteroids after 3 months can be successfully achieved in the majority of liver allograft recipients and is associated with a low rate of rejection, graft loss, and complications attributable to immunosuppressive medication.

Adolescent↗
PubMed1993

Can effluent hyaluronic acid or creatine kinase predict sinusoidal injury severity after cold ischemia?

It is well recognized that current selection criteria used to assess liver grafts before implantation are inaccurate and correlate poorly with graft outcome. A bench or laboratory-based test that could indicate the extent of liver injury immediately before implantation would be a valuable adjunct to clinical assessment. Hyaluronic acid (HA) and creatine kinase (BB component; CK-BB) levels in the caval effluent after liver perfusion have been suggested as indicators of preservation injury. Our objective was to investigate the relevance of preserved liver effluent HA and CK-BB as a predictor of early graft function. Perfused liver effluent HA and CK-BB levels were measured. Graft function was measured in terms of peak serum aspartate transaminase and its level on day 5 postoperatively as well as peak bilirubin level and prothrombin time. The cold ischemia time (CIT) was recorded. Statistical comparisons were made among HA level, CK-BB level, CIT, and graft function parameters. The study was conducted at The Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom. Fifty patients undergoing OLT were studied. HA level was measured in 50 patients and CK-BB level in 30 patients. The main outcome measures were graft function and graft outcome. The graft function data are grouped according to effluent HA levels above or below 400 micrograms/L. Thirteen patients (26%) had a level below 400 micrograms/L and the remaining 37 (74%) were above this threshold. There were no significant differences between the groups for these indicators of graft function. There was no difference between the 2 groups for CIT. The overall median HA level was 1212 micrograms/L (range 39-4000 micrograms/L). The median total CK activity in the perfusate was 302 IU/L (range 118-1155 IU/L). The proportion of CK-BB activity from this total was 146 IU/L (8-641 IU/L), or 48% of the total CK activity. In a multiple regression analysis with CK-BB activity as the dependent variable, there was no demonstrable numerical relationship to graft function. In a separate multiple regression analysis similar results were obtained for HA. We conclude that the level of HA or CK-BB levels should not be used in determining the suitability for implantation of a harvested hepatic allograft.

Adolescent↗
PubMed1993

Development of indications and results during 10 years of orthotopic liver transplantation.

Liver transplantation has rapidly emerged in recent years from an uncommon experimental procedure, limited to a few centers, to become a major international effort to support patients with advancing and decompensating liver disease. The excellent results which can be achieved with optimal timing and expert clinical management are now no longer in doubt. The greatest emphasis now must be on obtaining suitable high quality donors at the right time to give the patient the best opportunity to make a full and complete recovery.

Blood Transfusion↗