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Biomedical subjects

A K Burroughs

Publications and source records attributed to A K Burroughs.

At least 91 records · Page 5Linked to original sources
PubMed1999

Randomised controlled trials of ursodeoxycholic-acid therapy for primary biliary cirrhosis: a meta-analysis.

BACKGROUND: Ursodeoxycholic acid (UDCA) is the only approved treatment for primary biliary cirrhosis, but its effect on disease progression and survival is uncertain. The aim of this study was to clarify the efficacy of UDCA in primary biliary cirrhosis. METHODS: A systematic review, including the use of meta-analysis, was done for the randomised and switch-over phases of trials comparing UDCA with placebo, obtained from Medline and Embase databases, and from manual searches derived from review articles and abstracts of major international meetings. All trials had more than a mean of 6 months' follow-up and only included patients with primary biliary cirrhosis (PBC) according to established diagnostic criteria. FINDINGS: 17 relevant articles were identified: 11 randomised controlled trials, including 1272 patients, and six reports of the switch-over phases. UCDA had a favourable effect on liver biochemistry in most of the studies but not on symptoms or the progression of histological stage; two studies did not assess survival, liver transplantation, or complications of liver disease. Meta-analysis showed no difference between UDCA and placebo in the incidence of death (odds ratio 1.21, 95% CI 0.71-2.04), liver related death (0.72, 0.22-2.32), liver transplantation (1.27, 0.78-2.07), death or liver transplantation (1.26, 0.87-1.82), and in the development of complications of liver disease (1.11, 0.64-1.92). With the primary end point defined by the authors (a combined end point in three studies, and death or liver transplantation in the others) an odds ratio of 1.53 (0.97-2.42) was obtained. Assessment of the switch-over phases, during which there was a longer follow-up, did not change the results of the meta-analysis. INTERPRETATION: Published randomised controlled trials of UDCA do not show evidence of therapeutic benefit in PBC and its use as standard therapy needs to be re-examined.

Evidence-Based Medicine↗
PubMed1999

Mycophenolate mofetil monotherapy in stable liver transplant patients with cyclosporine-induced renal impairment: a preliminary report.

BACKGROUND: Cyclosporine is the most common maintenance immunosuppressant in liver transplants patients, but it is often associated with nephrotoxicity. METHODS: We evaluated the safety and efficacy of monotherapy with mycophenolate mofetil (1 g twice daily) in five stable liver transplant patients with cyclosporine-induced renal impairment despite reduction of cyclosporine to subtherapeutic levels. Follow-up was 8.4+/-2.4 (range: 6-12) months. RESULTS: No major side effects have been observed to date. Serum creatinine levels were significantly reduced from a median of 201 micromol/L before to 142 micromol/L at 3 months after mycophenolate (P=0.04) and remained low at 6 months. New onset cellular rejection occurred in only one patient after 3 months on mycophenolate monotherapy, and it responded completely to an intravenous course of methylprednisolone. CONCLUSIONS: Monotherapy with mycophenolate mofetil in a dose of 1 g twice daily seems to significantly improve cyclosporine-induced renal impairment in stable liver transplant patients without major side effects or significant risk of rejection.

Creatinine↗
PubMed1999

Bacterial infection in the pathogenesis of variceal bleeding.

Variceal bleeding is a life-threatening complication of cirrhosis. Potential risk factors include clinical, endoscopic, and haemodynamic factors, but why bleeding occurs unpredictably in individual patients is not known. We postulate that bacterial infections in patients with variceal haemorrhage may be the critical factor that triggers bleeding. In patients with large varices and a high wall tension, the release of endotoxin into the systemic circulation during episodes of bacterial infection results in a further increase in portal pressure through the induction of endothelin and possibly vasoconstrictive cyclo-oxygenase products. The subsequent contraction of hepatic stellate cells causes a rise in intrahepatic vascular resistance. Furthermore, endotoxin-induced nitric oxide and prostacyclin, and prostacyclin induced by endothelin could inhibit platelet aggregation, which may result in a further deterioration of primary haemostasis at the level of varix. We propose that the combination of these two effects leads to the onset of variceal haemorrhage.

Bacterial Infections↗
PubMed1999

Human herpesviruses 6 and 7 as potential pathogens after liver transplant: prospective comparison with the effect of cytomegalovirus.

Because cytomegalovirus (CMV) is an important opportunistic infection after liver transplant, we conducted a prospective study to see if the same applied to human herpesviruses (HHV)-6 and -7. We used polymerase chain reaction (PCR) methods optimised to detect active, not latent, infection and studied patients not receiving antiviral prophylaxis for CMV. Post-transplant, 536 blood samples were tested by PCR (median 7; range 4-50). Active infection with CMV was detected in 28/60 (47%), HHV-6 in 19/60 (32%), and HHV-7 in 29/60 (48%) of patients. The PCR-positive samples were tested by quantitative-competitive PCR to measure the virus load of each betaherpesvirus. The median peak virus load for CMV was significantly greater than that for HHV-6 or HHV-7. Detailed clinicopathological analyses for the whole population showed that CMV and HHV-6 were each significantly associated with biopsy-proven graft rejection. Individual case histories suggested that HHV-6 and HHV-7 may be the cause of some episodes of hepatitis and pyrexia. It is concluded that HHV-6 is a previously unrecognized contributor to the morbidity of liver transplantation, that HHV-7 may also be important and that both viruses should be included in the differential diagnosis of graft dysfunction.

Adult↗
PubMed1999

Infection and hemostasis in decompensated cirrhosis: a prospective study using thrombelastography.

Bacterial infections are common complications in decompensated cirrhosis, but their relationship with hemostasis has not been studied. We prospectively assessed whether infection affects hemostasis in cirrhosis using routine hemostasis tests and thrombelastography (TEG), a global test of hemostatic function. Eighty-four cirrhotic patients (Child-Pugh B: 26; C: 58) without overt bleeding or blood-product transfusion were prospectively evaluated with routine hemostasis tests and TEG on admission and/or the first day with signs of infection and 5 days later. There were 30 patients with infection; 15 had infection on admission, and 15 developed infection in hospital. In the patients who developed infection in hospital, there was a significant deterioration in all routine hemostasis tests except platelet count (PLT) and in all TEG parameters, on the first day of infection compared with 7 +/- 3 days previously. The same parameters significantly improved from the first day of infection to day 5 and after (P <.02) only in the 22 patients whose infection resolved, while the r, k, and alpha TEG parameters significantly worsened in the 8 patients with persistent infection. In those who developed infection in hospital and were cured (n = 11), the 5-day parameters did not differ from their preinfection values. In conclusion, bacterial infections frequently impair hemostasis in decompensated cirrhotic patients. Successful treatment of infection usually restores hemostasis parameters to preinfection levels in 5 days. Thus, infection may have a role in the bleeding diathesis of cirrhosis.

Adult↗
PubMed1999

Transjugular intrahepatic portosystemic shunt compared with endoscopic treatment for prevention of variceal rebleeding: A meta-analysis.

Endoscopic treatment (ET) is frequently used to prevent variceal rebleeding but this still occurs in about 50% of patients. Recently, transjugular intrahepatic portosystemic shunt (TIPS) has been compared with ET in several trials. Using a meta-analysis, we evaluated randomized trials comparing TIPS to ET assessing prevention of rebleeding, survival, and the effects on resource use and the quality of patients' lives. Medical databases were searched between January 1988 and January 1999 as well as published citations and conference proceedings. Sensitivity analyses for type of publication, methodological quality score, mean duration of follow-up, type of ET, etiology, and severity of liver disease were performed. Eleven randomized trials involving 811 patients fulfilled the selection criteria. The median follow-up ranged from 10 to 32 months. Variceal rebleeding was significantly more frequent with ET (47%) compared with TIPS (19%) (odds ratio [OR], 3.8; 95% confidence interval [CI], 2.8-5.2; P <.001), but there was no difference in mortality (OR, 0.97; 95% CI, 0.71-1.34). Post-treatment encephalopathy occurred significantly less often after ET (19%) than after TIPS (34%) (OR, 0.43; 95% CI, 0.30-0.60; P <.001). In the studies showing resource use this was more extensive for TIPS. The sensitivity analyses did not alter the main conclusion, and sole comparison with endoscopic ligation did not alter these results. In conclusion, in patients with variceal bleeding, TIPS compared with ET reduces the rebleeding rate, but does not improve survival, and increases the incidence of encephalopathy in a period of 1 to 2.5 years. Thus, TIPS cannot be recommended as the first choice treatment for prevention of variceal rebleeding.

Brain Diseases↗
PubMed1999

Posttransplantation lymphoproliferative disorder in liver recipients: characteristics, management, and outcome.

Posttransplantation lymphoproliferative disorder (PTLD) is a well-recognized complication of organ transplantation. The aim of this study, performed over 9 years, was to examine the histopathological findings, clinical course, and outcome of patients who, having undergone orthotopic liver transplantation (OLT), developed PTLD. The sample included 7 adult liver allograft recipients (1.7%), 4 men and 3 women, with a mean age of 53 years (range, 40 to 61 years) who developed PTLD 1 to 36 months post-OLT (mean, 6 months). Four patients received either antithymocyte globulin as primary immunosuppression or OKT3 for steroid-resistant cellular rejection. Four patients had localized hepatic tumor with or without regional lymph node involvement, 2 patients had extralymphoreticular disease (head of pancreas and chest wall), and 1 patient had spleen and lymph node involvement. All tumors were B-cell lymphomas; three polymorphic and four monomorphic. Clonality was assessed by immunostaining for kappa and lambda and gene rearrangement. Monoclonality was found in 4 patients and polyclonality in 2 (1 of whom progressed to monoclonality); in 2 patients, clonality could not be determined. Immunohistochemistry findings for the presence of the Epstein-Barr virus (EBV)-determined nuclear antigen and the latent membrane protein 1 were noted in lymphoma tissue in 6 patients. Immunosuppressive therapy was decreased in all patients. Polyclonal tumors were treated with acyclovir (1 patient is in complete remission and 1 patient died), and monoclonal tumors with systemic chemotherapy (2 patients are in complete remission and 2 patients died). One patient was treated with monoclonal antibodies (CD20) but failed to respond, and 1 patient was treated with excision and is in complete remission. The mortality rate was 43%; for the remainder, median survival is 21 months (range, 10 to 42 months). We conclude that PTLD may re-present early after OLT. EBV has a special role in the pathogenesis, combined with immunosuppressive therapy. The outcome is poor, and new therapeutic approaches are needed.

Adult↗
PubMed1999

A predictive model for failure to control bleeding during acute variceal haemorrhage.

BACKGROUND/AIMS: Variceal bleeding is a frequent complication of cirrhosis and is associated with a high risk of early rebleeding. In patients with peptic ulcers, continued bleeding or early rebleeding are risk factors for mortality and can be predicted by statistical models; however, no such models exist for acute variceal bleeding. METHODS: We prospectively evaluated failure to control bleeding in 695 consecutive patients with cirrhosis, admitted for haematemesis and/or melaena. Criteria were defined for failure to control bleeding, which comprised both continued bleeding or early rebleeding within 5 days of admission. There were 2 sequential groups of patients: (i) those with variceal bleeding initially treated with blood transfusion and vasoactive drugs, and if these failed followed by sclerotherapy (n = 385); (ii) those with variceal bleeding treated with injection sclerotherapy at diagnostic endoscopy (n = 144). The third group was those with bleeding from other sources related to portal hypertension (n = 166). RESULTS: Failure to control bleeding was noted in 169 (44%) patients in group 1, 55 (38%) in group 2 and 44 (25%) in group 3. Twenty variables that were evaluable within 6 h of admission, pertaining to severity of bleeding, severity of type of liver disease, mode of admission, and time of diagnostic endoscopy, were entered into a multivariate Cox model. Independent predictors of early rebleeding in group 1 were: active bleeding at endoscopy (irrespective of interval from admission) (p<0.0001), encephalopathy (p = 0.007), platelet count (p = 0.002), history of alcoholism (p = 0.002), presentation with haematemesis (p = 0.02), log urea (p = 0.03) and (shorter) interval to admission (p = 0.007). The variables predictive of 30-day mortality were: early bleeding (p<0.0007), bilirubin (p = 0.0006), encephalopathy (p<0.0001), (shorter) interval to admission (p<0.0001), and log urea (p = 0.004); a model based on these variables was also a good predictor of mortality in the other 2 groups. However, the model derived from group 1 for failure to control variceal bleeding was different in group 2, despite similar patient characteristics and a similar failure rate (following a single injection). This could suggest that sclerotherapy may induce bleeding in some patients independently of the baseline risk for failure to control bleeding. CONCLUSIONS: In cirrhotic patients who present with haematemesis or melaena, active variceal bleeding at diagnostic endoscopy is predictive of failure to control bleeding (continued bleeding or early rebleeding within 5 days of admission), and this failure is predictive of 30-day mortality.

Adolescent↗
PubMed1999

Correction of both prothrombin time and primary haemostasis by recombinant factor VII during therapeutic alcohol injection of hepatocellular cancer in liver cirrhosis.

We evaluated the efficacy of recombinant factor VII to correct impaired haemostasis in a patient with liver cirrhosis requiring an invasive procedure. A test intravenous bolus of 80 microg/kg of recombinant factor VII was given to a Jehovah's Witness, with a solitary 4.4-cm hepatocellular carcinoma and underlying hepatitis C virus cirrhosis, in an attempt to correct his haemostatic disorders and safely inject the tumour with alcohol. An extensive portal block had precluded consideration of liver transplantation. Haemostasis was evaluated by clotting assays, bleeding time and thromboelastography 10 min before and 10 min and 1, 2, 4, 8 and 24 h after factor VII infusion. Parameters of both coagulation (prothrombin time) and platelet function (bleeding time and the alpha and ma parameters of thrombelastography) were improved 10 min after factor VII infusion; improvements lasted 4 to 8 h or more. Platelet count did not change and there was no evidence of disseminated intravascular coagulation. The improvements in haemostatic parameters correlated significantly with the increases in factor VII plasma concentrations (p<0.04). Factor VII clearance was 25.1 U/h/kg and its half-life was 5.8 h. The same dose of recombinant factor VII was given to the patient 1 week later, just before the alcohol injections. The patient had no subsequent bleeding or other complication, with no change in haemoglobin levels over 24 h. Thus, recombinant factor VII represents a therapeutic advance, as it can correct fully both coagulation and platelet function defects in cirrhosis and allow invasive procedures to be performed safely.

Carcinoma, Hepatocellular↗
PubMed1999

Transjugular liver biopsy in the 1990s: a 2-year audit.

BACKGROUND: In view of the changing nature of transjugular liver biopsy, we performed an audit of the safety, adequacy and clinical impact of such biopsies in our centre over a 2-year period from 1995 to 1997. METHODS: One hundred and fifty-seven transjugular biopsies were carried out in 145 patients, with prothrombin time >5 s over control and/or platelet count <50 x 10(9)/L and/or gross ascites. RESULTS: Major complications were two (1.3%) capsular perforations, which were easily plugged with coils without sequelae. Biopsy sample was adequate for histological diagnosis in 90%, inadequate in 6% and technically unsuccessful in 4% of cases. Mean biopsy size was 14.8+/-7.7 (1-51) mm. Adequacy did not differ between cases with and without cirrhosis. Transjugular biopsy had a clinical impact (specific diagnosis or influence on patient's management) in 50% of acute liver disease, 62% of chronic liver disease and 87% of transplant patients (P<0.001). In chronic liver disease, it had a significantly greater clinical impact in cases trying to establish the stage rather than diagnosis (84% vs. 35%, P<0.001). CONCLUSIONS: Transjugular liver biopsy is a safe procedure for high-risk patients providing an adequate liver sample even in cirrhosis. It has a clinical impact in more than 80% of transplant patients and for staging chronic liver disease, but in only 50% (acute) or 35% (chronic) of liver disease when a diagnosis is sought.

Adolescent↗
PubMed1999

Prospective randomized trial of end-to-end versus side-to-side biliary reconstruction after orthotopic liver transplantation.

BACKGROUND: Biliary reconstruction is the Achilles heel of liver transplantation. Side-to-side anastomosis of donor and recipient bile duct has been claimed to be superior to end-to-end anastomosis in uncontrolled studies. METHODS: A total of 100 consecutive patients undergoing orthotopic liver transplantation were randomized after commencement of the transplant procedure to end-to-end or side-to-side anastomosis. No T tube drainage was employed. Endoscopic retrograde cholangiography was performed 2 weeks after transplantation and findings were reported by an experienced endoscopist as normal, leak or stricture. Median follow-up was 53 (range 35-63) months. RESULTS: Patient age, sex, the graft preservation time and indication for transplantation were similar in both groups. Sixty patients received end-to-end and 40 side-to-side anastomosis. Ten patients randomized to side-to-side anastomosis had an end-to-end procedure. The total number of biliary complications was similar in both groups (end-to-end 32 per cent versus side-to-side 30 per cent) as were the number of leaks (17 versus 18 per cent) and biliary strictures (15 versus 12 per cent). There was no difference in the number of biliary complications that required interventional treatment (22 per cent in both groups). CONCLUSION: Side-to-side and end-to-end biliary anastomosis at liver transplantation are equally effective.

Adolescent↗
PubMed1999

Transjugular intrahepatic portosystemic shunt.

The Transjugular Intrahepatic Portosystemic Shunt (TIPS) has now become an accepted part of the therapeutic armory available to the practicing clinician. It may stop variceal bleeding when traditional endoscopic techniques have failed, and can be used as secondary prevention of variceal bleeding, as well as a treatment for intractable ascites and the Budd-Chiari syndrome. It has afforded new insights into the mechanisms of these disorders and significantly advanced our knowledge of disease pathophysiology. It has done all these things, and yet is a procedure that may be performed without interrupting the surgical field, should the patient require a transplant at a later date. In this article, the various indications for TIPS are reviewed with a critical eye. Advances in placement technique, refinement of indications, and results are all discussed. The authors present an up-to-date assessment of the clinical trials performed using this radiologic shunt, as well as their conclusions regarding the various clinical indications.

Esophageal and Gastric Varices↗
PubMed1999

Disseminated intravascular coagulation in liver cirrhosis: fact or fiction?

OBJECTIVE: Cirrhosis is commonly associated with haemostatic dysfunction. The similarities of laboratory tests of disseminated intravascular coagulation (DIC) to those found in cirrhosis has led to the belief that DIC is a feature of the haemostatic failure of cirrhosis. METHODS: The aim of this study was to determine whether DIC is part of the coagulopathy of cirrhosis by applying quantitative tests for prothrombin fragment 1 + 2, antithrombin III, thrombin-antithrombin complex, and specific fribrinogen degradation products levels (XDP), as well as the thrombelastograph for detecting the Clot Lysis Index. RESULTS: Fifty-two stable cirrhotic patients (33 men, 19 women; mean age, 58.8 yr; range, 24-72 yr) with differing etiologies were studied. On tests of thrombin generation: thrombin-antithrombin complexes, fibrin(ogen) degradation products, and prothrombin fragments 1 + 2 were not found to be significantly different from an age- and gender-matched control group (p = 0.18, 0.3, and 0.67, respectively), whereas albumin, Factor V, fibrinogen, antithrombin III, and alpha2-antiplasmin were all significantly low (p = 0.0004, 0.002, 0.06, 0.004, and 0.004, respectively), reflecting reduced synthetic function and correlation in ascitic and non-ascitic patients. There was no correlation between impaired synthesis (antithrombin III and alpha2-antiplasmin) and indices of DIC (prothrombin fragment 1 + 2, thrombin-antithrombin complexes, and XDP) (p = not significant). The percentage of patients with high prothrombin fragments 1 + 2 and thrombin antithrombin levels in each Child grade group was similar. Thrombin time was significantly elevated in the cirrhotic group (a manifestation of low fibrinogen levels). The Clot Lysis Index as measured by thrombelastography was significantly abnormal, indicating mild hyperfibrinolysis. CONCLUSION: We conclude that DIC is not part of the coagulopathy in stable liver cirrhosis without recent complications.

Adult↗
PubMed1999

Single portal pressure measurement predicts survival in cirrhotic patients with recent bleeding.

BACKGROUND: Height of portal pressure correlates with severity of alcoholic cirrhosis. Portal pressure indices are not however used routinely as predictors of survival. AIMS: To examine the clinical value of a single portal pressure measurement in predicting outcome in cirrhotic patients who have bled. METHODS: A series of 105 cirrhotic patients who consecutively underwent hepatic venous pressure measurement were investigated. The main cause of cirrhosis was alcoholic (64.8%) and prior to admission all patients had bled from varices. RESULTS: During the follow up period (median 566 days, range 10-2555), 33 patients died, and 54 developed variceal haemorrhage. Applying Cox regression analysis, hepatic venous pressure gradient, bilirubin, prothrombin time, ascites, and previous long term endoscopic treatment were the only statistically independent predictors of survival, irrespective of cirrhotic aetiology. The predictive value of the pressure gradient was much higher if the measurement was taken within the first or the second week from the bleeding and there was no association after 15 days. A hepatic venous pressure gradient of at least 16 mm Hg appeared to identify patients with a greatly increased risk of dying. CONCLUSIONS: Indirectly measured portal pressure is an independent predictor of survival in patients with both alcoholic and non-alcoholic cirrhosis. In patients with a previous variceal bleeding episode this predictive value seems to be better if the measurement is taken within the first two weeks from the bleeding episode. A greater use of this technique is recommended for the prognostic assessment and management of patients with chronic liver disease.

Adult↗