Tacrolimus and cardiotoxicity in adult liver transplant recipients.
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Biomedical subjects
Publications and source records attributed to N D Finlayson.
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BACKGROUND/AIMS: The aim of this study was to analyse prognostic variables predicting mortality, shunt insufficiency, variceal rebleeding and encephalopathy following transjugular intrahepatic portosystemic stent-shunt for variceal haemorrhage. METHODS: Sixty-eight patients with cirrhosis who successfully underwent transjugular intrahepatic portosystemic stent-shunt for variceal haemorrhage were studied. Mean age was 54.8 years (s.e. 1.5); 41 were males and 27 were females. Mean Child score was 8.3 (s.e. 0.3). Cirrhosis was alcohol related in 47. The patients have been followed up for a mean of 10.8 (s.e. 1.1) months. The univariate association between 30 prognostic variables and post-treatment encephalopathy was tested by the Chi-squared or Wilcoxon rank-sum tests and multiple logistic regression was used to test the significance of factors adjusted for one another. Cox's proportional hazard regression was used to test the univariate and multivariate significance of the other three outcomes. RESULTS: Transjugular intrahepatic portosystemic stent-shunt was performed successfully in 89.5% of patients. Twenty-two patients have died and eight have been transplanted. Fourteen patients died within 30 days of transjugular intrahepatic portosystemic stent-shunt and death was predicted independently by hyponatraemia (p < 0.001) and by severe liver disease (Child C, p < 0.001). Eight patients died during follow up and survival in the long term was predicted independently by the presence of encephalopathy (p < 0.001) prior to transjugular intrahepatic portosystemic stent-shunt (p < 0.001). Shunt insufficiency was predicted by an initial portal pressure gradient of greater than 18 mmHg (p < 0.01). None of the variables analysed predicted variceal rebleeding. Encephalopathy following transjugular intrahepatic portosystemic stent-shunt was only predicted indepedently by its presence prior to transjugular intrahepatic portosystemic stent-shunt (p < 0.001). CONCLUSIONS: The results of this study suggest that patients with severe liver disease and hyponatraemia are liable to die early, and the presence of encephalopathy prior to transjugular intrahepatic portosystemic stent-shunt independently determines long-term survival. Patients in these groups should be considered high risk and worked up for orthotopic liver transplantation early. Shunt function in patients with an initial portal pressure gradient of > 18 mmHg requires close supervision. Encephalopathic patients should have smaller shunts and prophylactic measures to prevent worsening encephalopathy.
Oral isosorbide-5-mononitrate (Is-5-Mn) was given in doses of 10 and 40 mg acutely and chronically (twice daily for four weeks), allowing a nitrate free interval to 25 patients with cirrhosis. Both 10 mg and 40 mg Is-5-Mn reduced the hepatic venous pressure gradient acutely and chronically, without evidence of tolerance. This was achieved by a reduction in the wedged hepatic venous pressure. The effect on mean azygos blood flow was variable with no significant mean change seen acutely or after chronic use with either dose. The variability was dependent not on the dose used but on the initial azygos flow; the flow in patients with initially low values increased and those with high azygos flows decreased after nitrate challenge. The development of the porto-collateral flow seems an important parameter in predicting haemodynamic response to Is-5-Mn.
OBJECTIVES: Transjugular intrahepatic portosystemic stent-shunts (TIPSS) have been shown to reduce portal hypertension consistently and have recently been reported to arrest active variceal hemorrhage. This retrospective and nonrandomized study compares the results of TIPSS with esophageal transection (ET) and devascularization in patients with uncontrolled variceal hemorrhage admitted to a single center with an interest in variceal bleeding. PATIENTS AND METHODS: Two hundred and sixty cirrhotic patients have been referred with variceal bleeding over the past 7 yr. In 41 patients (15.8%), hemorrhage was uncontrolled despite two treatments with sclerotherapy. Thirty-eight patients were eligible for analysis. Nineteen were considered for ET and 19 for TIPSS. Patients in the two groups were well matched for age, sex, etiology of liver disease, and its severity and complications. They have been followed for 13 patient years (TIPSS-7, longest 20 months; ET-6, longest 23 months). Data for survival and rebleeding were analyzed by the Kaplan-Meier method on an intention-to-treat basis. RESULTS: Seven of the 19 were considered unfit for surgery, and 12 underwent esophageal transection and devascularization. TIPSS was undertaken successfully in 17 patients, the Palmaz stent being used in 4 and the Wallstent in 13. Successful TIPSS reduced the mean portal pressure gradient from 22.2 (SE 1.2) to 9.7 (SE 0.7) mm Hg (p < 0.001). Mortality within 30 days of the initial bleed was 42% in the TIPSS group compared with 79% in the ET group (p < 0.05). Rebleeding occurred in 15.6% patients with TIPSS, compared with 26.2% in the ET group. Encephalopathy in the two groups of patients was not significantly different (TIPSS 25% and ET 22%). TIPSS was followed by active infection in 20% compared with 36% after ET. CONCLUSIONS: This study shows that the overall mortality in this group of patients is high whatever the type of treatment used. TIPSS can be performed successfully on these patients who are often not suitable for surgery. Mortality rates were significantly lower in patients treated by TIPSS. Compared with ET, TIPSS should be regarded as the preferred mode of treatment for uncontrolled variceal hemorrhage in patients with cirrhosis.
We compared laparoscopy with histology in identifying fatty change, fibrosis, the degree of inflammatory activity, cirrhosis and the cause of liver disease. Laparoscopic liver biopsy was performed in 145 consecutive patients. The laparoscopist and the histologist were provided with similar clinical and biochemical information. Both scored the appearances on respective examinations for the degree of fatty change, fibrosis and activity, presence or absence of cirrhosis; and provided a provisional diagnosis. The final diagnosis was determined by clinicopathological conference and clinical follow-up. Laparoscopy was successfully performed in 142 patients (97.9%). Compared with histology, the sensitivity and specificity of laparoscopy for identifying fatty change were 96.4% and 100%, 100% and 95% for fibrosis and 94% and 95% for inflammatory activity, respectively. For cirrhosis, laparoscopy was 100% sensitive and 97.1% specific. Histology missed 10 cases of cirrhosis (6.1%). Histology did, however, provide additional information in 9 patients (6.3%) which contributed to the final diagnosis. Overall, histology is required in addition to laparoscopy in cases where the aetiology is unclear. The sensitivity and specificity in identifying fatty change, fibrosis, activity and cirrhosis are similar for laparoscopy and histology. The combination of information gained on laparoscopy with histology provides the diagnosis in most patients. Laparoscopy may replace the need for liver biopsy in patients in whom the aetiological diagnosis is not in question and the biopsy is being performed to stage the disease. We used it as an integral part of the work-up of a patient with liver disease.
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OBJECTIVE: To describe a patient with pulmonary and portal hypertension and to review the pathogenesis and management of this condition. PATIENT: A 22-year-old woman with portal hypertension and liver cirrhosis who later developed pulmonary hypertension. INTERVENTIONS: The patient received antibiotic therapy and underwent a splenectomy and proximal splenorenal shunt for portal hypertension. She later received hydralazine, digoxin and warfarin for pulmonary hypertension. MAIN OUTCOME MEASURES: After undergoing a splenorenal shunt the patient made a good recovery. However, she later developed pulmonary hypertension and died after undergoing a hysterectomy and a bilateral salpingo-oophorectomy. CONCLUSIONS: The concomitant development of portal and pulmonary hypertension in the same patient has a poor prognosis. The treatment available for patients with these conditions is unsatisfactory and most patients eventually die as a result of cardiovascular disease. Cardiopulmonary and liver transplantation should be considered in suitable patients.
BACKGROUND: Variceal bleeding is a common, life-threatening complication of primary biliary cirrhosis (PBC) that remains difficult to predict. OBJECTIVE: The aim of this study was to identify whether certain biochemical and hematological parameters may be used as predictors of variceal bleeding in patients with PBC. METHODS: Cox proportional hazard regression analysis was used to test whether various prognostic factors were significantly associated with the time of first bleeding in 63 patients with proven PBC, of whom 11 had subsequent bleeding. RESULTS: Both the first available platelet count and the bilirubin level were of significant value in predicting variceal bleeding, but only the platelet count was an independent predictor of bleeding. In the group of patients who subsequently bled, there was a progressive drop in the platelet count over the follow-up period, with a proportional increase in the risk of bleeding; a platelet count below 200 x 10(9)/L was strongly associated with variceal bleeding (p < 0.001). None of the patients with platelet count above 200 x 10(9)/L bled over a total of 136 patient-years follow-up. In the group who did not bleed, no change in platelet count was identified during follow up. CONCLUSION: We conclude that the platelet count can be used as a predictor of variceal bleeding in PBC.
Primary graft dysfunction occurs in up to 10% of liver transplant recipients and is the major reason for early mortality and retransplantation. The conventionally used markers of early graft function--i.e., correction of acidosis, glucose requirement, consumption of potassium, serum alanine transaminase (ALT), prothrombin time (PT), bile flow, resolution of encephalopathy and haemodynamic instability can be very misleading as they are dependent on numerous other factors. The aim of this study was to assess the use of indocyanine green clearance (ICG) as a measure of graft function. Peripheral ICG clearance was measured 18-24 hr after liver transplantation in twenty-three consecutive patients (24 transplants). Doppler ultrasonography confirmed normal hepatic arterial blood flow. Correlations between ICG clearance and other markers of graft function and outcome were sought. The mean ICG clearance was 406 mls/min (SD 137.5). A threshold value of 200 ml/min reliably predicted outcome. Significant correlations were found between ICG clearance and times to normalization of PT (P < 0.02) and to the correction of acidosis (P < 0.05). No correlation was found with ALT, PT, bile flow, glucose requirement, or consumption of potassium. ICG clearance measured on the day after liver transplantation accurately reflects graft function and may be used to predict graft survival and final outcome.
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The severity and range of histological liver lesions caused by alcohol abuse varies considerably; these lesions are not specific for alcoholic damage, and diagnosis of alcoholic liver disease depends on obtaining an adequate history of prolonged alcohol abuse and on excluding other known causes of liver disease. The clinical features of alcoholic liver disease vary greatly and they have been classified into various syndromes. However, the syndromes overlap, the histological features underlying them also overlap and they represent part of a wide clinical spectrum. Alcoholic fatty liver occurs more in younger patients and has a much better prognosis than alcoholic hepatitis or alcoholic cirrhosis, but the previous view that alcoholic fatty liver is an innocuous lesion can no longer be maintained. Alcoholic hepatitis and alcoholic cirrhosis cause more severe syndromes and more florid clinical features, and mortality is related to features of liver failure and variceal bleeding. Abstinence is the only means of ensuring the best possible survival.
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Epistaxis was diagnosed in 10 patients with apparent upper gastrointestinal bleeding, comprising a 0.55% incidence of hematemesis and melena in the population studied. A sufficient amount of blood can be swallowed during epistaxis to cause hematemesis and melena. Recent facial trauma or epistaxis, absence of a history of chronic dyspepsia, and impairment of blood coagulation emerge as strong indicators of the diagnosis and should lead to a careful examination of the nose and nasopharynx for the source of bleeding.
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A retrospective study of transfusion-related non-A, non-B viral hepatitis was conducted in seven patients. Findings showed that six recipients had been exposed to at least one unit of blood possessing a putative serological marker for non-A, non-B hepatitis, the M2 antigen or anti-M2IgM. The M2 markers were associated with non-A, non-B hepatitis that developed 3-7 weeks after transfusion. It sees increasingly probable that M2 markers may be useful for diagnosis and/or prevention of post-transfusion hepatitis.