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Biomedical subjects

P Burra

Publications and source records attributed to P Burra.

At least 37 records · Page 2Linked to original sources

Lymphoproliferative disorders in heart transplant recipients: role of hepatitis C virus (HCV) and Epstein-Barr virus (EBV) infection.

Post-transplant lymphoproliferative disorders (PTLD) are a well known complication after orthotopic heart transplantation (OHT). Although Epstein-Barr virus (EBV) infection has long been implicated in the pathogenesis of such disorders, other factors may play a part. Because of its lymphotropic properties, hepatitis C virus (HCV) may induce clonal expansion of B-lymphocytes and lead to PTLD. The aim of this study was to evaluate the potential association between HCV and EBV infection and PTLD in OHT patients. The retrospective study considered 404 adult patients screened for HCV. EBV serology, histology, and molecular analysis on tissue biopsies were performed in the PTLD patients (10/404, 2.5%). HCV positivity was found in 36/404 (8.9%) patients. The EBV genome was expressed on all neoplastic tissue samples analyzed. A higher proportion of HCV-positive patients developed PTLD than the HCV-negative cases (8% vs 2%, P = 0.017). EBV has a demonstrated role in the onset of PTLD, but HCV infection probably has to be considered as well.

Adolescent↗

Liver transplantation in Italy: current status. Study Group on Liver Transplantation of the Italian Association for the Study of the Liver (A.I.S.F.).

The first liver transplant in Italy was performed in 1982. With the improvement in results, the number of patients followed, in recent years, has substantially increased in all centres. In parallel, the indications for liver transplantation have expanded and have raised the need for more organized structures where patients can be referred for evaluation and transplantation. Indications and contraindications to liver transplantation in Italy, the role of retransplantation, paediatric liver transplantation, waiting list management, liver transplantation outside Italy and the new Italian laws on organ donation are discussed. The multidisciplinary Study Group on Liver Transplantation of the Italian Association for the Study of the Liver (AISF) has collected information from all the Italian centres to ascertain the degree of consistency in their methods.

Humans↗

The impact of liver disease and medical complications on quality of life and psychological distress before and after liver transplantation.

BACKGROUND/AIM: The impact of liver disease and medical complications on quality of life (QOL) and psychological distress before and after orthotopic liver transplantation (OLT) is a matter of growing interest. METHODS: Perceived QOL (LEIPAD Quality of Life test) and psychological distress (Brief Symptom Inventory, BSI) were assessed in 40 cirrhotic patients listed for OLT (Group A) and in 101 liver transplant recipients (Groups B to G=0-6, 7-12, 13-24, 25-36, 37-48, 49-60 months post-OLT). Patients were also evaluated for medical complications, blood levels of immunosuppressive agents and recurrence of liver disease. RESULTS: QOL and psychological distress were significantly better in most of the post-OLT groups than in cirrhotic patients. Among post-OLT patients, a significantly worse QOL was perceived at 13-24 months (Life Satisfaction: Group D vs G, p=0.024; Cognitive Functioning: Group D vs F, p=0.024), while significantly greater psychological distress was detected at 7-12 months (Anxiety and Interpersonal Sensitivity: Group C vs Group B, p=0.032 and p=0.023, respectively). Medical complications and immunosuppressive therapy did not influence QOL or psychological distress after OLT. Within 6 months after OLT, patients with HCV recurrence showed significantly greater Depression (p=0.023), Anxiety (p=0.038), Phobic Anxiety (p=0.001), and Paranoid Ideation (p=0.033) than anti-HCV negative patients. CONCLUSIONS: Liver transplantation improves psychological distress and most, but not all, QOL domains. Recurrent HCV infection is associated with greater psychological distress.

Adult↗

European collaborative study on factors influencing outcome after liver transplantation for hepatitis C. European Concerted Action on Viral Hepatitis (EUROHEP) Group.

BACKGROUND & AIMS: Liver transplantation for hepatitis C virus (HCV)-related liver disease is characterized by frequent graft infection by HCV. The prognosis and risk factors for morbidity and mortality in this condition were determined. METHODS: A retrospective study of 652 consecutive anti-HCV-positive patients undergoing liver transplantation between 1984 and 1995 in 15 European centers was conducted; 102 patients coinfected with hepatitis B virus (HBV) received immunoglobulin prophylaxis for antibody to hepatitis B surface antigen. RESULTS: Overall, 5-year survival was 72%. Five-year actuarial rates of hepatitis and cirrhosis were 80% and 10%. Genotypes 1b, 1a, and 2 were detected in 214 (80%), 24 (9%), and 24 (9%) of 268 patients analyzed. The only discriminant factor for patient or graft survival was hepatocellular carcinoma as primary indication. Independent risk factors for recurrent hepatitis included the absence of HBV coinfection before transplantation (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2-2.6; P = 0.005), genotype 1b (RR, 2; 95% CI, 1.3-2.9; P = 0.01), and age > 49 years (RR, 1.4; 95% CI, 1.1-1.8; P = 0.01). CONCLUSIONS: The results of transplantation for HCV-related disease are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory. Genotype 1b, age, and absence of pretransplantation coinfection by HBV are risk factors for recurrent HCV.

Female↗

Bone metabolism in orthotopic liver transplantation: a prospective study.

Bone mineral density (BMD) and mineral metabolism were assessed in 54 patients with end-stage liver disease who were evaluated for orthotopic liver transplantation (OLT) and assessed 3, 6, and 12 months after surgery in 26 patients who underwent OLT. Serum and urinary electrolyte and mineral levels, serum liver function test results, and parathyroid hormone (PTH), osteocalcin (BGP), 25-hydroxyvitamin D, and urinary hydroxyproline levels were assessed. BMD of the lumbar spine was measured at baseline and 3, 6, and 12 months after OLT. At baseline, 40.7% of patients had BMD below the fracture threshold (0.800 g/cm2). Using multiple stepwise regression analysis, we found that BMD was significantly (P < .0001) affected by age, serum creatinine level, and PTH level but not by indices of cholestasis or liver function. In the patients who underwent OLT, a 1.4% reduction (P < .006) was observed in BMD 3 months after OLT. Thereafter, BMD returned to pretransplant values. A significant increase in serum BGP was observed after 6 (P < .02) and 12 (P < . 005) months. PTH levels increased progressively 3 (P < .02), 6 (P < . 001), and 12 (P < .0001) months after OLT. This increase did not seem to be caused by cyclosporine-induced nephropathy. It was concluded that osteopenia is a major complication in hepatic cirrhosis, regardless of its causes. The increase in serum BGP levels 6 and 12 months after OLT indicates metabolic activation of osteoblasts. The increase in PTH levels after OLT warrants further investigation.

Absorptiometry, Photon↗

The effect of recurrence of HCV infection of life after liver transplantation.

The present study evaluated the quality of life (QOL) of adult cirrhotic patients before orthotopic liver transplantation (OLT), the effect of OLT on QOL in the long-term and the effect of HCV recurrence within medical complications on QOL. Three groups of patients were studied: 19 pre-OLT, 33 during the first year post-OLT and 41 1 to 5 years post-OLT. The patients completed questionnaires on QOL and underwent liver function tests, immunosuppressive drug blood level determinations and medical complications evaluation. Somatization and depression and anxiety scores improved significantly during the first year post-OLT compared with pre-OLT, but they worsened again during the 1-5-year period post-OLT. Physical functioning and life satisfaction scores improved significantly during the first year post-OLT completed with pre-OLT and the improvement persisted 1-5-year during the period post-OLT. Patients with HCV recurrence compared with patients without HCV recurrence during the first year post-OLT showed a significant worsening of most of the domains of QOL. In conclusion, OLT improved most of the domains of QOL by the end of the first post-transplant year, though the improvements did not all persist in the long-term. Recurrence of HCV infection plays a major role in the impairment of QOL after OLT.

Adult↗

Regional cerebral blood flow changes in patients with cirrhosis assessed with 99mTc-HM-PAO single-photon emission computed tomography: effect of liver transplantation.

BACKGROUND/AIMS: Previous studies showed contrasting results with regard to alterations of regional cerebral blood flow/metabolism in subjects with liver cirrhosis. The aim of the study was to extend these findings in a larger series of patients. In addition, we wanted to determine whether such alterations are reversed by successful liver transplantation. METHODS: The study group comprised 23 patients with liver cirrhosis and 13 normal controls. At entry to the study, all subjects underwent a complete neurological examination, EEG recordings and SPECT scanning. The severity of liver disease was determined according to the Child-Pugh score. Fourteen patients underwent a second SPECT examination 1 year after liver transplantation. RESULTS: Significant rCBF reductions, ranging from 6% to 7%, were found in the majority of the cortical regions of the whole group of patients with cirrhosis, as compared to controls. These reductions were more diffuse in patients with alcoholic liver disease, comprising almost all the assayed regions. Liver transplantation normalized cortical rCBF deficits so that postoperative perfusion indexes were superimposable on control values. However, the frontal cortex remained significantly more impaired in patients with alcoholic cirrhosis than in those with non-alcoholic cirrhosis. The differences in frontal rCBF between the two groups of patients ranged from 6 to 11%. CONCLUSIONS: Liver cirrhosis was associated with rCBF defects that depend upon the etiology of liver disease and that subsided after successful liver transplantation. The frontal defects in alcoholic cirrhosis either before or after surgery may imply a neurotoxic, possibly irreversible, action of ethanol.

Adult↗

[Neuroendocrine tumors and liver transplantation: review based on a case report].

A case of orthotopic liver transplantation (OLT) for secondary Neuroendocrine Tumor (NET), whose primary site was not detected at the time of surgery, is reported. The primary pancreatic lesion was found 20 months later in association with recurrence of neoplasm in the graft and with a paraneoplastic syndrome peculiar of glucagonoma. The patient started octreoide therapy with a decrease of the glucagone level but without reduction of the tumor size, nor disappearance of the clinical syndrome. A few months later the primary lesion was surgically removed, but her general condition deteriorated and the patient died waiting for liver retransplantation. A discussion about the management and the diagnostic tools for preoperative staging of these neoplasms and their ability to identify the primitive and secondary location of neuroendocrine tumors is presented.

Adult↗

The protective effects of L-arginine after liver ischaemia/reperfusion injury in a pig model.

Hepatic ischaemia/reperfusion is characterized by circulatory and metabolic derangement, liver dysfunction, and tissue damage. To evaluate the role of L-arginine, a substrate of nitric oxide, in ischaemia/reperfusion injury, total liver ischaemia was induced for 120 min in 22 Landrace x Large White female pigs, which were randomly assigned to a treatment group (10 animals) or a control group (12 animals). An L-arginine bolus (540 mg/kg i.v.) was administered to the treatment group 1 h before clamping the hepatic hilum, at clamping, at reperfusion, and at 1 and 2 h after reperfusion. The control animals received normal saline and an i.v. infusion. Liver function tests and analysis of serum, erythrocyte, and tissue malondialdehyde contents were performed at commencement of laparotomy, before reperfusion, and at 30 min and 7 days after reperfusion. Liver biopsies were taken at laparotomy, at 30 min, and at 7 days after reperfusion for histological and ultrastructural examination. Assessment of apoptosis included in situ end-labelling analysis and DNA gel electrophoresis. Survival at 7 days was better in the treated animals than in the controls (9/10 vs. 7/12). Tissue malondialdehyde content, aspartate aminotransferase, and lactate dehydrogenase levels were lower in the treatment group, in which morphological changes were significantly less evident than in the controls 30 min after reperfusion. At 7 days, differences between the groups with respect to cell integrity were apparent only on ultrastructural analysis. Glycogen content, 7 days after reperfusion, was higher in the treatment group than in the controls: 70.25 per cent vs. 21.66 per cent positive hepatocytes (score 3 vs. score 1). Multiparametric analysis showed fewer apoptotic cells in the treatment group at all times. Our data show that the administration of L-arginine reduces damage to liver tissue after ischaemia/reperfusion injury in a pig model. This may be explained not only by the known vasodilator, anti-aggregation, and superoxide inactivation effects of increased nitric oxide release, but possibly also by some other action of L-arginine, such as its influence on cellular metabolism.

Animals↗

Gastrectomy, lack of gastric first pass metabolism of ethanol and alcoholic liver disease. Results of a multicentre study.

BACKGROUND: Some conditions characterized by a loss (anatomical or functional) of parietal cells of the gastric antrum, containing an alcohol-dehydrogenase, may reduce the first pass metabolism of ethanol at that level and, simultaneously, raise its bioavailability. The observation that the first pass metabolism was drastically suppressed after gastrectomy would appear to suggest that the latter condition represents a risk for the development of liver damage in patients who continue to consume alcohol even in a non relevant amount. METHODS: Consecutively enrolled in the study were 304 individuals of both sexes aged between 45 and 70 years of whom 114 gastrectomized and 190 pair-matched control subjects all submitted to an Upper Gastrointestinal Endoscopy for whatever disturbance. All the patients were diagnosed as having liver disease with routine clinical and instrumental means. Information was collected concerning the mean daily alcohol intake, both before and after the operation. RESULTS: The overall prevalence of hepatic lesions was shown to be higher in the gastrectomized than in the control group (42.1% vs 25.8%, p = 0.005). Moreover, referring only to alcohol-related hepatic lesions (steatosis, steato-fibrosis and cirrhosis), the prevalence was higher in the gastrectomized patients than in the controls (29.8% vs 17.9%, p = 0.02). As far as concerns alcohol consumption, the gastrectomized group had consumed 71 g/day and the control group 39 g/day alcohol per person (p < 0.05) in a similar period of time (35 and 33 years, respectively). Also the non alcohol-related liver damage (especially the viral type) was slightly higher in the gastrectomized patients (gastrectomized 12.3% vs control 7.9%, p = ns). Accordingly, the percentage of serum markers of viral infection was higher in this group (HBs Ag: gastrectomized 3.9% vs control 2.2%, p = ns; anti-HCV: gastrectomized 13.5% vs control 5.0%, p = 0.03). Finally, to test the eventual damaging effects of gastrectomy alone (excluding ethanol and/or viral infection), two groups of patients with a medium to low alcoholic negative assumption (30-60 g ethanol/day) and no signs of viral infection (HBsAg and anti-HCV negative) were extrapolated. In these two selected groups, the prevalence of alcoholic-related hepatic lesions were not statistically different (28 gastrectomized 20.3% vs 44 control 18.4%). CONCLUSIONS: In conclusion, data emerging from investigations on the population under study indicate that the alcohol and viral infection appear to play a more important role in determining hepatic lesions than gastroresection.

Aged↗

Two cases of Kaposi's sarcoma in renal and liver transplant recipients treated with interferon.

We report two cases of Kaposi's sarcoma in recipients of solid organ transplants, presenting (Case 1) 12 months after liver transplantation and (Case 2) 7 months after kidney transplantation. Both patients share the following features: natives from the Mediterranean area (Southern Italy), multiple immunosuppressive regimen, infection with hepatitis B and cytomegalovirus. During the 3 yr of follow-up after the diagnosis, their immunosuppressive regimen was reduced and they were treated with alpha interferon with remission of the clinical findings. The management of Kaposi's sarcoma in organ transplant recipients remains a controversial issue because of the risks of organ rejection associated with the reduction of immunosuppression and with the use of interferon.

Adult↗

Human natriuretic factor in cirrhotic patients undergoing orthotopic liver transplantation.

We measured the plasma levels of atrial natriuretic factor (ANF) during orthotopic liver transplantation (OLT) in eight adult patients with cirrhosis and ascites. The aim of this study was to determine whether significant differences in ANF concentration may be detected during the individual phases of OLT and to correlate these changes with hemodynamics. In each patient a hemodynamic assessment was achieved using a Swan-Ganz fiber optic catheter for continuous monitoring of cardiac output (CO), systemic vascular resistance index (SVRI), right filling pressure as assessed by central venous pressure (CVP), and left filling pressure by means of pulmonary arterial wedge pressure (PAWP). During reperfusion a clear-cut increase in ANF values was observed (P < 0.05). Concurrently, an increase in CVP (P < 0.05) and a decrease in SVRI were observed without any significant increase in diuresis. These data suggest that ANF might play a role in the development of the reperfusion syndrome.

Adult↗

Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitis.

BACKGROUND/AIMS: Little is known about the pathogenesis of liver damage related to hepatitis C virus. The presence of steatosis or increased ferritin levels, and preliminary data on the relevance of iron as a prognostic factor prompted us to ascertain whether hepatitis C virus-related liver damage might be mediated by iron accumulation. METHODS: We evaluated the degree of hepatic inflammation and steatosis, serum ferritin, transferrin saturation and iron levels, tissue iron concentrations and iron index, liver glutathione and malondialdehyde in 33 males and 20 females with chronic hepatitis C virus- or hepatitis B virus-related hepatitis (42 + 11). We also considered six patients with both alcohol abuse and hepatitis C virus, four males with chronic alcoholic liver disease and four males with genetic hemochromatosis, giving a total of 67. All diagnoses were histologically confirmed. Patients with cirrhosis were excluded. RESULTS: Our data show that: 1. Steatosis is more frequent in hepatitis C virus and hepatitis C virus+alcohol abuse patients; 2. In males, serum ferritin and tissue iron are significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p < 0.01 and 0.05); transferrin saturation is higher (p < 0.05) in hepatitis C virus-positive than in hepatitis B virus-positive patients only when males and females are considered together; 3. Serum ferritin and transferrin saturation only correlate with liver iron (r = 0.833 and r = 0.695, respectively, p = 0.00001); tissue iron is significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p < 0.05); 4. In patients with chronic hepatitis, serum ferritin is a better marker of liver iron storage than transferrin saturation, both in males and in females; 5. Hepatitis C virus-positive patients have higher malondialdehyde levels and activation of turnover of glutathione, probably in response to free-radical-mediated liver damage. Females have lower liver iron levels but similar trends. CONCLUSIONS: These findings suggest that hepatitis C virus-related liver damage is characterized by increased iron storage (possibly induced by the virus) which elicits a free-radical-mediated peroxidation, with consequent steatosis and activation of glutathione turnover.

Adult↗

The effects of ethanol, 3,5,3'-triiodothyronine (T3) and oestradiol (E2) on thyroid hormone nuclear receptor expression in human hepatocyte primary cultures.

The possibility that ethanol regulated the expression of thyroid hormone receptor mRNA levels was explored in a model involving human hepatocyte primary culture. Ethanol (20, 50 and 100 mM for 24 h was found to have no effect on the steady-state levels of either triiodothyronine (T3) receptor alpha 1 or alpha 2 mRNAs. In contrast both T3 (1, 10 and 100 nM) and oestradiol (0.1, 1 and 10 ng/ml) treatments affected either one or both of these mRNA levels in a complex manner, showing that the model was capable of responding to other stimuli. Triiodothyronine receptor beta 1 mRNA was not assayed. The hypermetabolic effects of long-term ethanol consumption in humans appears not to be due to the direct effect of ethanol on the regulation of these receptors.

Culture Techniques↗