Biomedical subjects

Nancy Rolando

Publications and source records attributed to Nancy Rolando.

8 recordsLinked to original sources

PubMed2006

Incidence and risk factors for the development of prolonged and severe intrahepatic cholestasis after liver transplantation.

Predictive factors for intrahepatic cholestasis after orthotopic liver transplantation (OLT) have not yet been established. We sought to identify the incidence and risk factors associated with prolonged severe intrahepatic cholestasis (PSIC) after OLT. We assessed 428 consecutive patients undergoing their first OLT. PSIC was diagnosed if a serum bilirubin concentration was greater than 100 micromol/L and/or a 3-fold increase of alkaline phosphatase occurred within the first month after OLT and was sustained for at least 1 week in the absence of biliary complications. Multivariable logistic regression identified factors independently associated with PSIC. PSIC developed in 107 patients (25%). Independent risk factors by multivariable analysis were intraoperative transfusion of cryoprecipitate and platelets; nonidentical blood group status; suboptimal organ appearance; inpatient status before transplantation; and bacteraemia in the first month after transplantation. In contrast, acute liver failure, older age, and higher levels of serum sodium and serum potassium were all associated with a reduced likelihood of developing PSIC in the first month. There were 47 deaths in the PSIC group (44%) as opposed to 65 deaths in the non-PSIC group (20%) after OLT. A poor preoperative clinical status in conjunction with a suboptimal graft was associated with PSIC after OLT. Avoidance of suboptimal livers and ABO nonidentical grafts for young patients with poor synthetic function and for pretransplant inpatients may lessen this complication and reduce the associated early mortality.

Acute Disease↗

PubMed2005

Immunosuppression and donor age with respect to severity of HCV recurrence after liver transplantation.

In HCV cirrhotic patients after liver transplantation, survival and recurrence of HCV appears to be worsening in recent years. Donor age has been suggested as a cause. However, it is not clear if early and/or late mortality is affected and whether donor age is a key factor, as opposed to changes in immunosuppression. The aim of this study was to assess impact of donor age and other factors with respect to the severity of HCV recurrence posttransplant. A consecutive series of 193 HCV cirrhotic patients were transplanted with cadaveric donors, median age 41.5 years (13-73) and median follow-up of 38 months (1-155). Donor age and other factors were examined in a univariate/multivariate model for early/late survival, as well as fibrosis (grade 4 or more, Ishak score) with regular biopsies, 370 in total, from 1 year onwards. Results of the study indicated that donor age influenced only short-term (3 months) survival, with no significant effect on survival after 3 months. Known HCC independently adversely affected survival, as did the absence of maintenance azathioprine. Severe fibrosis (stage > or = 4) in 51 patients was related to neither donor age nor year of transplantation, but it was independently associated with combined biochemical/histological hepatitis flare (OR 2.9, 95% CI 1.76-4.9) whereas maintenance steroids were protective (OR 0.4, 95% CI 0.23-0.83). In conclusion, in this cohort donor age did not influence late mortality in HCV transplanted cirrhotic patients or development of severe fibrosis, which was related to absence of maintenance steroids and a hepatitis flare. Maintenance azathioprine gave survival advantage.

Adult↗

PubMed2003

Piperacillin-tazobactam versus ciprofloxacin plus amoxicillin in the treatment of infective episodes after liver transplantation.

An optimum antimicrobial regimen for bacterial infection after orthotopic liver transplantation has not been identified. In this prospective 4 year study of patients undergoing liver transplantation, patients were randomized to receive either piperacillin-tazobactam (112 patient episodes) or ciprofloxacin plus amoxicillin (105 patient episodes) for empirical treatment of infective episodes in the first 3 months after transplant. Metronidazole was added to the ciprofloxacin-amoxicillin regimen where anaerobic infection was suspected. Patient groups were comparable with respect to clinical, biochemical and haematological parameters. At the 72 h primary efficacy end-point, the overall response rate for the intention-to-treat group was 74/112 (66.1%) for piperacillin-tazobactam and 63/105 (60.0%) for ciprofloxacin plus amoxicillin (P=0.399); the corresponding figures for the per-protocol (PP) group were 73/82 (89.0%) (piperacillin-tazobactam) and 61/80 (76.3%) (ciprofloxacin plus amoxicillin) (P=0.038). At the end-of-study assessment, 58.9% of episodes in the piperacillin-tazobactam group had a successful clinical outcome, compared with 50.5% in the ciprofloxacin plus amoxicillin group (P=0.222); the corresponding figures for the PP group were 83.5% (piperacillin-tazobactam) and 68.8% (ciprofloxacin plus amoxicillin) (P=0.038). Staphylococci and aerobic Gram-negative bacilli were the predominant pathogens in both groups. Bacteria resistant to the study drugs were encountered, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and multiply-resistant Klebsiella spp. Empirical monotherapy with piperacillin-tazobactam is an effective treatment for infective episodes in liver transplant patients.

Adolescent↗

PubMed2003

Long-term mycophenolate mofetil monotherapy in combination with calcineurin inhibitors for chronic renal dysfunction after liver transplantation.

BACKGROUND: Calcineurin inhibitors (CNIs) are the first-line immunosuppressive agents administered after liver transplantation, but they cause renal impairment. Two recent randomized trials report cellular rejection and liver graft loss when mycophenolate mofetil (MMF) monotherapy was used as a renal-sparing agent. Our experience with MMF in the same setting but with longer follow-up is described. METHODS: In 45 patients with serum creatinine more than 120 micromol/L or creatinine clearance less than 50 mL/min, 2 g MMF per day was administered (median 29 months, 1-49 months) either as monotherapy (with all other immunosuppression withdrawn in 1 month) in 16 patients (group I) or in combination with low-dose CNI (trough tacrolimus </=5 ng/mL, cyclosporin A </=50 ng/mL) in 29 patients (18 patients without [group II] and 11 patients with [group III] previous refractory rejection [rejection after two episodes of treated rejection]). RESULTS: In group I (median interval receiving MMF, 33 months), only one patient (6%) experienced cellular rejection, and serum creatinine normalized in five of eight patients long term. In group II (median follow-up 26.5 months), none of 18 experienced rejection, and serum creatinine normalized in 6 of 10 long term. In group III (median follow-up 34 months), 5 of 11 patients (45%) experienced further rejection, one was not steroid responsive, and serum creatinine normalized in four of eight patients long term. There was no graft loss or death as a result of rejection. CONCLUSIONS: Our cohort with prolonged follow-up showed significant improvement in renal function with both MMF monotherapy and in combination with low-dose CNI with minimal rejection (five of six steroid responsive) and no graft loss. MMF substitution is a therapeutic strategy that deserves more extensive use in liver transplantation.

Adult↗

PubMed2003

Late hepatic artery thrombosis after orthotopic liver transplantation.

Late hepatic artery thrombosis (HAT) is a rare complication after orthotopic liver transplantation (OLT), conventionally described as occurring more than 30 days after surgery. Only a few reports document its course. In a consecutive series of 634 OLTs (704 grafts), 11 patients (1.7%) had late HAT, diagnosed a median of 6 months (range, 1.8 to 79 months) after OLT. Clinical variables were compared with those of 415 patients without HAT who had a complete database and follow-up, including cytomegalovirus (CMV) surveillance. At presentation, 11 patients had fever, 4 patients had jaundice. Hepatic abscesses were present in 6 patients (3 patients with biliary leak), 4 patients had biliary tree necrosis (2 patients with biliary leak), and 1 patient had no biliary complications. Five patients (45%) underwent accessory hepatic artery anastomosis versus 73 patients (17%) without HAT (P <.05). Five patients (45%) with late HAT had CMV infection versus 14% without HAT (P <.05). Two episodes of late HAT (11 and 79 months) occurred in patients who underwent re-OLT for early HAT (3.9%). Re-OLT was performed in 8 patients a median of 11 days (range, 3 to 37 days) after diagnosis (preceded by intravenous antibiotics and percutaneous drainage). The other 3 patients underwent partial hepatectomy (1 patient), external percutaneous drainage as unfit for surgery (1 patient), and antibiotic therapy only (1 patient). Death occurred in 4 patients who underwent re-OLT (50%) because of septicemia at 11, 23, and 60 days after re-OLT and 17 days after a third OLT. There was one late death (30 months) after partial hepatectomy (hepatitis C recurrence) and one death 6 months after long-term biliary drainage because of sepsis. The 5 survivors have good health with normal liver function test results at a median 52 months (range, 6 to 57 months). In conclusion, late HAT presents with fever caused by hepatic abscesses or biliary leak associated with biliary ischemia and necrosis. CMV infection and accessory hepatic artery anastomosis are risk factors for late HAT in our cohort. Early intervention followed by re-OLT can salvage patients.

Adult↗

PubMed2003

Epithelial colonies cultured from human explanted liver in subacute hepatic failure exhibit hepatocyte, biliary epithelial, and stem cell phenotypic markers.

The liver in subacute hepatic failure may become enriched for hepatic progenitor cells. Liver tissue from such a patient was collagenase digested and, from the nonparenchymal cell fraction, epithelioid colonies were developed. Albumin and alpha-1-antitrypsin (AAT) were secreted for greater than 120 days from these colonies. Reverse transcription-polymerase chain reaction showed expression of markers of both hepatocyte and biliary epithelial phenotypes (cytokeratins 7, 18, and 19, albumin and AAT, hepatocyte growth factor receptor, transforming growth factor beta receptor type II, gamma-glutamyl transpeptidase, biliary glycoprotein). The cell cycle regulator p21 was also expressed. The POU domain transcription factor octamer-binding protein 4 was present in these cells, but not in RNA or cDNA prepared from adult human liver. These markers were maintained even after 165 days culture. Proliferating epithelial-like cells with combined hepatocyte- and biliary-epithelial-specific functional markers and a stem cell marker can be isolated from the nonparenchymal fraction of liver cells in subacute hepatic failure.

Bile Ducts, Intrahepatic↗

PubMedDate not supplied

[SUPEROXID EXAGERATED PRODUCTION BY NEUTROPHILS OF PATIENTS WITH ACUTE ALCOHOLIC HEPATITIS: THERAPEUTIC IMPLICATIONS]

Alcoholic hepatitis represents the most severe form of alcoholic liver disease Recent research points to an exaggerated inflammatory response, mediated by neutrophils,as the basic mechanism of liver damage. This entity has a distinctive clinical picture and a characteristic histopathology and a poor outcome.Recent investigation reveals a complex network of intracellular and intercellular communication signals involving hepatocytes, endothelial cells, monocytes, lymphocytes, neutrophils,Ito and Kupffer cells, leading to massive migration of neutrophils from blood to liver.When neutrophils reach the liver, multiple cytokines produced locally by endothelium, hepatocytes and Kupffer cells, up-regulate their function. Activation of neutrophils leads to increased production of oxygen radicals(mainly superoxide)and hydrogen peroxide production.To date there is general agreement that measurement of superoxide production by neutrophils is a reliable way of determining neutrophil function and its activation.Thirty one patients with acute alcoholic hepatitis, twenty with compensated alcoholic liver disease end seventeen controls were studied.Patients with alcoholic hepatitis and alcoholic liver disease were enrolled on admission to the hospital and if they had no features of infection, bleeding or renal failure.The neutrophil stimuli used were opsonized zymosan and fMLP.The production of superoxide was similar in the three groups when neutrophils were not stimulated.After stimulation with opsonized zymosan,there was an increase in the production of superoxide from patients with acute alcoholic hepatitis in comparison to those with alcoholic liver disease and controls. This increase was statistically significant when fMLP was the stimulant(p<0.05). This is a reliable technique that can be use in the evaluation of different therapeutic modalities in acute alcoholic hepatitis

Journal Article↗

PubMedDate not supplied

[ALCOHOLIC HEPATITIS]

At present, the relation between alcoholic consumption and the development of hepatic injury is clearly defined. However, the influence of genetic factors, the existence of associated pathologies, and the concomitant use of other hepatotoxic agents should also be considered.During chronic drunkenness, great quantities of oxygen free radicals are produced, redox balance is disturbed, and the defensive capacity of natural antioxidants is exceeded. All these factors originate an "oxidative stress," that totally distorts the hepatocellular function. Llkewise, an increase in the acetaldehyde intracellular concentration modifies several cellular proteins, deteriorating even more the hepatic activity. The importance of the "neo-antigens" between cellular components and acetaldehyde is still undefined, as well as their role in the formation of the Mallory Bodies.On the other hand, the complex network of intercellular and intracellular communications that includes cytokines, adherence molecules and membrane receptors are essential elements to be considered in the alcoholic liver disease genesis. The endotoxin, the TNF-a, the IL-8, as well as the ROIs production seem to be the most important factors.With reference to Alcoholic Hepatitis, the development of an exaggerated inflammatory response with the existence of neutrophiles may be the main mechanism of hepatocellular injury (82, 167, 168.)The final diagnosis of Alcoholic Hepatitis is histological. This also enables to measure the injury severity and to determine the presence of fibrosis and/or cirrhosis, in which case prognosis is more uncertain.Should a history of exaggerated alcoholic ingestion exist, diagnosis could be clinically determined. There is a great variability of clinical symptoms, and some patients present chronic liver disease complications frequently. Those who develop severe liver insufficiency will present leukocytosis, icterus and fever. In these cases, mortality can be as high as 80 per cent. There is no relationship between the alteration of liver function tests and the injury severity.The usefulness of antioxidants in cirrhosis has been demonstrated in animal modeis and in some studies made in human voluntarles. However, their role as therapy within the context of Alcoholic Hepatitis has not been yet defined.In conclusion, several therapeutic approaches have been investigated and from all of them, only steroids have proven to be effective on patients properly selected. The discriminative function (DF) benefit has been confirmed in certain studies. Should a patient have a DIF of more than 93, he/she may receive corticosterold treatment. Contral ndicati ons are a bsol ute when the patientpresents infection, renal insufficiency or gastrointestinal bleeding.Once the patient has been compensated, ABSTINENCE is essential. Likewise, an appropriate nutritional support is an important part of the treatment.Where the possibility of Liver Transplant exists, this should be planned if there is a deterioration of the patient's general condition or if he/she compiles with the necessary criteria, since the survival rate in these cases is similar to those who received a transpiant due to other causes.

Journal Article↗