Elevated CD4+/CD25+ T-cell frequency and function during hepatitis C virus recurrence after liver transplantation.

BACKGROUND/AIM: Factors involved in hepatitis C virus (HCV) recurrence versus acute cellular rejection are not fully understood. The aim of the present study was to investigate whether patients with recurrence after liver transplantation (OLT) showed similar CD4(+)/CD25(+) cell frequency and function as those who became chronically infected. PATIENTS AND METHODS: After written informed consent, we enrolled 20 patients (group A) who underwent OLT with HCV recurrence within 6 months. HCV-RNA and hypertransaminasemia were used to assess the reactivation of viral hepatitis. CD4(+)/CD25(+) T cells were enumerated using a flow cytometry assay, gated on CD3 cells, stained for FoxP3. After immunomagnetic sorting (Dynal, Oslo, NW), Treg suppressor activity was measured, as the ability to inhibit proliferation of autologous CD4(+)/CD25(-) T cells (anti-CD3/CD28 stimulation-1:2, 1:20 ratio). Eight patients with acute hepatitis C who evolved to a chronic infection after 6 months (group B) were used as positive controls, while 10 healthy individuals were negative controls (group C). RESULTS: We did not observe any difference in CD4(+)/CD25(+) frequency or function among group A compared with group B (CD4(+)/CD25(+) = 14% +/- 2% versus CD4(+)/CD25(+) = 16% +/- 3%), although both groups were significantly increased with respect to group A (CD4(+)/CD25(+) = 6% +/- 3%; Mann-Whitney U test, P < .01). CONCLUSION: Patients developing HCV recurrence after OLT have the same immunoregulatory network as patients with acute hepatitis C evolving to persistent infection, likely suggesting that CD4(+)/CD25(+) numbers may be a marker to predict recurrence of HCV after OLT.

Strategies for the prevention of asthmatic, anaphylactic and anaphylactoid reactions during the administration of anesthetics and/or contrast media.

General anesthetics and contrast media can cause anaphylactic as well as anaphylactoid reactions. These events are of great concern to radiologists and anesthesiologists because of their relatively high prevalence, possible threat to life, and medical-legal consequences. Points discussed in this review are the critical evaluation of risk factors affecting prevention strategies, the need to be aware of pathogenic mechanisms relevant to prevention strategies, the use of alternative products if a culprit agent is known, the recognition of early signs of a reaction, the need to keep records of reactions on a patient's medical chart, the planning of prophylactic therapy, recommended actions after a reaction to an anesthetic or contrast medium, and the suggested establishment of allergy-anesthesiology centers to improve cooperation, and medical-legal issues. As any drug or contrast medium administered during general anesthesia or a diagnostic procedure can induce a potentially life-threatening or fatal event even in the absence of any evident risk factor in the patient's medical history or clinical status, we usually premedicate susceptible individuals at least to attenuate the severity of an unpredictable reaction, although we cannot rely on the efficacy of premedication to completely prevent a severe event. These recommendations, which are based on the literature and on the experience of our working group, aim to provide useful information for physicians and other specialists who operate in the absence of an allergy consultant.

Phase I clinical trial with the AMC-bioartificial liver.

UNLABELLED: Recently a bio-artificial liver (BAL) system has been developed at the Academic Medical Center (AMC) of Amsterdam to bridge patients with acute liver failure (ALF) to orthotopic liver transplantation (OLT). After successful testing of the AMC-BAL in rodents and pigs with ALF, a phase I study in ALF patients waiting for (OLT) was started in Italy. We present the safety outcome of the first 7 patients aged 21-56 years with coma grade III or IV The total AMC-BAL treatment time ranged from 8 to 35 hours. Three patients received 2 treatments with two different BAL's within three days. Six of the 7 patients were successfully bridged to OLT. One patient showed improved liver function after two treatments and did not need OLT. No severe adverse events of the BAL treatment were noted. CONCLUSION: Treatment of ALF patients with the AMC-BAL is a safe and feasible technique to bridge the waiting time for an adequate liver-graft.

Anaesthetic management and outcome in right-lobe living liver-donor surgery.

BACKGROUND AND OBJECTIVE: We reviewed retrospectively the anaesthetic management and perioperative course of eight right hepatectomies for living liver donation. METHODS: After preoperative psychiatric evaluation, eight ASA I-II individuals donated the right lobe of their liver to a family member. A graft-recipient body weight ratio of 0.8-1.0% was required for patient selection. Indications for liver transplantation were: hepatitis C viral-related cirrhosis in six patients; combined hepatitis C and B viral cirrhosis in one patient; multifocal hepatocellular carcinoma--four lesions, involving both liver lobes--of hepatitis C viral-related cirrhosis in another patient. Indication for adult-to-adult living-donor liver transplantation was retained in the latter because of rapid deterioration of liver disease, rare recipient's blood group and extended, unresectable hepatocellular carcinoma. Hepatitis C viral-related cirrhosis was casually the primary indication for adult-to-adult living-donor liver transplantation in this group. The condition of the donated hepatic lobe was optimized by appropriate drug and perfusion management. Preoperative investigations included: blood tests (full cell count and film, thyroid function tests, pregnancy tests, full virological tests and bacteriological cultures, and immunological typing), chest radiograph, electrocardiogram plus Doppler cardiac ultrasound, spirometry, aminopyrine breath test, liver Doppler examination, magnetic resonance imaging, angiography and cholangiography and a volumetric study of the whole liver and the right lobe. Haemoglobin and lactate concentrations, liver function tests and international normalized ratio were measured before and after operation. The volume and weight of the resected right lobe was calculated. Anaesthesia was induced with propofol 300 mL h(-1) and sufentanil 0.3 microg kg(-1) intravenously; cisatracurium, 0.15 mg kg(-1), was given to facilitate tracheal intubation. Anaesthesia was maintained during normocapnic ventilation of the lungs with oxygen 40% in air, isoflurane 1-1.5 MAC and sufentanil. Routine anaesthetic monitoring included electrocardiography, pulse oximetry, invasive blood pressure, central venous pressure, urine output, state of neuromuscular blockade and core temperature. Periods of hypotension (<80% of the preoperative blood pressure) or haemodynamic instability (requiring inotropic or vasoactive support) were registered. Total blood loss and transfusion (homologous, autologous or cell-saver blood) requirements were measured; volume replacements were derived. RESULTS: Data are presented as mean (range). There was no morbidity or mortality and no periods of intraoperative hypotension or haemodynamic instability. The operation time averaged 619 (525-780)min. Four donors were extubated in the operating room immediately after surgery; the others were extubated in the intensive care unit, where the mean extubation time was 16.3 (5-25)h after arrival. The estimated blood loss was 967 (550-1,600)mL. No homologous blood was administered; five donors received autologous blood, intraoperatively; three donors received a cell-saver blood transfusion. Intraoperative fluid replacement was with crystalloids, colloids and 4% albumin. Total urine output was 1,472 (700-3100)mL. Although intraoperative hypothermia occurred all subjects were normothermic at the end of operation. The pre- and immediately postoperative haemoglobin concentration averaged 13.6 (9.8-15.6) and 10.5 (6.9-13.0)gdL(-1), respectively. On the first postoperative day, the haemoglobin was 11.7 (8.4-15.1)gdL(-1). The donors' liver function tests were transiently elevated in the initial postoperative period. The intensive care unit discharge time was 2 (1-3) days. The hospital stay was 13 (7-17) days. There was no morbidity or mortality. CONCLUSIONS: The study demonstrates that right-lobe living-donor surgery was well tolerated, without intraoperative hypotension or haemodynamic instability, without perioperative anaesthetic or surgical complications, and with an excellent general outcome.

Significantly improved survival time in pigs with complete liver ischemia treated with a novel bioartificial liver.

Aim of the study was to evaluate treatment efficacy and safety of a scaled-up version of our porcine hepatocytes based BAL system in pigs with complete liver ischemia (LIS). Thirty-one pigs underwent total devascularization of the liver (LIS) by termino-lateral porta-caval shunts and sutures around the bile duct, the common hepatic and gastroduodenal arteries and their accessory branches. The hepato-duodenal ligament was completely transected. Four experimental groups were studied: the first control group (LIS Control, n = 10) received glucose infusion only, the second control group (LIS Plasmapheresis, n = 8) was connected to a centrifugal plasma-separator with a bottle representing the bioreactor volume, the third control group (LIS Empty-BAL, n = 5) received BAL treatment without cells, and the treated group (LIS Cell-BAL, n = 8) was connected for a maximum period of 24 hours to our scaled-up BAL seeded with around 14 billion viable primary porcine hepatocytes. BAL treatment significantly prolonged life in large animals (approximately 35 kg) with complete LIS (Controls, mean +/- SEM: 33.1 +/- 3 h, Cell-BAL: 51.1 +/- 3.4 h; p = 0.001; longest survivor 63 h). In addition, blood ammonia and total bilirubin levels decreased significantly, indicating metabolic activity of porcine hepatocytes in the bioreactor. No significant differences were noticed among the three control groups, indicating that there was no device effect and that the plasmapheresis procedure was well tolerated. No important adverse effects were observed.