refractory ascitis diagnosis by the study of labelled albumin pharmacokinetics

Conditions: Refractory Ascites in Patients With Cirrhosis

Summary: refractory ascites is an indication for liver transplantation, and includes ascites that is resistant to, or intractable by diuretic therapy (international ascites club). this definition is partly subjective; it can be established only a posteriori, following diuretic therapy administration to all patients, including those in whom untoward effects are prominent; and requires prolonged follow-up. an early diagnosis of refractory ascites would avoid giving diuretic therapy to patients in whom it will fail and identify rapidly candidates to liver transplantation. such diagnosis could be done with a pharmacokinetic (pk) study of radiolabeled albumin between the peritoneal cavity and serum.

main objective: assess the performances of pk parameters (transfer of labelled albumin) between peritoneal and vascular compartments, for the diagnosis of refractory ascitis, in patients with cirrhosis and abundant ascitis. design: proof of concept study. interventional cross-sectional study in beaujon hospital (clichy, france), 1 recruiting center and 1 non recruiting center. patients are recruited in the hepatology department (pr valla) and pk exploration is performed in the nuclear medicine department (pr lebtahi) of beaujon hospital. description of intervention: diuretics treatment discontinuation 7 days before exploration for patients with sensitive ascitis, and more than 7 days for those with refractory ascitis. the day of exploration, the patients come to hospital and stay in lying position. one intra-veinous injection of 0,015 megabecquerel(mbq) /kg labelled human serum albumin (iode-125 (125-i), séralb®cisbio), in compliance with market authorization, simultaneously to one intra-peritoneal injection of 200 mbq of labelled albumin (technetium 99m (99m-tc), vasculocis®, cisbio), off-label used. it follows 5 minutes mobilization of the patient (right and left lateral decubitus), then a scintigraphy will be performed using a gamma-camera symbia t2 (siemens®). repeated blood (5 ml) and peritoneal ascitis (3 ml) samples are performed before injection and every 30 minutes for 6 hours (catheter in place). diuretic treatment can be restarted the day after pk explorations. patients are followed-up at 1 month by phone call (for the collection of adverse events). measurements : radioactivity measurements of 99m-tc and 125-i in the biological samples are performed by a counter device in the nuclear medicine department (wizard 3000, packard®). unidirectional transfer of labelled albumin (125-i) from vascular compartment (plasma-p) to peritoneal compartment (ascitis-a) (tpa), unidirectional transfer of labelled albumin (99m-tc) from peritoneal (a) to vascular compartment (p) (tap), and the ratio tpa/tap are calculated from these measurements using matlab®.the gold standard is defined by the diagnosis of refractory ascitis performed before inclusion. statistical analyses: performances of the tap, of the tpa, and of the ratio tpa/tap for the diagnosis of refractory ascitis, will be computed using the receiver operating characteristic (roc) curve. number of patients : 30 patients (15 patients with refractory ascitis and 15 patients with sensitive or untreatable ascitis) will be included during a 24 months period (1 or 2 patients per month), and followed-up for 2 months. the pk explorations will be performed in nuclear medicine department not more than 4 weeks after inclusion. total length of study will be of 26 months.

Eligibility criteria:
inclusion criteria: * patients consulting in hepatology department of beaujon hospital * aged 18 - 80 years old * cirrhosis due to alcoholic and/or dysmetabolic and/or viral (hbv or hcv) cause, pathologically or clinically/biologically/radiologically proven. * volume of ascitis \>5 l, either sensible or refractory to diuretics drugs according iac criteria exclusion criteria: * infection in the 2 weeks prior to inclusion (suspected or proven) * upper gastrointestinal bleeding du to portal hypertension in the 2 weeks prior to inclusion * transjugular intrahepatic portosystemic shunt (tips) * advanced hepatocellular carcinoma * hepatic transplantation * unability to stay lying for 6 hours * pregnancy / lactation * renal deficiency (creat. clearance \< 60ml/min) * cardiac deficiency (≥ new york heart association (nyha) iii) or myocardial infarction (\<3 months) * other cause of ascitis * contra-indication to human albumin (125-i) or vasculosis (99m-tc) or other component of radio-pharmaceutics * no health insurance coverage * unability to go to the hospital for 1 day of exams * refuse to consent to study participation

Keywords: diagnostic performances ascites