High transferrin saturation and non-transferrin-bound iron in acute fulminant liver failure

50

Poster Sessions

Conclusions: Most of the biliary complications were successfuly managed by endoscopy. In 30% of cases combination with transhepatic intervention or surgery was neccessary. The best results of endoscopy can be obtained with papillary dysfunction, choledccholithiasis, anastomotic leaks and strictures. Unsatisfactory results were obtained with lymphoproliferation, biliary peritonitis and intrahepatic strictures.

nificative prognostic value of ABT in the study (p = 0.055) validation (p = 0.052) groups. In conclusion, our study shows that the risk of dying of cirrhotic on the liver waiting list is in relation with degree of severity disease and is better appreciated with simple indicators such (cut-off: 0.5%) or Pugh score (cut-off: 11/15).

I 1578

0 1580

LIVING RELATED LIVER TRANSPLANTATION FOR DECOYPENSATED END-STAGE LIVER DISEASE

G. Testa, M. Malaga, S. Nadalin, C. Valentin-Gamazo, A. Frilling, C.E. Broelsch. General and Transplantation Surgery University Essen, Germany

Introduction: Patients (pts) with decompensated end stage liver disease (DESLD) are considered questionable candidates for living related liver transplantation (LRLT) due to their reported poor outcome. Due to the present shortage of cadavetic organs, transplanting these pts in timely fashion is almost impossible. We present our results in pts with DESLD undergoing LRLT. Materials and Methods: From 8/98 to 1l/2000, 43 pts underwent right liver lobe LRLT (segments 5-8). 7/43 pts (16%) had DESLD, defined as a Child-Turcot-Pugh (CTP) > 13. All 7 pts were bed ridden, had a life expectancy < 1 month and 3 were in intensive care unit (ICU). Patient and graft survival, length of postoperative ICU-stay and graft function were analysed. Results: Seven pts with DESLD, median CPT score 13.5 (range 13-15), underwent LRLT, Mean follow up was 9 months (l-23 months). Median ICU-stay was 29 days (3-127 days). Only 1 patient had an uncomplicated postoperative course and 6/7 pts required 1 to 5 operative procedures after the transplantation. Post transplant dialysis was necessary in 4fl pts. To date 5 pts are alive; 4 are home and 1 is still hospitalized. Two pts died at 1 and 3 months after the transplantation. No patient required retransplantation. All grafts are functioning well with average bilirubin < 1.5 mg/dl. Patient and graft survival is 7 1%. Conclusion: The scarcity of cadaveric organs makes LRLT the only timely therapeutic option for pts with DESLD and their good survival justifies the risks taken by the donor.

I 1579

RISK FACTORS FOR MORTALITY ON THE LIVER WAITING LIST OF CIRRHOTIC PATIENTS LISTED FOR LIVER TRANSPLANTATION

M. Adler, D. Degree, A. Fancello, N. Bourgeois, 0. Le Moine, V. Donckier, P. Vereerstraeten. Department of Gastroenterology, Hopital Erasme, Belgium

Stagnation of the annual rate of liver transplantation contrasts with a sharp increase in the number of recipients listed and in the waiting time before transplantation on the list, this leading to a 10 to 30% mortality rate (UNOS, Eurotransplant data). The aim of our study was to determine risk factors associated with death on the waiting list of 134 cirrhotic patients listed between 1992 and 2000. Endpoints were either death while waiting (n = 21, 15%) or transplantation (n = 113). Thirty-two variables were registered at the time of the pretransplant work-up. Univariate and multivariate analyses were done in order to identify prognostic variables independently associated with risk of dying on the waiting list. Of the ten (presence of ascites, infected ascites, UNOS score, medical urgency code (MUC), Pugh score (cut-off: > = 1l), aminopyrine breath test (cut-off c = 0.5%), bilirubin, cholinesterase, albumin, prothrombin time), only aminopyrine breath test (ABT) was kept in the final multivariate model (p 0.0073). When ABT is excluded from the analysis, Pugh score (cut-off: > = 11) is the most powerful prognostic factor (p = 0.001). Internal validation, using the split sample technique, confirms the sig-

and the patients of liver as ABT

PROGNOSIS OF NON BILIARY PARENCHYMAL CIRRHOSIS IS BElTER PREDICTED USING TIME-DEPENDENT VARIABLES

M. Adler, G. Longheval, P. Vereerstraeten, P. Thiry, M. Delhaye, 0. Le Moine, J. Deviere. Department of Gastroenterology, Hopital Erasme, Belgium

As liver transplantation is now frequently offered to patients with end stage liver diseases, it is important to try new approaches in order to optimize accuracy of the prognostic evaluation. Between July 1994 and July 1996, 124 consecutive patients with non biliary cirrhosis (73 alcoholic, 35 viral, 16 other) confirmed by transjugular liver biopsy were included. Mean follow-up was 721 days (range 4 to 2202). The prognostic significance of 33 parameters was evaluated using univariate and multivariate analysis. During the follow-up, 54 (44%) patients died and 20 patients (16%) were transplanted. Four variables independently predicted a poor prognosis: three at time zero: albumin (p = 0.011 l), prothombin time (PT) (p = 0.0015), creatinin (p = 0.0031) and one during the six months follow-up: development of sepsis (p = 0.015). From the Cox model, a prognostic index (PI) was computed based upon the relative risk coefficient variables. The PI was validated using a split sample testing technique with a random sample of 50% of the population studied and disclosed the following results: 1 and 3 years survival: 93 and 81% with low PI; 16% and 12% with high PI (statistically not significant from the original series using log rank test). Conclusions: This study highlights the importance of adding information from the follow-up to time zero evaluation of patients with non biliary parenchymal cirrhosis in order to optimize the accuracy of the prognostic estimation and of the criteria to put a cirrhotic patients on a liver waiting list.

I

1596

HIGH TRANSFERRIN SATURATION AND NON-TRANSFERRIN-BOUND IRON IN ACUTE FULMINANT LIVER FAILURE

H. Isoniemi, L. von Bonsdorff, K. Hockerstedt, J. Parkkinen. Transplantation and Liver Surgery, Helsinki University, Helsinki, Finland

In normal conditions practically all iron in plasma is bound to transferrin and the level of non-transferrin-bound iron (NTBI) is very low. NTBI has ability to catalyse reactions leading to the production of highly toxic oxygen radicals and may also promote the growth of micro-organisms. Several lines of evidence suggest that NTBI might be toxic to liver cells. Hepatocytes, unlike many other cells, have clearance mechanism of NTBI in iron overload. Our aim was to study the occurrence of NTBI in acute fulminant and end-stage chronic liver failure immediately prior to the liver transplantation (LTx) and at discharge after LTx. Blood samples were investigated in 12 patients with acute fuhninant hepatitis (AHF) and 16 patients with primary biliary cirrhosis (PBC). NTBI was measured by the bleomycin-detectable iron (BDI) method and considered as positive if 10.1 PmohL. In AHF, 9/12 (75%) of the patients were positive for NTBI before LTx, whereas in PBC only 2/16 (12.5%) were positive. After LTx, all AHF patients were negative for NTBI. In AI-IF, the mean transferrin saturation was 84% before LTx and decreased to 35% after LTx. This was mainly due to a decrease of tbe mean serum total iron level to less than half

Category 2: Cirrhosis and its complications,

after LTx. Serum transferrin level was clearly below the reference level both before and after LTx in AI-IF. In PBC transferrin saturation was at normal range and total iron was low before LTx. Table 1. Median of BDI and mean levels of S-Fe and Transferrin and % of transferrin saturation Positive NTBI

BDI /LIllOl/L

s-Fe

Transferrin gil

Saturation

%

pmol/L

AHF (n = 12) Before LTx After LTx

9 (75%) 0 (0%)

0.48 0.02 p < 0.05

32.4 12.9 p < O.cOol

1.44 1.61 ns

84% 35% p < O.oool

PBC (n = 16) Before LTx After LTx

2 (12.5%) 2 (12.5%)

0.03 0.04 ns

16.24 14.86 ns

1.84 1.82 ns

40% 35% ns

indicate that the majority of patients with AHF have high transferrin saturation and NTBI. Theoretically, this could worsen acute liver cell damage and contribute to the susceptibility of these patients to infections with opportunistic bacteria and fungi. Our results

PO2 Category 2: Cirrhosis and its complications, pathophsyiology and clinical aspects

02

POSTPARACENTESIS NEUROHUMORAL CHANGES AND IMPAIRMENT OF RENAL WATER EXCRETION IN CHILD-PUGH C CIRRHOSIS WITH AND WITHOUT VOLUME REPLACEMENT

V. Degoricija, V. Zjacic-Rotkvic, B. Troskot, S. Sefer. Department of Internal Medicine, UH “Sisters of Charity”, Zagreb, Croatia In many centers paracentesis is considered as the treatment of choice for tense ascites. The mechanism of postparacentesis effective hypovolemia, the main cause of postparacentesis circulatory dysfunction syndrome remains unknown. The aim of the study was to assess postparacentesis neurohumoral changes and impairment of renal water excretion in patients with refractory tense ascites with and without volume replacement and bed rest 24 hours before and after the procedure. Methods: 40 patients with Child-Pugh C liver cirrhosis and tense ascites were randomly allocated into 4 groups. 30 patients were treated with paracentesis (6 1) associated with plasma volume expansion (200 ml 20% HA, 600 ml FFP, 900 ml solution of synthetic gelatin, which were doses with comparable oncotic power) and bed rest 24 hours before and after the procedure, versus 10 patients treated with paracentesis of 6 1 of ascites without volume replacement and no bed rest. MAP, pulse rate, HE, PRA, PAC, plasma ANP, urine flow rate, serum creatinine, creatinine clearance, osmolality clearance and free water clearance were measured before, 6 hours after start of the trial and on the 2”d, 31d, and 6” day. Results: Paracentesis of 6 1of ascites without plasma volume expansion and no bed rest 24 hours before and after the procedure is associated with statistically significant hypotension (p = 0.000). tachycardia (p = O.OOO), insufficient weight loss (p = 0.007). worsening of HE (p = 0.007), increase in PRA (p = 0.024), increase in PAC (p = O.OOO),decrease in plasma ANP (NS), decrease in creatinine clearance (p = 0.046), greater risk of development of hepatorenal syndrome. Therapeutic paracentesis of 6 1of ascites, bed rest 24 hours before and after the procedure and intravenous substitution of volume with HA, FFP or solution of synthetic

pathophsyiology

and clinical aspects

51

gelatin is safe, rapid and effective therapy, if intravascular volume is substituted simultaneously. Albumin is superior to the other plasma expanders with exception of the cost. However, comparison between groups did not provide significant differences at any time in negative free water clearance. Conclusion: None of the protocols did have aquaretic efficacy. The inability to excrete solute free water is one of the strongest predictors for developing hepatorenal syndrome. Patients with liver cirrhosis should be observed at least for 6 days after the large volume paracentesis for evidence of progressively deteriorating renal function, worsening electrolyte imbalance or development or worsening of HE.

0

19

SYNTHETIC COLLAGEN-OLIGOPEPTIDES INHIBIT BINDING OF PLATELET DERIVED GROWTH FACTOR BB TO THE HEPATIC EXTRACELLULAR MATRIX

M. Ruehl, R. Somasundaram, R. Farndale, G. Knight, M. Schmid, R. Ackermann, E.O. Riecken, D. Schuppan. Berlin, Germany Background/Objectives: The profibrogenic growth factor PDGF BB binds to collagens of the hepatic extracellular matrix, defining it as a cytokine store. We suggested a PDGF BB binding consensus sequence and tested synthetic collagen peptides of the structure (GPP)x or (GPO)x (0 = HYP). Methods: For binding studies and ligand blots the triple helical peptides (GPP)lo, (GPO)10 and the linear control (GAP)10 were immobilised. For inhibition studies coated native collagens (200 @well) or collagen peptides (30-60 ng/well) were incubated with 2 ng [1251]-PDGF together with the synthetic peptides. PDGF was immunolocalized on human cirrhotic liver slices after preincubation with the peptides. Results: 30-50% of [1251]-PDGF BB bound to immobilised native collagens I and VI (2 pg/well), their single chains and the . l(I)CB6 peptide. Binding to (GPP)lo and (GPO),0 was comparably high, whereas the linear peptide (GAP),0 showed no PDGF BB binding. Interaction of PDGF with different collagens was equally inhibited by the peptides and . l(I)CB6. Binding of PDGF BB to the matrix of cirrhotic liver could be inhibited by the triple helical synthetic peptides. Conclusions: The decamer triplets (GPP)x or (GPO)x are responsible for the specific binding of PDGF BB to liver collagens. The profibrogenie effect of collagen-bound PDGF BB can be neutralized by these peptides or their analogues.

029

A LA CARTE: TREATMENT OF PORTAL HYPERTENSION: PROSPECTIVE STUDY OF 30 PATIENTS

Jean-Marie Peron, Laurent Alric, Jerome Sanchez, Amani Asnacios, Karl Barange, Jean-Pierre Vinel. Hopato-Gastro-Enterologie, CHU Purpan, Toulouse, France

Aims: to assess whether l-the adjunction of isosorbide mononitrate (5-IMN) improves the hemodynamic response (defined as a fall of porto-hepatic venous pressure gradient (PHVPG) 320% or < 12 mmHg) to propranolol (P) and 2- hemodynamic response is predictive of the clinical response. Patients and Methods: 30 patients (19 males; age = 54 f 11 years) with cirrhosis (Child A = 8, B = 14, C = 8) were included for primary (n = 18) or secondary prevention (n = 12) of varicea’l bleeding. PHVPG was measured before then after P. Non-Responders: to P were given 51 M and PHVPG was measured again. Thereafter the patients were followed for 11.35 f 9.35 months. Results: HVPG decreased from 19.1 f 4.9 to 17.25 f 6.10 mmHg after P (-10.2 f 21.3%, p < 0.05). 12 patients were responders (R) (40%). 51 MN was prescribed to non-responders (NR), induced a further PHVPG decrease of 8.83 f 18.67% (p < 0.05 vs P alone) and 5 additional patients (27.7%) became R:. Variceal bleeding occurred in 6 NR: and 2 R20%): vs 6.7%, p < 0.05). Patients treated to prevent