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161 Chronic liver failure attenuates the CNS consequences of subsequent acute liver failure by ‘priming’ of muscle glutamine synthetase capacity
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Poster Sessions
160 SEVERE PRIMARY HHV8 INFECTION FOLLOWING TRANSPLANTATION WITH ANTI-HHV8-POSITIVE LIVER GRAFTS
A.M. Roque-Afonso 1 , A.G. Marcelin 2 , E. Kimmoun 3 , M. Hurtova 3 , M. Tulliez 5 , M. Sebagh 4 , N. Dupin 6 , C. Guettier 4 , D. Samuel 3 , V. Calvez 2 , E. Dussaix 1 . 1 Virology, UPRES 3541, Hospital Paul Brousse, Villejuif, France; 2 Virology, UPRES 2387, Hopital Pitié-Salpêtrière, Paris, France; 3 Hepatology, UPRES 3541, Hopital Paul Brousse, Villejuif, France; 4 Pathology, UPRES 3541, Hopital Paul Brousse, Villejuif, France; 5 Pathology, Hopital Cochin, Paris, France; 6 Dermatology, Hopital Cochin, Paris, France Background: Post-transplant Kaposi’s sarcoma (KS) is a relatively common malignancy of solid-organ transplant recipients. KS results mainly from HHV-8 reactivation due to the therapeutic immunosuppression in previously infected recipients. The incidence of HHV8 transmission by liver allografts and the clinical manifestations of HHV8 primary infection in the liver transplant setting are poorly known. Methods: A total of 200 liver donors and their respective recipients were studied. HHV8 seroprevalence was assessed by the detection of antibodies to a latent nuclear antigen by using an immunofluorescence assay. Molecular methods and immuno-staining analyses were performed on samples from HHV8-infected patients. Results: A 2,5% HHV8 seroprevalence was found. Prevalence was identical among recipients (5/200) and donors (5/200). None of the 5 HHV8positive recipients developed KS up to 3 years after liver transplantation. No seroconversion was observed among the 5 recipients of HHV8-positive liver donors. However, 3 of them developed severe primary HHV8 infection within 6 months after transplantation. Two died harboring HHV-8 positive lymphoproliferation and visceral KS with no cutaneous manifestations. The third recipient has a six months follow-up after transplantation and has developed an HHV8-positive lymphoproliferation justifying the administration of anti-CD20. HHV8 DNA was detectable in peripheral blood mononuclear cells, serum and other tissues before and at the onset of HHV8 related diseases. Conclusions: In liver transplant recipients, HHV-8 primary infection can be associated with a fatal outcome. The organ donors screening for HHV-8 could enable clinical and viral monitoring and early therapeutic actions.
associated with subsequent acute deterioration of hepatic function and that this protective effect is mediated by increased ammonia-removal capacity by skeletal muscle (Funded by CIHR).
162 EVIDENCE FOR THE NEED OF LIFELONG PROPHYLAXIS AGAINST HEPATITIS B REINFECTION AFTER LIVER TRANSPLANTATION
J. Rosenau 1 , T. Solga 1 , I. Bottcher 1 , C.P. Strassburg 1 , J. Klempnauer 1 , M.P. Manns 1 , H.L. Tillmann 1 . 1 Department of Gastroenterology, Hepatology and Endocrinology/Hannover Medical School, Hannover, Germany; 2 Department of Visceral and Transplant Surgery/Hannover Medical School, Hannover, Germany Hepatitis-B-immunoglobuline (HBIg) has substantially reduced, and combined with lamivudine, almost eliminated HBV-reinfections after liver transplantation. However, necessary duration of prophylaxis is unclear. Available serum samples of HBsAg-negative patients receiving either HBIg-mono-prophylaxis (group A) or combined prophylaxis with lamivudine (group B) were tested for HBV viral load before and 3, 12 and 24 months after transplantation. HBV-DNA was determined using a recently developed HBV-DNA assay (COBAS TaqMan, Roche Molecular Systems), lower limit of detection 35 copies/ml. Before transplantation only 5/13 (38%) patients in group A and 8/27 (30%) in group B were HBV-DNA negative, whereas 3/13 (23%) in group A and 12/27 (44%) in group B had viral load above 1000 copies/ml. During follow up 7/27 (26%), 3/15 (20%) and 0/16 (0%) in group A versus 3/44 (7%), 1/33 (3%) and 1/30 (3%) in group B were HBV-DNA positive at 3, 12, 24 months post OLT. Reinfections occurred in 9/38 (24%) patients in group A and in 6/58 (10%) in group B. In two reinfected patients in group B YMDDmutations with high viral load were present at OLT. In two patients with YMDD-mutations, but low viral load, reinfections occurred after HBIg was stopped unintentionally. In other two patients either lamivudine or HBIg was stopped accidentally. As HBV-DNA is detectable in absence of HBsAg in many patients, especially under HBIg- mono-prophylaxis, lifelong combination prophylaxis with lamivudine appears necessary. Presumably all reinfections could have been prevented by currently available optimal patient management. Treatment of YMDD-mutants with adefovir dipivoxil appears crucial.
161 CHRONIC LIVER FAILURE ATTENUATES THE CNS CONSEQUENCES OF SUBSEQUENT ACUTE LIVER FAILURE BY ‘PRIMING’ OF MUSCLE GLUTAMINE SYNTHETASE CAPACITY
C. Rose, N. Chatauret, M. Belanger, P. Desjardins, R.F. Butterworth. Neuroscience Research Unit, CHUM, Saint-Luc Hospital, University of Montreal, Montreal ON, Canada Although brain edema is a common feature of acute liver failure (ALF) it is rarely observed in chronic or acute-on-chronic liver failure. In order to further elucidate the mechanisms implicated, male Sprague-Dawley rats were subjected to end-to-side portacaval anastomosis followed by hepatic artery ligation (HAL) either 24h (HAL-24h) or 4 weeks (HAL-4W) following shunt surgery. Body temperature and blood glucose were monitored and maintained throughout the experiments following HAL. Onset of encephalopathy was significantly delayed in the HAL-4W group of animals compared to HAL-24h and brain water concentrations measured by the gravimetric procedure were also significantly attenuated in this group (control: 80.12±0.09%; HAL-24h: 81.39±0.15% (p<0.01 of control); HAL-4W: 80.04±0.13% (ns of control)). Arterial ammonia concentration followed a similar pattern (control: 0.14±0.04 mM; HAL-24h: 1.51±0.07 mM (p<0.01 of control); HAL-4W: 0.52±0.09 mM (p<0.01 of control)). Activity of the ammonia-metabolizing enzyme glutamine synthetase was increased in skeletal muscle (by 52% p<0.01) but not in brain 4 weeks following portacaval anastomosis. These findings suggest that chronic liver failure delays the onset of brain edema in encephalopathy
163 ARTERIAL LACTATE AS A PROGNOSTIC MARKER IN PARACETAMOL-INDUCED ACUTE LIVER FAILURE: EVALUATION OF THE MODIFIED KING’S COLLEGE CRITERIA
L.E. Schmidt, F.S. Larsen. Department of Hepatology, Rigshospitalet, Copenhagen, Denmark Aims: The challenge in the management of acute liver failure (ALF) lies in identifying patients with a capacity for survival without liver transplantation. The present study aimed at evaluating the recently proposed lactate modification of the King’s College Hospital (KCH) selection criteria. Methods: Seventy-six consecutive patients with paracetamol-induced ALF were evaluated at the onset of grade 3-4 hepatic encephalopathy by the KCH criteria, the Sequential Organ Failure Assessment (SOFA) score, and the presence of a Severe Inflammatory Response Syndrome (SIRS). Results: Twenty-two of 27 patients (81%) who fulfilled the KCH criteria died in comparison with 19 of the 49 patients (39%) who did not (p=0.0006). Arterial lactate was significantly higher in nonsurvivors than in survivors (6.8 ± 4.8 mmol/L vs. 3.1 ± 2.1 mmol/L; p<0.0001). Adding the lactate modification to the KCH criteria increased the sensitivity from 54 to 86%, but reduced the specificity from 86 to 50%. SOFA-score was significantly higher in nonsurvivors than in survivors (15.6 ± 3.4 vs. 11.3 ± 2.9; p<0.0001). Thus, 33 out of 44 patients (75%) who had a SOFAscore above 12 died in comparison with 8 out of 32 patients (25%) who did not (p<0.0001). Twenty-eight of the 32 patients (88%) who had a SIRS died in comparison with 13 of 44 (30%) who did not (p<0.0001).
Poster Sessions
160 SEVERE PRIMARY HHV8 INFECTION FOLLOWING TRANSPLANTATION WITH ANTI-HHV8-POSITIVE LIVER GRAFTS
A.M. Roque-Afonso 1 , A.G. Marcelin 2 , E. Kimmoun 3 , M. Hurtova 3 , M. Tulliez 5 , M. Sebagh 4 , N. Dupin 6 , C. Guettier 4 , D. Samuel 3 , V. Calvez 2 , E. Dussaix 1 . 1 Virology, UPRES 3541, Hospital Paul Brousse, Villejuif, France; 2 Virology, UPRES 2387, Hopital Pitié-Salpêtrière, Paris, France; 3 Hepatology, UPRES 3541, Hopital Paul Brousse, Villejuif, France; 4 Pathology, UPRES 3541, Hopital Paul Brousse, Villejuif, France; 5 Pathology, Hopital Cochin, Paris, France; 6 Dermatology, Hopital Cochin, Paris, France Background: Post-transplant Kaposi’s sarcoma (KS) is a relatively common malignancy of solid-organ transplant recipients. KS results mainly from HHV-8 reactivation due to the therapeutic immunosuppression in previously infected recipients. The incidence of HHV8 transmission by liver allografts and the clinical manifestations of HHV8 primary infection in the liver transplant setting are poorly known. Methods: A total of 200 liver donors and their respective recipients were studied. HHV8 seroprevalence was assessed by the detection of antibodies to a latent nuclear antigen by using an immunofluorescence assay. Molecular methods and immuno-staining analyses were performed on samples from HHV8-infected patients. Results: A 2,5% HHV8 seroprevalence was found. Prevalence was identical among recipients (5/200) and donors (5/200). None of the 5 HHV8positive recipients developed KS up to 3 years after liver transplantation. No seroconversion was observed among the 5 recipients of HHV8-positive liver donors. However, 3 of them developed severe primary HHV8 infection within 6 months after transplantation. Two died harboring HHV-8 positive lymphoproliferation and visceral KS with no cutaneous manifestations. The third recipient has a six months follow-up after transplantation and has developed an HHV8-positive lymphoproliferation justifying the administration of anti-CD20. HHV8 DNA was detectable in peripheral blood mononuclear cells, serum and other tissues before and at the onset of HHV8 related diseases. Conclusions: In liver transplant recipients, HHV-8 primary infection can be associated with a fatal outcome. The organ donors screening for HHV-8 could enable clinical and viral monitoring and early therapeutic actions.
associated with subsequent acute deterioration of hepatic function and that this protective effect is mediated by increased ammonia-removal capacity by skeletal muscle (Funded by CIHR).
162 EVIDENCE FOR THE NEED OF LIFELONG PROPHYLAXIS AGAINST HEPATITIS B REINFECTION AFTER LIVER TRANSPLANTATION
J. Rosenau 1 , T. Solga 1 , I. Bottcher 1 , C.P. Strassburg 1 , J. Klempnauer 1 , M.P. Manns 1 , H.L. Tillmann 1 . 1 Department of Gastroenterology, Hepatology and Endocrinology/Hannover Medical School, Hannover, Germany; 2 Department of Visceral and Transplant Surgery/Hannover Medical School, Hannover, Germany Hepatitis-B-immunoglobuline (HBIg) has substantially reduced, and combined with lamivudine, almost eliminated HBV-reinfections after liver transplantation. However, necessary duration of prophylaxis is unclear. Available serum samples of HBsAg-negative patients receiving either HBIg-mono-prophylaxis (group A) or combined prophylaxis with lamivudine (group B) were tested for HBV viral load before and 3, 12 and 24 months after transplantation. HBV-DNA was determined using a recently developed HBV-DNA assay (COBAS TaqMan, Roche Molecular Systems), lower limit of detection 35 copies/ml. Before transplantation only 5/13 (38%) patients in group A and 8/27 (30%) in group B were HBV-DNA negative, whereas 3/13 (23%) in group A and 12/27 (44%) in group B had viral load above 1000 copies/ml. During follow up 7/27 (26%), 3/15 (20%) and 0/16 (0%) in group A versus 3/44 (7%), 1/33 (3%) and 1/30 (3%) in group B were HBV-DNA positive at 3, 12, 24 months post OLT. Reinfections occurred in 9/38 (24%) patients in group A and in 6/58 (10%) in group B. In two reinfected patients in group B YMDDmutations with high viral load were present at OLT. In two patients with YMDD-mutations, but low viral load, reinfections occurred after HBIg was stopped unintentionally. In other two patients either lamivudine or HBIg was stopped accidentally. As HBV-DNA is detectable in absence of HBsAg in many patients, especially under HBIg- mono-prophylaxis, lifelong combination prophylaxis with lamivudine appears necessary. Presumably all reinfections could have been prevented by currently available optimal patient management. Treatment of YMDD-mutants with adefovir dipivoxil appears crucial.
161 CHRONIC LIVER FAILURE ATTENUATES THE CNS CONSEQUENCES OF SUBSEQUENT ACUTE LIVER FAILURE BY ‘PRIMING’ OF MUSCLE GLUTAMINE SYNTHETASE CAPACITY
C. Rose, N. Chatauret, M. Belanger, P. Desjardins, R.F. Butterworth. Neuroscience Research Unit, CHUM, Saint-Luc Hospital, University of Montreal, Montreal ON, Canada Although brain edema is a common feature of acute liver failure (ALF) it is rarely observed in chronic or acute-on-chronic liver failure. In order to further elucidate the mechanisms implicated, male Sprague-Dawley rats were subjected to end-to-side portacaval anastomosis followed by hepatic artery ligation (HAL) either 24h (HAL-24h) or 4 weeks (HAL-4W) following shunt surgery. Body temperature and blood glucose were monitored and maintained throughout the experiments following HAL. Onset of encephalopathy was significantly delayed in the HAL-4W group of animals compared to HAL-24h and brain water concentrations measured by the gravimetric procedure were also significantly attenuated in this group (control: 80.12±0.09%; HAL-24h: 81.39±0.15% (p<0.01 of control); HAL-4W: 80.04±0.13% (ns of control)). Arterial ammonia concentration followed a similar pattern (control: 0.14±0.04 mM; HAL-24h: 1.51±0.07 mM (p<0.01 of control); HAL-4W: 0.52±0.09 mM (p<0.01 of control)). Activity of the ammonia-metabolizing enzyme glutamine synthetase was increased in skeletal muscle (by 52% p<0.01) but not in brain 4 weeks following portacaval anastomosis. These findings suggest that chronic liver failure delays the onset of brain edema in encephalopathy
163 ARTERIAL LACTATE AS A PROGNOSTIC MARKER IN PARACETAMOL-INDUCED ACUTE LIVER FAILURE: EVALUATION OF THE MODIFIED KING’S COLLEGE CRITERIA
L.E. Schmidt, F.S. Larsen. Department of Hepatology, Rigshospitalet, Copenhagen, Denmark Aims: The challenge in the management of acute liver failure (ALF) lies in identifying patients with a capacity for survival without liver transplantation. The present study aimed at evaluating the recently proposed lactate modification of the King’s College Hospital (KCH) selection criteria. Methods: Seventy-six consecutive patients with paracetamol-induced ALF were evaluated at the onset of grade 3-4 hepatic encephalopathy by the KCH criteria, the Sequential Organ Failure Assessment (SOFA) score, and the presence of a Severe Inflammatory Response Syndrome (SIRS). Results: Twenty-two of 27 patients (81%) who fulfilled the KCH criteria died in comparison with 19 of the 49 patients (39%) who did not (p=0.0006). Arterial lactate was significantly higher in nonsurvivors than in survivors (6.8 ± 4.8 mmol/L vs. 3.1 ± 2.1 mmol/L; p<0.0001). Adding the lactate modification to the KCH criteria increased the sensitivity from 54 to 86%, but reduced the specificity from 86 to 50%. SOFA-score was significantly higher in nonsurvivors than in survivors (15.6 ± 3.4 vs. 11.3 ± 2.9; p<0.0001). Thus, 33 out of 44 patients (75%) who had a SOFAscore above 12 died in comparison with 8 out of 32 patients (25%) who did not (p<0.0001). Twenty-eight of the 32 patients (88%) who had a SIRS died in comparison with 13 of 44 (30%) who did not (p<0.0001).