- Email: [email protected]
[185] CENTRILOBULAR NECRO-INFLAMMATORY CHANGES IN HCV-NEGATIVE LIVER TRANSPLANT RECIPIENTS RESPOND TO TREATMENT WITH STEROIDS AND MYCOPHENOLATE MOFETIL
02A. CIRRHOSIS AND COMPLICATIONS
11851 CENTRILOBULAR NECRO-INFLAMMATORY CHANGES IN HCV-NEGATIVE LIVER TRANSPLANT RECIPIENTS RESPOND TO TREATMENT WITH STEROIDS AND MYCOPHENOLATE MOFETIL R. Vigano’ , S. Fagiuoli’ , A. Sonzogni2, L. Pasulo’ , G. Gafiri’ , M. Colledan3, M. S tra ~zab o sco ~. ‘Dep of’ Internal Medicine, Gastroentrology Unit, Lioer Trans[)bnt Center; 2Dep of Lab Medicine, Pathology Unit: ”Dep of Surgery, Lung and Lioer Eansplant Surgery linit, Ospedali Riiiniti of Berganto, Berganto, Italy; ‘Dep of Internal Medicine, Section of Digextiue Diseuse, Tr-LEnsplunt Heputology, Yule Uniwer~xicv,New Huuen, USA E-mail: [email protected]
Background and Aims: Centrilobular Necro-inflammatory Changes of the graft (CNC) have been described in the early phases of chronic liver rejection, in HCV reinfection and “de novo” autoimmune hepatitis. CMC are associated with the development of delayed liver graft dysfunction and in this phase chronic rejection may still be responsive to increased immune-suppression. Methods: We have conducted a single-center, perspective, non-randomized pilot trial in which patients with CNC were treated with steroids and micophenolate mofetil (MMF) in addition to our institutional protocol (tacrolimus plus prednisone taper at 3 months). Patients, showing CNC with central vein endothelitis on liver biopsies, were treated with 0.5 to 1 mg/kg prednisone with rapid tapering in 6-8 weeks. MMF, 2 g was started at week 6. A second biopsy was performed before starting MMF and an additional biopsy 6 months after. Primary and secondary end-points were respectively, regression of the histologic lesion and normalization of LFTs. Results: CNC were diagnosed in 12 out of 201 adult liver Tx recipients (5.9%) after a median of 132 days (range 32-230) post-Tx. Six of these patients were HCV-infected. Donor characteristics (age, ICU stay, ischemia time, serum Na+, % steatosis) and average MELD were similar in the two groups. Acute cellular rejection (ACR) was more frequent in the CNC group than in controls (58% at a median o f 4 2 days after TX vs 13.3% at a median of 24 days after Tx p i 0.01). Evidence for prior ACR or early steroid withdrawal was found in 58% of the patients. Overall 8/12 patients responded. In HCV-negative patients a biochemical response was achieved in 6/6 of the patients after 2.6 months of therapy and histologic response was achieved in 516 after 5.3 months of therapy. Only 2/6 HCV-positive patients achieved a biochemical response after 1 month of therapy and histologic response after 12 months of therapy. Conclusion: CNC were found in 6% our Tx recipients. Results of the treatment differed according to the presence or absence of HCV infection. In HCV-negative patients the condition responded completely and rapidly to prednisone and maintenance therapy with MMF.
11861 BENEFIT OF PLASMAPHERESIS AND ANTICOAGULATION IN PATIENS TRANSPLANTED FOR END-STAGE LIVER DISEASE WITH HIGH RISK FOR ANTIPHOSPHOLIPID-ASSOCIATED VASCULAR EVENTS A.G. Villamil’, P. Casciato’, F. Nunez2, D. Alvarez’ , W Scorso2, M. Bujas2, E. de Santibanes’, A. Gadano’. ’Lioer Transplantation linit; Transfusional Unit, Hospital ltaliano de Buenos Aires, Argentina, S E-mail: [email protected]
’
Circulating antiphospholipid antibodies (aPL) are often present in patients with end-stage liver disease and are associated with patient morbidity and graft loss post-transplantation as a result of vascular thrombosis. Risk is increased in patients with pre-transplant antiphospholipid-related thrombotic events or high titer circulating aPL. Plasmapheresis has been proposed as an adequate therapy after the development of vascular complications in this group of patients.
-
A) PATHOPHYSIOLOGY
s79
Aim: To evaluate the impact of pre-OLT plasmapheresis associated with post-OLT anticoagulation in patients transplanted for end-stage liver disease with positive aPL and high risk for vascular complications. Patients and Methods: Fifteen patients with positive aPL and high risk criteria for vascular thrombosis who have undergone liver transplantation between1998 and 2005 were included. Patients were divided into two groups and the outcome was analyzed: Group A (n= 8): patients with no plasmapheresis pre-OLT and low dose aspirin & low weight heparin postOLT. Group B (n= 7)): patients who received plasmapheresis with fresh frozen plasma 1-2 hours pre-OLT, followed by post-OLT anticoagulation that was maintained for at least 6 months. Clinical and Doppler ultrasound evaluations were performed immediately before OLT and at different timepoints during the first six months post-OLT (weekly the first month and monthly thereafter). Etiology and severity of cirrhosis and immunosuppression did not differ between both groups. Immunosuppressive regimen included cyclosporine ( n = 8) or tacrolimus ( n = 7 ) + mycophenolate + steroids. Results: 6/8 patients in group A developed complications post-OLT related to aPL (cerebrovascular ischemia n = 3, humeral thrombosis n = 1, hepatic artery thrombosis n = 1, intestinal ischemia n = 1, catastrophic antiphospholipid syndrome n = 2 ) that resulted in grafts loss ( n = I), irreversible neurologic damage ( n = I ) and death ( n = I). Median time post-OLT was 3.6&2.2 months. In 416 patients the complications developed within 2-16 days post severe acute cellular rejection. In Group B 117 patients developed an antiphospholipid-associated complication post-OLT: extensive intestinal ischemia + livedo reticularis at 4.5 months post-OLT, resulting in patient’s death with multiorgan failure unresponsive to repeated plasmapheresis. Conclusion: Plasmapheresis pre-OLT associated with anticoagulation post-OLT may be an effective strategy to prevent aPL associated vascular complications in high risk patients.
02A. CIRRHOSIS AND COMPLICATIONS A) PATHOPHYSIOLOGY
11871 PORTAL HYPERTENSION CONTRIBUTES TO SPATIAL REFERENCE MEMORY DEFICIT IN THE RAT M.A. Aller’, M. Mendez2, M. Mendez-Lopez2, F. Sanchez-Patan’ , L. Lopez2, R. Anchuelo’, I. Mejia’, J. Arias’, J.L. Arias2. ’Department of Surgery I, School of Medicine, Contplutense University, Madrid; ’Depurtment of Psychohiology, School of P~xychology,Uniuersity of Ooiedo, Ooiedo, Spain E-mail: [email protected]
Background and Aims: Hepatic Encephalopathy produces attention deficit, disorientation and amnesia. Even today, however, these cognitive deficits are not related to the different etiopathogenia of hepatic encephalopathy. There are three types of hepatic encephalopathy: A (with acute hepatic insufficiency), B (with portosystemic shunts) and C (with cirrhosis and portal hypertension or portosystemic collateral circulation). The Objective is to study the alterations of memory in types B and C of experimental hepatic encephalopathy Methods: 46 male Wistar rats were used: Control groups (C; n = lo), Sham-operated (SO; n = X), with Triple Partial Portal Vein Ligation (TPVL; n = lo), with End-to-side Portacaval Shunts (PCA; n = 8) and with Cirrhosis by Thioacetamide (TAA; n = 10). To assay amnesic alterations, the animals were subject to the Morris water maze everyday for five days. Results: The ANOVA test shows the differences between the groups in terms of learning ability. The Tukey test, in turn, demonstrates that group C is able to become oriented from the second day of learning; the SO group learns from the third day, the PCA-group only achieves an adequate spatial
11851 CENTRILOBULAR NECRO-INFLAMMATORY CHANGES IN HCV-NEGATIVE LIVER TRANSPLANT RECIPIENTS RESPOND TO TREATMENT WITH STEROIDS AND MYCOPHENOLATE MOFETIL R. Vigano’ , S. Fagiuoli’ , A. Sonzogni2, L. Pasulo’ , G. Gafiri’ , M. Colledan3, M. S tra ~zab o sco ~. ‘Dep of’ Internal Medicine, Gastroentrology Unit, Lioer Trans[)bnt Center; 2Dep of Lab Medicine, Pathology Unit: ”Dep of Surgery, Lung and Lioer Eansplant Surgery linit, Ospedali Riiiniti of Berganto, Berganto, Italy; ‘Dep of Internal Medicine, Section of Digextiue Diseuse, Tr-LEnsplunt Heputology, Yule Uniwer~xicv,New Huuen, USA E-mail: [email protected]
Background and Aims: Centrilobular Necro-inflammatory Changes of the graft (CNC) have been described in the early phases of chronic liver rejection, in HCV reinfection and “de novo” autoimmune hepatitis. CMC are associated with the development of delayed liver graft dysfunction and in this phase chronic rejection may still be responsive to increased immune-suppression. Methods: We have conducted a single-center, perspective, non-randomized pilot trial in which patients with CNC were treated with steroids and micophenolate mofetil (MMF) in addition to our institutional protocol (tacrolimus plus prednisone taper at 3 months). Patients, showing CNC with central vein endothelitis on liver biopsies, were treated with 0.5 to 1 mg/kg prednisone with rapid tapering in 6-8 weeks. MMF, 2 g was started at week 6. A second biopsy was performed before starting MMF and an additional biopsy 6 months after. Primary and secondary end-points were respectively, regression of the histologic lesion and normalization of LFTs. Results: CNC were diagnosed in 12 out of 201 adult liver Tx recipients (5.9%) after a median of 132 days (range 32-230) post-Tx. Six of these patients were HCV-infected. Donor characteristics (age, ICU stay, ischemia time, serum Na+, % steatosis) and average MELD were similar in the two groups. Acute cellular rejection (ACR) was more frequent in the CNC group than in controls (58% at a median o f 4 2 days after TX vs 13.3% at a median of 24 days after Tx p i 0.01). Evidence for prior ACR or early steroid withdrawal was found in 58% of the patients. Overall 8/12 patients responded. In HCV-negative patients a biochemical response was achieved in 6/6 of the patients after 2.6 months of therapy and histologic response was achieved in 516 after 5.3 months of therapy. Only 2/6 HCV-positive patients achieved a biochemical response after 1 month of therapy and histologic response after 12 months of therapy. Conclusion: CNC were found in 6% our Tx recipients. Results of the treatment differed according to the presence or absence of HCV infection. In HCV-negative patients the condition responded completely and rapidly to prednisone and maintenance therapy with MMF.
11861 BENEFIT OF PLASMAPHERESIS AND ANTICOAGULATION IN PATIENS TRANSPLANTED FOR END-STAGE LIVER DISEASE WITH HIGH RISK FOR ANTIPHOSPHOLIPID-ASSOCIATED VASCULAR EVENTS A.G. Villamil’, P. Casciato’, F. Nunez2, D. Alvarez’ , W Scorso2, M. Bujas2, E. de Santibanes’, A. Gadano’. ’Lioer Transplantation linit; Transfusional Unit, Hospital ltaliano de Buenos Aires, Argentina, S E-mail: [email protected]
’
Circulating antiphospholipid antibodies (aPL) are often present in patients with end-stage liver disease and are associated with patient morbidity and graft loss post-transplantation as a result of vascular thrombosis. Risk is increased in patients with pre-transplant antiphospholipid-related thrombotic events or high titer circulating aPL. Plasmapheresis has been proposed as an adequate therapy after the development of vascular complications in this group of patients.
-
A) PATHOPHYSIOLOGY
s79
Aim: To evaluate the impact of pre-OLT plasmapheresis associated with post-OLT anticoagulation in patients transplanted for end-stage liver disease with positive aPL and high risk for vascular complications. Patients and Methods: Fifteen patients with positive aPL and high risk criteria for vascular thrombosis who have undergone liver transplantation between1998 and 2005 were included. Patients were divided into two groups and the outcome was analyzed: Group A (n= 8): patients with no plasmapheresis pre-OLT and low dose aspirin & low weight heparin postOLT. Group B (n= 7)): patients who received plasmapheresis with fresh frozen plasma 1-2 hours pre-OLT, followed by post-OLT anticoagulation that was maintained for at least 6 months. Clinical and Doppler ultrasound evaluations were performed immediately before OLT and at different timepoints during the first six months post-OLT (weekly the first month and monthly thereafter). Etiology and severity of cirrhosis and immunosuppression did not differ between both groups. Immunosuppressive regimen included cyclosporine ( n = 8) or tacrolimus ( n = 7 ) + mycophenolate + steroids. Results: 6/8 patients in group A developed complications post-OLT related to aPL (cerebrovascular ischemia n = 3, humeral thrombosis n = 1, hepatic artery thrombosis n = 1, intestinal ischemia n = 1, catastrophic antiphospholipid syndrome n = 2 ) that resulted in grafts loss ( n = I), irreversible neurologic damage ( n = I ) and death ( n = I). Median time post-OLT was 3.6&2.2 months. In 416 patients the complications developed within 2-16 days post severe acute cellular rejection. In Group B 117 patients developed an antiphospholipid-associated complication post-OLT: extensive intestinal ischemia + livedo reticularis at 4.5 months post-OLT, resulting in patient’s death with multiorgan failure unresponsive to repeated plasmapheresis. Conclusion: Plasmapheresis pre-OLT associated with anticoagulation post-OLT may be an effective strategy to prevent aPL associated vascular complications in high risk patients.
02A. CIRRHOSIS AND COMPLICATIONS A) PATHOPHYSIOLOGY
11871 PORTAL HYPERTENSION CONTRIBUTES TO SPATIAL REFERENCE MEMORY DEFICIT IN THE RAT M.A. Aller’, M. Mendez2, M. Mendez-Lopez2, F. Sanchez-Patan’ , L. Lopez2, R. Anchuelo’, I. Mejia’, J. Arias’, J.L. Arias2. ’Department of Surgery I, School of Medicine, Contplutense University, Madrid; ’Depurtment of Psychohiology, School of P~xychology,Uniuersity of Ooiedo, Ooiedo, Spain E-mail: [email protected]
Background and Aims: Hepatic Encephalopathy produces attention deficit, disorientation and amnesia. Even today, however, these cognitive deficits are not related to the different etiopathogenia of hepatic encephalopathy. There are three types of hepatic encephalopathy: A (with acute hepatic insufficiency), B (with portosystemic shunts) and C (with cirrhosis and portal hypertension or portosystemic collateral circulation). The Objective is to study the alterations of memory in types B and C of experimental hepatic encephalopathy Methods: 46 male Wistar rats were used: Control groups (C; n = lo), Sham-operated (SO; n = X), with Triple Partial Portal Vein Ligation (TPVL; n = lo), with End-to-side Portacaval Shunts (PCA; n = 8) and with Cirrhosis by Thioacetamide (TAA; n = 10). To assay amnesic alterations, the animals were subject to the Morris water maze everyday for five days. Results: The ANOVA test shows the differences between the groups in terms of learning ability. The Tukey test, in turn, demonstrates that group C is able to become oriented from the second day of learning; the SO group learns from the third day, the PCA-group only achieves an adequate spatial