- Email: [email protected]
A pilot study of transcatheter arterial interferon embolization for hepatocellular carcinoma
30
Poster Sessions
Results: In the course of I/R we observed a significant decrease of p38 activity by up to 85%. ERK and JNK activities increased in the course of the experiment by 4-fold (ERK) and 3-fold (JNK). ANP increased the activity of all three MAPKs: by up to 30-fold for ~38, 14-fold for ERK, and 3-fold for JNK. Conclusion: This work represents a systematic investigation of MAPKs during I/R of the isolated perfused rat liver. The hepatoprotective peptide ANP is shown to activate all three MAPKs. The implications of these observations for hepatoprotection are currently being investigated. (supported by DFG Ge 576 14-1)
0270
ANTIBODIES TO MINICHROMOSOMAL MAINTENANCE PROTEINS (MCM-2 AND -5) DISTINGUISH BENIGN FROM NEOPLASTIC FOCAL LIVER LESIONS
H.S. Saeed, G. Callagy, L. HapperIield, G. Williams, D. Wight, R. Alexander. Department of Medicine, Addenbrooke’s Hospital, Univ.
administration and during 3 days with CC4. The hepatic homogenate and plasma were used for measurement of MDA, glutathione (GSH) and ammonia concentration (AC). Red blood cells (RBC) resistance was evaluated by the intensity of their hemolysis. The conventional liver functional tests (ALT, AST and GGT) were determined as well. Results: CC&-intoxication resulted in marked LPO increase, in decrease GSH (p x 0.001) in liver tissue and in increase of RBC hemolysis and AC in blood and liver. After P treatment MDA content was significantly decreased in blood (p < 0.001) and liver (p < 0.001) whereas GSH content was markedly increased in the rat liver by 83.3%. The indices of RBC hemolysis and ALT, AST and GGT activities have shown a marked tendency to normalization; AC was slightly decreased @ < 0.05). Conclusions: P treatment of CC4 intoxicated rats leads to the pronounced reduction of LPO in the liver and blood, improves antioxidant defense and RBC resistance, those very likely connected with the natural antioxidants presence in Propolis. Propolis may become a perspective agent in treatment of liver diseases.
of Cambridge, UK
Accurate histological diagnosis of focal lesions in the liver can be difficult, especially with small specimens. Recently, antibodies to minichromosomal maintenance proteins (Mcm), an essential part of the pre-replicative complex of the cell, have proved effective indicators of malignancy in cervical smears. Aim: To determine the usefulness of antibodies to Mcm-2 and -5 in the evaluation of focal liver lesions. Methods: Twenty-four patients with focal liver lesions undergoing guided liver biopsy were studied. The histological diagnoses were Focal Nodular Hyperplasia (FNH) (n = 8), Hepatic Adenoma (HA, n = 5), well-differentiated Hepatocellular Carcinoma (WD-HCC, n = 6) and moderately differentiated HCC (MD-HCC, n = 5). Paraffin embedded sections were stained with antibodies to Mcm-2 and -5 after antigen retrieval. Two observers scored each section independently, counting the percentage of Mcm stained hepatocytes per high power field (x40 magnification) in at least two fields. Results: The median and range of Mcm staining for each group is shown in the table-
FNH HA WD-HCC MD-HCC
Mcm-2 range
Mcm-2 median
Mcm-5 range
Mcmd median
3.7-12.5 l-10 2048 80-85
9 3.8 34 83
5-22 1-17 29-63 77-90
12 12 46 87
In every case, Mcm-2 and -5 positive hepatocytes were detected more frequently in malignant lesions than benign tumours. In all cases Mcm scores for MD-HCC exceeded those for WD-HC. Mcm-2 and -5 staining did not correlate with serum alpha-foetoprotein levels in HCC. Conclusions: 1) Mcm-2 and -5 staining of hepatocytes in focal liver lesions may aid the distinction between benign and malignant primary liver tumours. 2) The proportion of Mcm positive hepatocytes in HCC may be related to phenotype, although a larger series would be required to address this issue. The role of Mcm proteins in HCC merits further study.
I 313
PROTECTIVE EFFECTS OF PROPOLIS AGAINST HEPATOTOXlClTV INDUCED BY CCL4 IN RATS
D. Uzbekova, V.G. Makarova, L.G. Chugunova. Medical University, Russia
Aim: To investigate the hepatoprotective effects of beehive product Propolis (P) on CCL-induced liver cell damage. Methods: Male rats were injected i.m. with 150 mg CC4 for 3 days. P extract (10 mg/kg/day) was given to rats per OSfor 3 days prior to CC14
ALPHA-V-BETA& INTEGRIN-MEDIATED ADENOVIRAL TRANSFER OF INTERLEUKIN-12 AT THE PERIPHERY OF HEPATIC COLON CANCER METASTASES INDUCES VCAM-1 EXPRESSION AND T-CELL RECRUITMENT G. Mazzolini, I. Narvaiza, M. Bustos, I. Gabari, M. Duarte, R. Bilbao, C. Qian, J. Prieto, I. Melero. Pamplona, Spain
Introduction: Intratumoral injections of recombinant adenoviruses encoding for IL12 (AdCMVIL-12) have shown intense anti-tumor effects. In most cases the antitumor activity needs the action of cytolytic T-lymphocytes. We have shown that IL12 gene transfer synergizes with adoptive T-cell therapy not only symplifying the obtention of CTL cultures but also rendering liver metastases more sensitive for immune attack. We had observed that systemic injection of recombinant adenovirus resulted in a rim of gene transduction around experimental liver tumor nodules. Results: We observed tha this zone of higher infection is dependent on the .integrin, acting as an adenovims internalization receptor, which is overexpressed in tissues surrounding liver metastases. When AdCMVIL-12 is given into a subcutaneous tumor nodule in mice bearing also concomitant liver tumors, a fraction of AdCMVIL-12 reaches systemic circulation and infects liver tissue especially at the malignant/healthy tissular interface. As a result of the expression at this location of the interleukin-12 transgenes, VCAM-1 is induced on vessel cells and mediates the recruitment of adoptively transferred antitumor cytolytic T-lymphocytes. Conclusions: i) adenovims preferentially transfer genes to the area limiting liver metastases because of selective expression in this place of .integrin, ii) by virtue of IL-12 expression at this location VCAM-1 is expressed on tumor endothelium, iii) VCAM- 1 is required for the tumor infiltration by CTLs.
I322
A PILOT STUDY OF TRANSCATHETER ARTERIAL INTERFERON EMBOLIZATION FOR HEPATOCELLULAR CARCINOMA
C. Hui, M. Yuen, C. Ooi, M. Wong, 0. Chan, C. Wong, C. Lai. Queen Mary Hospital, Hong Kong
Background: Subcutaneous high dose (50 x lo6 IU/m’ thrice weekly) interferon-alpha (IFN-a) is effective in 30% of patients with hepatocellular carcinoma (HCC) [Lai CL et. al., Hepatology 19931. A pilot study on transcatheter arterial interferon embolization (TAIE) was performed to determine the efficacy and safety of this treatment. Method: 18 patients with biopsy-proven inoperable HCC (M:F 15:3, median age 64 years) were recruited. The patients were randomized to receive IFN-cr2b 10 MU/m* (5 patients), 30 MU/m* (8 patients), or 50
Category 1: Liver transplantation, surgery, acute liver failure MU/m* (5 patients) intraarterially followed by gelfoam embolization once every 8 weeks. Tumor size was assessed by CT scan performed after 5 sessions of TAIE. Side effects were closely monitored. Results: Each patient received a median of 4 sessions of TAIE. Two patients had only one session of TAIE because of liver failure and tumor lysis. In the other 16 patients, tumor became undetectable in 2/16 (12.5%), showed ~50% decrease in 4/16 (25%), 25-50% decrease in 5/16 (31.2%), and was stable in size in 5/16 (31.2%). One patient had metastases to the brain. Alpha-fetoprotein showed a median decrease of 22.3% after each session of TAIE. There were seven deaths (median survival 15.23 months): 4 from liver failure, 1 each from brain metastases, ruptured HCC and tumor lysis. The only side effects observed were fever in all the patients (median 6 days, range O-21 days). There was no deterioration in liver function attributable to IFN. Conclusion: TAIE was effective and safe in treating HCC. Further studies are required to compare the efficacy of TAIE with other forms of treatment for HCC.
I 325
OUTCOME OF PATIENTS WITH HBeAG NEGATIVE HEPATITIS B AWAITING LIVER TRANSPLANTATION TREATED WITH LAMIVUDINE
(OLT)
P. Andreone, M. Biselli, H. Munira, A.S.F. Lok, S. Romano, A. Gramenzi, C. Cursaro, M. Bemardi. Dipartimento di Medicim Interna, Cardioangiologia ed Epatologia, Universita di Bologna, Italy LAM seems to improve liver disease in HBeAg(+) patients with decompensated HBV-cirrhosis, but its efficacy in HBeAg(-) was not examined. We evaluated the impact of LAM on liver function in 28 candidates awaiting OLT for HBeAg(-) decompensated HBV-cirrhosis. All were HBV-DNA(+) by PCR and received LAM 100 mg/day from the day of listing. Sixteen had Child-Pugh score 7, and 12 had superimposed HCC. Fourteen patients were not considered because they did not reach 6 mo treatment (10 underwent OLT before 6 mo, 3 died for HCC and 1 dropped-out). The remaining 14 were followed for 15 9 mo. After 3, 6 and 9 mo HBV-DNA by PCR was undetectable in 5/14, lo/14 and 1 l/l 1 patients, respectively, while ALT normalized in 6/14, 11/14 and 8/11, respectively. One patient developed LAM resistance after 18 mo, without liver decompensation and 1 became HBsAg(-). Comparing baseline parameters of liver function to those of last visit, a significant improvement was observed in prothrombin activity (42 11% vs 54 16%, p = 0.01). serum bilirubin (2.7 1.3 vs 1.6 0.7 mg/dl, p = O.OOl), presence of ascites (6/14 vs 2/14, p = 0.04). and Child-Pugh score (8 vs 6.5, p = 0.01). Because of liver function improvement 2 patients (14.2%) were placed on low priority status for OLT (UNOS 3), and 5 (35.8%) on inactive status (UNOS 7). LAM has an important role in HBeAg(-) decompensated HBV-cirrhosis not only because HBV-DNA suppression decreases the risk of recurrent hepatitis B post-OLT, but the improvement of clinical status may delay the need for OLT in an era of organ shortage.
I
338
ACCURACY OF THE MAYO CLINIC MODEL TO PREDICT SURVIVAL IN PATIENTS WITH ELECTIVE TIPS
M. Cazzaniga, V. Valeriano, M. Merli, 0. Riggio, A. Lovaria, A. Nicolini, D. Meregaglia, F. Salerno. Internal Medicine, University of Milan, Italy Survival of patients undergoing TIPS is often unpredictable. A mathematical mode1 including bilirubin, creatinine, PT and etiology has been developed by the Mayo clinic to predict death in such patients (Hepatology 2ooO; 31:864. We applied this model to a population of 141 consecutive cirrhotic patients (mean age 58 + 11 years; 90 males/51 females; 68% with viral etiology), who underwent elective TIPS between 1993 and 1999. Ninety-nine procedures were performed for
31
prevention of variceal rebleeding and 42 for refractory ascites. During a mean follow-up of 31 months (range 0.2-93), 57 patients died (40.4%). According to the model, 3- and 12-month expected survivals were 73% and 60%. These figures did not differ from observed survivals of 90% and 79% (P > 0.1). Furthermore, the population was stratified into two groups: 9 patients with high risk to die (Risk Score > 1.8) and 132 with low risk (RS < 1.8). The survival curves of the 2 groups were significantly different (log rank test P = 0.0001). A ROC curve built to assess the accuracy of RS in predicting 3-month survivals showed an area under the curve of 76% (95% C.I. = 63-90%). With RS > 1.8, sensitivity was 33%, specificity 96%, positive predictive value 44% and negative predictive value 94%. The Mayo clinic mode1 has been validated in our TIPS population. However, its sensitivity should be improved by future refinements.
I 345
CALCINEURIN INHIBITOR MONOTHERAPY AB-INITIO AFTER LIVER TRANSPLANTATION: 4 YEAR FOLLOW UP
L. Dagher, N. Rolando, D. Patch, B. Davidson, A. Burroughs, K. Rolles. Liver Transplantation Unit, Royal Free Hospital, UK Background: Short term safety/efficacy of calcineurin inhibitor monotherapy has been reported by us (Transplantation 1999; 69:1195). Aim: Our total experience and long term results are reported here. Patients: 68 consecutively had microemulsified cyclosporin (MC) (n = 37) or tacrolimus (T) (n = 31), mean follow up of 878 days (range 19 to 1650 days). Differences in actuarial 1 and 4 years graft (77% and 73%) or patient survival (79% and 74%) were no different between drugs. CMV disease (all hepatitis) occurred in 7% and CMV infection in 9%. Septicemia or bacteraemia occurred in 5 (7%) and only one death from sepsis at 32 days. Protocol biopsies showed no rejection in 19%, mild in 52%, moderate in 40%. severe in 8%; steroid resistant rejection in 8%. Two had chronic rejection (3%) (MC group). 16 (24%) had creatinine z 140 mm01 which was reversible in most, and 9 (13%) hypertension. During follow-up maintenance monotherapy was unchanged in 87% of T and 70% of MC patients. No de novo malignancies have been seen so far. Conclusion: Calcineurin inhibitor monotherapy is safe and effective in the long term and is a viable immunosuppressive strategy ab initio in liver transplantation. Tacrolimus monotherapy results in less need to change therapy and currently chronic rejection has not been observed.
I 351
ANTI-INTERFERON ALPHA ANTIBODIES IN CHILDREN WlTH CHRONIC VIRAL HEPATITIS
B. Elkabes, S. Semra, Ozlem S. Suoglu, 0. Tulin, Gunay Saner. Pediatric Gastmentemlogy and Hepatology, Istanblul University School of Medicine, Turkey Alpha interferon (IFN), the primary treatment for chronic hepatitis B and C, can induce antibody formation which may cause treatment failure. We evaluated our patients with chronic viral hepatitis (aged 1-15 yrs) at the end of six months treatment with regard to binding anti-interferon antibodies. The hepatitis B patients were in two treatment groups all receiving 5 million UlmUthrice weekly IFN: IFN alone (Group 1, n = 20) or with lamivudine (Group 2, n = 22). All hepatitis C patients (Group 3, n = lo), received 3 million U/m2/thrice weekly IFN + ribavirin. For antibody detection, ELIZA kit (A4-240 ANAWA) was used. The rate of antibody formation in the 3 groups were 40%, 27.3% and 20% respectively. The type of interferon (alpha 2a or 2b) didn’t influence antibody formation. Lineer regression analysis revealed only a weak correlation between anti-interferon antibodies and treatment failure in hepatitis B patients (r = 0.508 in Group 1, r = 0.789 in Group 2), and no correlation in hepatitis C patients. Interestingly, 7 patients who had high titre antibodies were all non-responders.
Poster Sessions
Results: In the course of I/R we observed a significant decrease of p38 activity by up to 85%. ERK and JNK activities increased in the course of the experiment by 4-fold (ERK) and 3-fold (JNK). ANP increased the activity of all three MAPKs: by up to 30-fold for ~38, 14-fold for ERK, and 3-fold for JNK. Conclusion: This work represents a systematic investigation of MAPKs during I/R of the isolated perfused rat liver. The hepatoprotective peptide ANP is shown to activate all three MAPKs. The implications of these observations for hepatoprotection are currently being investigated. (supported by DFG Ge 576 14-1)
0270
ANTIBODIES TO MINICHROMOSOMAL MAINTENANCE PROTEINS (MCM-2 AND -5) DISTINGUISH BENIGN FROM NEOPLASTIC FOCAL LIVER LESIONS
H.S. Saeed, G. Callagy, L. HapperIield, G. Williams, D. Wight, R. Alexander. Department of Medicine, Addenbrooke’s Hospital, Univ.
administration and during 3 days with CC4. The hepatic homogenate and plasma were used for measurement of MDA, glutathione (GSH) and ammonia concentration (AC). Red blood cells (RBC) resistance was evaluated by the intensity of their hemolysis. The conventional liver functional tests (ALT, AST and GGT) were determined as well. Results: CC&-intoxication resulted in marked LPO increase, in decrease GSH (p x 0.001) in liver tissue and in increase of RBC hemolysis and AC in blood and liver. After P treatment MDA content was significantly decreased in blood (p < 0.001) and liver (p < 0.001) whereas GSH content was markedly increased in the rat liver by 83.3%. The indices of RBC hemolysis and ALT, AST and GGT activities have shown a marked tendency to normalization; AC was slightly decreased @ < 0.05). Conclusions: P treatment of CC4 intoxicated rats leads to the pronounced reduction of LPO in the liver and blood, improves antioxidant defense and RBC resistance, those very likely connected with the natural antioxidants presence in Propolis. Propolis may become a perspective agent in treatment of liver diseases.
of Cambridge, UK
Accurate histological diagnosis of focal lesions in the liver can be difficult, especially with small specimens. Recently, antibodies to minichromosomal maintenance proteins (Mcm), an essential part of the pre-replicative complex of the cell, have proved effective indicators of malignancy in cervical smears. Aim: To determine the usefulness of antibodies to Mcm-2 and -5 in the evaluation of focal liver lesions. Methods: Twenty-four patients with focal liver lesions undergoing guided liver biopsy were studied. The histological diagnoses were Focal Nodular Hyperplasia (FNH) (n = 8), Hepatic Adenoma (HA, n = 5), well-differentiated Hepatocellular Carcinoma (WD-HCC, n = 6) and moderately differentiated HCC (MD-HCC, n = 5). Paraffin embedded sections were stained with antibodies to Mcm-2 and -5 after antigen retrieval. Two observers scored each section independently, counting the percentage of Mcm stained hepatocytes per high power field (x40 magnification) in at least two fields. Results: The median and range of Mcm staining for each group is shown in the table-
FNH HA WD-HCC MD-HCC
Mcm-2 range
Mcm-2 median
Mcm-5 range
Mcmd median
3.7-12.5 l-10 2048 80-85
9 3.8 34 83
5-22 1-17 29-63 77-90
12 12 46 87
In every case, Mcm-2 and -5 positive hepatocytes were detected more frequently in malignant lesions than benign tumours. In all cases Mcm scores for MD-HCC exceeded those for WD-HC. Mcm-2 and -5 staining did not correlate with serum alpha-foetoprotein levels in HCC. Conclusions: 1) Mcm-2 and -5 staining of hepatocytes in focal liver lesions may aid the distinction between benign and malignant primary liver tumours. 2) The proportion of Mcm positive hepatocytes in HCC may be related to phenotype, although a larger series would be required to address this issue. The role of Mcm proteins in HCC merits further study.
I 313
PROTECTIVE EFFECTS OF PROPOLIS AGAINST HEPATOTOXlClTV INDUCED BY CCL4 IN RATS
D. Uzbekova, V.G. Makarova, L.G. Chugunova. Medical University, Russia
Aim: To investigate the hepatoprotective effects of beehive product Propolis (P) on CCL-induced liver cell damage. Methods: Male rats were injected i.m. with 150 mg CC4 for 3 days. P extract (10 mg/kg/day) was given to rats per OSfor 3 days prior to CC14
ALPHA-V-BETA& INTEGRIN-MEDIATED ADENOVIRAL TRANSFER OF INTERLEUKIN-12 AT THE PERIPHERY OF HEPATIC COLON CANCER METASTASES INDUCES VCAM-1 EXPRESSION AND T-CELL RECRUITMENT G. Mazzolini, I. Narvaiza, M. Bustos, I. Gabari, M. Duarte, R. Bilbao, C. Qian, J. Prieto, I. Melero. Pamplona, Spain
Introduction: Intratumoral injections of recombinant adenoviruses encoding for IL12 (AdCMVIL-12) have shown intense anti-tumor effects. In most cases the antitumor activity needs the action of cytolytic T-lymphocytes. We have shown that IL12 gene transfer synergizes with adoptive T-cell therapy not only symplifying the obtention of CTL cultures but also rendering liver metastases more sensitive for immune attack. We had observed that systemic injection of recombinant adenovirus resulted in a rim of gene transduction around experimental liver tumor nodules. Results: We observed tha this zone of higher infection is dependent on the .integrin, acting as an adenovims internalization receptor, which is overexpressed in tissues surrounding liver metastases. When AdCMVIL-12 is given into a subcutaneous tumor nodule in mice bearing also concomitant liver tumors, a fraction of AdCMVIL-12 reaches systemic circulation and infects liver tissue especially at the malignant/healthy tissular interface. As a result of the expression at this location of the interleukin-12 transgenes, VCAM-1 is induced on vessel cells and mediates the recruitment of adoptively transferred antitumor cytolytic T-lymphocytes. Conclusions: i) adenovims preferentially transfer genes to the area limiting liver metastases because of selective expression in this place of .integrin, ii) by virtue of IL-12 expression at this location VCAM-1 is expressed on tumor endothelium, iii) VCAM- 1 is required for the tumor infiltration by CTLs.
I322
A PILOT STUDY OF TRANSCATHETER ARTERIAL INTERFERON EMBOLIZATION FOR HEPATOCELLULAR CARCINOMA
C. Hui, M. Yuen, C. Ooi, M. Wong, 0. Chan, C. Wong, C. Lai. Queen Mary Hospital, Hong Kong
Background: Subcutaneous high dose (50 x lo6 IU/m’ thrice weekly) interferon-alpha (IFN-a) is effective in 30% of patients with hepatocellular carcinoma (HCC) [Lai CL et. al., Hepatology 19931. A pilot study on transcatheter arterial interferon embolization (TAIE) was performed to determine the efficacy and safety of this treatment. Method: 18 patients with biopsy-proven inoperable HCC (M:F 15:3, median age 64 years) were recruited. The patients were randomized to receive IFN-cr2b 10 MU/m* (5 patients), 30 MU/m* (8 patients), or 50
Category 1: Liver transplantation, surgery, acute liver failure MU/m* (5 patients) intraarterially followed by gelfoam embolization once every 8 weeks. Tumor size was assessed by CT scan performed after 5 sessions of TAIE. Side effects were closely monitored. Results: Each patient received a median of 4 sessions of TAIE. Two patients had only one session of TAIE because of liver failure and tumor lysis. In the other 16 patients, tumor became undetectable in 2/16 (12.5%), showed ~50% decrease in 4/16 (25%), 25-50% decrease in 5/16 (31.2%), and was stable in size in 5/16 (31.2%). One patient had metastases to the brain. Alpha-fetoprotein showed a median decrease of 22.3% after each session of TAIE. There were seven deaths (median survival 15.23 months): 4 from liver failure, 1 each from brain metastases, ruptured HCC and tumor lysis. The only side effects observed were fever in all the patients (median 6 days, range O-21 days). There was no deterioration in liver function attributable to IFN. Conclusion: TAIE was effective and safe in treating HCC. Further studies are required to compare the efficacy of TAIE with other forms of treatment for HCC.
I 325
OUTCOME OF PATIENTS WITH HBeAG NEGATIVE HEPATITIS B AWAITING LIVER TRANSPLANTATION TREATED WITH LAMIVUDINE
(OLT)
P. Andreone, M. Biselli, H. Munira, A.S.F. Lok, S. Romano, A. Gramenzi, C. Cursaro, M. Bemardi. Dipartimento di Medicim Interna, Cardioangiologia ed Epatologia, Universita di Bologna, Italy LAM seems to improve liver disease in HBeAg(+) patients with decompensated HBV-cirrhosis, but its efficacy in HBeAg(-) was not examined. We evaluated the impact of LAM on liver function in 28 candidates awaiting OLT for HBeAg(-) decompensated HBV-cirrhosis. All were HBV-DNA(+) by PCR and received LAM 100 mg/day from the day of listing. Sixteen had Child-Pugh score 7, and 12 had superimposed HCC. Fourteen patients were not considered because they did not reach 6 mo treatment (10 underwent OLT before 6 mo, 3 died for HCC and 1 dropped-out). The remaining 14 were followed for 15 9 mo. After 3, 6 and 9 mo HBV-DNA by PCR was undetectable in 5/14, lo/14 and 1 l/l 1 patients, respectively, while ALT normalized in 6/14, 11/14 and 8/11, respectively. One patient developed LAM resistance after 18 mo, without liver decompensation and 1 became HBsAg(-). Comparing baseline parameters of liver function to those of last visit, a significant improvement was observed in prothrombin activity (42 11% vs 54 16%, p = 0.01). serum bilirubin (2.7 1.3 vs 1.6 0.7 mg/dl, p = O.OOl), presence of ascites (6/14 vs 2/14, p = 0.04). and Child-Pugh score (8 vs 6.5, p = 0.01). Because of liver function improvement 2 patients (14.2%) were placed on low priority status for OLT (UNOS 3), and 5 (35.8%) on inactive status (UNOS 7). LAM has an important role in HBeAg(-) decompensated HBV-cirrhosis not only because HBV-DNA suppression decreases the risk of recurrent hepatitis B post-OLT, but the improvement of clinical status may delay the need for OLT in an era of organ shortage.
I
338
ACCURACY OF THE MAYO CLINIC MODEL TO PREDICT SURVIVAL IN PATIENTS WITH ELECTIVE TIPS
M. Cazzaniga, V. Valeriano, M. Merli, 0. Riggio, A. Lovaria, A. Nicolini, D. Meregaglia, F. Salerno. Internal Medicine, University of Milan, Italy Survival of patients undergoing TIPS is often unpredictable. A mathematical mode1 including bilirubin, creatinine, PT and etiology has been developed by the Mayo clinic to predict death in such patients (Hepatology 2ooO; 31:864. We applied this model to a population of 141 consecutive cirrhotic patients (mean age 58 + 11 years; 90 males/51 females; 68% with viral etiology), who underwent elective TIPS between 1993 and 1999. Ninety-nine procedures were performed for
31
prevention of variceal rebleeding and 42 for refractory ascites. During a mean follow-up of 31 months (range 0.2-93), 57 patients died (40.4%). According to the model, 3- and 12-month expected survivals were 73% and 60%. These figures did not differ from observed survivals of 90% and 79% (P > 0.1). Furthermore, the population was stratified into two groups: 9 patients with high risk to die (Risk Score > 1.8) and 132 with low risk (RS < 1.8). The survival curves of the 2 groups were significantly different (log rank test P = 0.0001). A ROC curve built to assess the accuracy of RS in predicting 3-month survivals showed an area under the curve of 76% (95% C.I. = 63-90%). With RS > 1.8, sensitivity was 33%, specificity 96%, positive predictive value 44% and negative predictive value 94%. The Mayo clinic mode1 has been validated in our TIPS population. However, its sensitivity should be improved by future refinements.
I 345
CALCINEURIN INHIBITOR MONOTHERAPY AB-INITIO AFTER LIVER TRANSPLANTATION: 4 YEAR FOLLOW UP
L. Dagher, N. Rolando, D. Patch, B. Davidson, A. Burroughs, K. Rolles. Liver Transplantation Unit, Royal Free Hospital, UK Background: Short term safety/efficacy of calcineurin inhibitor monotherapy has been reported by us (Transplantation 1999; 69:1195). Aim: Our total experience and long term results are reported here. Patients: 68 consecutively had microemulsified cyclosporin (MC) (n = 37) or tacrolimus (T) (n = 31), mean follow up of 878 days (range 19 to 1650 days). Differences in actuarial 1 and 4 years graft (77% and 73%) or patient survival (79% and 74%) were no different between drugs. CMV disease (all hepatitis) occurred in 7% and CMV infection in 9%. Septicemia or bacteraemia occurred in 5 (7%) and only one death from sepsis at 32 days. Protocol biopsies showed no rejection in 19%, mild in 52%, moderate in 40%. severe in 8%; steroid resistant rejection in 8%. Two had chronic rejection (3%) (MC group). 16 (24%) had creatinine z 140 mm01 which was reversible in most, and 9 (13%) hypertension. During follow-up maintenance monotherapy was unchanged in 87% of T and 70% of MC patients. No de novo malignancies have been seen so far. Conclusion: Calcineurin inhibitor monotherapy is safe and effective in the long term and is a viable immunosuppressive strategy ab initio in liver transplantation. Tacrolimus monotherapy results in less need to change therapy and currently chronic rejection has not been observed.
I 351
ANTI-INTERFERON ALPHA ANTIBODIES IN CHILDREN WlTH CHRONIC VIRAL HEPATITIS
B. Elkabes, S. Semra, Ozlem S. Suoglu, 0. Tulin, Gunay Saner. Pediatric Gastmentemlogy and Hepatology, Istanblul University School of Medicine, Turkey Alpha interferon (IFN), the primary treatment for chronic hepatitis B and C, can induce antibody formation which may cause treatment failure. We evaluated our patients with chronic viral hepatitis (aged 1-15 yrs) at the end of six months treatment with regard to binding anti-interferon antibodies. The hepatitis B patients were in two treatment groups all receiving 5 million UlmUthrice weekly IFN: IFN alone (Group 1, n = 20) or with lamivudine (Group 2, n = 22). All hepatitis C patients (Group 3, n = lo), received 3 million U/m2/thrice weekly IFN + ribavirin. For antibody detection, ELIZA kit (A4-240 ANAWA) was used. The rate of antibody formation in the 3 groups were 40%, 27.3% and 20% respectively. The type of interferon (alpha 2a or 2b) didn’t influence antibody formation. Lineer regression analysis revealed only a weak correlation between anti-interferon antibodies and treatment failure in hepatitis B patients (r = 0.508 in Group 1, r = 0.789 in Group 2), and no correlation in hepatitis C patients. Interestingly, 7 patients who had high titre antibodies were all non-responders.