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148 Fulminant autoimmune hepatitis: Clinical presentation, outcome and prognostic factors
Category 1." Liver Transplantation~Surgery~Acute Liver Failure
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FULMINANT AUTOIMMUNE HEPATITIS: CLINICAL PRESENTATION, OUTCOME AND PROGNOSTIC FACTORS
A.G. Villamil 1, R Casciato 1, E. Mullen 2, D. Bustos3, D. Giunta 1, J.C. Bandi 1, O.A. Galdame 1, M. Ciardnllo 1, E. de SantibaSes I . 1Liver
Transplantation Unit, Hospital Italiano, Buenos Aires, Argentina," 2Anatomia Patologica, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina," ~Inmunoserologia, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina Introduction: Fulminant hepatic failure is an unusual form of presentation
of autoimmune hepatitis (AIH). Yet, genetic and geographic factors may itfftuence susceptibility and clinical expression. Aim: To evaluate the clinical presentation, response to treatment and outcome of fulminant AIH. We additionally analyzed prognostic factors associated with a poor outcome (requirement o f liver transplantation or death). Patients and Methods: We retrospectively reviewed 88 consecutive patients evaluated for fulminant hepatic t~ailure between 1994 and June 2004 in our Liver Transplantation Unit. Thirty one patients fulfilled criteria for fulminant AIH (negative viral serology, non-hepatotoxic drugs, normal copper metabolism and a positive test for ANAL, ASMA, anti LKM-1 or anti-LC1 (anti-liver cytosol) with associated hypergammaglobulinemia and/or a biopsy compatible with AIH). Corticosteroids were started at diagnosis in 25 patients (prednisone 60 m ~ d a y until death, transplantation or liver recovery'). Biochemical and clinical variables pre and post-steroids were analyzed. Results: Of 31 patients with fulminant AIH, 3 patients were cirrhotic and were excluded from the analysis. Only one patient developed encephalopathy within 7 days after jaundice (hyperacute), 13 patients between 7 and 28 days (acute) while 17 (60%) patients had a subacute presentation (>28 days). 19/28 patients died or required liver transplantation (median time 7.9 days, 2 ~ 7 days). Transjugular liver biopsy was performed in 23 patients. 17/19 patients with sub-massive or massive necrosis died (n= 5) or were tsansplanted (n= 12). ANA and/or ASMA were positive in 22 patients, LC in 2 and LKM-1 in 4 patients. All patients with LC or LKM were unresponsive to steroids and required transplantation (n 4) or died (n 2). Nine patients recovered with steroids, and azathioprine was added as soon as they improved liver synthetic function. Variables associated with a bad prognosis were: prothrombin time <20% or grade IV encephalopathy at diagnosis, LC or LKM-1 (+), massive or sub-massive necrosis, no >20% improvement ofprothrombin time at day 3 post-steroids
(p < 0.05). Conclusion: Fuhninant autoimmune hepatitis is not unusual in our population. Disease course is aggressive, with death or requirement of liver transplantation in 67% of patients. Early diagnosis and treatment of this condition may improve survival.
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COMPARISON OF PORTAL VEIN EMBOLIZATION V E R S U S PORTAL VEIN LIGATION FOR INDUCTION OF H Y P E R P L A S I A OF THE FUTURE REMNANT LIVER VOLUME USING A MINI-PIG MODEL
C. Wilros I , L. Moeller t , C. Lenk I , M. Michelsen 1, C. Hillert 1, K. Helmke 2, G. Krupski 3, X. Rogiers I , D.C. Broering I . ~Department of
Hepatobiliary Surgery and Visceral Transplantation, University Hospital Hamburg-Eppendo~f Hamburg, Germany; 2Department of Pediatric Radiology, University Hospital HambuN-Eppendorf Hamburg, Germany," 3Department of Radiology, University Hospital HambuN-Eppendo~ Hamburg, Germany Introduction: The extent of hepatectomies is limited by the functional reserve of the remnant liver. The introduction of preoperative portal vein occlusion techniques to induce a preoperative hyperplasia of the future
61
liver remnant reduced the risk of postoperative liver failure. However, it was remained a matter of debate whether partial portal vein embolization or ligation of the portal branches was the preferable technique. We compared both techniques under standardised conditions in a large animal model. Methods: Mini-pigs with a weight of 23 to 55 kilograms were used. Thirteen animals underwent portal-vein-ligation (PL), 11 animals portal-veinembolization (PE) of 75% of the liver volume. Six mini-pigs underwent a sham operation (S). The growth response of the non-occluded liver lobe and the occluded liver lobes were assessed by segmental liver weight to body weight ratio (SLBWR) four weeks postoperatively. Hepatocellular damage and liver function were monitored by serum determinations. Duplex ultrasound examinations of hepatic flow parameters before and one hour after ligatiorfernbolization and after 4 weeks were undertaken. Ex-situ arteriograms and portograrns were used to show adaptive changes in both vascular beds. Results: The SLBWR of the non-occluded lobe was highest after PE (0.85; p < 0.05) versus 0.6 (p < 0.05) after PL. In the S-group it was 0.4. In contrast, the weight indices of the occluded lobes were significantly reduced. Transaminases were not significant elevated after both occlusion techniques. Global serum parameters reflected normal liver function. After PL, there was a temporary reversal portal flow one hour after occlusion. After four weeks, the PL group consistently exhibited hepatopetal portal flow in the ligated lobes, which was present, but significantly decreased after PE. The ex-situ angiography after PE and PL revealed the development of portal nee -collaterals in the portal-occluded liver parts. Conclusion: PE is the more effective technique to increase tile future liver remnant. This is due to a more effective, durable occlusion of the portal branches. Formation of collaterals between occluded and non-occluded liver parts seems to be the cause o f inferior regeneration in tile ligation group. The level of growth in the non-occluded lobes is balanced by atrophy in the occluded lobes.
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INVESTIGATION INTO THE ROLE OF BIFIDOBACTERIUM AND LACTOBACILLUS IN ISCHEMIA/REPERFUSION LIVER INJURY IN RATS
H.C. Xing 1, L.J. Li 1, K.J. Xu 1, T. Shen 1, YB. Chen I , Y Chen I , S.Z. Fu I , C.L. Chen I , J.G. Wang I , D. Yan I , EW. Dai 2, J.F. Sheng I , Y.S. Yu I , X.Y. Sha 2 . lI£ey Laboratory of Infectious Disease, Ministry of Public
Health of China, Institute of Infectious Disease, Department of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China," 2Zhejiang Academy of Medical Sciences, China Background and Aims: The intestinal microflora plays a crucial role in some severity liver disease. The aim of this study was to investigate the intestinal microflora status related to hepatic I/R injury and evaluate the effects of Lactobacillus and Bifidobacterium on hepatic I/R injury. Methods: Forty-eight Spragu~Dawley rats were administrated with Bifidob acterium Catenulatum ZYB 0401 (1.2 × 109 CFU, n = 9), Lactobacillus Fermentum ZYL0401 (1.2× 109 CFU, n = 9), Bifidobacterium Catenulatum ZYB0401 combination with Lactobacillus Fermentum ZYL0401 (n 8), gentarnicin (n= 7), or saline [tile control group (n = 7) and tile model group (n= 8)] by daily garage for 7 clays. On the sixth clay, all rats, except for ones in the control group (with sham operation), were subjected to inflow occlusion of liver for 20rain. After 2 2 h of hepatic reperfusion, all experimental rats were sacrificed and liver enzymes, malondialdehydea (MDA), superoxide dismutase (SOD), plasma endotoxin, intestinal bacteria counts, intestinal mucosal histology, bacterial translocation to kidney were studied. Results: Hepatic I/R increased liver enzymes and MDA and decreased SOD, which associated with plasma endotoxin elevation (p < 0.01), the disturbance of intestinal bacterial population, intestinal mucosa impaired, and the increase in the incidence o f bacterial translocation to kidney (p < 0.05).
•]
FULMINANT AUTOIMMUNE HEPATITIS: CLINICAL PRESENTATION, OUTCOME AND PROGNOSTIC FACTORS
A.G. Villamil 1, R Casciato 1, E. Mullen 2, D. Bustos3, D. Giunta 1, J.C. Bandi 1, O.A. Galdame 1, M. Ciardnllo 1, E. de SantibaSes I . 1Liver
Transplantation Unit, Hospital Italiano, Buenos Aires, Argentina," 2Anatomia Patologica, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina," ~Inmunoserologia, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina Introduction: Fulminant hepatic failure is an unusual form of presentation
of autoimmune hepatitis (AIH). Yet, genetic and geographic factors may itfftuence susceptibility and clinical expression. Aim: To evaluate the clinical presentation, response to treatment and outcome of fulminant AIH. We additionally analyzed prognostic factors associated with a poor outcome (requirement o f liver transplantation or death). Patients and Methods: We retrospectively reviewed 88 consecutive patients evaluated for fulminant hepatic t~ailure between 1994 and June 2004 in our Liver Transplantation Unit. Thirty one patients fulfilled criteria for fulminant AIH (negative viral serology, non-hepatotoxic drugs, normal copper metabolism and a positive test for ANAL, ASMA, anti LKM-1 or anti-LC1 (anti-liver cytosol) with associated hypergammaglobulinemia and/or a biopsy compatible with AIH). Corticosteroids were started at diagnosis in 25 patients (prednisone 60 m ~ d a y until death, transplantation or liver recovery'). Biochemical and clinical variables pre and post-steroids were analyzed. Results: Of 31 patients with fulminant AIH, 3 patients were cirrhotic and were excluded from the analysis. Only one patient developed encephalopathy within 7 days after jaundice (hyperacute), 13 patients between 7 and 28 days (acute) while 17 (60%) patients had a subacute presentation (>28 days). 19/28 patients died or required liver transplantation (median time 7.9 days, 2 ~ 7 days). Transjugular liver biopsy was performed in 23 patients. 17/19 patients with sub-massive or massive necrosis died (n= 5) or were tsansplanted (n= 12). ANA and/or ASMA were positive in 22 patients, LC in 2 and LKM-1 in 4 patients. All patients with LC or LKM were unresponsive to steroids and required transplantation (n 4) or died (n 2). Nine patients recovered with steroids, and azathioprine was added as soon as they improved liver synthetic function. Variables associated with a bad prognosis were: prothrombin time <20% or grade IV encephalopathy at diagnosis, LC or LKM-1 (+), massive or sub-massive necrosis, no >20% improvement ofprothrombin time at day 3 post-steroids
(p < 0.05). Conclusion: Fuhninant autoimmune hepatitis is not unusual in our population. Disease course is aggressive, with death or requirement of liver transplantation in 67% of patients. Early diagnosis and treatment of this condition may improve survival.
•
COMPARISON OF PORTAL VEIN EMBOLIZATION V E R S U S PORTAL VEIN LIGATION FOR INDUCTION OF H Y P E R P L A S I A OF THE FUTURE REMNANT LIVER VOLUME USING A MINI-PIG MODEL
C. Wilros I , L. Moeller t , C. Lenk I , M. Michelsen 1, C. Hillert 1, K. Helmke 2, G. Krupski 3, X. Rogiers I , D.C. Broering I . ~Department of
Hepatobiliary Surgery and Visceral Transplantation, University Hospital Hamburg-Eppendo~f Hamburg, Germany; 2Department of Pediatric Radiology, University Hospital HambuN-Eppendorf Hamburg, Germany," 3Department of Radiology, University Hospital HambuN-Eppendo~ Hamburg, Germany Introduction: The extent of hepatectomies is limited by the functional reserve of the remnant liver. The introduction of preoperative portal vein occlusion techniques to induce a preoperative hyperplasia of the future
61
liver remnant reduced the risk of postoperative liver failure. However, it was remained a matter of debate whether partial portal vein embolization or ligation of the portal branches was the preferable technique. We compared both techniques under standardised conditions in a large animal model. Methods: Mini-pigs with a weight of 23 to 55 kilograms were used. Thirteen animals underwent portal-vein-ligation (PL), 11 animals portal-veinembolization (PE) of 75% of the liver volume. Six mini-pigs underwent a sham operation (S). The growth response of the non-occluded liver lobe and the occluded liver lobes were assessed by segmental liver weight to body weight ratio (SLBWR) four weeks postoperatively. Hepatocellular damage and liver function were monitored by serum determinations. Duplex ultrasound examinations of hepatic flow parameters before and one hour after ligatiorfernbolization and after 4 weeks were undertaken. Ex-situ arteriograms and portograrns were used to show adaptive changes in both vascular beds. Results: The SLBWR of the non-occluded lobe was highest after PE (0.85; p < 0.05) versus 0.6 (p < 0.05) after PL. In the S-group it was 0.4. In contrast, the weight indices of the occluded lobes were significantly reduced. Transaminases were not significant elevated after both occlusion techniques. Global serum parameters reflected normal liver function. After PL, there was a temporary reversal portal flow one hour after occlusion. After four weeks, the PL group consistently exhibited hepatopetal portal flow in the ligated lobes, which was present, but significantly decreased after PE. The ex-situ angiography after PE and PL revealed the development of portal nee -collaterals in the portal-occluded liver parts. Conclusion: PE is the more effective technique to increase tile future liver remnant. This is due to a more effective, durable occlusion of the portal branches. Formation of collaterals between occluded and non-occluded liver parts seems to be the cause o f inferior regeneration in tile ligation group. The level of growth in the non-occluded lobes is balanced by atrophy in the occluded lobes.
~0]
INVESTIGATION INTO THE ROLE OF BIFIDOBACTERIUM AND LACTOBACILLUS IN ISCHEMIA/REPERFUSION LIVER INJURY IN RATS
H.C. Xing 1, L.J. Li 1, K.J. Xu 1, T. Shen 1, YB. Chen I , Y Chen I , S.Z. Fu I , C.L. Chen I , J.G. Wang I , D. Yan I , EW. Dai 2, J.F. Sheng I , Y.S. Yu I , X.Y. Sha 2 . lI£ey Laboratory of Infectious Disease, Ministry of Public
Health of China, Institute of Infectious Disease, Department of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China," 2Zhejiang Academy of Medical Sciences, China Background and Aims: The intestinal microflora plays a crucial role in some severity liver disease. The aim of this study was to investigate the intestinal microflora status related to hepatic I/R injury and evaluate the effects of Lactobacillus and Bifidobacterium on hepatic I/R injury. Methods: Forty-eight Spragu~Dawley rats were administrated with Bifidob acterium Catenulatum ZYB 0401 (1.2 × 109 CFU, n = 9), Lactobacillus Fermentum ZYL0401 (1.2× 109 CFU, n = 9), Bifidobacterium Catenulatum ZYB0401 combination with Lactobacillus Fermentum ZYL0401 (n 8), gentarnicin (n= 7), or saline [tile control group (n = 7) and tile model group (n= 8)] by daily garage for 7 clays. On the sixth clay, all rats, except for ones in the control group (with sham operation), were subjected to inflow occlusion of liver for 20rain. After 2 2 h of hepatic reperfusion, all experimental rats were sacrificed and liver enzymes, malondialdehydea (MDA), superoxide dismutase (SOD), plasma endotoxin, intestinal bacteria counts, intestinal mucosal histology, bacterial translocation to kidney were studied. Results: Hepatic I/R increased liver enzymes and MDA and decreased SOD, which associated with plasma endotoxin elevation (p < 0.01), the disturbance of intestinal bacterial population, intestinal mucosa impaired, and the increase in the incidence o f bacterial translocation to kidney (p < 0.05).