- Email: [email protected]
[161] HEPATITIS E VIRUS INFECTION CAN EVOLVE TO CHRONIC HEPATITIS IN ORGAN-TRANSPLANT PATIENTS
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POSTERS
11591 BEST CANDIDATES FOR PRETRANSPLANT TRANSARTERIAL CHEMOTHERAPY TO RETARD TUMOR PROGRESSION AND ACCEPTABLE WAITING TIME IN PATIENTS WITH HEPATOCELLULAR CARCINOMA MEETING THE MILAN CRITERIA J.W. Janc’, J.Y. Choi’, C.R. You’, C.W. Kim’, S.W. Nam’, S.H. Bae’, S.H. Cho’, S.K. Yoon’, N.T. Han’, K.W. Chung2, B.S. Kim3. ’Departnzent of‘ Internal Medicine, The Catholic Unioersity of‘ Korea, Seoul; Ewha Woman j. University, Seoul; ’Sunchunhyang 7Jnioersity School QfMedicine, Seoul, South Korea E-mail: [email protected]
Background and Aims: Although transarterial chemotherapy is attempted to retard tumor progression in hepatocellular carcinoma (HCC) patients awaiting orthotopic liver transplantation (OLT), information regarding the appropriate patient selection for the therapy and its efficacy is lacking. This study was conducted to address the practical issues of how long HCC patients would remain adequately within the restrictive criteria with transarterial chemotherapy and of which patients could hold the longest acceptable waiting time as the best candidates for such therapy. Methods: In total, 180 consecutive patients meeting the Milan criteria were included in the study. Transarterial chemo-lipiodolization using epirubicin 50mg/m2 and/or cisplatin 60mg/m2 was repeated at one-totwo monthly intervals, until donor liver was available. From the analyses of dropouts from the list, acceptable waiting times prior to OLT and best candidates for pretransplant transarterial therapy were explored. Results: During the follow-up, 70 (38.9%) patients dropped off the waiting list. The median time to dropout was significantly shorter in Child-Pugh class B/C than in A patients (17.0 vs. 33.3 months, P 1 0.001). Risk factor analysis identified Child-Pugh classification to be the strongest predictor of dropouts (P 1 0.00 1). On multivariate analysis, alpha-fetoprotein (AFP) level >lo0 ngiml, tumor size >3 cm and multiple nodules remained independent predictors of dropout for Child A group (all P < 0.05), whereas none were predictive of dropout for Child B/C group. Child A patients with single nodule of 1 3 cm and AFP 1 I00 ngiml were found to be at the lowest risk of dropout, with only 22.5% dropout rate up to 41 months. Dropout due to death was significantly frequent in Child B/C than Child A group (32.5% vs. 3.6%, P<0.001), whereas dropout due to tumor progression were similar between the two groups. Conclusions: The acceptable waiting times prior to OLT appear to be around 3 and 1.5 years for Child A and B/C groups undergoing transarterial chemotherapy, respectively. Thus, OLT should be considered within these periods, according to Child-Pugh classification. Child class A patients with one nodule of 1 3 cm and AFP 1 100 ngiml may be the best candidates for pretransplant chemo-lipiodolization, being at the lowest risk of dropout.
11601 CLINICAL OUTCOME OF HCV-RELATED GRAFT CIRRHOSIS AND PROGNOSTIC VALUE OF HEPATIC VENOUS PRESSURE GRADIENT G. Kalambokis’ , D. Samonakis’ , l? Manousou’ , F. Grillo2, A.l? Dhillon2, D. Patch’, K. Rolles’, A.K. Burroughs’. ’Department of Liuer Transplantation and Hepatobiliary Medicine, Royal Free Hospital, London; ’Histopathology Depwtnzent, Royal F e e Hospital, London, 7JK E-mail: [email protected] Background and Aims: Hepatitis C virus (HCV) graft cirrhosis has a rapid progression prompting early consideration for retransplantation. We evaluated the natural history of HCV-related graft cirrhosis in patients transplanted in our center. Methods: We investigated: ( 1 ) progression of graft cirrhosis from histological diagnosis in 48 (Tshak stage 6: 57%; stage 5: 43%) of228 consecutive patients with serial biopsies; (2) predictors of decompensation and mortality including hepatic venous pressure gradient (HVPG), measured in 29
patients. Thirteen patients who developed stage 4 fibrosis and remained at this stage were also evaluated. Results: Graft cirrhosis was diagnosed at a median o f 4 8 ( 1 2-1 64) months post-transplant. Baseline parameters were similar in stage 5 and 6. Faster development (<48 months) was independently associated with tacrolimus and non-use of azathioprine and prednisolone. Median follow-up from diagnosis of cirrhosis was 21 (1-76) months. Decompensation (ascites 82%; variceal bleeding 9%; encephalopathy 9%) occurred in 23% at a median of 9 (1-49) months, but 40% remained free of decompensation 5 years after diagnosis. Survival among compensated patients and liverrelated survival (excluding decompensation-related deaths) was 74% at 5 years, falling rapidly after decompensation (12% at I year). HVPG was 3 I0 mmHg in 38%. Decompensation rate, and decompensation and es were significantly higher in patients with a HVPG 310mmHg than those without (45% vs. 5.5%, p=0.01; 66% vs. 6% at 3 years, p=0.02; 26% vs. 0% at 3 years, p=0.04) but similar in stage 5 or 6. A high HVPG (>lOmmHg), a Child-Pugh score 37, and albumin levels <32 gidL were independently associated with decompensation and mortality. No episode of decompensation or liver related-death occurred in patients who remained stage 4. HCV genotype (lb, 35%) and immunosuppression used after onset of cirrhosis (cyclosporine, 35%; tacrolimus, 52%) did not influence the outcome. Conclusions: Ishak stage 5 and 6 HCV-related fibrosis have similar prognosis post-transplant. Decompensation leads to a very shortened survival. An HVPG 3 10 mmHg, in addition to liver dysfunction (Child-Pugh class >A, albumin levels <32 g/dL), gives independent prognostic information before decompensation, allowing relisting in better clinical condition.
11611 CHRONIC HEPATITIS E VIRUS INFECTION CAN EVOLVE TO HEPATITIS IN ORGAN-TRANSPLANT PATIENTS N. Kamar’, J.M. Peron2, L. Ouezzani’, J.M. Mansuy3, J. Selves4, J. Guitard’, 0. Cointault’ , C. Bureau’, D. Durand’ , J.P. Vinel’, J. Izopet3, L. Rostaing’ . ‘Multi-Organ Transplant linit, Rangiieil Hospital, Toulouse; 2Department of‘ He~~ato-Gastroenterology, Purpan Hospital, Toulouse; ”Department of‘ Viroloa, Purpan Hospital, Toulouse; Departnzent of Pathology, Puypan Hospital, Toulouse, Fyance E-mail: [email protected]
Introduction: Hepatitis E virus (HEV) is a RNA virus that causes not only epidemics of acute hepatitis in developing countries, but also might be endemic in industrialized countries. Chronic hepatitis E has never been described. Patients: We identified 13 cases of hepatitis E infection that occurred in 13 organ-transplant patients (3 liver-, 8 kidney-, and 2 kidney-pancreastransplant patients) who presented with unexplained elevation of liver enzymes levels. Six were asymptomatic while the 7 remaining patients presented with fatigue. Two patients had been in contact with animals and none had travelled abroad recently. At diagnosis, there was a significant increase in liver enzymes level, from 23 (12-95) to 115 (37436) lUiL for AST (p=0.0015), from 26 (10-102) to 245 (66-874) lU/L for ALT (p=0.0015), from 32 (8-1 164) to 132 (40-3482) lU/L for :,GT (p = 0.00 I5), and from I05 (26-226) to 249 ( 1 07-822) for alkaline phosphate (p = 0.0015). Classical causes of hepatitis were ruled out. HEV serology was negative in all patients but one. HEV RNA was positive in the sera of all patients, and in the stool (n = 3) when tested. Nine patients underwent a liver biopsy at diagnosis which revealed signs of non specific portal tract modest inflammation. HEV RNA became negative within three months in 7 patients (group I). The six other patients developed a chronic hepatitis defined by persisting elevated transaminase levels, and positive HEV RNA in the sera and stools, respectively 6, 9, 10, 12, 13, and 24 months after diagnosis (group TI). The time between the transplantation and the diagnosis was significantly shorter in group TI, ( 8 2f17 vs. 31.6+10 months; p = 0.02). At diagnosis and one month later (Ml), leukocyte counts and platelets counts were significantly lower in group 11. At M1, AST and
OIB. LIVER TRANSPLANTATION/SURGERY/ACUTELIVER FAILURE ALT levels were significantly higher in group TI. A second liver biopsy performed in 2 patients, respectively 12 and 18 months after diagnosis revealed signs of chronic active hepatitis associated to liver fibrosis. Conclusion: HEV infection of immunosuppressed patients can lead to chronic infection. The consequences of this new entity on the liver function of these patients are still unknown.
11621 LAMIVUDINE MONOPROPHYLAXIS PREVENTS HBV INFECTION IN RECIPIENTS UNDERGOING LIVE DONOR LIVER TRANSPLANTATION BECAUSE OF NON-HBV RELATED DISEASES, HAVING THEIR GRAFTS FROM CORE-ANTIBODY POSITIVE DONORS Z. Karasu’, M. Akyildiz’, T. Ozacag, F. Yilmaz3, U S . Akarca’, G. Ersoz’, F, Gunsarl, U. Aydin4, M. Kilic4, T. Ilter’ , ‘Depurtnzent of Gastroenterology; ’Department of Microhiology; ’Department of Pathology; 4Department of General Surgerji, Ege Uniuersih~Medical School, Izmir, Turkey E-mail: [email protected] Background: Liver grafts from HBc-Ab positive donors can transmit HBV infection to transplant recipients. Transmission rate of HBV from HBc-Ah+ living donors is reported to be similar to cadaveric donors in the absence of prophylaxis. However, the use of prophylactic regimens may prevent disease transmission to recipients of hepatitis core antibody positive donors. Aim: To investigate the efficacy of lamivudine l00mg/day in prevention of transmission of HBV infection to those patients undergoing liver transplantation due to non-HBV related liver diseases, receiving their grafts from anti-HBc positive living donors. Methods: Between June 1999 and October 2006, we have performed 260 adult to adult live donor liver transplantation. Seventy-seven patients underwent liver transplantation because of non-HBV related diseases. Thirty of 77 patients had their grafts from anti-HBc positive donors. All patients having their grafts from anti-HBc positive donors have been treated with lamivudine I00 mgiday. Serum transaminases and Hepatitis B surface antigen (HBsAg) has been investigated in the serum of patients monthly in first 6 months and with 3-month periods thereafter; HBV DNA has been investigated every 6 months. Results: None ofthe 30 adult patients experienced HBV reinfection under lamivudine monoprophylaxis. HBsAg or HBVDNA was not detected in any patients. Mean follow up duration was 28 (1-70) months. Conclusion: Our experience in adult to adult living related liver transplantation suggests that lamivudine monoprohylaxis can prevent HBsAg seroconversion in patients undergoing liver transplantation due to nonHBV related liver diseases, who have their grafts from anti-HBc positive donors
11631 CORRELATION BETWEEN HEPATOCYTE AND HEPATIC PROGENITOR CELL REGENERATION AND MODEL FOR END STAGE LIVER DISEASE (MELD) SCORE IN ACUTE SEVERE LIVER IMPAIRMENT A. Katoonizadeh’>*,F. Nevens’, C. Verslype’, J. Pirenne3, T. Roskams2.
‘Dep~rtnzentof Hepmlogy; ’Departnzent of Puthologv; ”Depvtnzent of‘ Ahdominal Trunsplunt Surgery, University Hospitul Gasthuisberg, K. 11 Leuwen, Leuwen, Belgium E-mail: [email protected] Background and Aims: The restitutive response of the liver to different injuries involves proliferation of cells of different lineage: 1 ) mature hepatocytes; unipotent “committed’ cells; which are numerous and contribute to normal cell turnover and respond rapidly to liver injury; 2) the Hepatic Progenitor Cells (HPCs), located in the canals of Hering, which are activated when loss of hepatocytes is massive or combined with inhibition
~
B) CLINICAL
S71
of proliferative capacity of hepatocytes. In chronic hepatitis progenitor cell expansion is an important source of hepatocyte regeneration, however little is known about the liver regeneration and the HPCs response in acute severe liver impairment (ASLI) in humans. We undertook this study to investigate the role of hepatocyte proliferation and of HPCs activatioddifferentiation in liver repopulation in ASLl and their correlations with clinical parameters. Patients and Methods: Formalin-fixed, paraffin embedded liver specimens from 74 consecutive patients with ASLl (59 patients had acute liver failure) seen in the department of hepatology over the last 10 years were selected (mean age: 4 3 f 1 7 yrs; MIF: 28/46). Of those 10 died without transplantation, 40 were transplanted and 24 survived without transplantation. The etiology was viral hepatitis (n = 13), drug-induced (n = 2 I ) and cryptogenic (n = 40). Immunohistochemistry was performed for CK7, CKl9 (number of HPCs and intermediate hepatocytes), Ki67(Mib-1) (number of proliferating hepatocytes) and p2 I (number of replicationarrested hepatocytes). The percentage of hepatocyte loss was also assessed on H&E-stained sections. Results: Our results show that 50‘X loss of hepatocytes is associated with significant decrease in the number of proliferating hepatocytes and significant increase in the number of HPCs. This increase is related to the disease severity: the HPCs number was positively correlated with MELD score and negatively correlated with survival. HPC expansion occurs early (within one week) in the disease course. However, development of intermediate hepatocytes, suggesting HPCs differentiation towards mature hepatocytes, takes at least 1 week time. The number of proliferating hepatocytes and percentage hepatocyte loss were independent parameters in predicting outcome. Conclusion: In SALl there is good correlation between histopathological parameters (percentage hepatocyte loss, number of proliferating hepatocytes and HPCs) and clinical findings or outcome.
11641 CHRONIC RENAL FAILURE POST LIVER TRANSPLANT; PREVALENCE AND RATE OF DECLINE J.A. Leithead, J.W. Ferguson, P.C. Hayes. Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinhurgh, UK E-mail: [email protected] Chronic renal dysfunction is a recognised cause of morbidity and mortality post liver transplantation. However, the definition of chronic renal dysfunction varies widely and it’s true prevalence and clinical significance is underestimated. Our aim was to assess the prevalence of Chronic Kidney Disease (CKD) following elective liver transplantation. Methods: A single-centre retrospective study of 135 consecutive patients who received 148 liver transplants between 01/01/96 and 31/12/00. 106 survived for the 5 year follow-up period. GFR was calculated using the MDRD6 equation. As per the National Kidney Foundation a GFR of >90, 60-89, <60 and < I 5 defined normal renal function, mildly reduced GFR, CKD and kidney failure respectively. Values are expressed as mean and standard deviation. Results: Mean age at time oftransplantation was 50.1f10.9 (M:F= 1:l.l). 97% were of European ethnic origin. Indications for transplantation were PBC (33%), alcoholic liver disease (22%), HCV (lo%), others (35%). Pre-transplantation 38% had a reduced GFR and 7% met the criteria for CKD. Post operatively, 60%, 74%, 81% and 80%)had some degree of renal impairment and 15%, 27%, 26% and 28% had CKD at 1, 6, 12 and 60 months respectively. The mean GFR at 5 years was 44+12 in those with CKD and 81+16 in those without. Two patients (2%) developed kidney failure and required dialysis. Mean GFR at 5 years was 31ml/min/1.73m2 less than the pre-operative level. The fastest rate of decline was observed during the peri-operative period. Thereafter, GFR stabilised. Although there was no significant difference in the mean GFR between 1 and 5 years of the group as a whole, 46% demonstrated a deterioration at a rate greater than that expected with age. Of this cohort 86% had a reduced GFR, 37% had
POSTERS
11591 BEST CANDIDATES FOR PRETRANSPLANT TRANSARTERIAL CHEMOTHERAPY TO RETARD TUMOR PROGRESSION AND ACCEPTABLE WAITING TIME IN PATIENTS WITH HEPATOCELLULAR CARCINOMA MEETING THE MILAN CRITERIA J.W. Janc’, J.Y. Choi’, C.R. You’, C.W. Kim’, S.W. Nam’, S.H. Bae’, S.H. Cho’, S.K. Yoon’, N.T. Han’, K.W. Chung2, B.S. Kim3. ’Departnzent of‘ Internal Medicine, The Catholic Unioersity of‘ Korea, Seoul; Ewha Woman j. University, Seoul; ’Sunchunhyang 7Jnioersity School QfMedicine, Seoul, South Korea E-mail: [email protected]
Background and Aims: Although transarterial chemotherapy is attempted to retard tumor progression in hepatocellular carcinoma (HCC) patients awaiting orthotopic liver transplantation (OLT), information regarding the appropriate patient selection for the therapy and its efficacy is lacking. This study was conducted to address the practical issues of how long HCC patients would remain adequately within the restrictive criteria with transarterial chemotherapy and of which patients could hold the longest acceptable waiting time as the best candidates for such therapy. Methods: In total, 180 consecutive patients meeting the Milan criteria were included in the study. Transarterial chemo-lipiodolization using epirubicin 50mg/m2 and/or cisplatin 60mg/m2 was repeated at one-totwo monthly intervals, until donor liver was available. From the analyses of dropouts from the list, acceptable waiting times prior to OLT and best candidates for pretransplant transarterial therapy were explored. Results: During the follow-up, 70 (38.9%) patients dropped off the waiting list. The median time to dropout was significantly shorter in Child-Pugh class B/C than in A patients (17.0 vs. 33.3 months, P 1 0.001). Risk factor analysis identified Child-Pugh classification to be the strongest predictor of dropouts (P 1 0.00 1). On multivariate analysis, alpha-fetoprotein (AFP) level >lo0 ngiml, tumor size >3 cm and multiple nodules remained independent predictors of dropout for Child A group (all P < 0.05), whereas none were predictive of dropout for Child B/C group. Child A patients with single nodule of 1 3 cm and AFP 1 I00 ngiml were found to be at the lowest risk of dropout, with only 22.5% dropout rate up to 41 months. Dropout due to death was significantly frequent in Child B/C than Child A group (32.5% vs. 3.6%, P<0.001), whereas dropout due to tumor progression were similar between the two groups. Conclusions: The acceptable waiting times prior to OLT appear to be around 3 and 1.5 years for Child A and B/C groups undergoing transarterial chemotherapy, respectively. Thus, OLT should be considered within these periods, according to Child-Pugh classification. Child class A patients with one nodule of 1 3 cm and AFP 1 100 ngiml may be the best candidates for pretransplant chemo-lipiodolization, being at the lowest risk of dropout.
11601 CLINICAL OUTCOME OF HCV-RELATED GRAFT CIRRHOSIS AND PROGNOSTIC VALUE OF HEPATIC VENOUS PRESSURE GRADIENT G. Kalambokis’ , D. Samonakis’ , l? Manousou’ , F. Grillo2, A.l? Dhillon2, D. Patch’, K. Rolles’, A.K. Burroughs’. ’Department of Liuer Transplantation and Hepatobiliary Medicine, Royal Free Hospital, London; ’Histopathology Depwtnzent, Royal F e e Hospital, London, 7JK E-mail: [email protected] Background and Aims: Hepatitis C virus (HCV) graft cirrhosis has a rapid progression prompting early consideration for retransplantation. We evaluated the natural history of HCV-related graft cirrhosis in patients transplanted in our center. Methods: We investigated: ( 1 ) progression of graft cirrhosis from histological diagnosis in 48 (Tshak stage 6: 57%; stage 5: 43%) of228 consecutive patients with serial biopsies; (2) predictors of decompensation and mortality including hepatic venous pressure gradient (HVPG), measured in 29
patients. Thirteen patients who developed stage 4 fibrosis and remained at this stage were also evaluated. Results: Graft cirrhosis was diagnosed at a median o f 4 8 ( 1 2-1 64) months post-transplant. Baseline parameters were similar in stage 5 and 6. Faster development (<48 months) was independently associated with tacrolimus and non-use of azathioprine and prednisolone. Median follow-up from diagnosis of cirrhosis was 21 (1-76) months. Decompensation (ascites 82%; variceal bleeding 9%; encephalopathy 9%) occurred in 23% at a median of 9 (1-49) months, but 40% remained free of decompensation 5 years after diagnosis. Survival among compensated patients and liverrelated survival (excluding decompensation-related deaths) was 74% at 5 years, falling rapidly after decompensation (12% at I year). HVPG was 3 I0 mmHg in 38%. Decompensation rate, and decompensation and es were significantly higher in patients with a HVPG 310mmHg than those without (45% vs. 5.5%, p=0.01; 66% vs. 6% at 3 years, p=0.02; 26% vs. 0% at 3 years, p=0.04) but similar in stage 5 or 6. A high HVPG (>lOmmHg), a Child-Pugh score 37, and albumin levels <32 gidL were independently associated with decompensation and mortality. No episode of decompensation or liver related-death occurred in patients who remained stage 4. HCV genotype (lb, 35%) and immunosuppression used after onset of cirrhosis (cyclosporine, 35%; tacrolimus, 52%) did not influence the outcome. Conclusions: Ishak stage 5 and 6 HCV-related fibrosis have similar prognosis post-transplant. Decompensation leads to a very shortened survival. An HVPG 3 10 mmHg, in addition to liver dysfunction (Child-Pugh class >A, albumin levels <32 g/dL), gives independent prognostic information before decompensation, allowing relisting in better clinical condition.
11611 CHRONIC HEPATITIS E VIRUS INFECTION CAN EVOLVE TO HEPATITIS IN ORGAN-TRANSPLANT PATIENTS N. Kamar’, J.M. Peron2, L. Ouezzani’, J.M. Mansuy3, J. Selves4, J. Guitard’, 0. Cointault’ , C. Bureau’, D. Durand’ , J.P. Vinel’, J. Izopet3, L. Rostaing’ . ‘Multi-Organ Transplant linit, Rangiieil Hospital, Toulouse; 2Department of‘ He~~ato-Gastroenterology, Purpan Hospital, Toulouse; ”Department of‘ Viroloa, Purpan Hospital, Toulouse; Departnzent of Pathology, Puypan Hospital, Toulouse, Fyance E-mail: [email protected]
Introduction: Hepatitis E virus (HEV) is a RNA virus that causes not only epidemics of acute hepatitis in developing countries, but also might be endemic in industrialized countries. Chronic hepatitis E has never been described. Patients: We identified 13 cases of hepatitis E infection that occurred in 13 organ-transplant patients (3 liver-, 8 kidney-, and 2 kidney-pancreastransplant patients) who presented with unexplained elevation of liver enzymes levels. Six were asymptomatic while the 7 remaining patients presented with fatigue. Two patients had been in contact with animals and none had travelled abroad recently. At diagnosis, there was a significant increase in liver enzymes level, from 23 (12-95) to 115 (37436) lUiL for AST (p=0.0015), from 26 (10-102) to 245 (66-874) lU/L for ALT (p=0.0015), from 32 (8-1 164) to 132 (40-3482) lU/L for :,GT (p = 0.00 I5), and from I05 (26-226) to 249 ( 1 07-822) for alkaline phosphate (p = 0.0015). Classical causes of hepatitis were ruled out. HEV serology was negative in all patients but one. HEV RNA was positive in the sera of all patients, and in the stool (n = 3) when tested. Nine patients underwent a liver biopsy at diagnosis which revealed signs of non specific portal tract modest inflammation. HEV RNA became negative within three months in 7 patients (group I). The six other patients developed a chronic hepatitis defined by persisting elevated transaminase levels, and positive HEV RNA in the sera and stools, respectively 6, 9, 10, 12, 13, and 24 months after diagnosis (group TI). The time between the transplantation and the diagnosis was significantly shorter in group TI, ( 8 2f17 vs. 31.6+10 months; p = 0.02). At diagnosis and one month later (Ml), leukocyte counts and platelets counts were significantly lower in group 11. At M1, AST and
OIB. LIVER TRANSPLANTATION/SURGERY/ACUTELIVER FAILURE ALT levels were significantly higher in group TI. A second liver biopsy performed in 2 patients, respectively 12 and 18 months after diagnosis revealed signs of chronic active hepatitis associated to liver fibrosis. Conclusion: HEV infection of immunosuppressed patients can lead to chronic infection. The consequences of this new entity on the liver function of these patients are still unknown.
11621 LAMIVUDINE MONOPROPHYLAXIS PREVENTS HBV INFECTION IN RECIPIENTS UNDERGOING LIVE DONOR LIVER TRANSPLANTATION BECAUSE OF NON-HBV RELATED DISEASES, HAVING THEIR GRAFTS FROM CORE-ANTIBODY POSITIVE DONORS Z. Karasu’, M. Akyildiz’, T. Ozacag, F. Yilmaz3, U S . Akarca’, G. Ersoz’, F, Gunsarl, U. Aydin4, M. Kilic4, T. Ilter’ , ‘Depurtnzent of Gastroenterology; ’Department of Microhiology; ’Department of Pathology; 4Department of General Surgerji, Ege Uniuersih~Medical School, Izmir, Turkey E-mail: [email protected] Background: Liver grafts from HBc-Ab positive donors can transmit HBV infection to transplant recipients. Transmission rate of HBV from HBc-Ah+ living donors is reported to be similar to cadaveric donors in the absence of prophylaxis. However, the use of prophylactic regimens may prevent disease transmission to recipients of hepatitis core antibody positive donors. Aim: To investigate the efficacy of lamivudine l00mg/day in prevention of transmission of HBV infection to those patients undergoing liver transplantation due to non-HBV related liver diseases, receiving their grafts from anti-HBc positive living donors. Methods: Between June 1999 and October 2006, we have performed 260 adult to adult live donor liver transplantation. Seventy-seven patients underwent liver transplantation because of non-HBV related diseases. Thirty of 77 patients had their grafts from anti-HBc positive donors. All patients having their grafts from anti-HBc positive donors have been treated with lamivudine I00 mgiday. Serum transaminases and Hepatitis B surface antigen (HBsAg) has been investigated in the serum of patients monthly in first 6 months and with 3-month periods thereafter; HBV DNA has been investigated every 6 months. Results: None ofthe 30 adult patients experienced HBV reinfection under lamivudine monoprophylaxis. HBsAg or HBVDNA was not detected in any patients. Mean follow up duration was 28 (1-70) months. Conclusion: Our experience in adult to adult living related liver transplantation suggests that lamivudine monoprohylaxis can prevent HBsAg seroconversion in patients undergoing liver transplantation due to nonHBV related liver diseases, who have their grafts from anti-HBc positive donors
11631 CORRELATION BETWEEN HEPATOCYTE AND HEPATIC PROGENITOR CELL REGENERATION AND MODEL FOR END STAGE LIVER DISEASE (MELD) SCORE IN ACUTE SEVERE LIVER IMPAIRMENT A. Katoonizadeh’>*,F. Nevens’, C. Verslype’, J. Pirenne3, T. Roskams2.
‘Dep~rtnzentof Hepmlogy; ’Departnzent of Puthologv; ”Depvtnzent of‘ Ahdominal Trunsplunt Surgery, University Hospitul Gasthuisberg, K. 11 Leuwen, Leuwen, Belgium E-mail: [email protected] Background and Aims: The restitutive response of the liver to different injuries involves proliferation of cells of different lineage: 1 ) mature hepatocytes; unipotent “committed’ cells; which are numerous and contribute to normal cell turnover and respond rapidly to liver injury; 2) the Hepatic Progenitor Cells (HPCs), located in the canals of Hering, which are activated when loss of hepatocytes is massive or combined with inhibition
~
B) CLINICAL
S71
of proliferative capacity of hepatocytes. In chronic hepatitis progenitor cell expansion is an important source of hepatocyte regeneration, however little is known about the liver regeneration and the HPCs response in acute severe liver impairment (ASLI) in humans. We undertook this study to investigate the role of hepatocyte proliferation and of HPCs activatioddifferentiation in liver repopulation in ASLl and their correlations with clinical parameters. Patients and Methods: Formalin-fixed, paraffin embedded liver specimens from 74 consecutive patients with ASLl (59 patients had acute liver failure) seen in the department of hepatology over the last 10 years were selected (mean age: 4 3 f 1 7 yrs; MIF: 28/46). Of those 10 died without transplantation, 40 were transplanted and 24 survived without transplantation. The etiology was viral hepatitis (n = 13), drug-induced (n = 2 I ) and cryptogenic (n = 40). Immunohistochemistry was performed for CK7, CKl9 (number of HPCs and intermediate hepatocytes), Ki67(Mib-1) (number of proliferating hepatocytes) and p2 I (number of replicationarrested hepatocytes). The percentage of hepatocyte loss was also assessed on H&E-stained sections. Results: Our results show that 50‘X loss of hepatocytes is associated with significant decrease in the number of proliferating hepatocytes and significant increase in the number of HPCs. This increase is related to the disease severity: the HPCs number was positively correlated with MELD score and negatively correlated with survival. HPC expansion occurs early (within one week) in the disease course. However, development of intermediate hepatocytes, suggesting HPCs differentiation towards mature hepatocytes, takes at least 1 week time. The number of proliferating hepatocytes and percentage hepatocyte loss were independent parameters in predicting outcome. Conclusion: In SALl there is good correlation between histopathological parameters (percentage hepatocyte loss, number of proliferating hepatocytes and HPCs) and clinical findings or outcome.
11641 CHRONIC RENAL FAILURE POST LIVER TRANSPLANT; PREVALENCE AND RATE OF DECLINE J.A. Leithead, J.W. Ferguson, P.C. Hayes. Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinhurgh, UK E-mail: [email protected] Chronic renal dysfunction is a recognised cause of morbidity and mortality post liver transplantation. However, the definition of chronic renal dysfunction varies widely and it’s true prevalence and clinical significance is underestimated. Our aim was to assess the prevalence of Chronic Kidney Disease (CKD) following elective liver transplantation. Methods: A single-centre retrospective study of 135 consecutive patients who received 148 liver transplants between 01/01/96 and 31/12/00. 106 survived for the 5 year follow-up period. GFR was calculated using the MDRD6 equation. As per the National Kidney Foundation a GFR of >90, 60-89, <60 and < I 5 defined normal renal function, mildly reduced GFR, CKD and kidney failure respectively. Values are expressed as mean and standard deviation. Results: Mean age at time oftransplantation was 50.1f10.9 (M:F= 1:l.l). 97% were of European ethnic origin. Indications for transplantation were PBC (33%), alcoholic liver disease (22%), HCV (lo%), others (35%). Pre-transplantation 38% had a reduced GFR and 7% met the criteria for CKD. Post operatively, 60%, 74%, 81% and 80%)had some degree of renal impairment and 15%, 27%, 26% and 28% had CKD at 1, 6, 12 and 60 months respectively. The mean GFR at 5 years was 44+12 in those with CKD and 81+16 in those without. Two patients (2%) developed kidney failure and required dialysis. Mean GFR at 5 years was 31ml/min/1.73m2 less than the pre-operative level. The fastest rate of decline was observed during the peri-operative period. Thereafter, GFR stabilised. Although there was no significant difference in the mean GFR between 1 and 5 years of the group as a whole, 46% demonstrated a deterioration at a rate greater than that expected with age. Of this cohort 86% had a reduced GFR, 37% had