- Email: [email protected]
813 RESULTS OF LIVER TRANSPLANTATION IN ADULT POLYCYSTIC LIVER DISEASE: REPORT OF A SINGLE CENTER EXPERIENCE
POSTERS of not giving priority to patients that have developed hepatic encephalopathy may be reconsidered in those with alcoholic cirrhosis. 811 A MODIFIED CHILD-TURCOTTE-PUGH (CTP) FOR SELECTION OF PATIENTS AFFECTED BY CIRRHOSIS CANDIDATES TO LIVER TRANSPLANTATION (LT) WITH LOW MODEL FOR END-STAGE LIVER DISEASE SCORE (MELD) S. Gitto1 , M. Biselli1 , A. Gramenzi1 , L. Brodosi1 , R. Di Donato1 , G. Vitale1 , S. Lorenzini1 , M. Ravaioli2 , G.L. Grazi2 , A.D. Pinna2 , M. Bernardi1 , P. Andreone1 , Bologna Liver Transplantation Group (BLTG). 1 Department of Clinical Medicine, 2 Department of General Surgery and Organ Transplantation, University of Bologna, Bologna, Italy E-mail: [email protected] Background and Aims: Model for End-Stage Liver Disease (MELD) is widely used for organ allocation, even if it shows a better prognostic accuracy among patients with high score. The aim of this study was to investigate whether other factors were able to better select the low MELD candidates with cirrhosis. Methods: The drop-out rate of 284 cirrhotic patients with MELD <18 listed for LT between January 2003 and March 2009 was evaluated. Univariate analysis was developed by means of actual survival curves taking into account the presence of competing risk represented by LT. Binary logistic regression analysis was used to determine the independent predictors of drop-out. Results: During a median follow-up of 19 months (1 day – 75 months), 54 (19%) patients died, 17 (6%) withdrew from the list because too sick to be transplanted, and 66 (23.2%) underwent LT. At multivariate analysis CTP score >7 (Hazard ratio (HR) 12.9; 95% Confidence Interval (95% CI) 1.7–98.6), serum sodium ≤137 mEq/L (HR 5.3; 95% CI 2.1–13.3) and glomerular filtration rate ≤90 ml/min estimated by the Modification of Diet in Renal Disease formula (MDRD-GFR) (HR 3.1; 95% CI 1.2–7.8) were independently associated with the probability of drop-out at 12 months. We integrated CTP [CTP-sodium-renal function (CTP-SRF)] by adding 1 point if MDRDGFR was >90 ml/min, 2 points if MDRD-GFR was 90–61 ml/min, and 3 points if MDRD-GFR was ≤60 ml/min, plus 1 point if serum sodium was >137 mEq/L, 2 points if serum sodium was 137–135 mEq/L, 3 points if serum sodium was <135 mEq/L. The area under the curve (AUC) for the CTP-SRF, showed an excellent diagnostic accuracy at 6- and 12-month (0.864 and 0.835, respectively), better than CTP (0.722; p = 0.013 and 0.731; p = 0.005; respectively) and MELD (0.515; p < 0.001 and 0.538; p < 0.001; respectively). The best predictive value of CTP-SRF was 12 (sensitivity 83.9% and specificity 73.6%). Patients with CTP-SRF score >12 experienced a 12-month probability of dropout 13-fold higher (HR 13.3; 95% CI 4.9–36.1) than patients with score ≤12. Conclusions: CTP-SRF was found to significantly improve the accuracy of CTP and MELD in predicting waitlist dropout among patients with low MELD score. 812 OUTCOME OF LIVER TRANSPLANTATION IN RECIPIENTS OLDER THAN 65 YEARS: A SINGLE CENTER EXPERIENCE I. Graziadei1 , K. Nachbaur1 , H. Zoller1 , W. Mark2 , W. Vogel1 . 1 Internal Medicine II, 2 Transplant Surgery, Medical University of Innsbruck, Innsbruck, Austria E-mail: [email protected] Advanced age was considered a relative contraindication for liver transplantation (LT) in the past. The percentage of older patients referred for LT assessment has markedly increased in almost all LT centers over the last years. The data regarding the outcome of older patients have been contradictory. Therefore, we aimed to evaluate the long-term survival of LT recipients older than 65 years.
Between 1982 and 2008, 106 out of 1011 patients (10.5%), who underwent LT at our institution, were older than 65 years. Almost all of these patients were transplanted after 1995. The mean age was 67.5 (65.0–76.4) years and the majority of patients were male (76%). Regarding underlying liver disease the percentage of non-alcoholic steatohepatitis associated cirrhosis was significantly higher in the older age group (15.9% vs. 5.8%, p < 0.01) compared to the younger LT cohort. In contrast, alcoholic liver disease was more common in recipients under 65 years (20.4% vs. 14.1%, p < 0.01). Significantly more patients in the older group presented with a concomitant hepatocellular carcinoma (40.6% vs. 23.7%, p < 0.01). Both groups did not differ with regard to Child–Pugh classification and mean MELD score. The median follow-up of the older patients was 3.2 compared to 5.7 years of the younger cohort. The actuarial patient survival rates at 1-, 5- and 10-years with 85%, 65% and 56% were slightly lower in the older recipients compared to 87%, 75% and 66% of recipients ≤65 years. The major causes of death in the elderly were sepsis (n = 13) in the early postoperative period and de-novo cancer (n = 6), HCV/HCC recurrence (each n = 5) and cardiovascular complications (n = 4) in the late one. The incidence of de-novo cancers and cardiovascular diseases were significantly higher in the older age cohort. The percentage of reLTs did not differ between both groups (7.8% vs. 6.5%). Although overall survival was better for younger patients, this study shows that LT recipients older than 65 years have a favourable outcome after LT with a 5- and 10-year survival of 65% and 56% indicating that liver transplantation should be considered in patients older than 65 years. 813 RESULTS OF LIVER TRANSPLANTATION IN ADULT POLYCYSTIC LIVER DISEASE: REPORT OF A SINGLE CENTER EXPERIENCE A. Patris1 , E. Bonaccorsi-Riani2 , O. Ciccarelli2 , P. Goffette3 , Y. Pirson4 , J. Lerut2 , Z. Hassoun1 . 1 Division of Gastroenterology, 2 Abdominal Transplantation Unit, 3 Department of Radiology, 4 Division of Nephrology, Cliniques Universitaires Saint-Luc, Brussels, Belgium E-mail: [email protected] Introduction: Polycystic liver disease (PCLD) occurs either in an isolated form (Autosomal Dominant Polycystic Liver Disease [ADPLD]) or in association with Autosomal Dominant Polycystic Kidney Disease (ADPKD). It remains an uncommon and controversial indication for liver transplantation (LT). Objectives: 1. to assess the results of LT in patients with massive PCLD; 2. to determine whether previous hepatic surgery is associated with a higher rate of complications following LT; 3. to examine the evolution of renal function after LT in order to determine whether pre-emptive renal transplantation is justified in case of ADPKD without (pre-)terminal renal failure. Methods: We retrospectively reviewed the medical charts of 19 patients (15 females) who underwent LT for PCLD between 1999 and 2008. Fifteen patients had ADPKD (12 females). Three received a combined liver and kidney transplantation (LKT) for associated terminal (n = 1) or pre-terminal renal failure. Two patients had previous kidney transplantation (KT) and 7 had undergone hepatic surgery. Results: Median duration of follow-up is 30 months [5–112]. All patients are alive and relieved of their symptoms. Their median Karnofsky score is 90% [80–100]. Intervention tended to be longer (10:30 h vs. 7:20 h, p = 0.098) in the group who had previous surgery. There was no significant difference in intra-operative blood transfusion, severity of postoperative complications, length of ICU or hospital stay. Median pre-LT GFR of ADPLD and ADPKD patients (excluding those who underwent LKT or previous KT) is 89.5 ml/min/1.73m2 [69–114] and 69 ml/min/1.73m2 [33–120] respectively (p = 0.129).
Journal of Hepatology 2010 vol. 52 | S183–S317
S315
POSTERS Median GFR 1 year post-LT is 68 ml/min/1.73m2 [57–95] and 51 ml/min/1.73m2 [29–85] respectively (p = 0.089). Median decrease in GFR at one year post-LT is 17.5 ml/min/1.73m2 and 18 ml/min/1.73m2 respectively (p = 0.694). Conclusions: LT is an effective treatment for selected patients with massive PCLD. Prior conservative surgery tends to increase the length of the transplant operation. Renal function decreases at an identical rate after LT in ADPLD and ADPKD patients with pre-LT GFR >30 ml/min/1.73m2 . Thus, pre-emptive renal transplantation would not have been justified in the latter. 814 ATP-BINDING CASSETTE TRANSPORTER GENE POLYMORPHISMS AS INDEPENDENT PREDICTIVE FACTORS FOR SEVERE RECURRENT HEPATITIS C AFTER LIVER TRANSPLANTATION S. Iacob1,2,3 , V.R. Cicinnati1,2 , A. Dechene1 , C.G. Klein1,2 , I. Popescu3 , A. Paul2 , G. Gerken1 , S. Beckebaum1,2 . 1 Department of Gastroenterology and Hepatology, 2 Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany; 3 Fundeni Clinical Institute of Digestive Diseases and Liver Transplantation, Bucharest, Romania E-mail: [email protected] Background: Hepatitis C Virus (HCV) reinfection after liver transplantation (LT) has a critical influence on graft and patient survival. Hepatic insulin resistance increases expression of the ATPbinding cassette (ABC) transporter G8 implicated in the regulation of cholesterol metabolism as well as the severity of HCV infection. Expression of multidrug resistance (MDR)1 gene expression has been shown to be increased in activated hepatic stellate cells in chronic liver diseases. Aim: To assess predictive factors of severe HCV recurrence after LT. Methods: We genotyped ABCG8 (C1199A and C1895T) and MDR1 (C3435T) in 165 LT recipients (46 with recurrent hepatitis C after LT, 119 controls transplanted for other liver diseases) by PCR-restriction fragment length polymorphism assay. Uni- and multivariate logistic regression analyses were used to identify predictors of severe HCV recurrence following LT. Results: Analyses of single nucleotide polymorphisms (SNPs) revealed the following results: ABCG8 exon 8 C1199A (CC 69.1%, CA 29.7%, AA 1.2%), ABCG8 exon 13 C1895T (CC 46.1%, CT 44.2%, TT 9.7%), and MDR1 exon 26 C3435T (CC 22.4%, CT 40%, TT 37.6%). In the univariate analysis ABCG8 C1199C (p = 0.006), MDR1 T3435T (p = 0.03), presence of type 2 diabetes mellitus (p = 0.01), acute rejection episodes (p = 0.002), cytomegalovirus infection (p = 0.005), lower cholinesterase (p = 0.0003), higher direct bilirubin (p = 0.03) and aspartate aminotransferase (p = 0.01) were identified as predictors of severe HCV recurrence. Independent predictors of severe HCV recurrence included ABCG8 C1199C (p = 0.01), MDR1 T3435T (p = 0.03), and presence of type 2 diabetes mellitus (p = 0.03). Conclusions: HCV LT recipients with ABCG8 and MDR1 polymorphisms have a significantly higher prevalence of advanced fibrosis. Active screening of these mutations may help to predict and to manage severe HCV recurrence in LT recipients. 815 A PILOT STUDY: SORAFENIB IN PATIENTS WITH POST LIVER TRANSPLANT RECURRENCE OF HCC M. Lu, Y. Chen, C. Cai, X. Yi, G. Chen. The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China E-mail: [email protected] This study aims to evaluate efficacy, tolerability and mechanism of sorafenib monotherapy in patients with recurrence after liver transplantation. Twenty-three patients with hepatocellular carcinoma recurrence after liver transplantation treated with S316
sorafenib monotherapy (400 mg Bid) were defined as sorafenib group and twenty-four patients with similar characteristics who received best support care were defined as the control group. Responses of the recurrent lesions were measured by RECIST criteria using CT or MRI scans. Time to progression (TTP) and overall survival (OS) were analyzed by Kaplan Meier survival functions. Tissue VEGF levels, serum VEGF levels, FK506 concentrations in relation to sorafenib therapy, rejection reactions and adverse reactions were also measured. At the end of April 2009, there were 15 deaths in the sorafenib group and 21 deaths in the control group. The median OS of the sorafenib group was significantly longer than the control group. Radiologically confirmed time to disease progress of sorafenib group was 7.0 months. After six months of treatment, 15 patients showed stable disease (SD) in sorafenib group, and median SD duration was 9.5 months. Positive ratio of VEGF staining of the two groups was not significantly different. In the sorafenib group, VEGF expression before treatment was 123.05±34.02 pg/ml and increased to 220.22±67.14 pg/ml after 4 weeks treatment (P0.05). The blood FK506 concentration of sorafenib group was 6.87±2.64 ng/ml before treatment and increased to 9.0±2.4 ng/ml after treatment (P < 0.01). The incidence of hand-foot skin response, alopecia, hypertension and diarrhea were significantly higher in the sorafenib group compared to the control group. Other adverse events showed no significant difference in two groups. 816 DUCTULAR REACTION IN HEPATITIS C RECURRENCE POST LIVER TRANSPLANTATION E. Prakoso1,2 , J. Kench3 , A. Clouston4 , D. Bowen1,2 , G. McCaughan1,2 , N. Shackel1,2 . 1 Liver Immunobiology Laboratory, Centenary Institute Sydney, 2 AW Morrow Gastroenterology & Liver Centre, 3 Dept. of Anatomical Pathology, Royal Prince Alfred Hospital Sydney, Camperdown, NSW, 4 Envoi Pathology, Brisbane, QLD, Australia E-mail: [email protected] Background and Aims: The ductular reaction (DR) is a cellular reaction of ductular phenotype, occurring in association with liver injury and fibrosis. The appearance of DR in the setting of hepatocellular or cholangiocyte injury suggests there are regenerating hepatic progenitor cells (HPCs). In patients with HCV recurrence post-liver transplantation (LTx), the pathogenesis of progressive fibrosis is unclear and the role of DR in this setting is unknown. We aimed to characterise DR, HPC, replicative arrest and intrahepatic proliferation in patients with HCV recurrence post-LTx and to correlate these changes with liver fibrosis and steatosis. Methods: Immunohistochemistry was performed on liver biopsy specimens taken from patients with HCV recurrence post-LTx. Donor livers (n = 15) were used as controls. Image analysis was used to quantify DR (ck7) and a-SMA (activated stellate cells and myofibroblasts). HPC was calculated by counting isolated ck7positive cells in the periportal area. Hepatocellular proliferation and replicative arrest were assessed by counting Ki-67 and p21-positive hepatocyte nuclei respectively. Fibrosis was staged (F0–4) according to Scheuer’s score. Results: There were 105 patients with 194 liver biopsy specimens. DR, HPC, a-SMA, replicative arrest, proliferative index and replicative arrest ratio were higher in HCV recurrence patients vs control donors (p ≤ 0.020). There was a significant positive correlation between DR and HPC (r s = 0.629, p < 0.001). Further, there were also significant positive correlations between DR and HPC with a-SMA, fibrosis, portal and total Scheuer’s scores (p < 0.001). DR also positively correlated to proliferative index (p < 0.001). Steatosis (p = 0.018) and lobular score (p = 0.003) only correlated to HPC but not to DR. DR plateaud and HPC peaked at F3 fibrosis. Conclusions: The DR and HPC responses post-LTx correlate with the extent of fibrosis in early stage liver injury. The lack of a correlation in the latter stages of injury is probably related to the diminished
Journal of Hepatology 2010 vol. 52 | S183–S317
Between 1982 and 2008, 106 out of 1011 patients (10.5%), who underwent LT at our institution, were older than 65 years. Almost all of these patients were transplanted after 1995. The mean age was 67.5 (65.0–76.4) years and the majority of patients were male (76%). Regarding underlying liver disease the percentage of non-alcoholic steatohepatitis associated cirrhosis was significantly higher in the older age group (15.9% vs. 5.8%, p < 0.01) compared to the younger LT cohort. In contrast, alcoholic liver disease was more common in recipients under 65 years (20.4% vs. 14.1%, p < 0.01). Significantly more patients in the older group presented with a concomitant hepatocellular carcinoma (40.6% vs. 23.7%, p < 0.01). Both groups did not differ with regard to Child–Pugh classification and mean MELD score. The median follow-up of the older patients was 3.2 compared to 5.7 years of the younger cohort. The actuarial patient survival rates at 1-, 5- and 10-years with 85%, 65% and 56% were slightly lower in the older recipients compared to 87%, 75% and 66% of recipients ≤65 years. The major causes of death in the elderly were sepsis (n = 13) in the early postoperative period and de-novo cancer (n = 6), HCV/HCC recurrence (each n = 5) and cardiovascular complications (n = 4) in the late one. The incidence of de-novo cancers and cardiovascular diseases were significantly higher in the older age cohort. The percentage of reLTs did not differ between both groups (7.8% vs. 6.5%). Although overall survival was better for younger patients, this study shows that LT recipients older than 65 years have a favourable outcome after LT with a 5- and 10-year survival of 65% and 56% indicating that liver transplantation should be considered in patients older than 65 years. 813 RESULTS OF LIVER TRANSPLANTATION IN ADULT POLYCYSTIC LIVER DISEASE: REPORT OF A SINGLE CENTER EXPERIENCE A. Patris1 , E. Bonaccorsi-Riani2 , O. Ciccarelli2 , P. Goffette3 , Y. Pirson4 , J. Lerut2 , Z. Hassoun1 . 1 Division of Gastroenterology, 2 Abdominal Transplantation Unit, 3 Department of Radiology, 4 Division of Nephrology, Cliniques Universitaires Saint-Luc, Brussels, Belgium E-mail: [email protected] Introduction: Polycystic liver disease (PCLD) occurs either in an isolated form (Autosomal Dominant Polycystic Liver Disease [ADPLD]) or in association with Autosomal Dominant Polycystic Kidney Disease (ADPKD). It remains an uncommon and controversial indication for liver transplantation (LT). Objectives: 1. to assess the results of LT in patients with massive PCLD; 2. to determine whether previous hepatic surgery is associated with a higher rate of complications following LT; 3. to examine the evolution of renal function after LT in order to determine whether pre-emptive renal transplantation is justified in case of ADPKD without (pre-)terminal renal failure. Methods: We retrospectively reviewed the medical charts of 19 patients (15 females) who underwent LT for PCLD between 1999 and 2008. Fifteen patients had ADPKD (12 females). Three received a combined liver and kidney transplantation (LKT) for associated terminal (n = 1) or pre-terminal renal failure. Two patients had previous kidney transplantation (KT) and 7 had undergone hepatic surgery. Results: Median duration of follow-up is 30 months [5–112]. All patients are alive and relieved of their symptoms. Their median Karnofsky score is 90% [80–100]. Intervention tended to be longer (10:30 h vs. 7:20 h, p = 0.098) in the group who had previous surgery. There was no significant difference in intra-operative blood transfusion, severity of postoperative complications, length of ICU or hospital stay. Median pre-LT GFR of ADPLD and ADPKD patients (excluding those who underwent LKT or previous KT) is 89.5 ml/min/1.73m2 [69–114] and 69 ml/min/1.73m2 [33–120] respectively (p = 0.129).
Journal of Hepatology 2010 vol. 52 | S183–S317
S315
POSTERS Median GFR 1 year post-LT is 68 ml/min/1.73m2 [57–95] and 51 ml/min/1.73m2 [29–85] respectively (p = 0.089). Median decrease in GFR at one year post-LT is 17.5 ml/min/1.73m2 and 18 ml/min/1.73m2 respectively (p = 0.694). Conclusions: LT is an effective treatment for selected patients with massive PCLD. Prior conservative surgery tends to increase the length of the transplant operation. Renal function decreases at an identical rate after LT in ADPLD and ADPKD patients with pre-LT GFR >30 ml/min/1.73m2 . Thus, pre-emptive renal transplantation would not have been justified in the latter. 814 ATP-BINDING CASSETTE TRANSPORTER GENE POLYMORPHISMS AS INDEPENDENT PREDICTIVE FACTORS FOR SEVERE RECURRENT HEPATITIS C AFTER LIVER TRANSPLANTATION S. Iacob1,2,3 , V.R. Cicinnati1,2 , A. Dechene1 , C.G. Klein1,2 , I. Popescu3 , A. Paul2 , G. Gerken1 , S. Beckebaum1,2 . 1 Department of Gastroenterology and Hepatology, 2 Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany; 3 Fundeni Clinical Institute of Digestive Diseases and Liver Transplantation, Bucharest, Romania E-mail: [email protected] Background: Hepatitis C Virus (HCV) reinfection after liver transplantation (LT) has a critical influence on graft and patient survival. Hepatic insulin resistance increases expression of the ATPbinding cassette (ABC) transporter G8 implicated in the regulation of cholesterol metabolism as well as the severity of HCV infection. Expression of multidrug resistance (MDR)1 gene expression has been shown to be increased in activated hepatic stellate cells in chronic liver diseases. Aim: To assess predictive factors of severe HCV recurrence after LT. Methods: We genotyped ABCG8 (C1199A and C1895T) and MDR1 (C3435T) in 165 LT recipients (46 with recurrent hepatitis C after LT, 119 controls transplanted for other liver diseases) by PCR-restriction fragment length polymorphism assay. Uni- and multivariate logistic regression analyses were used to identify predictors of severe HCV recurrence following LT. Results: Analyses of single nucleotide polymorphisms (SNPs) revealed the following results: ABCG8 exon 8 C1199A (CC 69.1%, CA 29.7%, AA 1.2%), ABCG8 exon 13 C1895T (CC 46.1%, CT 44.2%, TT 9.7%), and MDR1 exon 26 C3435T (CC 22.4%, CT 40%, TT 37.6%). In the univariate analysis ABCG8 C1199C (p = 0.006), MDR1 T3435T (p = 0.03), presence of type 2 diabetes mellitus (p = 0.01), acute rejection episodes (p = 0.002), cytomegalovirus infection (p = 0.005), lower cholinesterase (p = 0.0003), higher direct bilirubin (p = 0.03) and aspartate aminotransferase (p = 0.01) were identified as predictors of severe HCV recurrence. Independent predictors of severe HCV recurrence included ABCG8 C1199C (p = 0.01), MDR1 T3435T (p = 0.03), and presence of type 2 diabetes mellitus (p = 0.03). Conclusions: HCV LT recipients with ABCG8 and MDR1 polymorphisms have a significantly higher prevalence of advanced fibrosis. Active screening of these mutations may help to predict and to manage severe HCV recurrence in LT recipients. 815 A PILOT STUDY: SORAFENIB IN PATIENTS WITH POST LIVER TRANSPLANT RECURRENCE OF HCC M. Lu, Y. Chen, C. Cai, X. Yi, G. Chen. The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China E-mail: [email protected] This study aims to evaluate efficacy, tolerability and mechanism of sorafenib monotherapy in patients with recurrence after liver transplantation. Twenty-three patients with hepatocellular carcinoma recurrence after liver transplantation treated with S316
sorafenib monotherapy (400 mg Bid) were defined as sorafenib group and twenty-four patients with similar characteristics who received best support care were defined as the control group. Responses of the recurrent lesions were measured by RECIST criteria using CT or MRI scans. Time to progression (TTP) and overall survival (OS) were analyzed by Kaplan Meier survival functions. Tissue VEGF levels, serum VEGF levels, FK506 concentrations in relation to sorafenib therapy, rejection reactions and adverse reactions were also measured. At the end of April 2009, there were 15 deaths in the sorafenib group and 21 deaths in the control group. The median OS of the sorafenib group was significantly longer than the control group. Radiologically confirmed time to disease progress of sorafenib group was 7.0 months. After six months of treatment, 15 patients showed stable disease (SD) in sorafenib group, and median SD duration was 9.5 months. Positive ratio of VEGF staining of the two groups was not significantly different. In the sorafenib group, VEGF expression before treatment was 123.05±34.02 pg/ml and increased to 220.22±67.14 pg/ml after 4 weeks treatment (P0.05). The blood FK506 concentration of sorafenib group was 6.87±2.64 ng/ml before treatment and increased to 9.0±2.4 ng/ml after treatment (P < 0.01). The incidence of hand-foot skin response, alopecia, hypertension and diarrhea were significantly higher in the sorafenib group compared to the control group. Other adverse events showed no significant difference in two groups. 816 DUCTULAR REACTION IN HEPATITIS C RECURRENCE POST LIVER TRANSPLANTATION E. Prakoso1,2 , J. Kench3 , A. Clouston4 , D. Bowen1,2 , G. McCaughan1,2 , N. Shackel1,2 . 1 Liver Immunobiology Laboratory, Centenary Institute Sydney, 2 AW Morrow Gastroenterology & Liver Centre, 3 Dept. of Anatomical Pathology, Royal Prince Alfred Hospital Sydney, Camperdown, NSW, 4 Envoi Pathology, Brisbane, QLD, Australia E-mail: [email protected] Background and Aims: The ductular reaction (DR) is a cellular reaction of ductular phenotype, occurring in association with liver injury and fibrosis. The appearance of DR in the setting of hepatocellular or cholangiocyte injury suggests there are regenerating hepatic progenitor cells (HPCs). In patients with HCV recurrence post-liver transplantation (LTx), the pathogenesis of progressive fibrosis is unclear and the role of DR in this setting is unknown. We aimed to characterise DR, HPC, replicative arrest and intrahepatic proliferation in patients with HCV recurrence post-LTx and to correlate these changes with liver fibrosis and steatosis. Methods: Immunohistochemistry was performed on liver biopsy specimens taken from patients with HCV recurrence post-LTx. Donor livers (n = 15) were used as controls. Image analysis was used to quantify DR (ck7) and a-SMA (activated stellate cells and myofibroblasts). HPC was calculated by counting isolated ck7positive cells in the periportal area. Hepatocellular proliferation and replicative arrest were assessed by counting Ki-67 and p21-positive hepatocyte nuclei respectively. Fibrosis was staged (F0–4) according to Scheuer’s score. Results: There were 105 patients with 194 liver biopsy specimens. DR, HPC, a-SMA, replicative arrest, proliferative index and replicative arrest ratio were higher in HCV recurrence patients vs control donors (p ≤ 0.020). There was a significant positive correlation between DR and HPC (r s = 0.629, p < 0.001). Further, there were also significant positive correlations between DR and HPC with a-SMA, fibrosis, portal and total Scheuer’s scores (p < 0.001). DR also positively correlated to proliferative index (p < 0.001). Steatosis (p = 0.018) and lobular score (p = 0.003) only correlated to HPC but not to DR. DR plateaud and HPC peaked at F3 fibrosis. Conclusions: The DR and HPC responses post-LTx correlate with the extent of fibrosis in early stage liver injury. The lack of a correlation in the latter stages of injury is probably related to the diminished
Journal of Hepatology 2010 vol. 52 | S183–S317