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Non virological factors associated with fibrosis progression after hepatitis C virus (HCV) graft reinfection
36
Poster Sessions
from sepsis. Occurence of the hilar strictures was not related to prolonged cold ischemia time, acute rejection or CMV-related disease. Twenty-four patients with a narrowed choledoco-choledocal anastomosis (16 over a T-tube) were drained by plastic stents. The stricture was associated with a bile leak in 8 patients. In 13 patients, after 9 to 12 months of stenting (2 to 4 stents placed in the same session, replaced every 3 months), the stenosis resolved. Two patients are doing well with their stents in place for less than 1 year. If, despite stenting, the stricture was still present 12 months after the first insertion of stent(s), endoscopic treatment was considered as a failure; it occurred in 7 patients who were subsequently surgically managed. In 2 cases, the stent caused a perforation of the hepatic artery at the hilum, with massive bleeding; 1 patient died, the other one was retransplanted. MRC performed in the last 32 patients with hilar or anastomotic strictures gave a correct image of the biliary tree in all of them. Conclusion: biliary complications after LT can usually be managed endoscopically (success rate 53% for hilar strictures and 60% for anastomotic strictures). Surgery may be a second step procedure after endoscopic failure. Endoscopy-related severe complications occurred in 2/53 patients (1 death). MRC enables detection of biliary abnormalities in 100% of the cases.
Aim: to evaluate whether liver cell proliferation might predict disease progression in HCV recurrence. Materials and methods: 46 liver biopsies from 14 men, transplanted at KCH, London for HCV+ cirrhosis were studied. All were HCV-RNA+, 86% with abnormal ALT. A mean of 3 liver biopsies for each patient were performed. Grading and staging was scored by Ishak. A progression of chronic hepatitis was classified as >2 increase of staging. PCNA (proliferating cell nuclear antigen) was localized by immunoperoxidase. PCNA labelling index (PCNA-LI) was performed by image analysis as ratio between strong positive and total nuclei. Results: Median baseline PCNA-LI was 1.4. 7 patients had baseline PCNA-LI > 1.4 (group 1) and 7 patients PCNA-LI < 1.4 (group 2). The grading was higher in patients with PCNA > 1.4 compared to those with PCNA < 1.4 (7.9 + 2.2 vs 5.6 + 1.8, p < 0.01). Staging was similar in the two groups (1.4 + 0.5 vs 1.0 + 0, p = NS). All group 1 patients and 5/7 of group 2 showed fibrosis progression. Fibrosis progressed more rapidly in patients with higher PCNA respect to those with lower PCNA (10.6 + 8.8 vs 50.0 + 31.1 months, p < 0.01). Cirrhosis developed in 71% of group 1 patients and none of group 2 within 4 years (p < 0.01). Conclusions: High PCNA-LI during HCV recurrence predicts the risk of developing early fibrosis/cirrhosis after transplantation.
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LEVEL OF REPLICATION AND GENOTYPES OF HEPATITIS A VIRUS IN FULMINANT AND NON-FULMINANT HEPATITIS
Guillermo Rezende I , Anne Marie Roque-Afonso 2, Elisabeth Dussaix 2, Didier Samuel1, Michele Gigou 1, Cvrille Fera¥ 1.1Centre
Hepato-Biliaire, Hopital Paul Brousse, Wtllejuif"2Virologie, Hopital Paul Brousse, Villejuif France Fulminant hepatitis is a rare and severe complication of acute hepatitis A virus infection. Liver transplantation can be necessary, but spontaneous recovery is frequent. There are no data on the level of viral replication according to the clinical form of hepatitis A. Patients and Methods: We reviewed the files of 50 patients with acute hepatitis A diagnosed on the basis of anti-HAV IgM positivity. Nineteen patients had fulminant hepatitis (defined by encephalopathy and factor V < 50%), 10 were transplanted because of deep coma and a factor V level below 30%, and one died before transplantation. HAV RNA was quantified by real-time PCR on stored admission serum samples. The HAV genotype was determined by direct sequencing of amplified HAV RNA coding for VP1/2A. Results: HAV RNA was detected in serum by RT-PCR in 39/50 patients. Mean viral load was 3.9 log (4-1.15, range 0.69-6.39). In univariate analysis, encephalopathy and the factor V level were related to female gender, HAV PCR negativity, low serum HAV RNA levels, genotypes other than Ia, and acetaminophen exposure. In multivariate analysis, low or undetectable HAV viral load and a high hilirubin level were independently associated with both low factor V levels and fulminant hepatitis, and also with death or transplantation. Conelusion: The low viral replication observed during fulminant hepatitis A suggests that liver failure in this setting is principally due to an excessive immune response. HAV viral load might thus serve as a decision aid for liver transplantation.
NON VIROLOGICAL FACTORS ASSOCIATED WITH FIBROSIS PROGRESSION AFTER HEPATITIS C VIRUS (HCV) GRAFT REINFECTION
Didier Mennecier 1, Francoise Roudot-Thoraval 2, Georges Philippe Pageaux 3, Filomena Conti 4, Daniel Dhumeaux I , Christophe Duvoux i. 1Liver Transplant Unit, Henri Mondor Hospital
Creteil; 2Department of Biostatistics, Henri Mondor Hospital Creteil; 3Liver Transplant Unit, Saint Eloi Hospital, Montpellier; 4Liver Transplant Unit, Cochin Hospital, Paris, France Following liver transplantation for C cirrhosis, the severity of HCV recurrence varies from one patient to another. The aim of this study was to identify the non virological factors linked to the rate of fibrosis progression (RFP) on the graft. Patients and Methods: 96 patients presenting with HCV graft reinfection were retrospectively studied (men 72, women 24, age: 51.4 + 8.5 years). RFP was calculated by dividing the fibrosis score F on the last liver biopsy specimen with the duration of follow-up. 41 parameters were analysed. The threshold of 0.4 (median RFP/year of the study population) was chosen to discriminate low and high RFP. Results: The median follow-up was 51 months (ext: 12-110). 48 patients (50%) had RFP > 0.4. By univariate analysis, factors associated with a high RFP included recent transplantation (1997-1999), the use of tacrolimus, the absence of treatment for hypertension, ALT and GGT activities at the time of the last liver biopsy. By multivariate analysis, tacrolimus (p = 0.001, RR: 5.8, 95% CI: 1.9-17.8) and ALT activity (p = 0.05, RR: 5.73, 95% CI: 2.10-15.7) were independent predictors of a high RFP. The use of antihypertensive drugs was associated with a low RFP (p = 0.03, RR: 0.32, 95% CI: 0.02-0.90). Conclusion: These results suggest that new factors, such as tacrolimus and anti-hypertensive treatment, could potentially be linked to fibrosis progression in post-transplant recurrent HCV infection. These parameters could easily be taken into account to limit the consequences of HCV recurrence.
['-~-] LIVER CELL PROLIFERATION AND SEVERITY OF HEPATITIS C RECURRENCE AFTER LIVER TRANSPLANT Maria Francesca Donato 1, Francesca Agnelli 1, Eliana Arosio 1, Valentina Monti 1, Mafia Rita Balestrieri 1, Paolo Rizzi 2, Massimo Colombo I . 1Division of Hepatology, IRCCS Maggiore Hospital,
Milan, Italy; 21nstitute of Liver Studies, King's College Hospital, London, UK Histological predictors of hepatitis C progression after liver transplantation are debated.
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GENETIC EVOLUTION OF HEPATITIS C VIRUS AFTER LIVER TRANSPLANTATION
Anna Feliu, Xavier Forns, Montserrat Garcia-Retortillo, Eduardo Moitinho, Juan Rod6s. Liver Unit, IMD, Hospital Clinic,
Barcelona, Spain In patients with HCV-related cirrhosis undergoing liver transplantation (LT) recurrence of HCV infection is universal. The implantation of a new
Poster Sessions
from sepsis. Occurence of the hilar strictures was not related to prolonged cold ischemia time, acute rejection or CMV-related disease. Twenty-four patients with a narrowed choledoco-choledocal anastomosis (16 over a T-tube) were drained by plastic stents. The stricture was associated with a bile leak in 8 patients. In 13 patients, after 9 to 12 months of stenting (2 to 4 stents placed in the same session, replaced every 3 months), the stenosis resolved. Two patients are doing well with their stents in place for less than 1 year. If, despite stenting, the stricture was still present 12 months after the first insertion of stent(s), endoscopic treatment was considered as a failure; it occurred in 7 patients who were subsequently surgically managed. In 2 cases, the stent caused a perforation of the hepatic artery at the hilum, with massive bleeding; 1 patient died, the other one was retransplanted. MRC performed in the last 32 patients with hilar or anastomotic strictures gave a correct image of the biliary tree in all of them. Conclusion: biliary complications after LT can usually be managed endoscopically (success rate 53% for hilar strictures and 60% for anastomotic strictures). Surgery may be a second step procedure after endoscopic failure. Endoscopy-related severe complications occurred in 2/53 patients (1 death). MRC enables detection of biliary abnormalities in 100% of the cases.
Aim: to evaluate whether liver cell proliferation might predict disease progression in HCV recurrence. Materials and methods: 46 liver biopsies from 14 men, transplanted at KCH, London for HCV+ cirrhosis were studied. All were HCV-RNA+, 86% with abnormal ALT. A mean of 3 liver biopsies for each patient were performed. Grading and staging was scored by Ishak. A progression of chronic hepatitis was classified as >2 increase of staging. PCNA (proliferating cell nuclear antigen) was localized by immunoperoxidase. PCNA labelling index (PCNA-LI) was performed by image analysis as ratio between strong positive and total nuclei. Results: Median baseline PCNA-LI was 1.4. 7 patients had baseline PCNA-LI > 1.4 (group 1) and 7 patients PCNA-LI < 1.4 (group 2). The grading was higher in patients with PCNA > 1.4 compared to those with PCNA < 1.4 (7.9 + 2.2 vs 5.6 + 1.8, p < 0.01). Staging was similar in the two groups (1.4 + 0.5 vs 1.0 + 0, p = NS). All group 1 patients and 5/7 of group 2 showed fibrosis progression. Fibrosis progressed more rapidly in patients with higher PCNA respect to those with lower PCNA (10.6 + 8.8 vs 50.0 + 31.1 months, p < 0.01). Cirrhosis developed in 71% of group 1 patients and none of group 2 within 4 years (p < 0.01). Conclusions: High PCNA-LI during HCV recurrence predicts the risk of developing early fibrosis/cirrhosis after transplantation.
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LEVEL OF REPLICATION AND GENOTYPES OF HEPATITIS A VIRUS IN FULMINANT AND NON-FULMINANT HEPATITIS
Guillermo Rezende I , Anne Marie Roque-Afonso 2, Elisabeth Dussaix 2, Didier Samuel1, Michele Gigou 1, Cvrille Fera¥ 1.1Centre
Hepato-Biliaire, Hopital Paul Brousse, Wtllejuif"2Virologie, Hopital Paul Brousse, Villejuif France Fulminant hepatitis is a rare and severe complication of acute hepatitis A virus infection. Liver transplantation can be necessary, but spontaneous recovery is frequent. There are no data on the level of viral replication according to the clinical form of hepatitis A. Patients and Methods: We reviewed the files of 50 patients with acute hepatitis A diagnosed on the basis of anti-HAV IgM positivity. Nineteen patients had fulminant hepatitis (defined by encephalopathy and factor V < 50%), 10 were transplanted because of deep coma and a factor V level below 30%, and one died before transplantation. HAV RNA was quantified by real-time PCR on stored admission serum samples. The HAV genotype was determined by direct sequencing of amplified HAV RNA coding for VP1/2A. Results: HAV RNA was detected in serum by RT-PCR in 39/50 patients. Mean viral load was 3.9 log (4-1.15, range 0.69-6.39). In univariate analysis, encephalopathy and the factor V level were related to female gender, HAV PCR negativity, low serum HAV RNA levels, genotypes other than Ia, and acetaminophen exposure. In multivariate analysis, low or undetectable HAV viral load and a high hilirubin level were independently associated with both low factor V levels and fulminant hepatitis, and also with death or transplantation. Conelusion: The low viral replication observed during fulminant hepatitis A suggests that liver failure in this setting is principally due to an excessive immune response. HAV viral load might thus serve as a decision aid for liver transplantation.
NON VIROLOGICAL FACTORS ASSOCIATED WITH FIBROSIS PROGRESSION AFTER HEPATITIS C VIRUS (HCV) GRAFT REINFECTION
Didier Mennecier 1, Francoise Roudot-Thoraval 2, Georges Philippe Pageaux 3, Filomena Conti 4, Daniel Dhumeaux I , Christophe Duvoux i. 1Liver Transplant Unit, Henri Mondor Hospital
Creteil; 2Department of Biostatistics, Henri Mondor Hospital Creteil; 3Liver Transplant Unit, Saint Eloi Hospital, Montpellier; 4Liver Transplant Unit, Cochin Hospital, Paris, France Following liver transplantation for C cirrhosis, the severity of HCV recurrence varies from one patient to another. The aim of this study was to identify the non virological factors linked to the rate of fibrosis progression (RFP) on the graft. Patients and Methods: 96 patients presenting with HCV graft reinfection were retrospectively studied (men 72, women 24, age: 51.4 + 8.5 years). RFP was calculated by dividing the fibrosis score F on the last liver biopsy specimen with the duration of follow-up. 41 parameters were analysed. The threshold of 0.4 (median RFP/year of the study population) was chosen to discriminate low and high RFP. Results: The median follow-up was 51 months (ext: 12-110). 48 patients (50%) had RFP > 0.4. By univariate analysis, factors associated with a high RFP included recent transplantation (1997-1999), the use of tacrolimus, the absence of treatment for hypertension, ALT and GGT activities at the time of the last liver biopsy. By multivariate analysis, tacrolimus (p = 0.001, RR: 5.8, 95% CI: 1.9-17.8) and ALT activity (p = 0.05, RR: 5.73, 95% CI: 2.10-15.7) were independent predictors of a high RFP. The use of antihypertensive drugs was associated with a low RFP (p = 0.03, RR: 0.32, 95% CI: 0.02-0.90). Conclusion: These results suggest that new factors, such as tacrolimus and anti-hypertensive treatment, could potentially be linked to fibrosis progression in post-transplant recurrent HCV infection. These parameters could easily be taken into account to limit the consequences of HCV recurrence.
['-~-] LIVER CELL PROLIFERATION AND SEVERITY OF HEPATITIS C RECURRENCE AFTER LIVER TRANSPLANT Maria Francesca Donato 1, Francesca Agnelli 1, Eliana Arosio 1, Valentina Monti 1, Mafia Rita Balestrieri 1, Paolo Rizzi 2, Massimo Colombo I . 1Division of Hepatology, IRCCS Maggiore Hospital,
Milan, Italy; 21nstitute of Liver Studies, King's College Hospital, London, UK Histological predictors of hepatitis C progression after liver transplantation are debated.
~-]
GENETIC EVOLUTION OF HEPATITIS C VIRUS AFTER LIVER TRANSPLANTATION
Anna Feliu, Xavier Forns, Montserrat Garcia-Retortillo, Eduardo Moitinho, Juan Rod6s. Liver Unit, IMD, Hospital Clinic,
Barcelona, Spain In patients with HCV-related cirrhosis undergoing liver transplantation (LT) recurrence of HCV infection is universal. The implantation of a new