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461 Apolipoprotein E polymorphism may protect from hepatitis C virus (HCV) infection
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Poster Sessions
(6.8% ± 0.73%) than in non-responders (13.4% ± 1.3%). Fifty four patients had an HCV-RNA concentration in serum <800000 IU/ml and of them 21 (38.8%) were responders and 33 (61.2%) non-responders. On the other hand, thirty three patients had <5% of infected hepatocytes and of them 19 (57.6%) were responders and 14 (42.4%) non-responders. In a logistic regression analysis considering gender, ALT, necroimflammatory activity, fibrosis score etc, the only independent factors associated with the response were the percentage of infected hepatocytes (p= 0.0005; OR: 2.1825; 95% CI: 1.4079-3.3833) and age (p= 0.013; OR; 1.0643; 95% CI: 1.0134-1.1178) but not the serum HCV-RNA concentration. In conclusion, the percentage of infected hepatocytes in the pretreatment liver biopsy is a better predictive factor of response than the serum HCV-RNA concentration.
of treated and 19.5% of untreated developed ascites, 3.8% of treated and 5.6% of untreated had variceal bleeding, 1.1% of treated and 3.1% of untreated developed portal-systemic encephalopathy and 11.9% of treated and 20.9% of untreated patients dead from liver-related causes. By the Kaplan-Meier method and the log-rank test IFN treated patients showed a significantly lower incidence of HCC (p = 0.028), of ascites (p = 0.020), and of liver-related death (p = 0.003). No significant difference was observed on varices appearance of worsening, variceal bleeding and portal-systemic encephalopathy occurrence. Our results indicate that one or more courses of IFN therapy may delay HCC development and improve survival in patients with compensated HCV-cirrhosis, while seem to have a trivial effect on portal hypertension-related complications.
461 APOLIPOPROTEIN E POLYMORPHISM MAY PROTECT FROM 459 CORRELATION BETWEEN LIVER ELASTICITY MEASURED BY TRANSIENT ELASTOGRAPHY AND LIVER FIBROSIS ASSESSED BY MORPHOMETRY IN PATIENTS WITH HCV CHRONIC HEPATITIS
M. Ziol 1,2 , N. Barget 3 , L. Sandrin 4 , C. Fournier 4 , F. Mal 3 , F. Kazemi 3 , A. Kettaneh 5 , M. Beaugrand 3 . 1 EA 3406, Univertisy Paris 13, Paris, France; 2 Pathologie Department, Hopital Jean Verdier, Bondy, France; 3 Liver Unit, Hopital Jean Verdier, Bondy, France; 4 Echosens, Paris, France; 5 Internal Medicine Department, Hopital JeanVerdier, Bondy Liver fibrosis (LF) evaluation by non-invasive techniques is a major challenge. FibroScan a new non-invasive system based on transient elastography measures liver elasticity. A previous prospective study in 220 patients with chronic hepatitis showed that liver elasticity could be used to predict fibrosis stage (FS) assessed by Metavir scoring system. This prospective study was designed to further study the correlation between liver elasticity and fibrosis in 69 patients with chronic HCV hepatitis using fibrosis area fraction (FAF) measured on liver biopsies. All patients had a liver biopsy providing a large sample suitable for morphometric analysis and a liver elasticity measurement within less than 4 months. FS was evaluated by Metavir score and FAF by quantitative image analysis of 5 micrometers thick picro-sirius stained sections. The FAF was assessed using interactive thresholding of greyscale converted digital image of 10 to 20 consecutive fields (x 200) for each liver biopsy. Within the studied population (20 F1, 21 F2, 5 F3 and 23 F4 patients), FAF was 6.3 ± 6.2 (range 0.3 - 28.8) and highly correlated to FS (Spearman correlation r = 0.66, p < 0.0001). The correlation coefficients were r = 0.65 and r = 0.74 (both p < 0.0001) between liver elasticity and FAF or FS, respectively. Liver elasticity accurately reflects hepatic fibrosis area in patients with chronic HCV hepatitis and thus appears to be a reliable non-invasive tool to measure liver fibrosis.
460 INTERFERON (IFN) THERAPY HAS LITTLE EFFECT ON PROGRESSION OF PORTAL HYPERTENSION IN HEPATITIS C VIRUS (HCV) RELATED CIRRHOSIS
L. Benvegnu, F. Pasin, M. Gios, A. Ferrari, A. Alberti. Dpt. of Clinical and Experimental Medicine - University of Padova, Padova, Italy The effect of IFN therapy on complications of HCV-related cirrhosis is not fully understood. There are data indicating that hepatocellular carcinoma (HCC) might be prevented or delayed, while much less clear is the effect on portal hypertension and esophageal varices. We have conducted a longterm follow-up study of 380 consecutive patients with compensated HCVrelated cirrhosis. 185 patients were treated with one or more courses of IFN therapy, while 195 remained untreated. All patients were followed-up with periodical (every 6 months) evaluation and abdominal ultrasound and with periodical (every 12-24 months) esophagogastroduodenoscopy. During a mean follow-up period of 88.8 ± 42.0 months, 15.1% of IFN treated and 22.6% of untreated patients developed HCC, 19.8% of treated and 24.8% of untreated showed esophageal varices appearance or worsening, 11.9%
HEPATITIS C VIRUS (HCV) INFECTION
T. Mueller 1 , R. Gessner 2 , C. Sarrazin 3 , J. Halangk 4 , A. Bergk 1 , F. van Boemmel 1 , B. Wiedenmann 1 , U. Hopf 1 , T. Berg 1 . 1 Medizinische Klinik Mit Schwerpunkt Hepatologie Und Gastroenterologie, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany; 2 Institut Fuer Klinische Chemie Und Biochemie, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany; 3 Klinik Und Poliklinik Fuer Innere Medizin II, Universitaetskliniken Des Saarlandes, Homburg, Saar, Germany; 4 Klinik Fuer Paediatrie, Charité - Universitaetsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany Background: Low-density lipoprotein-receptors (LDL-R) are likely to mediate the hepatocellular uptake of HCV-virions complexed with plasma lipoproteins. Polymorphism within the gene encoding apolipoprotein E (apoE), a major structural compound of lipoproteins and natural ligand of LDL-R, may influence this crucial step of HCV-infection. In this study we determined the apoE-polymorphism in chronically HCV-infected patients compared to patients with non-HCV associated chronic liver disease and healthy controls. Subjects and methods: We genotyped 701 chronically HCV-infected patients, 283 individuals with non-HCV associated liver disease and 523 healthy controls. ApoE genotyping (ApoE2, E3, E4) was performed by PCR and RFLP analysis. Inflammation (grade) and fibrosis (stage) of 563 liver biopsies from chronic HCV-carriers were classified according to the Scheuer score. Degree of liver steatosis was separately analyzed. Results: Comparison of apoE-allele frequencies in chronically HCVinfected patients revealed significant differences compared to healthy controls (p=0.002) and patients with non-HCV associated chronic liver disease (p=0.028). This was primarily due to a substantial under-representation of the apoE4-allele in chronically HCV-infected patients (10.5% vs. 13.9% in non-HCV infected patients vs. 14.0% in controls; p=0.011). The proportion of the apoE4-allele was decreased in the group of patients with absent or mild hepatic steatosis but very similar for severe hepatic fibrosis and inflammation. Conclusions: The under-representation of the apoE4-allele in chronically HCV-infected patients suggests a protective role of the apoE4-allele during HCV-infection. ApoE4-allele- carrier seem to be less susceptible for the development of liver steatosis. However we could not confirm previous findings that apoE4 protects from severe hepatic fibrosis.
Poster Sessions
(6.8% ± 0.73%) than in non-responders (13.4% ± 1.3%). Fifty four patients had an HCV-RNA concentration in serum <800000 IU/ml and of them 21 (38.8%) were responders and 33 (61.2%) non-responders. On the other hand, thirty three patients had <5% of infected hepatocytes and of them 19 (57.6%) were responders and 14 (42.4%) non-responders. In a logistic regression analysis considering gender, ALT, necroimflammatory activity, fibrosis score etc, the only independent factors associated with the response were the percentage of infected hepatocytes (p= 0.0005; OR: 2.1825; 95% CI: 1.4079-3.3833) and age (p= 0.013; OR; 1.0643; 95% CI: 1.0134-1.1178) but not the serum HCV-RNA concentration. In conclusion, the percentage of infected hepatocytes in the pretreatment liver biopsy is a better predictive factor of response than the serum HCV-RNA concentration.
of treated and 19.5% of untreated developed ascites, 3.8% of treated and 5.6% of untreated had variceal bleeding, 1.1% of treated and 3.1% of untreated developed portal-systemic encephalopathy and 11.9% of treated and 20.9% of untreated patients dead from liver-related causes. By the Kaplan-Meier method and the log-rank test IFN treated patients showed a significantly lower incidence of HCC (p = 0.028), of ascites (p = 0.020), and of liver-related death (p = 0.003). No significant difference was observed on varices appearance of worsening, variceal bleeding and portal-systemic encephalopathy occurrence. Our results indicate that one or more courses of IFN therapy may delay HCC development and improve survival in patients with compensated HCV-cirrhosis, while seem to have a trivial effect on portal hypertension-related complications.
461 APOLIPOPROTEIN E POLYMORPHISM MAY PROTECT FROM 459 CORRELATION BETWEEN LIVER ELASTICITY MEASURED BY TRANSIENT ELASTOGRAPHY AND LIVER FIBROSIS ASSESSED BY MORPHOMETRY IN PATIENTS WITH HCV CHRONIC HEPATITIS
M. Ziol 1,2 , N. Barget 3 , L. Sandrin 4 , C. Fournier 4 , F. Mal 3 , F. Kazemi 3 , A. Kettaneh 5 , M. Beaugrand 3 . 1 EA 3406, Univertisy Paris 13, Paris, France; 2 Pathologie Department, Hopital Jean Verdier, Bondy, France; 3 Liver Unit, Hopital Jean Verdier, Bondy, France; 4 Echosens, Paris, France; 5 Internal Medicine Department, Hopital JeanVerdier, Bondy Liver fibrosis (LF) evaluation by non-invasive techniques is a major challenge. FibroScan a new non-invasive system based on transient elastography measures liver elasticity. A previous prospective study in 220 patients with chronic hepatitis showed that liver elasticity could be used to predict fibrosis stage (FS) assessed by Metavir scoring system. This prospective study was designed to further study the correlation between liver elasticity and fibrosis in 69 patients with chronic HCV hepatitis using fibrosis area fraction (FAF) measured on liver biopsies. All patients had a liver biopsy providing a large sample suitable for morphometric analysis and a liver elasticity measurement within less than 4 months. FS was evaluated by Metavir score and FAF by quantitative image analysis of 5 micrometers thick picro-sirius stained sections. The FAF was assessed using interactive thresholding of greyscale converted digital image of 10 to 20 consecutive fields (x 200) for each liver biopsy. Within the studied population (20 F1, 21 F2, 5 F3 and 23 F4 patients), FAF was 6.3 ± 6.2 (range 0.3 - 28.8) and highly correlated to FS (Spearman correlation r = 0.66, p < 0.0001). The correlation coefficients were r = 0.65 and r = 0.74 (both p < 0.0001) between liver elasticity and FAF or FS, respectively. Liver elasticity accurately reflects hepatic fibrosis area in patients with chronic HCV hepatitis and thus appears to be a reliable non-invasive tool to measure liver fibrosis.
460 INTERFERON (IFN) THERAPY HAS LITTLE EFFECT ON PROGRESSION OF PORTAL HYPERTENSION IN HEPATITIS C VIRUS (HCV) RELATED CIRRHOSIS
L. Benvegnu, F. Pasin, M. Gios, A. Ferrari, A. Alberti. Dpt. of Clinical and Experimental Medicine - University of Padova, Padova, Italy The effect of IFN therapy on complications of HCV-related cirrhosis is not fully understood. There are data indicating that hepatocellular carcinoma (HCC) might be prevented or delayed, while much less clear is the effect on portal hypertension and esophageal varices. We have conducted a longterm follow-up study of 380 consecutive patients with compensated HCVrelated cirrhosis. 185 patients were treated with one or more courses of IFN therapy, while 195 remained untreated. All patients were followed-up with periodical (every 6 months) evaluation and abdominal ultrasound and with periodical (every 12-24 months) esophagogastroduodenoscopy. During a mean follow-up period of 88.8 ± 42.0 months, 15.1% of IFN treated and 22.6% of untreated patients developed HCC, 19.8% of treated and 24.8% of untreated showed esophageal varices appearance or worsening, 11.9%
HEPATITIS C VIRUS (HCV) INFECTION
T. Mueller 1 , R. Gessner 2 , C. Sarrazin 3 , J. Halangk 4 , A. Bergk 1 , F. van Boemmel 1 , B. Wiedenmann 1 , U. Hopf 1 , T. Berg 1 . 1 Medizinische Klinik Mit Schwerpunkt Hepatologie Und Gastroenterologie, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany; 2 Institut Fuer Klinische Chemie Und Biochemie, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany; 3 Klinik Und Poliklinik Fuer Innere Medizin II, Universitaetskliniken Des Saarlandes, Homburg, Saar, Germany; 4 Klinik Fuer Paediatrie, Charité - Universitaetsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany Background: Low-density lipoprotein-receptors (LDL-R) are likely to mediate the hepatocellular uptake of HCV-virions complexed with plasma lipoproteins. Polymorphism within the gene encoding apolipoprotein E (apoE), a major structural compound of lipoproteins and natural ligand of LDL-R, may influence this crucial step of HCV-infection. In this study we determined the apoE-polymorphism in chronically HCV-infected patients compared to patients with non-HCV associated chronic liver disease and healthy controls. Subjects and methods: We genotyped 701 chronically HCV-infected patients, 283 individuals with non-HCV associated liver disease and 523 healthy controls. ApoE genotyping (ApoE2, E3, E4) was performed by PCR and RFLP analysis. Inflammation (grade) and fibrosis (stage) of 563 liver biopsies from chronic HCV-carriers were classified according to the Scheuer score. Degree of liver steatosis was separately analyzed. Results: Comparison of apoE-allele frequencies in chronically HCVinfected patients revealed significant differences compared to healthy controls (p=0.002) and patients with non-HCV associated chronic liver disease (p=0.028). This was primarily due to a substantial under-representation of the apoE4-allele in chronically HCV-infected patients (10.5% vs. 13.9% in non-HCV infected patients vs. 14.0% in controls; p=0.011). The proportion of the apoE4-allele was decreased in the group of patients with absent or mild hepatic steatosis but very similar for severe hepatic fibrosis and inflammation. Conclusions: The under-representation of the apoE4-allele in chronically HCV-infected patients suggests a protective role of the apoE4-allele during HCV-infection. ApoE4-allele- carrier seem to be less susceptible for the development of liver steatosis. However we could not confirm previous findings that apoE4 protects from severe hepatic fibrosis.