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The severity of histologic lesions is not related to liver HCV RNA level in patients with chronic hepatitis C
Viral
hepatitis:
1 P/CO6/037
clinical
117
aspects
1P/CO6/039 1
)
THE SEVERITY OF HISTOLOGIC LESIONS IS NOT RELATED TO LIVER HCV RNA LEVEL IN PATIENTS WITH CHRONIC HEPATITIS C A Gervais’. M Martinet’. N Bover*. M Pouteau’. C Castelnau’. C Deaott”. S Erlinaer’. P Marcellin’ INSERM U 24 and Service d’Hepatologie ; **Service d’Anatomie et Cytologie Pathologiques, Hopital Beaujon, Clichy, France
TIMING AND DOSE EFFECT OF ALPHA-INTERFERON ON EARLY VIRAL KlNETICS IN CHRONIC HEPATITIS C Ruvoletto MG, Pontisso P, Casarin C, Mialiorato I, Chemello L, Cavalletto L, Alberti A. Dipartimento di Medicina Clinica, Clinica Medica 2, Universim di Padova
The aim of the study was to compare the amount of HepaMis C virus IHCV) RNA in the liver of patients with cirrhosis, chronic hepatitis C kih elevated ALT and chronic hepatitis C with normal ALT. ’ Patients and Methods : Fourty patients were studied, 10 v&h cirrhosis (group 1) ; 10 with chronic hepatitis C and elevated MT with a Knodell score above 6 (group 2) ; 10 with chronic hepatitis C and elevated ALT with a Knodell score below 6 (group 3) ; 10 with chronic hepatitis C and normal ALT (group 4).For each patient a frozen liver tissue sample kept at -80°C and a serum sample at -2O”C, were available. Total liver RNA was extracted with guanidium isothiocvanate. Qualitv of liver samples was assessed bv 28s RNAr amplification. Hepatic HCV RNA ‘quantitation was performed by competitive PCR (InGeN. Vienna Lab). Quantitation of serum HCV RNA was performed by branched DNA (Quantiplex 2.0, Chiron Diagnostics). Results were analysed by non parametric tests (Krsuskal Wallis and Spearman coefficient). Results : Median liver HCV RNA amount was not different in the four groups : group 1: 10.1 lo6 copies/g (0.1 to 140) group2: 9.9 lo6 copies/g (0.1 to 132) group 3: 8.5 106 copies/g (0.4 to 73.7) group 4: 9.7 lo6 copies/g (0.8 to 100). Median serum HCV RNA was not different in the four groups. No correlation was found between serum and liver HCV RNA levels. Conclusion : In patients with chronic hepatitis C, liver HCV RNA amount is variable and is not related with serum HCV RNA level. There was no relation with the histologic severity of the liver disease. This result is consistent with the view that hepatic dammages are more related to immune mediated mechanisms than to direct cytopathogenicity of the virus.
Recent data indicate that hepatitis C virus (HCV) replicates continuously with a very high virus production and that high dose interferon (lEN) can improve response rate. To assess the relative effect of treatment frequency and dose in the reduction of circulating virus, we have analyzed early kinetics of HCV in 12 patients treated with different schedules of alpha-IFN. Viral load was measured by the bDNA assay (Quantiplex 2.0, Chiron Corp.) at day 0,7 and 14 in 6 patients treated with 1OMU tiw (Group A) and in 6 patients treated with 3MU daily (Group B). Reduction of HCV RNA values (Log10 Meq/ml) within the first two weeks of treatment are shown in the following table: Day 14 Dav 7 Group A (lOMU tiw) -0.07 -0.38 median Group B (3MU daily) -0.59 -0.67 median None of the patients of Group A was HCV RNA negative by PCR both at day 7 and at day 14, while 316 patients of Group B had undetectable viraemia by PCR at the same time points. ln conclusion, daily tiequency of low dose lFN administration appear to be effective in suppression of HCV replication in the early phase of treatment.
1 P/CO6/040
EVOLUTION OF RISK FACTORS AND CHARACTERISTICS OF PATIENTS WITH CHRONIC HEPATITIS C BETWEEN 1990 AND 1997 IN AN URBAN AREA IN FRANCE. A. Bastie. M. Fourv. C. H&de. I. Lonion. J.M. MCtreau. C. Douvin. A. Mallat. D: Dhumeaux. F. Roudot-Thoravah Departments of Hepatology and Public Health, Creteil, France. Since the recognition of hepatitis C virus (HCV), efforts have been
made for improving the screening of infected patients. The marked reduction in the incidence of post-transfusional hepatitis C since 1991 may lead to epidemiological changes in HCV infections newly diagnosed. The aim of this study was to examine upon a seven-year period the changes in the epidemiological features of hepatitis C infections in unselected patients attending a French medical unit. Patients and methods. 1,080 consecutive patients (618 men, 462 women, mean age 44.1214.4 yrs) with chronic HCV infection were studied RWllts 1990-91 (n=191)
1992-93 (n=318)
1994-95 (n = 276)
1996-97 (n=295)
Males/Females 60%-40% Age at diagnosis (*) 45+15 Source of infection -Transfusion 45% - IVDU 21%
57%-43% 44*14
53%-47% 44*14
60%~40% 43f14
45% 23%
33% 29%
28% 33%
Duration of disease (*)12.0+8.4 -Transfused-IVDU 12.4-11.0
13.6+8.9 14.6-10.9
14.4f8.3 17.1-11.0
15.1f7.4 18.4-12.5
21.4% 19.0% Cirrhosis 15.5% 9.0% 18.1-7.0 17.5-l 1.7 Transfused-IVDU 27.3-9.7 13.3-3.7 (‘) years Conclusions. These results show that : i) transfused patients represent
a decreasing part of infected patients ; they are now detected with a longer disease duration and nevertheless less severe henatic lesions : ii) TVDU increase-in number, with a stable severity of disease ; iii) this evolution should be responsible for a lesser incidence rate of cirrhosis and carcinoma than previously feared.
1
EFFICACY OF 3 vs. 5 MU IFN-ALPHA GIVEN DAILY FOLLOWED BY A TIW MAINTENANCE REGIMEN IN CHRONIC HEPATITIS C: A RANDOMIZED TRIAL. AS Hadzivannis. Ch Paoaioannou. E Soanou, E Manesis and SJ Hadzivannis. Academic Department of Medicine, Hippokration General Hospital, Athens, Greece. Background: Viral kinetic studies suggest that daily administration of IFN-a in chronic hepatitis C (CHC) is more effective than the tiw scheme. Aim: To evaluate the efficacy of 3 and 5 MU IFN-a given daily for 1 month, followed by 11 months of maintenance tiw therapy with the same dose. Patients and methods: 36 na’fve patients with CHC with detectable HCV-RNA in serum, high ALT levels and histologic activity were randomized to receive 3 or 5 MU IFN-a. Serum samples were collected daily during the first week, twice weekly for weeks 2. 3 and 4 and monthly thereafter. HCV-RNA was determined with the Amplicor HCV Monitor test. Samples negative for HCV-RNA were retested with a very sensitive RT-PCR technique. Results: Daily IFN-a administration was well tolerated except for one patient who withdrew because of hemoglobin drop. The overall virological and biochemical response rates were 76.9% and 84.6% respectively. The virological response was achieved within a median of 4 days. The 5 MU regimen appeared to be associated with earlier and more frequent responses compared to 3 MU (87.5% vs. 72.2%). All patients with HCV types la, 2, 3 and 63.6% of patients with type I b achieved virological response. No breakthroughs have occurred so far during a 7 month mean maintenance period with the tiw scheme. Conclusions: 1) Daily administration of 3 or 5 MU IFN-a for one month in CHC is associated with a very high rate of complete virological response, which is effectively maintained by the classical scheme of tiw IFN administration. 2) A virological response appears to be achieved in 100% of genotype la, 2 and 3 infections and in approximately two thirds of genotype 1 b. 3) The frequency of sustained responses after stop of therapy is under study.
hepatitis:
1 P/CO6/037
clinical
117
aspects
1P/CO6/039 1
)
THE SEVERITY OF HISTOLOGIC LESIONS IS NOT RELATED TO LIVER HCV RNA LEVEL IN PATIENTS WITH CHRONIC HEPATITIS C A Gervais’. M Martinet’. N Bover*. M Pouteau’. C Castelnau’. C Deaott”. S Erlinaer’. P Marcellin’ INSERM U 24 and Service d’Hepatologie ; **Service d’Anatomie et Cytologie Pathologiques, Hopital Beaujon, Clichy, France
TIMING AND DOSE EFFECT OF ALPHA-INTERFERON ON EARLY VIRAL KlNETICS IN CHRONIC HEPATITIS C Ruvoletto MG, Pontisso P, Casarin C, Mialiorato I, Chemello L, Cavalletto L, Alberti A. Dipartimento di Medicina Clinica, Clinica Medica 2, Universim di Padova
The aim of the study was to compare the amount of HepaMis C virus IHCV) RNA in the liver of patients with cirrhosis, chronic hepatitis C kih elevated ALT and chronic hepatitis C with normal ALT. ’ Patients and Methods : Fourty patients were studied, 10 v&h cirrhosis (group 1) ; 10 with chronic hepatitis C and elevated MT with a Knodell score above 6 (group 2) ; 10 with chronic hepatitis C and elevated ALT with a Knodell score below 6 (group 3) ; 10 with chronic hepatitis C and normal ALT (group 4).For each patient a frozen liver tissue sample kept at -80°C and a serum sample at -2O”C, were available. Total liver RNA was extracted with guanidium isothiocvanate. Qualitv of liver samples was assessed bv 28s RNAr amplification. Hepatic HCV RNA ‘quantitation was performed by competitive PCR (InGeN. Vienna Lab). Quantitation of serum HCV RNA was performed by branched DNA (Quantiplex 2.0, Chiron Diagnostics). Results were analysed by non parametric tests (Krsuskal Wallis and Spearman coefficient). Results : Median liver HCV RNA amount was not different in the four groups : group 1: 10.1 lo6 copies/g (0.1 to 140) group2: 9.9 lo6 copies/g (0.1 to 132) group 3: 8.5 106 copies/g (0.4 to 73.7) group 4: 9.7 lo6 copies/g (0.8 to 100). Median serum HCV RNA was not different in the four groups. No correlation was found between serum and liver HCV RNA levels. Conclusion : In patients with chronic hepatitis C, liver HCV RNA amount is variable and is not related with serum HCV RNA level. There was no relation with the histologic severity of the liver disease. This result is consistent with the view that hepatic dammages are more related to immune mediated mechanisms than to direct cytopathogenicity of the virus.
Recent data indicate that hepatitis C virus (HCV) replicates continuously with a very high virus production and that high dose interferon (lEN) can improve response rate. To assess the relative effect of treatment frequency and dose in the reduction of circulating virus, we have analyzed early kinetics of HCV in 12 patients treated with different schedules of alpha-IFN. Viral load was measured by the bDNA assay (Quantiplex 2.0, Chiron Corp.) at day 0,7 and 14 in 6 patients treated with 1OMU tiw (Group A) and in 6 patients treated with 3MU daily (Group B). Reduction of HCV RNA values (Log10 Meq/ml) within the first two weeks of treatment are shown in the following table: Day 14 Dav 7 Group A (lOMU tiw) -0.07 -0.38 median Group B (3MU daily) -0.59 -0.67 median None of the patients of Group A was HCV RNA negative by PCR both at day 7 and at day 14, while 316 patients of Group B had undetectable viraemia by PCR at the same time points. ln conclusion, daily tiequency of low dose lFN administration appear to be effective in suppression of HCV replication in the early phase of treatment.
1 P/CO6/040
EVOLUTION OF RISK FACTORS AND CHARACTERISTICS OF PATIENTS WITH CHRONIC HEPATITIS C BETWEEN 1990 AND 1997 IN AN URBAN AREA IN FRANCE. A. Bastie. M. Fourv. C. H&de. I. Lonion. J.M. MCtreau. C. Douvin. A. Mallat. D: Dhumeaux. F. Roudot-Thoravah Departments of Hepatology and Public Health, Creteil, France. Since the recognition of hepatitis C virus (HCV), efforts have been
made for improving the screening of infected patients. The marked reduction in the incidence of post-transfusional hepatitis C since 1991 may lead to epidemiological changes in HCV infections newly diagnosed. The aim of this study was to examine upon a seven-year period the changes in the epidemiological features of hepatitis C infections in unselected patients attending a French medical unit. Patients and methods. 1,080 consecutive patients (618 men, 462 women, mean age 44.1214.4 yrs) with chronic HCV infection were studied RWllts 1990-91 (n=191)
1992-93 (n=318)
1994-95 (n = 276)
1996-97 (n=295)
Males/Females 60%-40% Age at diagnosis (*) 45+15 Source of infection -Transfusion 45% - IVDU 21%
57%-43% 44*14
53%-47% 44*14
60%~40% 43f14
45% 23%
33% 29%
28% 33%
Duration of disease (*)12.0+8.4 -Transfused-IVDU 12.4-11.0
13.6+8.9 14.6-10.9
14.4f8.3 17.1-11.0
15.1f7.4 18.4-12.5
21.4% 19.0% Cirrhosis 15.5% 9.0% 18.1-7.0 17.5-l 1.7 Transfused-IVDU 27.3-9.7 13.3-3.7 (‘) years Conclusions. These results show that : i) transfused patients represent
a decreasing part of infected patients ; they are now detected with a longer disease duration and nevertheless less severe henatic lesions : ii) TVDU increase-in number, with a stable severity of disease ; iii) this evolution should be responsible for a lesser incidence rate of cirrhosis and carcinoma than previously feared.
1
EFFICACY OF 3 vs. 5 MU IFN-ALPHA GIVEN DAILY FOLLOWED BY A TIW MAINTENANCE REGIMEN IN CHRONIC HEPATITIS C: A RANDOMIZED TRIAL. AS Hadzivannis. Ch Paoaioannou. E Soanou, E Manesis and SJ Hadzivannis. Academic Department of Medicine, Hippokration General Hospital, Athens, Greece. Background: Viral kinetic studies suggest that daily administration of IFN-a in chronic hepatitis C (CHC) is more effective than the tiw scheme. Aim: To evaluate the efficacy of 3 and 5 MU IFN-a given daily for 1 month, followed by 11 months of maintenance tiw therapy with the same dose. Patients and methods: 36 na’fve patients with CHC with detectable HCV-RNA in serum, high ALT levels and histologic activity were randomized to receive 3 or 5 MU IFN-a. Serum samples were collected daily during the first week, twice weekly for weeks 2. 3 and 4 and monthly thereafter. HCV-RNA was determined with the Amplicor HCV Monitor test. Samples negative for HCV-RNA were retested with a very sensitive RT-PCR technique. Results: Daily IFN-a administration was well tolerated except for one patient who withdrew because of hemoglobin drop. The overall virological and biochemical response rates were 76.9% and 84.6% respectively. The virological response was achieved within a median of 4 days. The 5 MU regimen appeared to be associated with earlier and more frequent responses compared to 3 MU (87.5% vs. 72.2%). All patients with HCV types la, 2, 3 and 63.6% of patients with type I b achieved virological response. No breakthroughs have occurred so far during a 7 month mean maintenance period with the tiw scheme. Conclusions: 1) Daily administration of 3 or 5 MU IFN-a for one month in CHC is associated with a very high rate of complete virological response, which is effectively maintained by the classical scheme of tiw IFN administration. 2) A virological response appears to be achieved in 100% of genotype la, 2 and 3 infections and in approximately two thirds of genotype 1 b. 3) The frequency of sustained responses after stop of therapy is under study.