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Long term follow-up of interferon α-2b treatment in children with chronic hepatitis C
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LONG TERM FOLLOW-UP OF INTERFERON a-2b TREATMENT IN CHILDREN WITH CHRONIC HEPATITIS C W. Sluzewski, K.A. Youseif, I. Mozer-Lisewska Department of Infectious Diseases and Child Neurology, Institut of Paediatrics, Karol Marcinkowski University of Medical Sciences, Poznan, Poland. The aim of the study was the assessement of the effect of recombinant ct-2b interferon (INF) on the course and clinical picture of chronic hepatitis C in children two years after the end of treatment. In the period 1994-1997 16 patients with chronic hepatitis C, aged from 2,5 - 15 years (mean 9,5+3,2), were selected for the study. Selection was based on at least 6 months duration of the hepatitis C, liver biopsy, and positive HCV-RNA (RT-PCR) test. Ten patients had genotype lb, and 6 patients la. Duration of illness was 2,23+1,12 y. INF-tx-2b was administrated s.c. 3 MU tiw. during 6 months. The patients were followed up for 24 months after completion of INF-ct-2b cure. The results in the end of treatment were positive in 8 patients (5 genotype la and 4 genotype lb). Sustained response - normal ALT activity and no detectable HCV-RNA at the end of treatment and throughout the observation period to 6 months after stopping the INF-ct-2bwas observed in all these children. In the end of the period of 24 months follow-up 5 of these children had still the sustained response (3 genotype la and 2 genotype lb). The response to INF-ct 2b treatment was better in younger children with lesser duration of HCV infection.
SUCCESSFUL TRIPLE COMBINATION TREATMENT OF PATIENTS WITH CHRONIC HEPATITIS C NOT RESPONDING TO INTERFERON PLUS RIBAVIRIN R. Stauber, E Hackl, K. Schiitze, B. Bauer, C. Datz, R. Hubmann, R Ferenci Austrian Hepatitis Study Group, Austria. There is currently no treatment option for patients with chronic hepatitis C not responding to dual combination treatment with interferon-o~ plus rihavirin. We investigated triple combination treatment with interferon-ribavirin-amantadin, including induction dosing of interferon, in patients not responding to previous standard combination treatment with interferon-
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CARDIAC OUTPUT MEASUREMENT IN PORTAL HYPERTENSIVE RATS: A NEW METHOD N. Veal. E Moal. J. Wan~. E Oberti, R. Trouvt, P. Calts UPRESS EA 2170, Angers, France. Portal hypertension (PHT) causes the development of a venous collateral circt, lation (VCC) and a hyperkinetie syndrome which is associated with an increase in cardiac output (CO). The use of radioactive microspheres to measure CO and VCC blood flow is the method of reference in PHT animal models. We previously showed that the blood flow measurement with transit time ultrasound (TTU) method was better than the radioactive microsphere method to study pharmacological variations of VCC blood flow. Moreover, it is possible to measure CO with the TTU method : an intravenous injection of saline results in a dilution of the blood which is detected by a "VI'U probe placed around an artery. Aim: To validate the use of the TTU dilution in the measurement of (,O. Methods: Reproducibility and accuracy of this new method were assessed in sham rats and in PHT rats. CO measured with TFU-dilution was compared to CO measured with radioactive microspheres with or without terlipressin treatment. Results: intra and interobserver reproducibilities were excellent (r2=0.98, 0.96 respectively). CO was significantly higher in PHT rats than in sham rats. CO measurements without treatment were similar between techniques with a good correlation (r2=0.58, p<0.0001). In the treated group, CO variations due to terlipressin were similar between techniques (-33.5_+20 vs -33.0_+19 %) and were well correlated (r2=0.60, p<0.0001). Conclusions: The "VFU-dilution is a valid method to measure CO in PHT rats and in sham rats. This method is accurate, reproducible anti provides low cost and repetitive CO measurements without open chest surgery.
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AL T
Week 2 0/17 neg. 2/17 normal (12%) Week 12 8/17 neg. (47%) 8/17 normal (47%) Conclusion: This preliminary report indicates that triple combination treatment with daily interferun-~ plus ribavirin plus amantudine for 3 months is able to induce virological response in a substantial number of nonresponders to a p~vious standard dual combination treatment.
TREATMENT OF INTERFERON IN CHRONIC HEPATITIS C PATIENTS WITH NORMAL ALT: RESULTS OF A CONTROLLED STUDY S. Coll, J. Santol, M.C. Vila, M. Hombrados, M.D. Gimenez, M. Mailer, R.M. Morillas, R. Sol/t, R. Planas Liver Section, Hospital del Mar, Hospital Univ Germans Trias i Pujol, Badalona, Spain. Since interferon (IFN) treatment in chronic hepatitis C (CI-IC) patients with persistently normal ALT serum levels is controversial, we conducted a control study in 47 e r i c patients with normal ALT levels (3 times over a 6 month period), and positive serum HCV-RNA. Twenty seven patients (Group 1) were treated with alpha-2b IFN, 5MU, 3 times a week during 12 months if serum HCV-RNA became negative. Twenty patients (Group 2) were included as untreated controls. All patients were foUowod-up after treatment during 6 months. Virological end of treatment response was observed significantly more frequently in IFN-treated than in control patients (8/27 or 29.6% vs 0/20, p<0.05). However, sustained virological response was observed in only three IFN-trcated patients (I1,1%) and in any of the control group (hiS). Although the frequency of ALT flare-ups during the treatment period was similar (13/27 or 48.1% in Group 1 vs 5/20 or 25% in Group 2), ALT remain increased at the end of follow-up in four patients of group 1 (14.1%), and in one in Group 2 (5%, NS). Since IFN monotherapy induces clearance of viremia in a small proportion of patients, but may also induce worsening of the serum ALT levels in a higher proportion, these results do not support the use of IFN monotherapy in these patients. By contrast, RCTs are necessary to determine which of these patients would benefit from ft~mbination antiviral therapy.
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LONG TERM FOLLOW-UP OF INTERFERON a-2b TREATMENT IN CHILDREN WITH CHRONIC HEPATITIS C W. Sluzewski, K.A. Youseif, I. Mozer-Lisewska Department of Infectious Diseases and Child Neurology, Institut of Paediatrics, Karol Marcinkowski University of Medical Sciences, Poznan, Poland. The aim of the study was the assessement of the effect of recombinant ct-2b interferon (INF) on the course and clinical picture of chronic hepatitis C in children two years after the end of treatment. In the period 1994-1997 16 patients with chronic hepatitis C, aged from 2,5 - 15 years (mean 9,5+3,2), were selected for the study. Selection was based on at least 6 months duration of the hepatitis C, liver biopsy, and positive HCV-RNA (RT-PCR) test. Ten patients had genotype lb, and 6 patients la. Duration of illness was 2,23+1,12 y. INF-tx-2b was administrated s.c. 3 MU tiw. during 6 months. The patients were followed up for 24 months after completion of INF-ct-2b cure. The results in the end of treatment were positive in 8 patients (5 genotype la and 4 genotype lb). Sustained response - normal ALT activity and no detectable HCV-RNA at the end of treatment and throughout the observation period to 6 months after stopping the INF-ct-2bwas observed in all these children. In the end of the period of 24 months follow-up 5 of these children had still the sustained response (3 genotype la and 2 genotype lb). The response to INF-ct 2b treatment was better in younger children with lesser duration of HCV infection.
SUCCESSFUL TRIPLE COMBINATION TREATMENT OF PATIENTS WITH CHRONIC HEPATITIS C NOT RESPONDING TO INTERFERON PLUS RIBAVIRIN R. Stauber, E Hackl, K. Schiitze, B. Bauer, C. Datz, R. Hubmann, R Ferenci Austrian Hepatitis Study Group, Austria. There is currently no treatment option for patients with chronic hepatitis C not responding to dual combination treatment with interferon-o~ plus rihavirin. We investigated triple combination treatment with interferon-ribavirin-amantadin, including induction dosing of interferon, in patients not responding to previous standard combination treatment with interferon-
[
L coe/o32 I
C06/030
]
CARDIAC OUTPUT MEASUREMENT IN PORTAL HYPERTENSIVE RATS: A NEW METHOD N. Veal. E Moal. J. Wan~. E Oberti, R. Trouvt, P. Calts UPRESS EA 2170, Angers, France. Portal hypertension (PHT) causes the development of a venous collateral circt, lation (VCC) and a hyperkinetie syndrome which is associated with an increase in cardiac output (CO). The use of radioactive microspheres to measure CO and VCC blood flow is the method of reference in PHT animal models. We previously showed that the blood flow measurement with transit time ultrasound (TTU) method was better than the radioactive microsphere method to study pharmacological variations of VCC blood flow. Moreover, it is possible to measure CO with the TTU method : an intravenous injection of saline results in a dilution of the blood which is detected by a "VI'U probe placed around an artery. Aim: To validate the use of the TTU dilution in the measurement of (,O. Methods: Reproducibility and accuracy of this new method were assessed in sham rats and in PHT rats. CO measured with TFU-dilution was compared to CO measured with radioactive microspheres with or without terlipressin treatment. Results: intra and interobserver reproducibilities were excellent (r2=0.98, 0.96 respectively). CO was significantly higher in PHT rats than in sham rats. CO measurements without treatment were similar between techniques with a good correlation (r2=0.58, p<0.0001). In the treated group, CO variations due to terlipressin were similar between techniques (-33.5_+20 vs -33.0_+19 %) and were well correlated (r2=0.60, p<0.0001). Conclusions: The "VFU-dilution is a valid method to measure CO in PHT rats and in sham rats. This method is accurate, reproducible anti provides low cost and repetitive CO measurements without open chest surgery.
184
I
HCV-RNA
AL T
Week 2 0/17 neg. 2/17 normal (12%) Week 12 8/17 neg. (47%) 8/17 normal (47%) Conclusion: This preliminary report indicates that triple combination treatment with daily interferun-~ plus ribavirin plus amantudine for 3 months is able to induce virological response in a substantial number of nonresponders to a p~vious standard dual combination treatment.
TREATMENT OF INTERFERON IN CHRONIC HEPATITIS C PATIENTS WITH NORMAL ALT: RESULTS OF A CONTROLLED STUDY S. Coll, J. Santol, M.C. Vila, M. Hombrados, M.D. Gimenez, M. Mailer, R.M. Morillas, R. Sol/t, R. Planas Liver Section, Hospital del Mar, Hospital Univ Germans Trias i Pujol, Badalona, Spain. Since interferon (IFN) treatment in chronic hepatitis C (CI-IC) patients with persistently normal ALT serum levels is controversial, we conducted a control study in 47 e r i c patients with normal ALT levels (3 times over a 6 month period), and positive serum HCV-RNA. Twenty seven patients (Group 1) were treated with alpha-2b IFN, 5MU, 3 times a week during 12 months if serum HCV-RNA became negative. Twenty patients (Group 2) were included as untreated controls. All patients were foUowod-up after treatment during 6 months. Virological end of treatment response was observed significantly more frequently in IFN-treated than in control patients (8/27 or 29.6% vs 0/20, p<0.05). However, sustained virological response was observed in only three IFN-trcated patients (I1,1%) and in any of the control group (hiS). Although the frequency of ALT flare-ups during the treatment period was similar (13/27 or 48.1% in Group 1 vs 5/20 or 25% in Group 2), ALT remain increased at the end of follow-up in four patients of group 1 (14.1%), and in one in Group 2 (5%, NS). Since IFN monotherapy induces clearance of viremia in a small proportion of patients, but may also induce worsening of the serum ALT levels in a higher proportion, these results do not support the use of IFN monotherapy in these patients. By contrast, RCTs are necessary to determine which of these patients would benefit from ft~mbination antiviral therapy.