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RBV non responders (NR) with chronic hepatitis C (CHC)
140
Poster Sessions
estimated at 200 000, the majority of whom are currently unaware of their infection. In August 2002, the Department of Health (DH) contacted all GPs in the UK and provided them with educational material relating to chronic HCV. Our aim was to determine the knowledge base and practice patterns of GPs in East London. A self questionnaire was sent to 850 GPs in East London, composed of eight closed and four open ended questions. All answers were contained within the DH document. 85% of GPs were aware that HCV was common in drug users and more common than HIV. However 15% believed that the presence of antibodies to the virus indicated that the patient no longer had active disease and the majority (55%) believed that materno-fetal transmission occurred in more than 50% of infected women. 54% of GPs believed that blood transfusion in the 1990s carried a high risk of transmitting the virus but 85% knew that transmission could be prevented by meticulous hygiene in drug users. Knowledge regarding the natural history of HCV was limited and only 36% knew that therapy was effective in more than 50% of cases. The DH campaign to inform health care professionals appears to have failed and many GPs remain poorly informed about this virus and its effects. Further education is urgently required to help our colleagues in general practice obtain up-todate information about this infection.
473 COMPARTIMENTALIZATION OF HEPATITIS C VIRUS AND RESPONSE TO THERAPY
G. Diliberto 1 , D. Ducoulombier 1 , A.-M. Roque-Afonso 2 , M. Gigou 2 , E. Dussaix 2 , C. Guettier 2 , D. Samuel 2 , C. Feray 1 . 1 Unité INSERM 481, Faculté Médecine X Bichat, Paris, France; 2 UPRESS 1596, Hôpital Paul Brousse, Villejuif, France We have previously reported the persistent replication in blood mononuclear cells (BMC) of HCV variants defined in the 5 untranslated region (5 UTR). This was more frequent in patients with multiple potentially infective events (IVDU or multiple transfusions) and persisted over time. The purpose of this study was to determine the relation between such HCV compartmentalization and response to therapy. Patients and methods: Viral IRES (5 UTR) in plasma and in blood mononuclear cells (BMC) were amplified in100 naive subjects. Sequences were compared by SSCP, and by line probe assay or cloning when required. Sampling were performed before liver biopsy in 80 patients and before therapy by pegylated interferon/ribavirin in 50 patients followed more than 6 months after therapy. Results: SSCP profiles were different between plasma and PBMC in 39 patients. Among these 39 patients, 13 had different HCV genotypes in PBMC and plasma (genotypic compartmentalization). The compartmentalization was more frequent in case of past IVDU (25/42 vs 14/58; p <0.01). Sustained virological response was related to infection by genotype 2 or 3 (12/20 vs 7/30), duration of infection (19 y±6 vs14±6) and 5 UTR compartmentalization (15/20 vs 5/30, p<0.001). Compartmentalization was an independent variable in multivariate analysis and was not correlated to duration (or age) of infection or to histological severity of hepatitis. These results confirm that the compartmentalization defined in viral IRES is more frequent in former IVDU likely reflecting repeated infective events. Patients in whom BMC and plasma variants are different seem to be excellent candidates for therapy.
474 IMPACT OF PREEMPTIVE THERAPY OF HCV AND HBV ON OCCURRENCE OF HEPATIC COMPLICATIONS FOLLOWING BONE MARROW TRANSPLANTATION (BMT)
M.H. El-Sayed 1 , A. El-Haddad 2 , I. Abdel-Kadir 2 , H.K. Mahmoud 2 . 1 Pediatric Department, Hematology/Oncology Division/Children’s Hospital, Ain Shams University, Cairo, Egypt; 2 Bone Marrow Transplantation Center, National Cancer Institute, Cairo, Egypt Background/aim: Liver disease was an important cause of mortality in a retrospective survey of BMT recipients; 37.5% of HCV and 39.8% of
HBV-infected patients suffered hepatic complications and had less survival probability. This study assesses the impact of preemptive therapy of HCV and HBV on occurrence of BMT-related hepatic complications. Methods: Sixteen HCV-RNA+(genotype 4) (median age:13years) BMT-recipients received a combination of Interferon alpha-2b (3 mIU/m2 SC/day) two weeks, one month before BMT, plus ribavirin (15mg/kg.b.w./day; maximum:1200mg/day) continuously till end of immunosuppression. Patients were monitored by HCV quantitation at baseline, 4,12 and 24 weeks. Eight HBsAg+ve (3 HBcAb+ve and 6 HBV-DNA+)(median age:8.5years) recipients received lamivudine (3mg/kgbw,od;maximum:100mg/d) 2 weeks before BMT. HBsAg/Ab, HBeAg/Ab, HBV-DNA were tested at baseline, 2 weeks and bimonthly thereafter. Results: HCV-RNA became undetectable in one (6.25%) at 4 weeks and 3 (18.7%) at 12 weeks. Six patients (37.5%) showed >2 log drop of HCV-RNA at 4 through 12 weeks. One developed mild veno-occlusive disease, two (12.5%) grade I acute graft-versus-host-disease (AGVHD), two (12.5%) died of BMT-related infections; none suffered hepatic GVHD. None of the children (n=8) receiving lamivudine suffered HBVreactivations. HBV-DNA dropped (<105 copies/ml) before BMT in HBVDNA+ patients (n=6) and was undetectable at 10 weeks in all except one. One developed grade I AGVHD, 2 chronic GVHD and two died of infections. Conclusions: Preemptive therapy of HCV and HBV before BMT in areas endemic for those viruses may decrease the incidence of hepatic complications, though, a larger study group and further follow up is required to draw firm conclusions.
475 SUSTAINED VIROLOGICAL RESPONSE (SVR) TO PEGINTERFERON ALFA-2A (40KD) (PEGASYS) PLUS RIBAVIRIN (RBV) AND AMANTADINE (AMA) VS INDUCTION THERAPY WITH INTERFERON ALFA-2A (ROFERON-A) PLUS RBV AND AMA IN IFN/RBV NON RESPONDERS (NR) WITH CHRONIC HEPATITIS C (CHC
S. Fargion 1 , M. Borzio 2 , A. Maraschi 1 , A. Cargnel 3 . Gel Gruppo Epatologico Lombardo; 1 Dipartimento Medicina Interna, Università Di Milano, Ospedale Maggiore IRCCS, Milano, Italy; 2 I Divisione Medicina Generale, Ospedale Civile Melegnano, Melegnano, Italy; 3 II Divisione Malattie Infettive, Ospedale Sacco, Milano, Italy Background: Despite the use of combination therapy (IFN+RBN), still a large proportion of CHC patients does not respond to therapy. Aim: To determine the benefit of a triple combination regimen (PEG-IFN or daily IFN, plus RBV and AMA) in NR to IFN/RBV. Patients: 185 patients who failed to respond to a prior course of 12-week of IFN/RBV therapy, have been randomized to receive 180 mcg onceweekly of PEG-IFN alfa-2a (40KD) plus RBV (800-1000mg/day) and AMA (200mg daily) (group A) for 48 weeks or IFN alfa-2a (6 MIU daily for 4 weeks, 3 MIU daily for 20 weeks, and then 3 MIU tiw for 24 weeks) plus RBV (800-1000mg/day) and AMA (200mg/day) (group B) for 24 weeks. Patients with detectable HCV-RNA after 24 weeks of treatment were considered non responders, and therapy discontinued. Results: Baseline patient characteristics did not differ in the two groups. Nineteen percent of patients discontinued therapy. End of treatment was 47 and 25% (p=0.06) and SVR 24 and 19%, in group A and B, respectively, with an overall SVR of 22%. SVR was 39% and 18% in genotype non-1 and 1 (p=0.05). Patients of age < 40 years (p=0.05) and viral load > 2MU (p=0.01) responded significantly better PEG-IFN. Conclusions: A proportion of patients with chronic hepatitis C not responders to IFN/RBV can eradicate HCV-RNA infection with triple therapy, especially if they have non-1 genotypes. Younger subjects (< 40 years) and those with higher viral load seem to benefit more from treatment with PEG-IFN.
Poster Sessions
estimated at 200 000, the majority of whom are currently unaware of their infection. In August 2002, the Department of Health (DH) contacted all GPs in the UK and provided them with educational material relating to chronic HCV. Our aim was to determine the knowledge base and practice patterns of GPs in East London. A self questionnaire was sent to 850 GPs in East London, composed of eight closed and four open ended questions. All answers were contained within the DH document. 85% of GPs were aware that HCV was common in drug users and more common than HIV. However 15% believed that the presence of antibodies to the virus indicated that the patient no longer had active disease and the majority (55%) believed that materno-fetal transmission occurred in more than 50% of infected women. 54% of GPs believed that blood transfusion in the 1990s carried a high risk of transmitting the virus but 85% knew that transmission could be prevented by meticulous hygiene in drug users. Knowledge regarding the natural history of HCV was limited and only 36% knew that therapy was effective in more than 50% of cases. The DH campaign to inform health care professionals appears to have failed and many GPs remain poorly informed about this virus and its effects. Further education is urgently required to help our colleagues in general practice obtain up-todate information about this infection.
473 COMPARTIMENTALIZATION OF HEPATITIS C VIRUS AND RESPONSE TO THERAPY
G. Diliberto 1 , D. Ducoulombier 1 , A.-M. Roque-Afonso 2 , M. Gigou 2 , E. Dussaix 2 , C. Guettier 2 , D. Samuel 2 , C. Feray 1 . 1 Unité INSERM 481, Faculté Médecine X Bichat, Paris, France; 2 UPRESS 1596, Hôpital Paul Brousse, Villejuif, France We have previously reported the persistent replication in blood mononuclear cells (BMC) of HCV variants defined in the 5 untranslated region (5 UTR). This was more frequent in patients with multiple potentially infective events (IVDU or multiple transfusions) and persisted over time. The purpose of this study was to determine the relation between such HCV compartmentalization and response to therapy. Patients and methods: Viral IRES (5 UTR) in plasma and in blood mononuclear cells (BMC) were amplified in100 naive subjects. Sequences were compared by SSCP, and by line probe assay or cloning when required. Sampling were performed before liver biopsy in 80 patients and before therapy by pegylated interferon/ribavirin in 50 patients followed more than 6 months after therapy. Results: SSCP profiles were different between plasma and PBMC in 39 patients. Among these 39 patients, 13 had different HCV genotypes in PBMC and plasma (genotypic compartmentalization). The compartmentalization was more frequent in case of past IVDU (25/42 vs 14/58; p <0.01). Sustained virological response was related to infection by genotype 2 or 3 (12/20 vs 7/30), duration of infection (19 y±6 vs14±6) and 5 UTR compartmentalization (15/20 vs 5/30, p<0.001). Compartmentalization was an independent variable in multivariate analysis and was not correlated to duration (or age) of infection or to histological severity of hepatitis. These results confirm that the compartmentalization defined in viral IRES is more frequent in former IVDU likely reflecting repeated infective events. Patients in whom BMC and plasma variants are different seem to be excellent candidates for therapy.
474 IMPACT OF PREEMPTIVE THERAPY OF HCV AND HBV ON OCCURRENCE OF HEPATIC COMPLICATIONS FOLLOWING BONE MARROW TRANSPLANTATION (BMT)
M.H. El-Sayed 1 , A. El-Haddad 2 , I. Abdel-Kadir 2 , H.K. Mahmoud 2 . 1 Pediatric Department, Hematology/Oncology Division/Children’s Hospital, Ain Shams University, Cairo, Egypt; 2 Bone Marrow Transplantation Center, National Cancer Institute, Cairo, Egypt Background/aim: Liver disease was an important cause of mortality in a retrospective survey of BMT recipients; 37.5% of HCV and 39.8% of
HBV-infected patients suffered hepatic complications and had less survival probability. This study assesses the impact of preemptive therapy of HCV and HBV on occurrence of BMT-related hepatic complications. Methods: Sixteen HCV-RNA+(genotype 4) (median age:13years) BMT-recipients received a combination of Interferon alpha-2b (3 mIU/m2 SC/day) two weeks, one month before BMT, plus ribavirin (15mg/kg.b.w./day; maximum:1200mg/day) continuously till end of immunosuppression. Patients were monitored by HCV quantitation at baseline, 4,12 and 24 weeks. Eight HBsAg+ve (3 HBcAb+ve and 6 HBV-DNA+)(median age:8.5years) recipients received lamivudine (3mg/kgbw,od;maximum:100mg/d) 2 weeks before BMT. HBsAg/Ab, HBeAg/Ab, HBV-DNA were tested at baseline, 2 weeks and bimonthly thereafter. Results: HCV-RNA became undetectable in one (6.25%) at 4 weeks and 3 (18.7%) at 12 weeks. Six patients (37.5%) showed >2 log drop of HCV-RNA at 4 through 12 weeks. One developed mild veno-occlusive disease, two (12.5%) grade I acute graft-versus-host-disease (AGVHD), two (12.5%) died of BMT-related infections; none suffered hepatic GVHD. None of the children (n=8) receiving lamivudine suffered HBVreactivations. HBV-DNA dropped (<105 copies/ml) before BMT in HBVDNA+ patients (n=6) and was undetectable at 10 weeks in all except one. One developed grade I AGVHD, 2 chronic GVHD and two died of infections. Conclusions: Preemptive therapy of HCV and HBV before BMT in areas endemic for those viruses may decrease the incidence of hepatic complications, though, a larger study group and further follow up is required to draw firm conclusions.
475 SUSTAINED VIROLOGICAL RESPONSE (SVR) TO PEGINTERFERON ALFA-2A (40KD) (PEGASYS) PLUS RIBAVIRIN (RBV) AND AMANTADINE (AMA) VS INDUCTION THERAPY WITH INTERFERON ALFA-2A (ROFERON-A) PLUS RBV AND AMA IN IFN/RBV NON RESPONDERS (NR) WITH CHRONIC HEPATITIS C (CHC
S. Fargion 1 , M. Borzio 2 , A. Maraschi 1 , A. Cargnel 3 . Gel Gruppo Epatologico Lombardo; 1 Dipartimento Medicina Interna, Università Di Milano, Ospedale Maggiore IRCCS, Milano, Italy; 2 I Divisione Medicina Generale, Ospedale Civile Melegnano, Melegnano, Italy; 3 II Divisione Malattie Infettive, Ospedale Sacco, Milano, Italy Background: Despite the use of combination therapy (IFN+RBN), still a large proportion of CHC patients does not respond to therapy. Aim: To determine the benefit of a triple combination regimen (PEG-IFN or daily IFN, plus RBV and AMA) in NR to IFN/RBV. Patients: 185 patients who failed to respond to a prior course of 12-week of IFN/RBV therapy, have been randomized to receive 180 mcg onceweekly of PEG-IFN alfa-2a (40KD) plus RBV (800-1000mg/day) and AMA (200mg daily) (group A) for 48 weeks or IFN alfa-2a (6 MIU daily for 4 weeks, 3 MIU daily for 20 weeks, and then 3 MIU tiw for 24 weeks) plus RBV (800-1000mg/day) and AMA (200mg/day) (group B) for 24 weeks. Patients with detectable HCV-RNA after 24 weeks of treatment were considered non responders, and therapy discontinued. Results: Baseline patient characteristics did not differ in the two groups. Nineteen percent of patients discontinued therapy. End of treatment was 47 and 25% (p=0.06) and SVR 24 and 19%, in group A and B, respectively, with an overall SVR of 22%. SVR was 39% and 18% in genotype non-1 and 1 (p=0.05). Patients of age < 40 years (p=0.05) and viral load > 2MU (p=0.01) responded significantly better PEG-IFN. Conclusions: A proportion of patients with chronic hepatitis C not responders to IFN/RBV can eradicate HCV-RNA infection with triple therapy, especially if they have non-1 genotypes. Younger subjects (< 40 years) and those with higher viral load seem to benefit more from treatment with PEG-IFN.