- Email: [email protected]
ED) treatment programme for women with an latrogenic hepatitis C virus (HCV) infection
2884
female; 56% were Caucasian. 32% were African-American. and 12% were Latino. Fifty-eight percent had genotype 1. The average length of hepatitis C infection was 29 years, and 56% had relatively advanced liver disease. Seventy-one percent had a preexisting psychiatric diagnosis, with depression (58%) being the most common. The most common side effects were flu-like symptoms (75%), irritability (73%) and depression (69%). The dropout rate was 15%, with 3 dropouts due to side effects, 3 due to exacerbation of psychiatric disease, and 2 to worsening liver disease. The end-of-treatment response rate was 71%. CONCLUSION: Although recovering injection drug users exhibit high psychiatric comorbidity and relatively advanced liver disease, combination interferon/ribavirin therapy can be safe, tolerable, and efficacious. Larger studies are neededto further improve treatment options in this population.
The Efficacy of Intederon-,~ Induction Treatment With or Without Ribavirin in Chronic Hepatitis C: Interim Analysis Hakan Senturk, Cerrahpasa Medical Faculty, Istanbul Turkey; Galip Ersoz, Ege Univ, Medical Faculty, Izmir Turkey; Resat Ozaras, Cerrahpasa Medical Faculty, Istanbul Turkey; Sabahattin Kaymakoglu, Istanbul Medical Faculty, Istanbul Turkey; Hakan Bozkaya, Ankara Univ, Medical Faculty, Ankara Turkey; All Mert, Cerrahpasa Medical Faculty, Istanbul Turkey; Selim Karayalcin, Mithat Bozdayi, Ankara Univ, Medical Faculty, Ankara Turkey; Yucel Batur, Ege Univ, Medical Faculty, Izmir Turkey Aim: to compare the efficacy of interferon-p, induction treatment with or without dbavirin in chronic hepatitis C. Methods: The inclusion criteria included anti-HCV positive by second generation ELISA, serum ALT of at least xl.5 of upper limit of normal. HCV-RNApositive by PCR, liver biopsy findings of chronic hepatitis. Exclusion criteria were presence of HBsAo, or decompensation. One hundred twenty five naive patients (66 male, 59 female, mean age:48-+9, range:21-70)were enrolled, and randomized into two arms: In the first, patients received 5MU/day of interferon-~2b(IFN)for 4 weeks followed by 3MU/day for the next 4 weeks. Treatment was continued with 3MU tiw IFN for another 40 weeks. Ribavirin was administered as 1000-1200 mg/day according to body weight for 48 weeks. In the second arm, patients received placebo (provided by Schering&Plough, USA) in addition to IFN. Flltynine patients were placed in ribavirin arm, and 66 in placebo. Sara were collected for HCVRNA quantitation and genotyping. Quantitation was done by b-DNA (Quantiplex HCV-RNA, Chiron Corporation, USA) and genotypes were determined using a second-generation corebased PCR method. Results: Up to this analysis, 9 patients discontinued treatment: Four before and 5 after the end of third month. The results for the biochemical response at 12, 24, and 48 weeks were available from 118,109, and 70 patients respectively, the results for virological response at 12 and 48 weeks were available from 81 and 66 patients respectively. While the biochemical response rates were significantly higher in the ribavirin group: 45/ 55(82%)vs 30/63(48%) at 12, 39/50(78%) vs 24/59(41%) at 24, and 30/33(91%) vs 20/ 37(54%)at 48 weeks, p
2885 Re-Treatment Virologic Response in Chronic Hepatitis C Virologfu N N - R e s I ~
2887 Evaluation of a Bdof Group-Based Psyckologicel/IEdocetional(PWch/EO) Treatment Programme lot Women with an latrogenic Hepatitis C Virus (HCV) Infection. Barbara M. Coughian, John O. Sheehan, Mater Misericordiae Hosp, Dublin Ireland; Alan Cart, Univ Coil Dublin, Dublin Ireland: Alice M. Cockram, John P. Crowe, Mater Misericordiae Hosp, Dublin Ireland Aim: To develop and evaluate a PsyclVEd treatment programme designed to improve adjustment and enhance adaptive coping skills in women with an iatrogenic HCV infection. Methods:Pa,'tici~nts: Thirty-two women with chronic HCV infection were assigned to a treatment (n=18) or centrol(n=14)group and assessed at (Time 1) before and (Time 2) after the treatment group's participation in the PsyclvED programme. In addition the treatment group was assessed at three months follow-up (Time 3). The PsyclVEd programme was facilitated by a psychologist and a nurse and ran for two hours per week over seven weeks. Measures:The Hepatitis C Suntey Questionnaireand Goals Pre and Post Treatment Questionnaire (Cough/an, Sheehan, Carr & Crowe, unpublished), General Health Questionnaire (Goldberg, 1988), Short Form-36 Health Survey (Jenkinson & Coulter, 1993) and Culture Free Sell-esteem Inventory (Battle, 1992). Results: A series of mixed model ANOVAs were carried out on all measures and significant Group X Time effects were observed as expected for physical functioning (F=9.01, p<.01) and social serf-esteem (F=5.30, p<.05). A series of repeated measures ANOVAs were carded out on all measures and a significant time effect was observed as expected for a sustained improvement in psychological well-being (F = 8.01, p<.O1)at three months post treatment. The main qualitative theme centered on the women's perception of their achievements after the PsyclVEd treatment programme. Overall, most women felt more positive and informed about their illness, reported more confidence and felt they had greater ability to control and cope with their lives. Conclusion: Participation in a Psych/Ed treatment programme was perceived as a positive experience and associated with improvements in physical functioning, social sell-esteem and psychological well-being in women with an iatrogenic HCV infection.
2m
(NR) and Responder-Relapcers (NR) tn Intederen (IFN) Monntkerepy: IFli =-2b
Induction Followed by Combination Ribavirin/Intederon a-2b vs Combination Rihavirin/Intederen a-2b (780 MIU/52 Weeks Rehatron Therapy).
latederen-slpha Therapy and the IL-18 Pathway in Chronic Hepatitis C Patients: IFN-alpha Therapy Enhances Circulating IL-18 Binding Protein Levels
Neville R. Pimstone, John B. Canio, Michelle H. Chiang, Janet Kokosinsld, Jeny S. Powell, Theparet Saicheur, Paul I. Sheykhzadeh,Univ of CA, Davis, Sacramento, CA; Andy S. Yu, Stanford Univ, Palo Alto, CA
Arthur Kaser, Wolfoang Vogel, Dept of Gastroenterology, Univ Hosp, Innsbruck Austria; Oaniela Novick, Menachem Rubinstein, Weizmann Institute of Science, Rehovot Israel; Charles A. Dinarello, Univ of Colorado Health Science Ctr, Denver, CO; Herbert Tilg, Dept of Gastroenterology, Univ Hosp, Innsbruck Austria
Background: A low baseline viral count predicts a better virologic outcome with dbavirin/IFN therapy for chronic hepatitis C. Aim: The purpose of the study was to determine if IFN induction prior to combination ribavirin/IFN therapy in patients who were previously virologic nonresponders (NR) or responder-relapsers (RR) could (1) further lower the viral load and (2) ultimately confer a favorable virologic outcome. Study design: One hundred twenty six of the 200 patients enrolled have been followed for 78 weeks and are the basis of this report. Group I consisted of 85 patients who received daily induction IFN ~-2b of 10 MIU x 2 weeks and then started (week O) on combination ribavirin/IFN ~2b x 52 weeks. Group II consisted of 31 patients who received comination ribavirin/IFN ~-2b x 52 weeks. All patients in both groups received a total IFN dosage of 780 MIU and were followed for 78 weeks after starting combination therapy. Virologic response (VR) is defined as no detectable virus in blood samples by RT-PCR assay (lower limit of detection <100 coples/ml). Virologic sustained response (V-SR) is defined as no detectable virus 26 weeks after stopping therapy. Results: (1) The ratio of NR:RR was 64:36 in either group. (2) Induction using IFN ~-2b for 2 weeks (Group 1) resulted in an overall VR of 47%, with 40% in the NR subgroup and 62% in the RR subgroup (p
Background. IL-18, formerly called IFN-gamma-inducing factor, is centrally involved in the development of acute liver injury. Recently, IL-18 binding protein (IL-18BP) has been identified as a potent natural antagonist of IL-18. We set out to determine whether IFN-alpha might exert anti-inflammatory properties by modulating IL-18BP levels. Methods.lxlOTIU IFN-a2b were administered daily to 14 chronic hepatitis C patients. Plasma samples obtained before initiation of treatment and at various time-points thereafter were assayed for IL-18BP by a recently developed ELISA system. Results. Pretreatment levels of IL-18BP were 8,48 +- 1,75 ng/mL. Following a single injection of lx1071U IFN-a, IL-18BP levels increased significantly after 6h and reached peak levels at 24h (27,48 +- 2,55, P
2889 High Body Mass index is an Independent Risk Factor for Non-Response to Antiviral Treatment in Chronic Hepatitis C. Brian L Bressler, George Tomlinson, lan R. Wanless, Jenny E. Heathcote, Univ of Toronto, Toronto Canada
2886
Aim: To determine if Body Mass Index was an independent predictor of response to antiviral treatment in patients with chronic hepatitis C. Methods: Retrospective review of all patients at o single center with chronic hepatitis C treated with antiviral medication since 1989. A sustained response (SR) was defined as either negative HCV RNA by PCR and/or normal ALT (only in those treated prior to availability of HCV RNA testing) at the end of 6-month fo//ow-up. All patients were classified into one of three BMI groups (normal = <26kg/m 2,overweight = 2530kg/m2, obese>3Okg/m2). Statistical Methods: Multiple logistic regression was used to assessthe relationship betweenan SR and the risk factors sex, ethanol consumption, genotype, cirrhosis and BMI group. Statistical significance of each risk factor was assessed with a likelihood ratio test comparing models with and without the risk factor. Results: A total of 253 patients were treated with either IFN monotherapy or IFN in combination with ribavirin. Patients were excluded if there was missing data in any of the following parameters (except
Treating Hepatitis C in Recovering Injection Drug Users Diana L. Sylvestre, Roberta Aron, Deborah R. Greene, Patricia Perkins, Organization to Achieve Solutions in Substance-Abuse, Oakland, CA BACKGROUND:Despite the high prevalence of hepatitis C in recovering injection drug users, there is little data on the safety, tolerability, and efficacy of combination interferon/ribavirin therapy in this group. METHODS: Fifty-two recovering injection drug users enrolled in a methadone maintenance program with active hepatitis C were treated with interferon/ribavirin combination therapy at standard dosing regimens. A unique group education/treatment protocol was used. Enrollment was based on fibrosis as demonstrated either by biopsy or by surrogate chemical markers: splenomegaly, thrombocytopenia, or hypoalbuminemia. RESULTS: The average age of the treatment group was 49; 54% were male and 46% were
A-568
female; 56% were Caucasian. 32% were African-American. and 12% were Latino. Fifty-eight percent had genotype 1. The average length of hepatitis C infection was 29 years, and 56% had relatively advanced liver disease. Seventy-one percent had a preexisting psychiatric diagnosis, with depression (58%) being the most common. The most common side effects were flu-like symptoms (75%), irritability (73%) and depression (69%). The dropout rate was 15%, with 3 dropouts due to side effects, 3 due to exacerbation of psychiatric disease, and 2 to worsening liver disease. The end-of-treatment response rate was 71%. CONCLUSION: Although recovering injection drug users exhibit high psychiatric comorbidity and relatively advanced liver disease, combination interferon/ribavirin therapy can be safe, tolerable, and efficacious. Larger studies are neededto further improve treatment options in this population.
The Efficacy of Intederon-,~ Induction Treatment With or Without Ribavirin in Chronic Hepatitis C: Interim Analysis Hakan Senturk, Cerrahpasa Medical Faculty, Istanbul Turkey; Galip Ersoz, Ege Univ, Medical Faculty, Izmir Turkey; Resat Ozaras, Cerrahpasa Medical Faculty, Istanbul Turkey; Sabahattin Kaymakoglu, Istanbul Medical Faculty, Istanbul Turkey; Hakan Bozkaya, Ankara Univ, Medical Faculty, Ankara Turkey; All Mert, Cerrahpasa Medical Faculty, Istanbul Turkey; Selim Karayalcin, Mithat Bozdayi, Ankara Univ, Medical Faculty, Ankara Turkey; Yucel Batur, Ege Univ, Medical Faculty, Izmir Turkey Aim: to compare the efficacy of interferon-p, induction treatment with or without dbavirin in chronic hepatitis C. Methods: The inclusion criteria included anti-HCV positive by second generation ELISA, serum ALT of at least xl.5 of upper limit of normal. HCV-RNApositive by PCR, liver biopsy findings of chronic hepatitis. Exclusion criteria were presence of HBsAo, or decompensation. One hundred twenty five naive patients (66 male, 59 female, mean age:48-+9, range:21-70)were enrolled, and randomized into two arms: In the first, patients received 5MU/day of interferon-~2b(IFN)for 4 weeks followed by 3MU/day for the next 4 weeks. Treatment was continued with 3MU tiw IFN for another 40 weeks. Ribavirin was administered as 1000-1200 mg/day according to body weight for 48 weeks. In the second arm, patients received placebo (provided by Schering&Plough, USA) in addition to IFN. Flltynine patients were placed in ribavirin arm, and 66 in placebo. Sara were collected for HCVRNA quantitation and genotyping. Quantitation was done by b-DNA (Quantiplex HCV-RNA, Chiron Corporation, USA) and genotypes were determined using a second-generation corebased PCR method. Results: Up to this analysis, 9 patients discontinued treatment: Four before and 5 after the end of third month. The results for the biochemical response at 12, 24, and 48 weeks were available from 118,109, and 70 patients respectively, the results for virological response at 12 and 48 weeks were available from 81 and 66 patients respectively. While the biochemical response rates were significantly higher in the ribavirin group: 45/ 55(82%)vs 30/63(48%) at 12, 39/50(78%) vs 24/59(41%) at 24, and 30/33(91%) vs 20/ 37(54%)at 48 weeks, p
2885 Re-Treatment Virologic Response in Chronic Hepatitis C Virologfu N N - R e s I ~
2887 Evaluation of a Bdof Group-Based Psyckologicel/IEdocetional(PWch/EO) Treatment Programme lot Women with an latrogenic Hepatitis C Virus (HCV) Infection. Barbara M. Coughian, John O. Sheehan, Mater Misericordiae Hosp, Dublin Ireland; Alan Cart, Univ Coil Dublin, Dublin Ireland: Alice M. Cockram, John P. Crowe, Mater Misericordiae Hosp, Dublin Ireland Aim: To develop and evaluate a PsyclVEd treatment programme designed to improve adjustment and enhance adaptive coping skills in women with an iatrogenic HCV infection. Methods:Pa,'tici~nts: Thirty-two women with chronic HCV infection were assigned to a treatment (n=18) or centrol(n=14)group and assessed at (Time 1) before and (Time 2) after the treatment group's participation in the PsyclvED programme. In addition the treatment group was assessed at three months follow-up (Time 3). The PsyclVEd programme was facilitated by a psychologist and a nurse and ran for two hours per week over seven weeks. Measures:The Hepatitis C Suntey Questionnaireand Goals Pre and Post Treatment Questionnaire (Cough/an, Sheehan, Carr & Crowe, unpublished), General Health Questionnaire (Goldberg, 1988), Short Form-36 Health Survey (Jenkinson & Coulter, 1993) and Culture Free Sell-esteem Inventory (Battle, 1992). Results: A series of mixed model ANOVAs were carried out on all measures and significant Group X Time effects were observed as expected for physical functioning (F=9.01, p<.01) and social serf-esteem (F=5.30, p<.05). A series of repeated measures ANOVAs were carded out on all measures and a significant time effect was observed as expected for a sustained improvement in psychological well-being (F = 8.01, p<.O1)at three months post treatment. The main qualitative theme centered on the women's perception of their achievements after the PsyclVEd treatment programme. Overall, most women felt more positive and informed about their illness, reported more confidence and felt they had greater ability to control and cope with their lives. Conclusion: Participation in a Psych/Ed treatment programme was perceived as a positive experience and associated with improvements in physical functioning, social sell-esteem and psychological well-being in women with an iatrogenic HCV infection.
2m
(NR) and Responder-Relapcers (NR) tn Intederen (IFN) Monntkerepy: IFli =-2b
Induction Followed by Combination Ribavirin/Intederon a-2b vs Combination Rihavirin/Intederen a-2b (780 MIU/52 Weeks Rehatron Therapy).
latederen-slpha Therapy and the IL-18 Pathway in Chronic Hepatitis C Patients: IFN-alpha Therapy Enhances Circulating IL-18 Binding Protein Levels
Neville R. Pimstone, John B. Canio, Michelle H. Chiang, Janet Kokosinsld, Jeny S. Powell, Theparet Saicheur, Paul I. Sheykhzadeh,Univ of CA, Davis, Sacramento, CA; Andy S. Yu, Stanford Univ, Palo Alto, CA
Arthur Kaser, Wolfoang Vogel, Dept of Gastroenterology, Univ Hosp, Innsbruck Austria; Oaniela Novick, Menachem Rubinstein, Weizmann Institute of Science, Rehovot Israel; Charles A. Dinarello, Univ of Colorado Health Science Ctr, Denver, CO; Herbert Tilg, Dept of Gastroenterology, Univ Hosp, Innsbruck Austria
Background: A low baseline viral count predicts a better virologic outcome with dbavirin/IFN therapy for chronic hepatitis C. Aim: The purpose of the study was to determine if IFN induction prior to combination ribavirin/IFN therapy in patients who were previously virologic nonresponders (NR) or responder-relapsers (RR) could (1) further lower the viral load and (2) ultimately confer a favorable virologic outcome. Study design: One hundred twenty six of the 200 patients enrolled have been followed for 78 weeks and are the basis of this report. Group I consisted of 85 patients who received daily induction IFN ~-2b of 10 MIU x 2 weeks and then started (week O) on combination ribavirin/IFN ~2b x 52 weeks. Group II consisted of 31 patients who received comination ribavirin/IFN ~-2b x 52 weeks. All patients in both groups received a total IFN dosage of 780 MIU and were followed for 78 weeks after starting combination therapy. Virologic response (VR) is defined as no detectable virus in blood samples by RT-PCR assay (lower limit of detection <100 coples/ml). Virologic sustained response (V-SR) is defined as no detectable virus 26 weeks after stopping therapy. Results: (1) The ratio of NR:RR was 64:36 in either group. (2) Induction using IFN ~-2b for 2 weeks (Group 1) resulted in an overall VR of 47%, with 40% in the NR subgroup and 62% in the RR subgroup (p
Background. IL-18, formerly called IFN-gamma-inducing factor, is centrally involved in the development of acute liver injury. Recently, IL-18 binding protein (IL-18BP) has been identified as a potent natural antagonist of IL-18. We set out to determine whether IFN-alpha might exert anti-inflammatory properties by modulating IL-18BP levels. Methods.lxlOTIU IFN-a2b were administered daily to 14 chronic hepatitis C patients. Plasma samples obtained before initiation of treatment and at various time-points thereafter were assayed for IL-18BP by a recently developed ELISA system. Results. Pretreatment levels of IL-18BP were 8,48 +- 1,75 ng/mL. Following a single injection of lx1071U IFN-a, IL-18BP levels increased significantly after 6h and reached peak levels at 24h (27,48 +- 2,55, P
2889 High Body Mass index is an Independent Risk Factor for Non-Response to Antiviral Treatment in Chronic Hepatitis C. Brian L Bressler, George Tomlinson, lan R. Wanless, Jenny E. Heathcote, Univ of Toronto, Toronto Canada
2886
Aim: To determine if Body Mass Index was an independent predictor of response to antiviral treatment in patients with chronic hepatitis C. Methods: Retrospective review of all patients at o single center with chronic hepatitis C treated with antiviral medication since 1989. A sustained response (SR) was defined as either negative HCV RNA by PCR and/or normal ALT (only in those treated prior to availability of HCV RNA testing) at the end of 6-month fo//ow-up. All patients were classified into one of three BMI groups (normal = <26kg/m 2,overweight = 2530kg/m2, obese>3Okg/m2). Statistical Methods: Multiple logistic regression was used to assessthe relationship betweenan SR and the risk factors sex, ethanol consumption, genotype, cirrhosis and BMI group. Statistical significance of each risk factor was assessed with a likelihood ratio test comparing models with and without the risk factor. Results: A total of 253 patients were treated with either IFN monotherapy or IFN in combination with ribavirin. Patients were excluded if there was missing data in any of the following parameters (except
Treating Hepatitis C in Recovering Injection Drug Users Diana L. Sylvestre, Roberta Aron, Deborah R. Greene, Patricia Perkins, Organization to Achieve Solutions in Substance-Abuse, Oakland, CA BACKGROUND:Despite the high prevalence of hepatitis C in recovering injection drug users, there is little data on the safety, tolerability, and efficacy of combination interferon/ribavirin therapy in this group. METHODS: Fifty-two recovering injection drug users enrolled in a methadone maintenance program with active hepatitis C were treated with interferon/ribavirin combination therapy at standard dosing regimens. A unique group education/treatment protocol was used. Enrollment was based on fibrosis as demonstrated either by biopsy or by surrogate chemical markers: splenomegaly, thrombocytopenia, or hypoalbuminemia. RESULTS: The average age of the treatment group was 49; 54% were male and 46% were
A-568