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IFN plus ribavirin in HIV+ patients with chronic hepatitis C
Posters
I P/C06/69 I
[ P/C06/71 I
COGNITIVE BRAIN FUNCTION IS SUBCLINICALLY IMPAIRED IN PATIENTS WITH CHRONIC HEPATITIS C - DOES HEPATITIS C AFFECT THE BRAIN? L. Kramer, G. Funk, H. Hofer, E. Bauer, E Munda-Steindl, C. Madl, E Ferenci Dept. of Medicine IV, Univ. Vienna, Austria. Fatigue and depression occur more frequently in chronic hepatitis C virus (HCV) infection than in other causes of chronic liver disease. However there is no correlation between hepatic inflammation and cerebral symptoms. It has been hypothesised that HCV exerted a direct effect on the brain. We studied the impact of HCV infection on sensitive markers of cognitive brain function. Fifty-five noncirrhotic patients with chronic HCV infection (age, 45+14 years, mean±SD) were studied by P300 event-related potentials (an objective measure of cognitive processing) and by the SF-36 for assessment of health-related quality of life (HRQOL). P300 latency is related to signalprocessing speed; its amplitude reflects the amount of attention paid to a stimulus. Findings were compared to 55 matched healthy subjects. We found that cognitive processing was subclinically impaired in patients (P300 latency: 358+35 vs, 344+27ms in controls; p<0.05). Similarly, P300 amplitude was reduced in patients with HCV infection (12+7 vs. 18+7pV, p<0.01). HRQOL was significantly reduced in HCV infection but there was no clear correlation between neurophysiological function and HRQOL or activity of hepatitis. In 7 out of 8 patients who were followed during antiviral treatment, P300 latency improved after 12 weeks. In conclusion, patients with chronic HCV infection in the absence of cirrhosis exhibit a subclinical neurophysiological impairment. Cerebral function, however, seems to normalise with antiviral treatment. Our data might indicate a direct action of HCV infection on the brain.
TREATMENT OF CHRONIC HEPATITIS B WITH LAMIVUDINE IN RENAL TRANSPLANT RECIPIENTS J. Sperl, E Trunc~ka, J. Lficha, L. Noskovfi, E Sk~.lovfi,E Taimr, S. Vitko Institute for Clinical and Experimental Medicine, Prague, Czech Republic. Aim of the study: To evaluate the efficacy and safety of lamivudine in renal transplant recipients with chronic hepatitis B. Methods: 7 renal transplant recipients with chronic hepatitis B, mean age 41+8 yrs, were treated with lamivudine because o f slowly increasig serum ALT or acute manifestation of HBV reactivation. Before treatment, serum ALT were elevated in all patients (2-30N), HBeAg was positive in 5 patients, mean serum HBV DNA was 4200+2550 pg/mL. Liver biopsies showed cirrhosis in 1 patient, chronic hepatitis in 4 patients and fibrosing cholestatic hepatitis in 2 patients. The starting dose of lamivudine was 75 mg; during therapy it was adjusted according to graft function. Results: 1 patient with fibrosing ch'olestatic hepatitis died of liver failure after 2 months, 6 patients alive. Mean follow-up was 14+8 months (2-25). Lamivudine was well tolerated in all patients, no changes in graft function or cyclosporine interference were observed. HBV DNA disappeared from serum of all patients after 1 month; howerer, serum ALT activity became normal in the 6 surviving patients until after 6.6_+_2.9 moths. One patient developed resistence to lamivudine after 12 months. Conclusion: Lamivudine is safe and effective treatment of chronic hepatitis B or cirrhosis in renal transplant recipients. The effect in fibrosing cholestatic hepatitis is dubious.
[ P/CO6 O I
I P/CO 2 [
IRON DEPLETION AND INTERFERON (IFN) THERAPY: A MULTICENTER, RANDOMIZED TRIAL IN "NAIVE" PATIENTS WITH CHRONIC HEPATITIS C S. Fargion i, M. Ballar~, G. Belloni, E Bissoli, M. Borzio, R. Ceriani, G. FiorelliI, A.L. Fracanzani 1, M. Massari, M. Mattioli 1, A. Rossini, O. Rig¢,io. C. Trischitta iIRCCS Osp Magg Mi, Italy. It is still debated if in patients with chronic hepatitis C iron influences the response to IFN therapy and if iron depletion may improve it. To evaluate whether iron reduction by phlebotomy prior to IFN therapy improves the rate of biochemical and virological response in "naive" non-cirrhotic pts with chronic hepatitis C, we enrolled 112 (85 M, 27 F) HCV-RNA pos pts with ALT>I.5 UNL and liver iron concentration (LIC) >70 (M) and 50 (F) ug/100 rag dry tissue. Pts, stratified according to HCV genotypes (1-4 and 2-3) and yGT values, were randomized to weekly phlebotomy (56 cases) till iron depletion followed by IFN 6 MU t.i.w. (gpA) or to IFN alone 6 MU t.i.w. (56 cases) (gpB). After 4 months non responders discontinued therapy, while biochemical responders continued with 3 MU t.i.w, for further 8 months. At the end of treatment (12 months) 46% of pts in gpA and 31% in gpB had normal ALT and 33% and 21% were HCV-RNA neg. After 3 months of follow up (the study is ongoing) 25% and 20% of patients of gpA and 16% and 10% of gpB had normal ALT and neg HCV-RNA. In gpA biochemical response was better in pts with LIC<100, whereas viral eradication was not influenced by baseline LIC. Phlebotomy in association with IFN and/or antiviral agents should be considered in the therapy of chronic hepatitis C.
IFN PLUS RIBAVIRIN IN HIV+ PATIENTS WITH CHRONIC HEPATITIS C M. Ptrez-Olmeda, J. Gtnzalezt, J. Garcia-Samaniego,J. Arribas t, J. Pefial, V. Soriano lnstituto de Salud Carlos III, Madrid, Spain. 1Hospital La Paz, Madrid, Spain. CHC is now recognized as an increasing cause of morbidity in HIV+ subjects, in which progression to cirrhosis seem to be accelerated. The efficacy and safety of IFN plus RBV (IFN 3 MU tiw + RBV 1000/1200 rag/day during 6 months) for therapy of CHC was assessed in 18 HIVHCV co-infected patients (11 M; age 33 + 3; CD4+ count >300; HA] score 9.1 ± 1.8; 50% HCV-3a; 39% HCV-I; pre-treatment HCV-RNA 1,2 X 107). All had be~n previously treated with IFN during 1 year without sustained response (SR) (6 N-R and 12 RR). Eleven (66%) received concomitant anti-H1V drugs. Early biochemical and virology responses (3th month) were seen in 11/18 (61%), 7 of whom carried HCV-3a. Seven patients (38%) did not complete the end of therapy. Lost of follow-up occurred in 4 and suicidal ideation, deficient compliance, and anemia were recorded as causes of treatment withdrawal in the remaining eases. 6/11 patients (54.5%) who completed the end of treatment reached both biochemical and virological responses. HIV-RNA levels and the CD4+ count remained unchanged in all patients during IFN/RBV therapy. As expected, RR patients showed a higher response rate than NR (5/6; 83% vs 1/5; 20%; p<0.05). Likewise, those carrying HCV-3a tended to respond much better than those infected with HCV-I. SR (6 months after stopping IFN/RBV) was seen in 5/11 (45.5 %) subjects. The only person who relapsed carried HCV-I. Contusion: A 24-week course of [FN-RBV seems to be safe in H]VHCV coinfected individuals and provides a response rate for CHC similar to that reached in HIV-negative. Thus, prospective, randomized, large trials are warranted in this population.
114
I P/C06/69 I
[ P/C06/71 I
COGNITIVE BRAIN FUNCTION IS SUBCLINICALLY IMPAIRED IN PATIENTS WITH CHRONIC HEPATITIS C - DOES HEPATITIS C AFFECT THE BRAIN? L. Kramer, G. Funk, H. Hofer, E. Bauer, E Munda-Steindl, C. Madl, E Ferenci Dept. of Medicine IV, Univ. Vienna, Austria. Fatigue and depression occur more frequently in chronic hepatitis C virus (HCV) infection than in other causes of chronic liver disease. However there is no correlation between hepatic inflammation and cerebral symptoms. It has been hypothesised that HCV exerted a direct effect on the brain. We studied the impact of HCV infection on sensitive markers of cognitive brain function. Fifty-five noncirrhotic patients with chronic HCV infection (age, 45+14 years, mean±SD) were studied by P300 event-related potentials (an objective measure of cognitive processing) and by the SF-36 for assessment of health-related quality of life (HRQOL). P300 latency is related to signalprocessing speed; its amplitude reflects the amount of attention paid to a stimulus. Findings were compared to 55 matched healthy subjects. We found that cognitive processing was subclinically impaired in patients (P300 latency: 358+35 vs, 344+27ms in controls; p<0.05). Similarly, P300 amplitude was reduced in patients with HCV infection (12+7 vs. 18+7pV, p<0.01). HRQOL was significantly reduced in HCV infection but there was no clear correlation between neurophysiological function and HRQOL or activity of hepatitis. In 7 out of 8 patients who were followed during antiviral treatment, P300 latency improved after 12 weeks. In conclusion, patients with chronic HCV infection in the absence of cirrhosis exhibit a subclinical neurophysiological impairment. Cerebral function, however, seems to normalise with antiviral treatment. Our data might indicate a direct action of HCV infection on the brain.
TREATMENT OF CHRONIC HEPATITIS B WITH LAMIVUDINE IN RENAL TRANSPLANT RECIPIENTS J. Sperl, E Trunc~ka, J. Lficha, L. Noskovfi, E Sk~.lovfi,E Taimr, S. Vitko Institute for Clinical and Experimental Medicine, Prague, Czech Republic. Aim of the study: To evaluate the efficacy and safety of lamivudine in renal transplant recipients with chronic hepatitis B. Methods: 7 renal transplant recipients with chronic hepatitis B, mean age 41+8 yrs, were treated with lamivudine because o f slowly increasig serum ALT or acute manifestation of HBV reactivation. Before treatment, serum ALT were elevated in all patients (2-30N), HBeAg was positive in 5 patients, mean serum HBV DNA was 4200+2550 pg/mL. Liver biopsies showed cirrhosis in 1 patient, chronic hepatitis in 4 patients and fibrosing cholestatic hepatitis in 2 patients. The starting dose of lamivudine was 75 mg; during therapy it was adjusted according to graft function. Results: 1 patient with fibrosing ch'olestatic hepatitis died of liver failure after 2 months, 6 patients alive. Mean follow-up was 14+8 months (2-25). Lamivudine was well tolerated in all patients, no changes in graft function or cyclosporine interference were observed. HBV DNA disappeared from serum of all patients after 1 month; howerer, serum ALT activity became normal in the 6 surviving patients until after 6.6_+_2.9 moths. One patient developed resistence to lamivudine after 12 months. Conclusion: Lamivudine is safe and effective treatment of chronic hepatitis B or cirrhosis in renal transplant recipients. The effect in fibrosing cholestatic hepatitis is dubious.
[ P/CO6 O I
I P/CO 2 [
IRON DEPLETION AND INTERFERON (IFN) THERAPY: A MULTICENTER, RANDOMIZED TRIAL IN "NAIVE" PATIENTS WITH CHRONIC HEPATITIS C S. Fargion i, M. Ballar~, G. Belloni, E Bissoli, M. Borzio, R. Ceriani, G. FiorelliI, A.L. Fracanzani 1, M. Massari, M. Mattioli 1, A. Rossini, O. Rig¢,io. C. Trischitta iIRCCS Osp Magg Mi, Italy. It is still debated if in patients with chronic hepatitis C iron influences the response to IFN therapy and if iron depletion may improve it. To evaluate whether iron reduction by phlebotomy prior to IFN therapy improves the rate of biochemical and virological response in "naive" non-cirrhotic pts with chronic hepatitis C, we enrolled 112 (85 M, 27 F) HCV-RNA pos pts with ALT>I.5 UNL and liver iron concentration (LIC) >70 (M) and 50 (F) ug/100 rag dry tissue. Pts, stratified according to HCV genotypes (1-4 and 2-3) and yGT values, were randomized to weekly phlebotomy (56 cases) till iron depletion followed by IFN 6 MU t.i.w. (gpA) or to IFN alone 6 MU t.i.w. (56 cases) (gpB). After 4 months non responders discontinued therapy, while biochemical responders continued with 3 MU t.i.w, for further 8 months. At the end of treatment (12 months) 46% of pts in gpA and 31% in gpB had normal ALT and 33% and 21% were HCV-RNA neg. After 3 months of follow up (the study is ongoing) 25% and 20% of patients of gpA and 16% and 10% of gpB had normal ALT and neg HCV-RNA. In gpA biochemical response was better in pts with LIC<100, whereas viral eradication was not influenced by baseline LIC. Phlebotomy in association with IFN and/or antiviral agents should be considered in the therapy of chronic hepatitis C.
IFN PLUS RIBAVIRIN IN HIV+ PATIENTS WITH CHRONIC HEPATITIS C M. Ptrez-Olmeda, J. Gtnzalezt, J. Garcia-Samaniego,J. Arribas t, J. Pefial, V. Soriano lnstituto de Salud Carlos III, Madrid, Spain. 1Hospital La Paz, Madrid, Spain. CHC is now recognized as an increasing cause of morbidity in HIV+ subjects, in which progression to cirrhosis seem to be accelerated. The efficacy and safety of IFN plus RBV (IFN 3 MU tiw + RBV 1000/1200 rag/day during 6 months) for therapy of CHC was assessed in 18 HIVHCV co-infected patients (11 M; age 33 + 3; CD4+ count >300; HA] score 9.1 ± 1.8; 50% HCV-3a; 39% HCV-I; pre-treatment HCV-RNA 1,2 X 107). All had be~n previously treated with IFN during 1 year without sustained response (SR) (6 N-R and 12 RR). Eleven (66%) received concomitant anti-H1V drugs. Early biochemical and virology responses (3th month) were seen in 11/18 (61%), 7 of whom carried HCV-3a. Seven patients (38%) did not complete the end of therapy. Lost of follow-up occurred in 4 and suicidal ideation, deficient compliance, and anemia were recorded as causes of treatment withdrawal in the remaining eases. 6/11 patients (54.5%) who completed the end of treatment reached both biochemical and virological responses. HIV-RNA levels and the CD4+ count remained unchanged in all patients during IFN/RBV therapy. As expected, RR patients showed a higher response rate than NR (5/6; 83% vs 1/5; 20%; p<0.05). Likewise, those carrying HCV-3a tended to respond much better than those infected with HCV-I. SR (6 months after stopping IFN/RBV) was seen in 5/11 (45.5 %) subjects. The only person who relapsed carried HCV-I. Contusion: A 24-week course of [FN-RBV seems to be safe in H]VHCV coinfected individuals and provides a response rate for CHC similar to that reached in HIV-negative. Thus, prospective, randomized, large trials are warranted in this population.
114