- Email: [email protected]
Contrasting patterns of response to lamivudine monotherapy
Viral hepatitis: clinical aspects [
PIC06/33 [
NATURAL COURSE OF HCV INFECTION IN HAEMODIALYSED PATIENTS B. Nalpas, H. Zylberberg, H. Fontaine, E Carnot, C. Brtchot, S. Pal Liver unit and Inserm U370, Necker, Paris, France. Background/Aims: The aim of this study was to evaluate the impact of the frequent HCV infection (25%) in haernodialysed patients to precise the place of antiviral therapy. Methods: All the antiHCV-positive, HBsAg-and anti-HIV negative, haemodialyscd patients from our files who have been histologically evaluated before any anti-viral therapy. The date of HCV contamination, in the absence of known acute hepatitis (n=14), was arbitrarily assumed to be the date of the initiation of dialysis. Histopathologicsl results were compared to those of a historical cohort of immunocompetent anti-HCV positive patients previously described. Results: They were 44 dialysis pts candidates to renal transplantation (32 men, 12 women) with a mean age of 49 + 13 years, The mean duration of HCV infection was 5.9 + 6.3 years. HCV genotypes, known in 24, were la (6.8%), lb (54.6%), 2a (11.4%), 3a (4.5%) and 5 (2.3%) and 7 patients were HCV RNA negative at time of evaluation. The mean ALT value was 50 + 44 IU/I (UNL < 45) and only 30% had hype~ansaminasemia. The mean Knodell score was 4.9 + 3 and the rate of cirrhosis was 11.4 % (n=5). HCV RNA negative patients had a higher, although not significant, total KnodeU score than their positive counterparts (4.9"-+-2.8vs 3.6+3.3). All cirrhotics but one (80 %) were older than 45 at time of HCV infection against 48% in noncirthotics; their mean time to develop cirrhosis was 8 years. In our series of imrnunocompetent non hemodialysed patients, the rate of cirrhosis was 11% and the time to develop cirrhosis in patients infected after 45 years was 8+5 years. Conclusion : HCV positive hemodialysed patients do not strikingly differ from immunocempetent patients regarding the rate of cirrhosis and the time to develop cirrhosis. HCV positive bemodialysed should therefore be considered for anti-viral therapy.
I P/C06/35 ] IRON OVERLOAD (IO) AND SEVERITY OF LIVER DISEASE IN CHRONIC HEPATITIS C (CHC) PATIENTS L.I. FernAndez Salazar, J.A. Moreno, A. Garcia S/mchez1, O. Lo Iacono, L. Garcia Buey, A. Arnaiz-Villena2, R. Moreno-Otero Unit of Hepatology, Hospital de la Princesa, Madrid, Spain. IPathology Dpt, Hospital de la Princesa, Madrid, Spain. 2Immunology Dpt, Hospital 12 de Octubre, Madrid, Spain. Aims: To compare epidemiological, clinical, biochemical, virological, histological and therapeutical characteristics in CHC patients with and without IO, and the prevalence of hereditary haemochromatosis (HH) gene mutations in patients with IO. Patients and methods: We studied 300 CHC patients (1995-1998), considenng IO when serum ferritin was higher than 180 ng/ml in women and 280 ng/ml in men, and/or transfernn saturation higher than 45%. We analized: age, sex, CHC evol~on time, medical treatment, personal and familial story, ways of transmission, alcohol consumption, haemoglobine, platelet and leucocyte counts, coagulation study, transaminases (AST, ALT), GGT, FAL, TBIL, total pmtains, immunoglobulines, HCV viraemia, HCV genotype, fibrosis stage, cirrhosis presence, response to interferon treatment, and prevalence of HH gene mutations (C282Y, H63D) in IO patiants. Student's t and chi-squarad tests were used for statistics (p<0.05). Results: We observed IO in 39% (117/300) patients. Significantly statistic differences appeared in (non-IO and IO patients, respactivety): age (39.1+10.5 vs 42.5±10.5), sex (41.2%F and 58.7%M vs 28.2%F and 71.8%M), i.v. drug abuse (18.0% vs 9.4%), hypedipaemia, hyperglycamia or artedal hypertension (6.3% vs 13.6%), alcohol intake (18.1% vs 31.7%), AST (66.5:1;59.5 vs 99.2:1=71.1), ALT (118.8+105.2 vs 164.9+117.4), FAL (172.4£-65.4 vs 191.6+71.5), GGT (40.8:1:37 vs 75.1:1:56.5), TBIL (0.67x~0.31 vs 0.89~t0.53), fibrosis stage (2.05x'-0.9 vs 2.4:1:1.1), presence of cirrhosis (0.9% vs 16.2%), genotype lb (52.8% vs 70.9%), nonrasponsa to interferon (57.4% vs 87.0%). Allelic H63D frequence was 28.5% (8/28), and prevalence of haterocygotic and homocygotic patients were 42.8% (6/14) and 7.1% (1/14), respectively. We found no heterogygotic or homogygotic patients for C282Y mutation. Conclusions: 1. IO was associated to an older age and males. 2. Alcohol intake and metabolic disorders could explain IO, at least partially. 3. IO was associated to a higher level of citolysis, cholestasis, fibrosis stage, and cirrhosis. 4. Interferon response was worse in IO patients. 5. H63D (but no C282Y) mutation is common in CHC patients with IO.
I CONTRASTING PATTERNS OF RESPONSE TO LAMIVUDINE MONOTHERAPY R.A. de Man t. L.M.M. Wolters l, A.B. van Nunen I. H.G,M. Niesters2 IDept. of Hepatogastroenterology, Erasmus University Hospital Rotterdam, The Netherlands. 2Dept. of Virology, Erasmus University Hospital Rotterdam, The Netherlands. W e describe a cohort of patients trent~ with lamivudine, a reverse transcriptase inhibitor with a strong virus suplxcssive effect on the hepatitis B virus, Eighty-nine patients were inchdad in the intentinn to treat analysis. Evaluation with the Kaplan-Meier method was based on response to therapy of HBV D N A levels as well as normalisation of transaminases. Subgroup evaluation based on the per protocol data was performed on two groups within this cohort based on the H B V D N A level at the and of the=alr/.During a 52 weeks tzeatmant period, the chance of being H B V D N A negative at one point in time as measured
by the Digene Hybrid Capture assay (HCS) (limit of detection 1.Sx106geq/ml), the quantitative PCR assay (Q PeR) (limit of detection 1000 geqhnl), or the chance of normalisation of transaminas~ at one point in time is 78°6, 57% and 66% respectively. Ninetee~ out of 73 patients who had continuing active viral replication aRer at least 24 weeks of lamivudine therapy were evaluated for the emergence of mutations which are resistant to lamivudine. In 3 out of 19 patients a mutation in the highly conse~ative Y M D D region of the polymerasc gene was detected.Baseline viralload in thisgroup was significantlyhigher compared to the other 54 patientswho were treated for 24 weeks or longer. Third-one out of 73 patiants(46%) became negative by Q PCR. I-IBV D N A level at slmt of treatment was significantly lower compared to the 42 patients who stayed H B V D N A positive.Eleven consecutive patients within this group who bccsmc negative by qualitative P C R (limit of detection 400 geq/nd) were evaluated to obtain characteristics for lamivudine withdrawal. Ten out of eleven patients became H B e A g negative with anti-HBe in 6. H B c A g in the liverbiopsy was negntivc in ten out of eleven patients,nine out often obtained biopsieswere positive for H B V D N A , indicating low-level viralmplieation. In two patientsin W h o m lamivudine was withdrawn, rebound of virus occurred. In conclusion, the response to lamivudme using sensitiveH B V D N A assays is more variable as previously described. Criteriato stop lamivudin¢ therapy need furtherdevelopment.
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INJECTION VARICEAL SCLEROTHERAPY AND RISK OF HEPATITIS C VIRUS TRANSMISSION A. El-Ray 1, M. Romeih 2, M. Saber 2 IHepatogastroenterology and Tropical Medicine Department, Egypt. 2Biochemistry Department, Theodor Bilharz Research Institute, Imbaba Guiza, Egypt. Reuse of a disposable variceal injection sclerotherapy needle for more than one patient after disinfecting it for few minutes in a solution of 2% glutaraldehide is a practice observed in some endoscopycenters. The aim of this study is to investigate the possible transmission of hepatitis C virus (HCV) from one patient to the other as a consequence of this practice. This study was performed on twenty patients with liver cirrhosis of virus C etiology ( anti HCV positive by ELISA 3 ). All patients were subjected to regular injection sclerotherapy for eradication of their esophageal var/ces. After performing the intravariceai injection sclerotherapy, the injection needle was flushed with 10 mi sterile saline and the effluent was collected immediately after the procedure (F1). The needle is then flushed and immersed in 2% glutaraldehyde for 10 minutes, re.flushing was repeated with a similar amount of sterile saline and the effluent fluid was collected (F2). HCV- RNA detection was carried out in peripheral blood samples taken from the patients at the time of the endoscopic procedure and in Fland F2,using the reverse transcriptaso polymerase chain reaction method (RT-PCR). Results showed that all patients had a positive HCV viraemia on the day of the endoscopic procedure and that virus C particles were found in the effluent of the needle in 2 out of 20 patients in (F1). The effluent of the needle in the same 2 cases was still positive in the sample collected in (F2). It is concluded that Virus C hepatitis could be transmitted by reusing a disposable injection sclerotherapy needle even after flushing and immersing it in a solution of 2 % ghitaraldehyde for 10 minutes.
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PIC06/33 [
NATURAL COURSE OF HCV INFECTION IN HAEMODIALYSED PATIENTS B. Nalpas, H. Zylberberg, H. Fontaine, E Carnot, C. Brtchot, S. Pal Liver unit and Inserm U370, Necker, Paris, France. Background/Aims: The aim of this study was to evaluate the impact of the frequent HCV infection (25%) in haernodialysed patients to precise the place of antiviral therapy. Methods: All the antiHCV-positive, HBsAg-and anti-HIV negative, haemodialyscd patients from our files who have been histologically evaluated before any anti-viral therapy. The date of HCV contamination, in the absence of known acute hepatitis (n=14), was arbitrarily assumed to be the date of the initiation of dialysis. Histopathologicsl results were compared to those of a historical cohort of immunocompetent anti-HCV positive patients previously described. Results: They were 44 dialysis pts candidates to renal transplantation (32 men, 12 women) with a mean age of 49 + 13 years, The mean duration of HCV infection was 5.9 + 6.3 years. HCV genotypes, known in 24, were la (6.8%), lb (54.6%), 2a (11.4%), 3a (4.5%) and 5 (2.3%) and 7 patients were HCV RNA negative at time of evaluation. The mean ALT value was 50 + 44 IU/I (UNL < 45) and only 30% had hype~ansaminasemia. The mean Knodell score was 4.9 + 3 and the rate of cirrhosis was 11.4 % (n=5). HCV RNA negative patients had a higher, although not significant, total KnodeU score than their positive counterparts (4.9"-+-2.8vs 3.6+3.3). All cirrhotics but one (80 %) were older than 45 at time of HCV infection against 48% in noncirthotics; their mean time to develop cirrhosis was 8 years. In our series of imrnunocompetent non hemodialysed patients, the rate of cirrhosis was 11% and the time to develop cirrhosis in patients infected after 45 years was 8+5 years. Conclusion : HCV positive hemodialysed patients do not strikingly differ from immunocempetent patients regarding the rate of cirrhosis and the time to develop cirrhosis. HCV positive bemodialysed should therefore be considered for anti-viral therapy.
I P/C06/35 ] IRON OVERLOAD (IO) AND SEVERITY OF LIVER DISEASE IN CHRONIC HEPATITIS C (CHC) PATIENTS L.I. FernAndez Salazar, J.A. Moreno, A. Garcia S/mchez1, O. Lo Iacono, L. Garcia Buey, A. Arnaiz-Villena2, R. Moreno-Otero Unit of Hepatology, Hospital de la Princesa, Madrid, Spain. IPathology Dpt, Hospital de la Princesa, Madrid, Spain. 2Immunology Dpt, Hospital 12 de Octubre, Madrid, Spain. Aims: To compare epidemiological, clinical, biochemical, virological, histological and therapeutical characteristics in CHC patients with and without IO, and the prevalence of hereditary haemochromatosis (HH) gene mutations in patients with IO. Patients and methods: We studied 300 CHC patients (1995-1998), considenng IO when serum ferritin was higher than 180 ng/ml in women and 280 ng/ml in men, and/or transfernn saturation higher than 45%. We analized: age, sex, CHC evol~on time, medical treatment, personal and familial story, ways of transmission, alcohol consumption, haemoglobine, platelet and leucocyte counts, coagulation study, transaminases (AST, ALT), GGT, FAL, TBIL, total pmtains, immunoglobulines, HCV viraemia, HCV genotype, fibrosis stage, cirrhosis presence, response to interferon treatment, and prevalence of HH gene mutations (C282Y, H63D) in IO patiants. Student's t and chi-squarad tests were used for statistics (p<0.05). Results: We observed IO in 39% (117/300) patients. Significantly statistic differences appeared in (non-IO and IO patients, respactivety): age (39.1+10.5 vs 42.5±10.5), sex (41.2%F and 58.7%M vs 28.2%F and 71.8%M), i.v. drug abuse (18.0% vs 9.4%), hypedipaemia, hyperglycamia or artedal hypertension (6.3% vs 13.6%), alcohol intake (18.1% vs 31.7%), AST (66.5:1;59.5 vs 99.2:1=71.1), ALT (118.8+105.2 vs 164.9+117.4), FAL (172.4£-65.4 vs 191.6+71.5), GGT (40.8:1:37 vs 75.1:1:56.5), TBIL (0.67x~0.31 vs 0.89~t0.53), fibrosis stage (2.05x'-0.9 vs 2.4:1:1.1), presence of cirrhosis (0.9% vs 16.2%), genotype lb (52.8% vs 70.9%), nonrasponsa to interferon (57.4% vs 87.0%). Allelic H63D frequence was 28.5% (8/28), and prevalence of haterocygotic and homocygotic patients were 42.8% (6/14) and 7.1% (1/14), respectively. We found no heterogygotic or homogygotic patients for C282Y mutation. Conclusions: 1. IO was associated to an older age and males. 2. Alcohol intake and metabolic disorders could explain IO, at least partially. 3. IO was associated to a higher level of citolysis, cholestasis, fibrosis stage, and cirrhosis. 4. Interferon response was worse in IO patients. 5. H63D (but no C282Y) mutation is common in CHC patients with IO.
I CONTRASTING PATTERNS OF RESPONSE TO LAMIVUDINE MONOTHERAPY R.A. de Man t. L.M.M. Wolters l, A.B. van Nunen I. H.G,M. Niesters2 IDept. of Hepatogastroenterology, Erasmus University Hospital Rotterdam, The Netherlands. 2Dept. of Virology, Erasmus University Hospital Rotterdam, The Netherlands. W e describe a cohort of patients trent~ with lamivudine, a reverse transcriptase inhibitor with a strong virus suplxcssive effect on the hepatitis B virus, Eighty-nine patients were inchdad in the intentinn to treat analysis. Evaluation with the Kaplan-Meier method was based on response to therapy of HBV D N A levels as well as normalisation of transaminases. Subgroup evaluation based on the per protocol data was performed on two groups within this cohort based on the H B V D N A level at the and of the=alr/.During a 52 weeks tzeatmant period, the chance of being H B V D N A negative at one point in time as measured
by the Digene Hybrid Capture assay (HCS) (limit of detection 1.Sx106geq/ml), the quantitative PCR assay (Q PeR) (limit of detection 1000 geqhnl), or the chance of normalisation of transaminas~ at one point in time is 78°6, 57% and 66% respectively. Ninetee~ out of 73 patients who had continuing active viral replication aRer at least 24 weeks of lamivudine therapy were evaluated for the emergence of mutations which are resistant to lamivudine. In 3 out of 19 patients a mutation in the highly conse~ative Y M D D region of the polymerasc gene was detected.Baseline viralload in thisgroup was significantlyhigher compared to the other 54 patientswho were treated for 24 weeks or longer. Third-one out of 73 patiants(46%) became negative by Q PCR. I-IBV D N A level at slmt of treatment was significantly lower compared to the 42 patients who stayed H B V D N A positive.Eleven consecutive patients within this group who bccsmc negative by qualitative P C R (limit of detection 400 geq/nd) were evaluated to obtain characteristics for lamivudine withdrawal. Ten out of eleven patients became H B e A g negative with anti-HBe in 6. H B c A g in the liverbiopsy was negntivc in ten out of eleven patients,nine out often obtained biopsieswere positive for H B V D N A , indicating low-level viralmplieation. In two patientsin W h o m lamivudine was withdrawn, rebound of virus occurred. In conclusion, the response to lamivudme using sensitiveH B V D N A assays is more variable as previously described. Criteriato stop lamivudin¢ therapy need furtherdevelopment.
p/coal36
I
INJECTION VARICEAL SCLEROTHERAPY AND RISK OF HEPATITIS C VIRUS TRANSMISSION A. El-Ray 1, M. Romeih 2, M. Saber 2 IHepatogastroenterology and Tropical Medicine Department, Egypt. 2Biochemistry Department, Theodor Bilharz Research Institute, Imbaba Guiza, Egypt. Reuse of a disposable variceal injection sclerotherapy needle for more than one patient after disinfecting it for few minutes in a solution of 2% glutaraldehide is a practice observed in some endoscopycenters. The aim of this study is to investigate the possible transmission of hepatitis C virus (HCV) from one patient to the other as a consequence of this practice. This study was performed on twenty patients with liver cirrhosis of virus C etiology ( anti HCV positive by ELISA 3 ). All patients were subjected to regular injection sclerotherapy for eradication of their esophageal var/ces. After performing the intravariceai injection sclerotherapy, the injection needle was flushed with 10 mi sterile saline and the effluent was collected immediately after the procedure (F1). The needle is then flushed and immersed in 2% glutaraldehyde for 10 minutes, re.flushing was repeated with a similar amount of sterile saline and the effluent fluid was collected (F2). HCV- RNA detection was carried out in peripheral blood samples taken from the patients at the time of the endoscopic procedure and in Fland F2,using the reverse transcriptaso polymerase chain reaction method (RT-PCR). Results showed that all patients had a positive HCV viraemia on the day of the endoscopic procedure and that virus C particles were found in the effluent of the needle in 2 out of 20 patients in (F1). The effluent of the needle in the same 2 cases was still positive in the sample collected in (F2). It is concluded that Virus C hepatitis could be transmitted by reusing a disposable injection sclerotherapy needle even after flushing and immersing it in a solution of 2 % ghitaraldehyde for 10 minutes.
105