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Importance of HGV and TTV coinfection in the vertical transmission of HCV
Category 6: Viral hepatitis: clinical aspects HBV DNA -4.7 log10 by PCR regardless of baseline ALT level elevation. In contrast, there were large differences in response to LVD depending on baseline ALT: the mean difference in viral load reduction between high and low ALT groups was 1.64 log (p
I
575
OBSERVATIONAL CHRONIC
STUDY OF PATIENTS TREATED
FOR
HEPATITIS C IN FRANCE
F. Roudot-Thoraval’, l? Couzigou2, J.J. Raabe3, H. Desmorat4, P. Marcellin’. ‘Sante Publique, Hopi&l Hem-i Mondos Creteil; 2Hepato-Gastroenterologie, Hopital Haul-Leveque, Pessac; ‘Hepato-Gastroenterologie, CHR De Me@, Me@; 4Clinique Du Part, Toulouse; ‘Hepatologie, Hopital Beaujon, Clichy, France Objective: The objective of this observational study was to evaluate medical practices for the treatment of chronic hepatitis C, and to assess the observance, tolerance and efficacy of treatment outside clinical trials. Methods and Results: a sample of 50 specialists working in various settings participated in the study. All consecutive patients who were prescribed authorized antiviral drugs were enrolled. Demographic, epidemiological and virological data were collected before treatment; follow up was made according to the habits of each prescriber and included information on acceptability of the treatment, dose modifications and their motive. Between April 1st and December 31st 2001, 578 patients were enrolled. The epidemiological, virological and histological features of this group were similar to those patients usually treated in France. Fifty-seven percent of patients were naive of treatment, 16% were relapsers and 27% were non responders. In 93% of cases, treatment consisted of Peginterferon a-2b (PEG-IFN) and ribavirine at recommended doses: on average 1.4 kg/kg of PEG-IFN and 13 mg/kg of ribavirine (16 to 11 mg/kg according to weight), irrespective of gender, genotype and the existence of a previous treatment. All patients have been followed at least 24 weeks. Currently, 26 patients (4.5%) have withdrawn treatment; 110 (19%) patients have needed a dose reduction of PEG-IFN and/or ribavirine. The acceptability of treatment was good for 36% of patients, moderate or poor for 64% of patients. The latter were more often women (44 vs 34%, p=O, 02), they were older (48, 8 vs 44, 6 ans, p=O, OOl), for an equivalent dose of PEG-IFN and ribavirine. Nevertheless, a dose reduction was prescribed in only 32% of patients with moderate or poor tolerance, these patients receiving an average higher initial dose of PEG-IFN (1.5 vs 1.4 kg/kg, p=O.Ol). Virological response under treatment is now available for 299 patients: HCV-RNA is indetectable in 199 of them (66.6%, IC95% 61.2-71.9). Conclusion: This observational study shows that 1) most patients are treated according to recommendations 2) Early withdrawal of combination therapy remains rare, 3) Initial regimen is often continued despite moderate or poor tolerance, what may be valuable to reach virological response.
I
576
STEATOSIS
AFFECTS
CHRONIC
IN A GENOTYPE-DEPENDENT
HEPATITIS C PROGRESSION
WAY
L. Rubbia-Brandt’, l? Fabris2, S. Paganin3, G. Leandro4, P.-J. Male’, E. Giostra’, A. Carlotto6, L. Marchioro7, A. Smedile3, F. Negro’,5. ‘Division Of Clinical Pathology, University Hospital, Geneva, Switzerland; 2Division Of Infectious Diseases, Hospital Of Vicenza, Vicenza, Italy; ‘Department Of Gastroenterology, Ospedale San Giovanni, Torino, Italy; 41stituto Ricerche E Cura A Carattere Scient$co De Bellis, Castellana Grotte, Italy; ‘Division Of Gastroenterology And Hepatology, University Hospital, Geneva, Switzerland; 6Division Of Infectious Diseases, Hospital Of Schio, Schio, Italy; 7Division Of Pathology, Hospital Of Schio, Schio, Italy Liver steatosis is frequent
in chronic hepatitis
C, especially
in patients in-
167
fected with HCV genotype 3, but its clinical significance remains uncertain. We analysed the relationship between steatosis, fibrosis and other parameters by multivariable logistic regression in 755 chronic hepatitis C patients (178 had genotype 3). Liver histology showed chronic hepatitis without cirrhosis in 568, and with cirrhosis in other 187 (109 included at liver transplant); 315 patients (41.7%) had steatosis, scored as 1 (130% hepatocytes), 2 (30.60%) or 3 (>60%). Fibrosis was detected in 605, scored as 1 (Metavir 1 or 2), 3 (Metavir 3 or compensated cirrhosis), or 5 (decompensated cirrhosis). The table shows the results using steatosis or fibrosis as dependent variables, in all patients and in those with genotype 3 or non-3; p-value is reported for variables entered in the model (ns, not significant; ND, not done). Our data suggest that steatosis and inflammatory activity are associated with each other, but only in patients with genotype 3. Accordingly, fibrosis seems to depend on the presence of steatosis, but again only in patients with type 3. On the contrary, in patients with genotype other than 3, the fibrosis is associated with other clinical variables, such as past alcohol abuse and diabetes. In conclusion, steatosis of the liver may affect chronic hepatitis C progression, but preferentially in patients with genotype 3.
I
577
IMPORTANCE VERTICAL
OF HGV AND lTV
TRANSMISSION
COINFECTION
IN THE
OF HCV
A. Ruiz-Extremera’, E. Cervilla2, l? Munoz-Rueda2, E. Ocete’, A. Palacios2, M.A. Lopez-Ganido2, .I. Salmeron2. ‘Pediatric Unit; 2Gastroenterology Unit. University Hospital ‘San Cecilia’, Granada, Spain Objective: To find out if TTV and HGV infection influences the vertical transmission (VT) of HCV, and to study the corn--se of infection by these viruses in infected children. Patients and Methods: Using PCR we determined HCV-RNA, HGV-RNA and TTV-DNA in serum samples frozen at -80°C from 80 gestations of 70 women who were anti-HCV positive. We studied HCV-RNA in 80 children and HGV-RNA and TTV-DNA in the children of positive mothers, every 2 months during the first year and thereafter every six months annually. The average follow-up of the children were 33 & 32 months. Results: A total of 43 (54%) of gestating women were HGV and TTV negative (group I), 18 (22%) HGV positive (group II) and 19 (24%) TTV positive (group III). The HCV-RNA was more frequent in groups II (89%) and III (84%) than in I (58%), p < 0.01 and p < 0.05 respectively. Then concentration of HCV-RNA was greater in group I (1.4 & 2.3 x lo66 copies/ml) with respect to II (0.39 & 0.5 x lo6 copies/ml, p < 0.1) and to III (0.09 & 0.09 x lo6 copies/ml, p < 0.05). The VT was 50% for HGV, 32% for TTV and 12.5% for HCV (all the children presented with intermittent viremias and there was no seroconversion to anti-HCV). When only the HCV-RNA positive gestating was considered (n=25 group I, n=16 group II and n=16 group III), 32% of group I transmitted HCV to their children compared with 6% of those in group II and III, p
I
575
OBSERVATIONAL CHRONIC
STUDY OF PATIENTS TREATED
FOR
HEPATITIS C IN FRANCE
F. Roudot-Thoraval’, l? Couzigou2, J.J. Raabe3, H. Desmorat4, P. Marcellin’. ‘Sante Publique, Hopi&l Hem-i Mondos Creteil; 2Hepato-Gastroenterologie, Hopital Haul-Leveque, Pessac; ‘Hepato-Gastroenterologie, CHR De Me@, Me@; 4Clinique Du Part, Toulouse; ‘Hepatologie, Hopital Beaujon, Clichy, France Objective: The objective of this observational study was to evaluate medical practices for the treatment of chronic hepatitis C, and to assess the observance, tolerance and efficacy of treatment outside clinical trials. Methods and Results: a sample of 50 specialists working in various settings participated in the study. All consecutive patients who were prescribed authorized antiviral drugs were enrolled. Demographic, epidemiological and virological data were collected before treatment; follow up was made according to the habits of each prescriber and included information on acceptability of the treatment, dose modifications and their motive. Between April 1st and December 31st 2001, 578 patients were enrolled. The epidemiological, virological and histological features of this group were similar to those patients usually treated in France. Fifty-seven percent of patients were naive of treatment, 16% were relapsers and 27% were non responders. In 93% of cases, treatment consisted of Peginterferon a-2b (PEG-IFN) and ribavirine at recommended doses: on average 1.4 kg/kg of PEG-IFN and 13 mg/kg of ribavirine (16 to 11 mg/kg according to weight), irrespective of gender, genotype and the existence of a previous treatment. All patients have been followed at least 24 weeks. Currently, 26 patients (4.5%) have withdrawn treatment; 110 (19%) patients have needed a dose reduction of PEG-IFN and/or ribavirine. The acceptability of treatment was good for 36% of patients, moderate or poor for 64% of patients. The latter were more often women (44 vs 34%, p=O, 02), they were older (48, 8 vs 44, 6 ans, p=O, OOl), for an equivalent dose of PEG-IFN and ribavirine. Nevertheless, a dose reduction was prescribed in only 32% of patients with moderate or poor tolerance, these patients receiving an average higher initial dose of PEG-IFN (1.5 vs 1.4 kg/kg, p=O.Ol). Virological response under treatment is now available for 299 patients: HCV-RNA is indetectable in 199 of them (66.6%, IC95% 61.2-71.9). Conclusion: This observational study shows that 1) most patients are treated according to recommendations 2) Early withdrawal of combination therapy remains rare, 3) Initial regimen is often continued despite moderate or poor tolerance, what may be valuable to reach virological response.
I
576
STEATOSIS
AFFECTS
CHRONIC
IN A GENOTYPE-DEPENDENT
HEPATITIS C PROGRESSION
WAY
L. Rubbia-Brandt’, l? Fabris2, S. Paganin3, G. Leandro4, P.-J. Male’, E. Giostra’, A. Carlotto6, L. Marchioro7, A. Smedile3, F. Negro’,5. ‘Division Of Clinical Pathology, University Hospital, Geneva, Switzerland; 2Division Of Infectious Diseases, Hospital Of Vicenza, Vicenza, Italy; ‘Department Of Gastroenterology, Ospedale San Giovanni, Torino, Italy; 41stituto Ricerche E Cura A Carattere Scient$co De Bellis, Castellana Grotte, Italy; ‘Division Of Gastroenterology And Hepatology, University Hospital, Geneva, Switzerland; 6Division Of Infectious Diseases, Hospital Of Schio, Schio, Italy; 7Division Of Pathology, Hospital Of Schio, Schio, Italy Liver steatosis is frequent
in chronic hepatitis
C, especially
in patients in-
167
fected with HCV genotype 3, but its clinical significance remains uncertain. We analysed the relationship between steatosis, fibrosis and other parameters by multivariable logistic regression in 755 chronic hepatitis C patients (178 had genotype 3). Liver histology showed chronic hepatitis without cirrhosis in 568, and with cirrhosis in other 187 (109 included at liver transplant); 315 patients (41.7%) had steatosis, scored as 1 (130% hepatocytes), 2 (30.60%) or 3 (>60%). Fibrosis was detected in 605, scored as 1 (Metavir 1 or 2), 3 (Metavir 3 or compensated cirrhosis), or 5 (decompensated cirrhosis). The table shows the results using steatosis or fibrosis as dependent variables, in all patients and in those with genotype 3 or non-3; p-value is reported for variables entered in the model (ns, not significant; ND, not done). Our data suggest that steatosis and inflammatory activity are associated with each other, but only in patients with genotype 3. Accordingly, fibrosis seems to depend on the presence of steatosis, but again only in patients with type 3. On the contrary, in patients with genotype other than 3, the fibrosis is associated with other clinical variables, such as past alcohol abuse and diabetes. In conclusion, steatosis of the liver may affect chronic hepatitis C progression, but preferentially in patients with genotype 3.
I
577
IMPORTANCE VERTICAL
OF HGV AND lTV
TRANSMISSION
COINFECTION
IN THE
OF HCV
A. Ruiz-Extremera’, E. Cervilla2, l? Munoz-Rueda2, E. Ocete’, A. Palacios2, M.A. Lopez-Ganido2, .I. Salmeron2. ‘Pediatric Unit; 2Gastroenterology Unit. University Hospital ‘San Cecilia’, Granada, Spain Objective: To find out if TTV and HGV infection influences the vertical transmission (VT) of HCV, and to study the corn--se of infection by these viruses in infected children. Patients and Methods: Using PCR we determined HCV-RNA, HGV-RNA and TTV-DNA in serum samples frozen at -80°C from 80 gestations of 70 women who were anti-HCV positive. We studied HCV-RNA in 80 children and HGV-RNA and TTV-DNA in the children of positive mothers, every 2 months during the first year and thereafter every six months annually. The average follow-up of the children were 33 & 32 months. Results: A total of 43 (54%) of gestating women were HGV and TTV negative (group I), 18 (22%) HGV positive (group II) and 19 (24%) TTV positive (group III). The HCV-RNA was more frequent in groups II (89%) and III (84%) than in I (58%), p < 0.01 and p < 0.05 respectively. Then concentration of HCV-RNA was greater in group I (1.4 & 2.3 x lo66 copies/ml) with respect to II (0.39 & 0.5 x lo6 copies/ml, p < 0.1) and to III (0.09 & 0.09 x lo6 copies/ml, p < 0.05). The VT was 50% for HGV, 32% for TTV and 12.5% for HCV (all the children presented with intermittent viremias and there was no seroconversion to anti-HCV). When only the HCV-RNA positive gestating was considered (n=25 group I, n=16 group II and n=16 group III), 32% of group I transmitted HCV to their children compared with 6% of those in group II and III, p