- Email: [email protected]
610 IMPACT OF ETHNICITY ON VIRAL KINETICS AND SUSTAINED VIROLOGICAL RESPONSE RATES OF GENOTYPE 4, CHRONIC HEPATITIS C PATIENTS TREATED WITH PEG-INTERFERON-A2A PLUS RIBAVIRIN
S224
Poster Session − Friday, April 24
and treatment duration were set according to HCV genotype and body weight as per current standard recommendations. Dose reductions were dictated by individual patient tolerability. Results: 22 patients (M/F 15/7, median age 58 years) accepted to start PEG-IFN/RBV under informed consent. Median pre-treatment HCV-RNA level was 1.1 MIU/ml; median BMI was 25; median ALT was 1.9×UNL; 12 patients had HCV genotype 1, 8 genotype 2 and 2 genotype 3 infection. The distribution of HDs was as follows: ischemic heart disease, 9 patients; prior mechanical heart valve replacement, 7 patients; valvular and ischemic heart disease, 2 patients; chronic arrhythmias, 9 patients; cardiomyopathy, 5 patients; surgically corrected congenital heart disease, 2 patients. 19 patients (86%) completed the prescribed treatment schedule. Six-month post-rx data are available in 19 patients. Responses were as follows: sustained virological response, 63%; relapse, 31%; nonresponse, 6%. Dose reductions were needed in 6 cases for PEG-IFN and 6 cases for RBV. No serious adverse event was observed. The major adverse events were: anemia (Hgb < 10), 59%; thrombocytopenia, 27%; depression, 32%; flulike syndrome, 91%. No patient experienced recurrent angina, heart failure, new-onset or worsening arrhythmias. Post-treatment clinical history and examination, electrocardiography and echocardiography, did not show any sign of progression of the pre-existing HD. Conclusions: Treatment with PEG-IFN/RBV may be safely offered to CHC patients with co-existing, clinically significant HD. In this setting, response rates overlap with those obtained in non-HD patients, without additional safety issues. In qualified centers, CHC patients with overt HD should not be denied treatment, whenever indicated.
Conclusion: In this large cohort of patients, an RVR was achieved in a high proportion of patients, especially among patients with G2 and G3. Patient demographics differed by genotype. Baseline factors strongly associated with week-4 RVR were similar to those observed in randomised clinical trials.
609 BASELINE CHARACTERISTICS AND WEEK-4 RESPONSE AMONG 1546 CHC PATIENTS INFECTED WITH HCV GENOTYPE 1, 2, 3 AND 4: INTERIM RESULTS OF THE PROPHESYS COHORT
*Including histological status not yet assessed.
G. Dusheiko1 , F.A. Caruntu2 , M. Bourli`ere3 , D. Ouzan4 , S. Pol5 , C. Ferrari6 , M. Puoti7 , A. Tice8 , G.F. Silva9 , G. Lengyel10 , C. Ghent11 , D. Messinger12 , A. Tietz13 , A. Mangia14 . 1 Centre for Hepatology, Royal Free and University College School of Medicine, London, UK; 2 National Institute of Infectious Diseases, Bucharest, Romania; 3 Hˆ opital Saint-Joseph, Marseille, 4 Institut Arnault-Tzanck, Saint-Laurent-du-Var, 5 Hˆ opital Necker, Paris, France; 6 Azienda Ospedaliera − Ospedali Riuniti, Parma, 7 University of Brescia, Brescia, Italy; 8 University of Hawaii, Honolulu, Hawaii, USA; 9 Botucatu School of Medicine, Botucatu, Brazil; 10 Altal´ anos Orvostudom´anyi Kar II, Budapest, Hungary; 11 London Health Sciences Centre, London, ON, Canada; 12 Biometrics, IST GmbH, Mannheim, Germany; 13 Roche, Basel, Switzerland; 14 Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy E-mail: fi[email protected] Background and Aims: Peginterferon plus ribavirin is the standard of care in the treatment of chronic hepatitis C (CHC). Large cohorts of patients managed in routine clinical care can provide valuable additional information regarding demographics of patients currently under treatment and factors predictive of responses. The ongoing PROPHESYS cohort is a large, multinational cohort of patients under care for CHC. Here, we present the results of an interim analysis among patients treated with peginterferon alfa-2a (40KD; PEGASYS® ) and ribavirin (COPEGUS® ). Methods: All treatment-naive patients initiating treatment on or before 25 August 2008 with available hepatitis C virus (HCV) RNA data at baseline and week 4 are included in this analysis. Patients infected with more than one genotype of HCV RNA are assigned to the group with the most difficult to treat genotype of HCV (G1 > G4 > G3 > G2). Results: Baseline data and week-4 HCV RNA (<15 IU/mL) are presented in the table. The first dose of peginterferon alfa-2a was 180 mg/week in 99%, 94%, 97% and 100% of patients for G1, G2, G3 and G4 respectively. The most common RBV starting dose in mg/day for G1, G2, G3 and G4 patients was 1000/1200 (91%), 800 (63%), 800 (66%) and 1000/1200 (90%), respectively. By an MLR, baseline factors strongly associated with week-4 rapid virological response (RVR) in G1 were: lower viral load; higher alanine aminotransferase (ALT) ratio; younger age and no cirrhosis or unknown histological diagnosis.
Table 1. Patient data Parameter
G1 (N = 1118)
G2 (N = 126)
G3 (N = 241)
G4 (N = 61)
Female, n (%) Caucasian, n (%) Mean age, years Mean BMI (kg/m2 ) Median HCV RNA (IU/mL) Cirrhosis, n (%) Mean ALT ratio HCV RNA <15 IU/mL at week 4, n (%)
561 (50) 1034 (93) 46.5 25.9 1,248,000 334 (30) 2.42 236 (21)
64 (51) 93 (74) 51.1 26.8 1,524,467 20 (16) 1.95 103 (82)
82 (34) 210 (87) 40.4 24.9 764,950 30 (12) 2.70 176 (73)
24 (39) 37 (61) 45.4 26.6 192,579 9 (15) 2.05 19 (31)
Table 2. MLR analysis for G1 Factor
Categories
Odds ratio (95% CI)
p-value
Histological diagnosis HCV RNA (IU/mL) Age, years Mean ALT ratio Race
No cirrhosis* vs cirrhosis 400,000 vs >400,000 45 vs >45 >3 vs. 3 Caucasian vs other
2.11 6.06 1.98 2.18 2.58
0.001 <0.001 <0.001 <0.001 0.028
(1.44−3.10) (4.37−8.41) (1.43−2.73) (1.53−3.11) (1.11−6.01)
610 IMPACT OF ETHNICITY ON VIRAL KINETICS AND SUSTAINED VIROLOGICAL RESPONSE RATES OF GENOTYPE 4, CHRONIC HEPATITIS C PATIENTS TREATED WITH PEG-INTERFERON-A2A PLUS RIBAVIRIN I. Elefsiniotis1 , C. Pavlidis2 , D. Dimitropoulos3 , C. Mihas1 , E. Vezali1 , S. Koutsounas2 , E. Paraskevas3 . 1 University Department of Internal Medicine, Hepatology Unit, ‘Helena Venizelou’ Hospital of Athens, 2 Reference Center for Viral Hepatitis, I.K.A., 3 Department of Gastroenterology, “Agios Savvas” Hospital, Athens, Greece E-mail: [email protected] Background: Data concerning the efficacy of PEG-IFNa2a plus ribavirin treatment in treatment-naive, genotype 4-infected chronic hepatitis C (CHC) patients from Europe are limited. Objectives: To investigate the viral kinetics as well as the sustained virological response (SVR) rates and their predictors, in these patients. Methods: 123 patients were retrospectively analyzed. Early (EVR) and late (LVR) virological response were confirmed by undetectable (<50 IU/ml) serum HCV-RNA at week 12 and week 24 of treatment, respectively. SVR was confirmed by undetectable serum HCV-RNA at the end of treatment as well as six months later. Results: 108 of 123 patients (87.8%) included in the final analysis. 87 patients were men (80.55%), 22 (20.37%) had histologically confirmed cirrhosis and 72 (66.66%) exhibited HCV-RNA >600,000 IU/ml at baseline control. The majority of Caucasian patients (48/55, 87.27%) were prior intravenous drug users (IVDU) whereas none of 53 Egyptian patients were IVDU. Egyptian patients, compared to Caucasians, had higher BMI (26.4 vs 24.7 kg/m2 ), more often had high viral load (89.2 vs 69.8%), had higher fibrosis score (3.2 vs 2.4) and more often were cirrhotic (16 vs 6%). Overall, 43.5% of patients exhibited SVR, 42.6% were nonresponders and 13.9% were relapsers. EVR was observed in 40.74% and LVR in 59.25% of them. The positive predictive values of EVR and LVR were 72.97% and 86.27% whereas their negative predictive values were 64.29% and 92.85%, respectively.In the multiple logistic regression analysis only LVR (OR = 81.7, 95% CI: 19.76–337.8, p < 0.001) independently predicted SVR. Compared to a patient without LVR, a patient with LVR had 81.7 more chances of SVR achievement. EVR was
05g: VIRAL HEPATITIS − g) HEPATITIS C − CLINICAL (THERAPY) independently predicted SVR in Caucasian patients (p < 0.001) but not in Egyptian patients (p = 0.613), in whom the only independent predictor of SVR was the absence of cirrhosis (p = 0.004). Conclusions: SVR rates are comparable among Egyptian and Caucasian HCV-4 patients, despite their significant differences in baseline characteristics and in their early on-treatment virological data. Undetectable HCV-RNA at week 24 of treatment, using a sensitive qualitative PCR assay, seems to be a better predictor of SVR, than EVR, in these patients, irrespective of ethnicity and the other baseline parameters.
611 HEPATIC IMPAIRMENT IN EGYPTIAN CHILDREN WITH TYPE 1 DIABETES MELLITUS H. El-Karaksy1 , G. Anwar1 , S. Mansour1 , N. El-Koofy1 , R. El-Sayed1 , H. Helmy1 , H. Mina2 , M. Sabry2 , G. Esmat3 . 1 Pediatrics, Cairo University, 2 Pediatrics, National Hepatology and Tropical Medicine Research Institute, Cairo, 3 Tropical Medicine, Cairo University, Giza, Egypt E-mail: [email protected] Background and Aim: Hepatic involvement is not uncommon in type 1 diabetes mellitus (DM). The aim of this study was to determine the prevalence and etiology of hepatic impairment in children with type 1 DM. Methods: The study included 692 children (333 were males) with type 1 DM attending the Diabetes Endocrine and Metabolism Pediatric Unit (DEMPU) at Cairo University Pediatric Hospital. Their mean age was 9.65 + 4.18 years. All children were subjected to clinical examination for hepatomegaly, ALT determination, testing for HCV antibodies, and abdominal ultrasonography. Any child found to have hepatomegaly, raised ALT, positive HCV antibodies, and/or abnormal ultrasound was subjected to complete liver function tests, lipid profile, HbA1c, HBsAg, HCV RNA for those showing positive HCV antibodies. When indicated markers for autoimmune hepatitis, celiac screen and liver biopsy were performed. Results: Sixty (8.7%) were found to have abnormalities: hepatomegaly in 13 (1.9%), elevated ALT in 27 (3.9%), positive HCV antibodies in 25 (3.6%) and abnormal hepatic ultrasound in 31 (4.5%). Forty percent of HCV antibody positive children were HCV RNA positive. Blood transfusion and urinary catheter insertion were significantly associated with HCV positivity. Autoimmune hepatitis was diagnosed in one case. Glycogenic hepatopathy was diagnosed in 3 cases that underwent liver biopsy. Abnormalities were reversible in 37/60 after proper glycemic control. Conclusion: Diabetic children are at risk of acquisition of HCV. Poor glycemic control may predispose to hepatomegaly and elevated ALT. A four-week therapeutic trial of proper glycemic control is recommended prior to more invasive procedures.
612 WEEK 8 HCV-RNA IS THE OPTIMAL PREDICTOR OF RELAPSE IN NON-RVR PATIENTS WITH GENOTYPE 1/4 RANDOMISED TO 48 OR 72 WEEKS PEG-IFN ALFA-2A PLUS RBV T.-M. Scherzer1 , H. Kerschner2 , S. Beinhardt1 , K. Rutter1 , H. Hofer1 , P. Steindl-Munda1 , T. Popow-Kraupp2 , P. Ferenci1 . 1 Department of Internal Medicine III, 2 Department of Clinical Virology, Medical University, Vienna, Austria E-mail: [email protected] Background: In a recently completed large, multicentre randomised controlled trial, we showed that extending treatment duration with peginterferon alfa-2a (40KD) plus ribavirin reduces relapse and increases sustained virological response (SVR) rates in non-rapid virological response (RVR) patients with HCV genotype 1/4 infection. To determine which of these non-RVR patients would benefit most from extended treatment, SVR and relapse rates were determined according to viral load at weeks 8 and 12 of treatment.
S225
Methods: This analysis is based on the 187 patients enrolled at our centre (34% of all recruited patients). Patients who were HCV RNA-positive at week 4, but had >2 log drop, or <50 IU/mL HCV RNA at week 12 (early virological response [EVR]) were randomised to 48 (group A) or 72 (group B) weeks’ treatment. Samples obtained at weeks 2, 4, 8 and 12 were retested by the TaqMan™ (limit of detection: 10 IU/mL). Results: Of the 187 patients, 97 achieved an EVR and were randomised to 48 (n = 52; 51 completed treatment and follow-up) or 72 (n = 45; 41 completed treatment and follow-up) weeks of treatment. Patients with undetectable HCV RNA at weeks 8 and 12 had high rates of SVR for both 48 and 72 weeks of treatment. Irrespective of treatment duration, only two (6%) of the 35 HCV RNA-negative patients at week 8 relapsed (negative predictive value [NPV]: 94%). Of the 25 patients who became negative between week 8 and 12, seven (28%) relapsed, thus the NPV at week 12 was 72% (group A: 60%; group B: 80%). Patients with detectable HCV RNA at weeks 8 and 12 had lower relapse and higher rates of SVR with longer treatment duration. Conclusion: Measurement of HCV RNA at week 8 is the optimal time to identify patients most likely to benefit from extended peginterferon alfa-2a (40KD) plus ribavirin combination therapy. SVR
HCV RNA at week 8, n/N (%) Undetectable Detectable HCV RNA at week 12, n/N (%) Undetectable Detectable
Relapse rate
48 weeks (n = 52)
72 weeks (n = 41)
48 weeks (n = 52)
72 weeks (n = 41)
20/22 (91%) 11/30 (37%)
13/13 (100%) 15/28 (54%)
2/22 (9%) 17/28b (61%)
0/13 (0%) 4/19a (21%)
25/31 (81%) 6/21 (29%)
23/28 (82%) 4/12 (33%)
6/31 (19%) 13/19c (68%)
2/25 (8%) 2/7d (29%)
Nonresponders at week 24: a 9, b 2, c 2, d 7.
613 THE ANTIFIBROTIC PENTOXYPHILLINE/A-TOCOPHEROL ASSOCIATION DOES NOT LIMIT LIVER FIBROSIS PROGRESSION IN PATIENTS WITH CHRONIC HEPATITIS C − ANRS HC 10 H. Fontaine1,2 , S. Fernandes1,2 , B. Nalpas1,2 , P. Bedossa3 , J.-D. Grang´e4 , A. Tran5 , J. Gu´echot6 , S. Candon7 , F. Imbert-Bismut8 , S. Pol1,2 . 1 Hepatology Unit, Hˆ opital Cochin − APHP, 2 INSERM U567, Universit´e Paris Descartes, Paris, 3 Department of Pathology, Hˆopital Beaujon, AP-HP and INSERM, U773, Centre de Recherche Biom´edicale Bichat Beaujon, Universit´e Paris 7-Denis-Diderot, Clichy, 4 Hepatology Unit, Hˆopital Tenon- APHP, Paris, 5 Hepatology Unit, Hˆopital de l’Archet, Nice, 6 Service de Biochimie A, Hˆ opital Saint Antoine − APHP, 7 Immunology, Hˆopital Necker − APHP, 8 Department of Biochemistry, Hˆopital de la Piti´e-Salp´etri`ere − APHP, Paris, France E-mail: [email protected] Background and Aims: About 45% of patients are non responders to the ribavirine-pegylated interferon combination and there is no therapy proven to be efficient in limiting liver fibrosis progression. Aim: To analyse the efficacy and safety of the association of pentoxyphilline (anti-TNF activity) and a-tocopherol (antioxydant activity) in this population. Methods: 91 patients, non responders or refusing the recommended combination (49 M and 38 F, mean age: 53±10 years) were included in a prospective, randomised, placebo-controlled study. They were given pentoxyphilline 400 mg and tocopherol 500 mg (n = 46) or double placebo (n = 45), BID during one year. Baseline (BL) liver biopsies were performed less than 3 years before the inclusion and at the end of treatment. Criteria of judgement: 1. histopathology by morphometric analysis and Metavir scores; 2. variation of ALAT and non invasive tests (Fibrotest, hyaluronate, PIIIP, TNF-a) measured at the beginning, at 6 months and at the end of the treatment. Results: There were no BL differences in the histopathological severity between both groups. By comparison between BL and at the end of
Poster Session − Friday, April 24
and treatment duration were set according to HCV genotype and body weight as per current standard recommendations. Dose reductions were dictated by individual patient tolerability. Results: 22 patients (M/F 15/7, median age 58 years) accepted to start PEG-IFN/RBV under informed consent. Median pre-treatment HCV-RNA level was 1.1 MIU/ml; median BMI was 25; median ALT was 1.9×UNL; 12 patients had HCV genotype 1, 8 genotype 2 and 2 genotype 3 infection. The distribution of HDs was as follows: ischemic heart disease, 9 patients; prior mechanical heart valve replacement, 7 patients; valvular and ischemic heart disease, 2 patients; chronic arrhythmias, 9 patients; cardiomyopathy, 5 patients; surgically corrected congenital heart disease, 2 patients. 19 patients (86%) completed the prescribed treatment schedule. Six-month post-rx data are available in 19 patients. Responses were as follows: sustained virological response, 63%; relapse, 31%; nonresponse, 6%. Dose reductions were needed in 6 cases for PEG-IFN and 6 cases for RBV. No serious adverse event was observed. The major adverse events were: anemia (Hgb < 10), 59%; thrombocytopenia, 27%; depression, 32%; flulike syndrome, 91%. No patient experienced recurrent angina, heart failure, new-onset or worsening arrhythmias. Post-treatment clinical history and examination, electrocardiography and echocardiography, did not show any sign of progression of the pre-existing HD. Conclusions: Treatment with PEG-IFN/RBV may be safely offered to CHC patients with co-existing, clinically significant HD. In this setting, response rates overlap with those obtained in non-HD patients, without additional safety issues. In qualified centers, CHC patients with overt HD should not be denied treatment, whenever indicated.
Conclusion: In this large cohort of patients, an RVR was achieved in a high proportion of patients, especially among patients with G2 and G3. Patient demographics differed by genotype. Baseline factors strongly associated with week-4 RVR were similar to those observed in randomised clinical trials.
609 BASELINE CHARACTERISTICS AND WEEK-4 RESPONSE AMONG 1546 CHC PATIENTS INFECTED WITH HCV GENOTYPE 1, 2, 3 AND 4: INTERIM RESULTS OF THE PROPHESYS COHORT
*Including histological status not yet assessed.
G. Dusheiko1 , F.A. Caruntu2 , M. Bourli`ere3 , D. Ouzan4 , S. Pol5 , C. Ferrari6 , M. Puoti7 , A. Tice8 , G.F. Silva9 , G. Lengyel10 , C. Ghent11 , D. Messinger12 , A. Tietz13 , A. Mangia14 . 1 Centre for Hepatology, Royal Free and University College School of Medicine, London, UK; 2 National Institute of Infectious Diseases, Bucharest, Romania; 3 Hˆ opital Saint-Joseph, Marseille, 4 Institut Arnault-Tzanck, Saint-Laurent-du-Var, 5 Hˆ opital Necker, Paris, France; 6 Azienda Ospedaliera − Ospedali Riuniti, Parma, 7 University of Brescia, Brescia, Italy; 8 University of Hawaii, Honolulu, Hawaii, USA; 9 Botucatu School of Medicine, Botucatu, Brazil; 10 Altal´ anos Orvostudom´anyi Kar II, Budapest, Hungary; 11 London Health Sciences Centre, London, ON, Canada; 12 Biometrics, IST GmbH, Mannheim, Germany; 13 Roche, Basel, Switzerland; 14 Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy E-mail: fi[email protected] Background and Aims: Peginterferon plus ribavirin is the standard of care in the treatment of chronic hepatitis C (CHC). Large cohorts of patients managed in routine clinical care can provide valuable additional information regarding demographics of patients currently under treatment and factors predictive of responses. The ongoing PROPHESYS cohort is a large, multinational cohort of patients under care for CHC. Here, we present the results of an interim analysis among patients treated with peginterferon alfa-2a (40KD; PEGASYS® ) and ribavirin (COPEGUS® ). Methods: All treatment-naive patients initiating treatment on or before 25 August 2008 with available hepatitis C virus (HCV) RNA data at baseline and week 4 are included in this analysis. Patients infected with more than one genotype of HCV RNA are assigned to the group with the most difficult to treat genotype of HCV (G1 > G4 > G3 > G2). Results: Baseline data and week-4 HCV RNA (<15 IU/mL) are presented in the table. The first dose of peginterferon alfa-2a was 180 mg/week in 99%, 94%, 97% and 100% of patients for G1, G2, G3 and G4 respectively. The most common RBV starting dose in mg/day for G1, G2, G3 and G4 patients was 1000/1200 (91%), 800 (63%), 800 (66%) and 1000/1200 (90%), respectively. By an MLR, baseline factors strongly associated with week-4 rapid virological response (RVR) in G1 were: lower viral load; higher alanine aminotransferase (ALT) ratio; younger age and no cirrhosis or unknown histological diagnosis.
Table 1. Patient data Parameter
G1 (N = 1118)
G2 (N = 126)
G3 (N = 241)
G4 (N = 61)
Female, n (%) Caucasian, n (%) Mean age, years Mean BMI (kg/m2 ) Median HCV RNA (IU/mL) Cirrhosis, n (%) Mean ALT ratio HCV RNA <15 IU/mL at week 4, n (%)
561 (50) 1034 (93) 46.5 25.9 1,248,000 334 (30) 2.42 236 (21)
64 (51) 93 (74) 51.1 26.8 1,524,467 20 (16) 1.95 103 (82)
82 (34) 210 (87) 40.4 24.9 764,950 30 (12) 2.70 176 (73)
24 (39) 37 (61) 45.4 26.6 192,579 9 (15) 2.05 19 (31)
Table 2. MLR analysis for G1 Factor
Categories
Odds ratio (95% CI)
p-value
Histological diagnosis HCV RNA (IU/mL) Age, years Mean ALT ratio Race
No cirrhosis* vs cirrhosis 400,000 vs >400,000 45 vs >45 >3 vs. 3 Caucasian vs other
2.11 6.06 1.98 2.18 2.58
0.001 <0.001 <0.001 <0.001 0.028
(1.44−3.10) (4.37−8.41) (1.43−2.73) (1.53−3.11) (1.11−6.01)
610 IMPACT OF ETHNICITY ON VIRAL KINETICS AND SUSTAINED VIROLOGICAL RESPONSE RATES OF GENOTYPE 4, CHRONIC HEPATITIS C PATIENTS TREATED WITH PEG-INTERFERON-A2A PLUS RIBAVIRIN I. Elefsiniotis1 , C. Pavlidis2 , D. Dimitropoulos3 , C. Mihas1 , E. Vezali1 , S. Koutsounas2 , E. Paraskevas3 . 1 University Department of Internal Medicine, Hepatology Unit, ‘Helena Venizelou’ Hospital of Athens, 2 Reference Center for Viral Hepatitis, I.K.A., 3 Department of Gastroenterology, “Agios Savvas” Hospital, Athens, Greece E-mail: [email protected] Background: Data concerning the efficacy of PEG-IFNa2a plus ribavirin treatment in treatment-naive, genotype 4-infected chronic hepatitis C (CHC) patients from Europe are limited. Objectives: To investigate the viral kinetics as well as the sustained virological response (SVR) rates and their predictors, in these patients. Methods: 123 patients were retrospectively analyzed. Early (EVR) and late (LVR) virological response were confirmed by undetectable (<50 IU/ml) serum HCV-RNA at week 12 and week 24 of treatment, respectively. SVR was confirmed by undetectable serum HCV-RNA at the end of treatment as well as six months later. Results: 108 of 123 patients (87.8%) included in the final analysis. 87 patients were men (80.55%), 22 (20.37%) had histologically confirmed cirrhosis and 72 (66.66%) exhibited HCV-RNA >600,000 IU/ml at baseline control. The majority of Caucasian patients (48/55, 87.27%) were prior intravenous drug users (IVDU) whereas none of 53 Egyptian patients were IVDU. Egyptian patients, compared to Caucasians, had higher BMI (26.4 vs 24.7 kg/m2 ), more often had high viral load (89.2 vs 69.8%), had higher fibrosis score (3.2 vs 2.4) and more often were cirrhotic (16 vs 6%). Overall, 43.5% of patients exhibited SVR, 42.6% were nonresponders and 13.9% were relapsers. EVR was observed in 40.74% and LVR in 59.25% of them. The positive predictive values of EVR and LVR were 72.97% and 86.27% whereas their negative predictive values were 64.29% and 92.85%, respectively.In the multiple logistic regression analysis only LVR (OR = 81.7, 95% CI: 19.76–337.8, p < 0.001) independently predicted SVR. Compared to a patient without LVR, a patient with LVR had 81.7 more chances of SVR achievement. EVR was
05g: VIRAL HEPATITIS − g) HEPATITIS C − CLINICAL (THERAPY) independently predicted SVR in Caucasian patients (p < 0.001) but not in Egyptian patients (p = 0.613), in whom the only independent predictor of SVR was the absence of cirrhosis (p = 0.004). Conclusions: SVR rates are comparable among Egyptian and Caucasian HCV-4 patients, despite their significant differences in baseline characteristics and in their early on-treatment virological data. Undetectable HCV-RNA at week 24 of treatment, using a sensitive qualitative PCR assay, seems to be a better predictor of SVR, than EVR, in these patients, irrespective of ethnicity and the other baseline parameters.
611 HEPATIC IMPAIRMENT IN EGYPTIAN CHILDREN WITH TYPE 1 DIABETES MELLITUS H. El-Karaksy1 , G. Anwar1 , S. Mansour1 , N. El-Koofy1 , R. El-Sayed1 , H. Helmy1 , H. Mina2 , M. Sabry2 , G. Esmat3 . 1 Pediatrics, Cairo University, 2 Pediatrics, National Hepatology and Tropical Medicine Research Institute, Cairo, 3 Tropical Medicine, Cairo University, Giza, Egypt E-mail: [email protected] Background and Aim: Hepatic involvement is not uncommon in type 1 diabetes mellitus (DM). The aim of this study was to determine the prevalence and etiology of hepatic impairment in children with type 1 DM. Methods: The study included 692 children (333 were males) with type 1 DM attending the Diabetes Endocrine and Metabolism Pediatric Unit (DEMPU) at Cairo University Pediatric Hospital. Their mean age was 9.65 + 4.18 years. All children were subjected to clinical examination for hepatomegaly, ALT determination, testing for HCV antibodies, and abdominal ultrasonography. Any child found to have hepatomegaly, raised ALT, positive HCV antibodies, and/or abnormal ultrasound was subjected to complete liver function tests, lipid profile, HbA1c, HBsAg, HCV RNA for those showing positive HCV antibodies. When indicated markers for autoimmune hepatitis, celiac screen and liver biopsy were performed. Results: Sixty (8.7%) were found to have abnormalities: hepatomegaly in 13 (1.9%), elevated ALT in 27 (3.9%), positive HCV antibodies in 25 (3.6%) and abnormal hepatic ultrasound in 31 (4.5%). Forty percent of HCV antibody positive children were HCV RNA positive. Blood transfusion and urinary catheter insertion were significantly associated with HCV positivity. Autoimmune hepatitis was diagnosed in one case. Glycogenic hepatopathy was diagnosed in 3 cases that underwent liver biopsy. Abnormalities were reversible in 37/60 after proper glycemic control. Conclusion: Diabetic children are at risk of acquisition of HCV. Poor glycemic control may predispose to hepatomegaly and elevated ALT. A four-week therapeutic trial of proper glycemic control is recommended prior to more invasive procedures.
612 WEEK 8 HCV-RNA IS THE OPTIMAL PREDICTOR OF RELAPSE IN NON-RVR PATIENTS WITH GENOTYPE 1/4 RANDOMISED TO 48 OR 72 WEEKS PEG-IFN ALFA-2A PLUS RBV T.-M. Scherzer1 , H. Kerschner2 , S. Beinhardt1 , K. Rutter1 , H. Hofer1 , P. Steindl-Munda1 , T. Popow-Kraupp2 , P. Ferenci1 . 1 Department of Internal Medicine III, 2 Department of Clinical Virology, Medical University, Vienna, Austria E-mail: [email protected] Background: In a recently completed large, multicentre randomised controlled trial, we showed that extending treatment duration with peginterferon alfa-2a (40KD) plus ribavirin reduces relapse and increases sustained virological response (SVR) rates in non-rapid virological response (RVR) patients with HCV genotype 1/4 infection. To determine which of these non-RVR patients would benefit most from extended treatment, SVR and relapse rates were determined according to viral load at weeks 8 and 12 of treatment.
S225
Methods: This analysis is based on the 187 patients enrolled at our centre (34% of all recruited patients). Patients who were HCV RNA-positive at week 4, but had >2 log drop, or <50 IU/mL HCV RNA at week 12 (early virological response [EVR]) were randomised to 48 (group A) or 72 (group B) weeks’ treatment. Samples obtained at weeks 2, 4, 8 and 12 were retested by the TaqMan™ (limit of detection: 10 IU/mL). Results: Of the 187 patients, 97 achieved an EVR and were randomised to 48 (n = 52; 51 completed treatment and follow-up) or 72 (n = 45; 41 completed treatment and follow-up) weeks of treatment. Patients with undetectable HCV RNA at weeks 8 and 12 had high rates of SVR for both 48 and 72 weeks of treatment. Irrespective of treatment duration, only two (6%) of the 35 HCV RNA-negative patients at week 8 relapsed (negative predictive value [NPV]: 94%). Of the 25 patients who became negative between week 8 and 12, seven (28%) relapsed, thus the NPV at week 12 was 72% (group A: 60%; group B: 80%). Patients with detectable HCV RNA at weeks 8 and 12 had lower relapse and higher rates of SVR with longer treatment duration. Conclusion: Measurement of HCV RNA at week 8 is the optimal time to identify patients most likely to benefit from extended peginterferon alfa-2a (40KD) plus ribavirin combination therapy. SVR
HCV RNA at week 8, n/N (%) Undetectable Detectable HCV RNA at week 12, n/N (%) Undetectable Detectable
Relapse rate
48 weeks (n = 52)
72 weeks (n = 41)
48 weeks (n = 52)
72 weeks (n = 41)
20/22 (91%) 11/30 (37%)
13/13 (100%) 15/28 (54%)
2/22 (9%) 17/28b (61%)
0/13 (0%) 4/19a (21%)
25/31 (81%) 6/21 (29%)
23/28 (82%) 4/12 (33%)
6/31 (19%) 13/19c (68%)
2/25 (8%) 2/7d (29%)
Nonresponders at week 24: a 9, b 2, c 2, d 7.
613 THE ANTIFIBROTIC PENTOXYPHILLINE/A-TOCOPHEROL ASSOCIATION DOES NOT LIMIT LIVER FIBROSIS PROGRESSION IN PATIENTS WITH CHRONIC HEPATITIS C − ANRS HC 10 H. Fontaine1,2 , S. Fernandes1,2 , B. Nalpas1,2 , P. Bedossa3 , J.-D. Grang´e4 , A. Tran5 , J. Gu´echot6 , S. Candon7 , F. Imbert-Bismut8 , S. Pol1,2 . 1 Hepatology Unit, Hˆ opital Cochin − APHP, 2 INSERM U567, Universit´e Paris Descartes, Paris, 3 Department of Pathology, Hˆopital Beaujon, AP-HP and INSERM, U773, Centre de Recherche Biom´edicale Bichat Beaujon, Universit´e Paris 7-Denis-Diderot, Clichy, 4 Hepatology Unit, Hˆopital Tenon- APHP, Paris, 5 Hepatology Unit, Hˆopital de l’Archet, Nice, 6 Service de Biochimie A, Hˆ opital Saint Antoine − APHP, 7 Immunology, Hˆopital Necker − APHP, 8 Department of Biochemistry, Hˆopital de la Piti´e-Salp´etri`ere − APHP, Paris, France E-mail: [email protected] Background and Aims: About 45% of patients are non responders to the ribavirine-pegylated interferon combination and there is no therapy proven to be efficient in limiting liver fibrosis progression. Aim: To analyse the efficacy and safety of the association of pentoxyphilline (anti-TNF activity) and a-tocopherol (antioxydant activity) in this population. Methods: 91 patients, non responders or refusing the recommended combination (49 M and 38 F, mean age: 53±10 years) were included in a prospective, randomised, placebo-controlled study. They were given pentoxyphilline 400 mg and tocopherol 500 mg (n = 46) or double placebo (n = 45), BID during one year. Baseline (BL) liver biopsies were performed less than 3 years before the inclusion and at the end of treatment. Criteria of judgement: 1. histopathology by morphometric analysis and Metavir scores; 2. variation of ALAT and non invasive tests (Fibrotest, hyaluronate, PIIIP, TNF-a) measured at the beginning, at 6 months and at the end of the treatment. Results: There were no BL differences in the histopathological severity between both groups. By comparison between BL and at the end of