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Predictive factors of fibrosis progression in patients with mild hepatitis C
158
Poster Sessions
(1015 males; 1179 females), in different Catalonian counties. In samples for which a marker was positive, subsequent analyses were performed: transaminases, HBV DNA by PCR and HCV RNA by PCR as well as genotypes. Subjects who had positive results were interviewed to determine possible risk factors. Prevalences: hepatitis B 1.69% (95% CI, 1.62-1.76) and hepatitis C 2.64% (95% CI, 2.53-2.75). Hepatitis C virus prevalence increases with age (not that of hepatitis B virus). Only a small part (12.1%) of hepatitis B carriers had detectable HBV DNA levels whilst most of hepatitis C carriers (68.6%) had detectable HCV RNA. Hepatitis C virus genotype was predominantly 1 (79.3%). Risk factors: use of non-disposable materials for injection and surgery, dentistry intervention and previous hospitalisation. Due to the high representativity of the sample we estimate data can be extrapolated to general population.
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EFFICACY AND TOLERANCE OF INTERFERON ALFA-2a FOR TREATMENT OF CHRONIC HEPATITIS C IN HIV-INFECTED PATIENTS
D. Neau, P. Trimoulet, M. Winnock, B. Lebail, G. Chene, J.M. Ragnaud, M. Dupon. Bordeaux UniversityHospital France ROCO multicenter randomised trial proposed optimized IFN monotherapy to HIV-infected patients, with adjunction of ribavirin in non-responders at week 12 (W12). Methods: Patients were IFN-naive, HCV RNA-positive (Roche), with elevated ALT, histologically proven chronic hepatitis C (CHC), CD4 count > 250//zl, HIV RNA < 10,000 copies/ml. HCV genotype was determined (Innogenetics) and plasma load (Roche) measured at inclusion, W2, W4. Sixty-eight patients received either IFN alfa-2a 6 MU tiw (24 weeks), 3 MU tiw (24 weeks) (Group A, n = 31), or IFN 9 MU dally (two weeks), 3 MU daily (22 weeks), 3 MU tiw (24 weeks) (Group B, n = 37). Undetectable RNA at W12 defined early response. Results: Twenty-eight patients were infected with genotype 1, 25 with 3, 11 with 4, 2 with 2. Fourteen patients had stage 3-4 fibrosis (METAVIR). At W12, 4 patients (group B) had stopped treatment. Four patients in group A (12.9%) and 10 in B (29.4%) were early responders (p = 0.11), 11/14 infected with genotypes 2-3. Ten grades 3:4 side effects were reported: 1:0 (group A), 7:2 (B). HCV load decreased by 0.9log in genotypes 1-4-patients in each group, and by 2.8 (group A) and 3.91og (B) in genotypes 2-3 (p < 0.10). Conclusion: In HIV-infected patients, CHC treatment may provide lower response rates than in HIV-negative patients. HCV load decrease in genotypes 2-3-infected patients tended to depend upon the modality of IFN administration.
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THREE TIMES WEEKLY VERSUS DALLYDOSE ALPHA-IFN THERAPY IN PATIENTS WITH ACUTE HEPATITIS C (AHC)
P. Fabris, M.T. Giordani, G. Tositti, M.R. Biasin, M.U. Conforto, D. Infantolino, E de Lalla. Infectious Diseases Vicenza, Depatment of Pathology Castelfranco Veneto, S. Bortolo Hospital Vicenza, Italy It has been reported that alpha-IFN therapy is able to reduce the chronicization in patients with AHC but the best protocol of treatment is still undefined Aims: To compare the efficacy of daily dose (DD) versus three times weekly (TTW) alpha-IFN therapy in patients with AHC. Methods: Fourteen patients (M/F 10/4, mean age 32.2) with AHC three months after the onset of the disease were randomised to receive either 3 MU of alpha-2a-IFN daily for 36 consecutive days or 3 MU-TTW for 12 weeks. Six patients were assigned to the DD and 8 patients to the TTW protocol. Baseline viral titre and HCV genotype were tested in all patients. Primary response (HCV-RNA-neg at the end of therapy) and sustained response (HCV-RNA-neg 6 months after alpha-IFN suspension) were evaluated with qualitative PCR.
Results: At baseline, the two groups were comparable in term of mean age, ALT, viral titre and genotype. The primary response was higher in the dally dose group (6/6 versus 3/8, P < 0.05). Overall, the sustained response was 35.7% (5/14) and was significantly associated with lower baseline viral titre, female sex and genotype 3a. The rate of sustained response was 33.3% in patients treated with DD and 37.5% in patients treated with TTW protocol (P = NS) Conclusions: As in patients with chronic hepatitis C, low viral titre, genotype 3a and female sex represent favourable prognostic factors also in the treatment of AHC. In patients with AHC daily dose significantly increases the primary response but not the sustained response.
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PREDICTIVE FACTORS OF FIBROSIS PROGRESSION IN PATIENTS WITH MILD HEPATITIS C
L. Serfaty 1, A.M. Bonnand 2, y. Chrttien 2, O. Chazouilltres 1,2, Re. Poupon 2, R. Poupon 1.1 Service d'H(patologie, HOpitalSt-Antoine; 2lnserm U 370, Paris, France Treatment of mild hepatitis C is debatted because the risk of fibrosis progression is not clearly established. The aim of this study was to determine predictive factors of fibrosis progression in chronically HCV infected patients with mild hepatitis at initial liver biopsy. Methods: Patients with chronic hepatitis C referred to our Institution between 1995 and 1999 were selected according to the following criteria: at least 2 liver biopsies in a delay longer than one year, persistant HCV viremia between liver biopsies (IFN non responder or untreated patients), mild hepatitis (Knodell score < 4 and fibrosis < 1) at initial biopsy, no treatment prior to initial biopsy, negative HBV and HIV serologies, no other cause of chronic liver disease or immunosupression. Progression of fibrosis was defined as an increase in fibrosis score from 0/1 to 3 or 4 according to Knodell between initial and last biopsy. Results: 113 patients (64 men, median age 38 yrs) fulfilled the selection criteria. Median delay between the 2 biopsies was 57 mo (12-158). During follow-up, 30 patients were untreated and 83 were IFN non responders (median duration 12 mo (4-41), IFN associated with ribavirine in 11%). 34% had fibrosis progression in a median delay of 59 mo (9-112) and cirrhosis occurred in 11%. Fibrosis progression was significantly correlated with inflammatory score progression. In univariate analysis, predictive factors of fibrosis progression were ALT activity > 2N (p = 0.02), degree of steatosis > 30% (p = 0.02) and positive Perls staining (p = 0.03) at initial biopsy, and IFN treatment (p = 0.05). In multivariate analysis, independant predictive factors were ALT > 2N (OR 2.6 IC: 1.04-6.6), steatosis > 30% (OR 6.9 IC: 2.1-22.2) and positive Perls staining (OR 3.3 IC: 1.05-10.1). Conclusion: In patients with mild hepatitis C 1) progression of fibrosis occurs in 1/3 of cases after a median delay of 5 years, 2) significant steatosis and presence of iron assessed by Pets staining caracterize a subgroup of patients with high risk of fibrosis progression. These findings could have therapeutic implications for the managment of mild hepatitis C.
8~
LIVER STEATOSIS IN CHRONIC HEPATITIS C: A MORPHOLOGICAL SIGN SUGGESTING INFECTION WITH HCV GENOTYPE 3
L. Rubbia-Brandt, G. Lean&o, L. Spahr, E. Giostra, R. Quadri, P. Malee, E Negro. Clinical Pathology, UniversityHospital Geneva, Switzerland We wanted to identify factors associated with liver steatosis in chronic hepatitis C. Occurrence and severity of liver steatosis in 254 chronic hepatitis C patients were compared with gender, age (>50 or <50), presence of alcohol abuse, body mass index (BMI) (>26 or <26), history of intravenous drug addiction (IVDA), hepatitis C virus (HCV) genotype and liver disease grading and staging scores. Steatosis was
Poster Sessions
(1015 males; 1179 females), in different Catalonian counties. In samples for which a marker was positive, subsequent analyses were performed: transaminases, HBV DNA by PCR and HCV RNA by PCR as well as genotypes. Subjects who had positive results were interviewed to determine possible risk factors. Prevalences: hepatitis B 1.69% (95% CI, 1.62-1.76) and hepatitis C 2.64% (95% CI, 2.53-2.75). Hepatitis C virus prevalence increases with age (not that of hepatitis B virus). Only a small part (12.1%) of hepatitis B carriers had detectable HBV DNA levels whilst most of hepatitis C carriers (68.6%) had detectable HCV RNA. Hepatitis C virus genotype was predominantly 1 (79.3%). Risk factors: use of non-disposable materials for injection and surgery, dentistry intervention and previous hospitalisation. Due to the high representativity of the sample we estimate data can be extrapolated to general population.
~-~
EFFICACY AND TOLERANCE OF INTERFERON ALFA-2a FOR TREATMENT OF CHRONIC HEPATITIS C IN HIV-INFECTED PATIENTS
D. Neau, P. Trimoulet, M. Winnock, B. Lebail, G. Chene, J.M. Ragnaud, M. Dupon. Bordeaux UniversityHospital France ROCO multicenter randomised trial proposed optimized IFN monotherapy to HIV-infected patients, with adjunction of ribavirin in non-responders at week 12 (W12). Methods: Patients were IFN-naive, HCV RNA-positive (Roche), with elevated ALT, histologically proven chronic hepatitis C (CHC), CD4 count > 250//zl, HIV RNA < 10,000 copies/ml. HCV genotype was determined (Innogenetics) and plasma load (Roche) measured at inclusion, W2, W4. Sixty-eight patients received either IFN alfa-2a 6 MU tiw (24 weeks), 3 MU tiw (24 weeks) (Group A, n = 31), or IFN 9 MU dally (two weeks), 3 MU daily (22 weeks), 3 MU tiw (24 weeks) (Group B, n = 37). Undetectable RNA at W12 defined early response. Results: Twenty-eight patients were infected with genotype 1, 25 with 3, 11 with 4, 2 with 2. Fourteen patients had stage 3-4 fibrosis (METAVIR). At W12, 4 patients (group B) had stopped treatment. Four patients in group A (12.9%) and 10 in B (29.4%) were early responders (p = 0.11), 11/14 infected with genotypes 2-3. Ten grades 3:4 side effects were reported: 1:0 (group A), 7:2 (B). HCV load decreased by 0.9log in genotypes 1-4-patients in each group, and by 2.8 (group A) and 3.91og (B) in genotypes 2-3 (p < 0.10). Conclusion: In HIV-infected patients, CHC treatment may provide lower response rates than in HIV-negative patients. HCV load decrease in genotypes 2-3-infected patients tended to depend upon the modality of IFN administration.
~-]
THREE TIMES WEEKLY VERSUS DALLYDOSE ALPHA-IFN THERAPY IN PATIENTS WITH ACUTE HEPATITIS C (AHC)
P. Fabris, M.T. Giordani, G. Tositti, M.R. Biasin, M.U. Conforto, D. Infantolino, E de Lalla. Infectious Diseases Vicenza, Depatment of Pathology Castelfranco Veneto, S. Bortolo Hospital Vicenza, Italy It has been reported that alpha-IFN therapy is able to reduce the chronicization in patients with AHC but the best protocol of treatment is still undefined Aims: To compare the efficacy of daily dose (DD) versus three times weekly (TTW) alpha-IFN therapy in patients with AHC. Methods: Fourteen patients (M/F 10/4, mean age 32.2) with AHC three months after the onset of the disease were randomised to receive either 3 MU of alpha-2a-IFN daily for 36 consecutive days or 3 MU-TTW for 12 weeks. Six patients were assigned to the DD and 8 patients to the TTW protocol. Baseline viral titre and HCV genotype were tested in all patients. Primary response (HCV-RNA-neg at the end of therapy) and sustained response (HCV-RNA-neg 6 months after alpha-IFN suspension) were evaluated with qualitative PCR.
Results: At baseline, the two groups were comparable in term of mean age, ALT, viral titre and genotype. The primary response was higher in the dally dose group (6/6 versus 3/8, P < 0.05). Overall, the sustained response was 35.7% (5/14) and was significantly associated with lower baseline viral titre, female sex and genotype 3a. The rate of sustained response was 33.3% in patients treated with DD and 37.5% in patients treated with TTW protocol (P = NS) Conclusions: As in patients with chronic hepatitis C, low viral titre, genotype 3a and female sex represent favourable prognostic factors also in the treatment of AHC. In patients with AHC daily dose significantly increases the primary response but not the sustained response.
~-]
PREDICTIVE FACTORS OF FIBROSIS PROGRESSION IN PATIENTS WITH MILD HEPATITIS C
L. Serfaty 1, A.M. Bonnand 2, y. Chrttien 2, O. Chazouilltres 1,2, Re. Poupon 2, R. Poupon 1.1 Service d'H(patologie, HOpitalSt-Antoine; 2lnserm U 370, Paris, France Treatment of mild hepatitis C is debatted because the risk of fibrosis progression is not clearly established. The aim of this study was to determine predictive factors of fibrosis progression in chronically HCV infected patients with mild hepatitis at initial liver biopsy. Methods: Patients with chronic hepatitis C referred to our Institution between 1995 and 1999 were selected according to the following criteria: at least 2 liver biopsies in a delay longer than one year, persistant HCV viremia between liver biopsies (IFN non responder or untreated patients), mild hepatitis (Knodell score < 4 and fibrosis < 1) at initial biopsy, no treatment prior to initial biopsy, negative HBV and HIV serologies, no other cause of chronic liver disease or immunosupression. Progression of fibrosis was defined as an increase in fibrosis score from 0/1 to 3 or 4 according to Knodell between initial and last biopsy. Results: 113 patients (64 men, median age 38 yrs) fulfilled the selection criteria. Median delay between the 2 biopsies was 57 mo (12-158). During follow-up, 30 patients were untreated and 83 were IFN non responders (median duration 12 mo (4-41), IFN associated with ribavirine in 11%). 34% had fibrosis progression in a median delay of 59 mo (9-112) and cirrhosis occurred in 11%. Fibrosis progression was significantly correlated with inflammatory score progression. In univariate analysis, predictive factors of fibrosis progression were ALT activity > 2N (p = 0.02), degree of steatosis > 30% (p = 0.02) and positive Perls staining (p = 0.03) at initial biopsy, and IFN treatment (p = 0.05). In multivariate analysis, independant predictive factors were ALT > 2N (OR 2.6 IC: 1.04-6.6), steatosis > 30% (OR 6.9 IC: 2.1-22.2) and positive Perls staining (OR 3.3 IC: 1.05-10.1). Conclusion: In patients with mild hepatitis C 1) progression of fibrosis occurs in 1/3 of cases after a median delay of 5 years, 2) significant steatosis and presence of iron assessed by Pets staining caracterize a subgroup of patients with high risk of fibrosis progression. These findings could have therapeutic implications for the managment of mild hepatitis C.
8~
LIVER STEATOSIS IN CHRONIC HEPATITIS C: A MORPHOLOGICAL SIGN SUGGESTING INFECTION WITH HCV GENOTYPE 3
L. Rubbia-Brandt, G. Lean&o, L. Spahr, E. Giostra, R. Quadri, P. Malee, E Negro. Clinical Pathology, UniversityHospital Geneva, Switzerland We wanted to identify factors associated with liver steatosis in chronic hepatitis C. Occurrence and severity of liver steatosis in 254 chronic hepatitis C patients were compared with gender, age (>50 or <50), presence of alcohol abuse, body mass index (BMI) (>26 or <26), history of intravenous drug addiction (IVDA), hepatitis C virus (HCV) genotype and liver disease grading and staging scores. Steatosis was