6 2 4 A AASLD ABSTRACTS HEPATOLOGY October 2001

1807

VIROLOGICAL AND HISTOPATHOLOGICAL EFFICACY OF ANTI-VI- RAL THERAPY IN HCV-RELATED CIRRHOSIS. Anais Vallet Pichard, Ber- trand Nalpas, H~l~ne Fontaine, Marie Laure Chaix, Francoise Carnot, Chris- tian Brechot, Stanislas Pol, Necker Hospital, Paris France

Aim: To assess the efficacy of interferon and combined therapy (Interferon+ribavirin) according to HCV genotype in HCV+ve cirrhoties who have been exluded of muhicenter trials. Patients: All the I24 HCV+ve cirrhot- ics (88 men and 36 women, mean age of 54 +12 y) who had received one or more antiviral therapy in our unit and who were HBsAg-ve, HIV-ve, non alcoholics and non receiving immunosuppressive therapy. HCV genotypes were: ia or Ib (n=64); non 1 (n=50); unknown (n=10) Methods: Naturalis- tic design and intent-to-treat analysis.. The main end-point was the HCV RNA status 6 months after treatment discontinuation, a negative and positive HCV RNA corresponding to a response and non response, respectively. Results: 90 and 34 patients were treated by interferon alone (I) and combined therapy (I+R) for i2 months, respectively. Repartition of HCV genotypes, known in 110 patients, did not differ according treatment group (1 and non-l: 54 and 46% in group I, 61 and 39% in group I+R). In patients with HCV genotype 1, the rate of response was low (<10%) and similar in both treatment groups. However in patients with non-1 genotype, the rate of response was three times higher in I+R (38.5%) than in the I group (13.9%). Fourty-four non respond- ers, all having been initially treated with t, were retreated, 11 with I and 33 with I+R for 12 months. In patients infected with HCV genotype 1, the rates of response were similar in I ( i /4=20%) and I+R (3/I2=20%) groups while in patients with HCV non-i , the rate of response was 2-fold higher in I+R (8/ 18=44.4%) as compared to I (1/6=16.7%)(genotype was unknown in 4). Altogether, at the end of one or two rounds of therapy, 12/6I (19.7%) patients with genotype 1 and 24/49 (48.9%) with non-1 HCV genotype were sustained responders. 50 patients, including 18 responders and 32 non-responders, had a liver histopathological evaluation before and after therapy. Treatment was associated with a significant decrease in the HAI (mean -1.5 +-- 3.3) which was more striking in the 6 responders (-4.3 -+ 3.1 vs -1.1-+ 3.2, p=0.02). The mean fibrosis score did not significantly change following therapy (-0.36 - 1.1, NS) whatever the type of response; however 6 out of the 50 had a striking fibrosis regression of minus 2 units at least which was significantly more frequent in responders than in non-responders (5/15, 27.8% vs 1/32, 3.I%, p=0.02), in- dicating reversibility of cirrhosis. Conclusion: In cirrhotic patients infected with non 1 genotype, combined therapy is indicated, even after a first unsuc- cessful treatement, since leading to a sustained HCV RNA negativation in more than 40% of the cases, associated with a significant decrease in the HAI score and a striking fibrosis regression in about I0%. When infection is due to HCV genotype i, interferon alone and combined therapy appears to have a similarly low efficacy, even when repeated.

1808

INTERFERON TREATMENT ENHANCES SEROCONVERSION IN VERTI- CALLY HBV INFECTED CHILDREN. Deirdre A Kelly Dr, Jaswant Sira Mrs, Carla Lloyd, Paul Davies, Birmingham Children's Hosp, Birmingham Uk; Eliz- abeth H Boxafl, Birmingham Heartlands Hosp, Birmingham Uk

Background:We have previously reported the lack of short term efficacy of alpha interferon (INF) +/- prednisolone in vertically HBV infected children.q[ Aim:To evaluate the long term safety and efficacy of (INF) +/- prednisolone priming in an Asian subset of this group, q[ Methods & Subjects:Inclusion criteria: 2-16 years; HBeAg+ for 6 months; HBV DNA+. 46 children were recruited, mean age 9.4 years, (26 Asian from Indian subcontinent, 9 Oriental, 6 Afro-Caribbean and 5 Caucasian) and randomly assigned to one of three treatment groups. Control group, pred- nisolone primed group (prednisolone reducing from 2-0.5 mg/kg for 6 wks prior to interferon) and interferon only. Long-term follow-up was only available in 6 Asian control patients and thus only data on the asian subjects are included. The end points for treatment were HBV DNA negative by liquid hybridisation assay (Abbott) and seroconversion to anti HBe.q[ Results:The control group (n=6) were monitored untreated for a median of 110 months, Prednisolone + interferon (n= 9) and inter- feron only (n = 11) were both monitored for a median of 86 months. Seroconversion was more likely (p=0.02) in those with high initial ASTs (median 64 for serocon- verters vs. 49). el Conclusion: We demonstrate that treatment with interferon +/- prednisolone may enhance HBV seroconversion in Asian children from the Indian subcontinent, q[ Graph: Kaplan-Meier plot of seroconversion rates in Asian children in each treatment group. The rate of seroconversion is higher in the treated groups than controls (p=0.08). There is a trend for a higher rate of seroconversion occur- ring earlier in those receiving prednisolone priming vs. interferon alone.

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1809

A CONTROLLED STUDY OF ANTI-HBV VACCINE THERAPY IN HBSAG HEALTHY CARRIERS. Stanislas Pol, Marie Laure Chaix, Bertrand Nalpas, Pierre Tiollais, Marie Louise Michel, Christian Breehot, Necker Hospital, Paris France

Background and aim: Healthy HBsAg carriers have a potential risk of transmit- ring HBV, superinfection and hepatocellular carcinoma. Since HBV vaccine has been suggested to be efficacious in treating chronic hepatitis B and may induce vaccine-specific proliferative immune responses, we evaluate this issue in a randomized controlled study. Patients and methods: 28 HBs healthy carriers, all HBVDNA-negative by the Digene assay (cut-off value = 1.000.000 copies/ ml) antiHBe-positive,antiHCV- and antidelta-negative with normal transami- nase activities have been randomized in 3 groups: during a 12-month period, 10 were followed without treatment while 18 were given 5 intradeltoidian (n= 10) or intradermal (n=8) injections of a preS2/S vaccine (3 injections at one month-intervals followed by 2 at 3-month intervals, respectively). The primary end point was serum HBVDNA negativation at 6 and 12 months by using the Cobas HBV-PCR test (cut-off value = 200 copies/ml). Results: At inclusion, only 3/28 subjects had undetectable viremia by PCR. In the 25 others, the viral load was low (<100.000 in all but 1 with 238,000 copies/ml). At month 6 and 12, there was no significant variation in the quantitative HBV load by comparison with baseline values between non vaccinated and vacci- nated subjects although a decrease > 40% was observed in 33 and 35%, re- spectively. There was no variation according to the route of immunization. None developed transaminase flare-up, immune complexes disease or antiHBs. One vaccinated subject cleared HBsAg 26 months after vaccination. Conclu- sions: This trial shows that: 1. most of healthy HBsAg carriers has still detect- able HBV replication; 2. specific HBV vaccine therapy does not cancel this residual replication,

1810

ALFACON-1 IFN DAILY IN HCV CHRONIC HEPATITIS. Caterina Furlau, Infectious and Tropical Diseases Dept, La Sapienza Univ, Rome Italy; Silvia Sereno, Silvana Pugliese, Vittorio Laghi, La Sapienza Univ, Rome Italy

BACKGROUND AND AIM OF THE STUDY HCV-RNA clearance at the third month of IFN therapy is considered as predictive factor of sustained response (SR). Aim of the present study was to evaluate HCV-RNA clearance with alfacon-1 IFN 9/zg. daily at the third month of therapy in comparison with recombinant -alpha-IFN (R-alpha-IFN). MATERIAL AND METHOD Sevemy- eight HCV+ve pts. have been studied, 58 males and 20 females, (mean age 43.2, range 19 - 64, S.D.12.7+). All had abnormal AST/ALT level, all were HCV-RNA+ve, all underwent needle liver biopsy; no patient had cirrhosis. Eighteen pts. received alfacon-1 IFN 9 /~g.(3 MUI) daily (Group I), twenty received R-alpha-IFN 3 MUI daily (Group II), and forty received R-alpha-lFN 3 MUI three times a week (Group III). The three Groups were similar for demographic, histological and viral parameters. HCV-RNA was tested at the beginning and at the third month of therapy by PCR method (Amplicor Roche). RESULTS At the third month of therapy in Group I 15/18 pt.(83.3%) became HCV-RNA negative, two (11.1%) showed a strong reduction of HCV- RNA, and one (5.5%) remained unchanged; in Group II 11/20 pt. (55%) be- came negative, in Group III 18/40 (45%). The percentage of HCV-RNA clear- ance in Group I was major than in Group II, while no substantial difference was noted between Group II and Group III. In Group I a considerable number of patients became negative in comparison with Group If even if these data didn't reach statistical significance (p=0.13), no statistical significance also between Group II and Group IfI (p=0.65). On the contrary the higher number of negative pts. in Group I was statistically significant respect Group III (p=0.02). Moreover Alfacon-1 IFN daily was well tolerated, really all pts. had a good quality of life during treatment. Finally Alfacon-1 IFN was less expen- sive than R-alpha-fFN daily. CONCLUSION HCV-RNA clearance at the third month of therapy is universally accepted as prognostic favourable parameter of SR, so it is possible speculate that at the end of follow-up, daily Alfacon-1 IFN could have a major virologic response than R-alpha-IFN daily or three times a week.