558A AASLD ABSTRACTS HEPATOLOGY October 2001

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VIRAL LOAD IN HCV-RNA POSITIVE PREGNANT WOMEN. Annarosa Floreani, Dept of Surgical and Gastroenterological Sciences, Padova Italy; Cin- zia Santarossa, Pasquale Grella, Department of Obstetrics and Gynecology, Padova Italy; Giorgio Pal~, Department of Virology, Padova Italy; Vnicenzo Baldo, Department of Environmental and Public Health, Padova Italy; Patrizia Boccagni, Department of Surgical and Gastroenterological Sciences, Padova ltaly; Delia M Paternoster, Department of Obstetrics and Gynecology - Univer- sity of Padova (Italy), Padova Italy

The risk of HCV infection in the newborn is estimated to be around 5%, but becomes very high in the case of coinfection with HIV. One of the main factors associated with the vertical transmission of HCV is the viral load. AIMS: to investigate the behaviour of HCV viral load during pregnancy in relation to liver enzymes and vertical transmission. METHODS: 3,748 women seen con- secutively in their 1 st trimester of pregnancy were screened for HCV infection. Sixty-five were found antiHCV+/HCV-RNA+, and were followed-up with clinical and serological assessment, i.e. transaminases and quantitative PCR for viral load, in their 2 nd and 3 ra trimesters, and 6 months after delivery. All were anti-HIV and HBsAg negative. RESULTS: HCV-RNA was 12.0---19.9 x 106 copiesdml in the i st trimester and 10.9+13.3 x 106 in the 2 na , but increased to 19.5+25.1 x 106 in the 3 ra trimester. Six months after delivery, the viral load returned to the baseline levels; the changes in viral load did not reach any statistical significance, however. Transaminases tended towards a reduction from the baseline during the 2 nd and the 3 rd trimesters, then an increase in both AST and ALT was recorded 6 months after delivery. However, when the group whose AST/ALT were found abnormal at the first test was considered, no significant changes were recorded during the follow-up. The overall rate of vertical transmission was 4.6%. CONCLUSIONS: in HCV positive mothers monitoring transaminases during pregnancy is unnecessary and testing liver enzymes at the beginning of pregnancy is sufficient. Qualitative PCR should be done once during the pregnancy, but any staging of the liver disease should be taken after delivery. Quantitative PCR testing is expensive and pointless. Any decision for elective caesarean section in HCV-RNA positive mothers should be confirmed by other studies.

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EFFECT OF RIBAVIRIN ON VIRAL KINETICS IN HEPATITIS C VIRUS GENOTYPE 1 INFECTED PATIENTS TREATED WITH PEGYLATED IN- TERFERON ot2A. Stefan Zenzem, University Hospital Frankfurt, Frankfurt Germany; Eva Herrmann, University of Technology Darmstadt, Darmstadt Germany; Jung-Hun Lee, University Hospital Frankfurt, Frankfurt Germany; George Marinos, Prince of Wales Hospita], Randwick Australia; Marlene Modi, Hoffmann La-Roche, Nutley, NJ; W. Kurt Roth, Blutspendedienst Frankfurt, Frankfurt Germany

Ribavirin shows additive antiviral activity against the hepatitis C virus (HCV) in patients treated with interferon cz. The antiviral mechanism(s) of ribavirin is un- known, both direct antiviral and immunologicafiy mediated effects have been sug- gested. Mathematical modeling of viral kinetics can be applied to obtain information on the mechanism of action of ribavirin. Therefore, we studied the effect of rihavirin on HCV dynamics in patients with chronic hepatitis C, who were treated with the long-acting pegimerferon oL2a alone or in combination with ribavirin, Furthermore, initial viral kinetics were correlated with the virologic response at the end-of-treat- ment and the follow-up period. HCV-1 infected patients were randomly assigned to receive 48-wk treatment of 180/~g peginterferon cx2a qw without (group A; n= 17) or with 1000-1200 mg ribavirin qd (group B; n= 10) or standard combination ther- apy (3 MU tiw + 1000-1200 mg ribavirin qd; group C; n=9;). All groups were comparable for age and pretreatment ALT and viremia. Patients were evaluated twice before therapy and during treatment at day 1, 2, 3, 4, 5, 7, 14, 21, 28, 42, 56, and subsequently every 4 weeks. HCV RNA was quantitated by reverse transcrip- tion-polymerase chain reaction (Cobas Amplicor TM HCV Monitor 2.0). Mathemat- ical modeling of the initial viral kinetics was performed as previously described (Gastroenterology 2001;120:1438-47). Median of the first phase of virus decay, which approximately models the degradation rate of free virus, was 1.73 day "1 (95% CI 0.16 - 3.47 day-i), 2.74 day "1 (95°£ CI 0.09 - 4.80 day-t), and 0.14 day -1 (95% CI 0.0- 3.79 day -1) and median of the second phase decline of HCV RNA, which models the degradation rate of infected cells, was 0.05 day -1 (95°£ CI 0.0 - 0.12 day-l), 0.16 day -1 (95% CI 0.04 - 0.25 day-l), and 0.10 day -x (95% C10.0 - 2.01 day -x) in group A, B, and C, respectively. After 28 days the viral decay of group B became faster than that of group A (p < 0.001). At the end of therapy and the end of follow-up HCV RNA was undetectable in 12 of 17 and 2 of 17 patients treated with peginterferon cx2a alone, in all 10 and 5 of 10 patients treated with peginterferon c~2a plus ribavirin, and in 4 of 9 and 3 of 9 patients treated with standard combination. In conclusion, ribavirin had no significant effect on initial viral kinetics. After day 28, however, patients treated with peginterferon c~2a plus ribavirin showed a more pronounced viral decline than patients treated with peginterferon ~x2a alone. This suggests that ribavirin has only a weak and/or delayed antiviral effect which is responsible for the enhanced end-of-treatment and sustained virologic efficacy of combination therapy.

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VIRAL KINETICS OF HCV DURING DAILY-DOSE TREATMENT WITH INTERFERON ALFACON-1 VS RECOMBINANT INTERFERON ALPHA- 2A. Gaetano Scotto, Infectious Diseases University, Foggia Italy; Fazio Vincen- zina, II Laboratory OORR, Foggia Italy

Several correlations have been found for baseline viral load, genotype, sex and age as predictive parameters of sustained response in patients with chronic hepatitis C and treated with alpha-interferon; recently it was suggested that also early viral kinetics are a predictive parameter of treatment outcome. The aim of this study is to investigate the daily treatment with Alfaeon-1, a new bio-engineered man made type-1 IFN, vs recombinant alpha-2a interferon in determining rapid decline of viral load until it becomes undetectable. MATE- RIAL and METHODS: Twenty naive patients affected by chronic active hepa- titis, genotype lb, were randomly assigned in equal numbers to two groups; all patients presented similar baseline characteristics (age, sex, viral load, HAI score). A) Received interferon Alfacon-1, 9 microgr, subcutaneous; B) Re- ceived 3 MU recombinant interferon alpha-2a subcutaneous. The period of treatment both with Alfacon-1 and alpha-2a was of 28 days. We measured the viral load of all the patients at baseline, 24-48-72 hours, and 7-14-21-28 days. RESULTS: All the patients completed the study. The median baseline value of HCVRNA was 61.3 millions copies/ml in the group A and 61.1 millions in the group B. After 24 hours: 9.0 vs 16.0 millions, after 48 h.: 6.1 vs 15.5 millions, and after 72 h.: 5.8 vs 14.4 millions (p<0.05). During the first 24 hours the decline is very fast, thereafter the viral load decreases more slowly, with sig- nificant differences between the two groups: reductions> 1 log in the gr. A, < 1 log in the gr. B. In the following period, 7-14-21-28 days, the median of viral load hadn't presented any significant variation and at the end of treatment, we had HCVRNA: 5.2 millions copies/ml in the gr. A vs 14.6 millions in the gr. B (p<0.05). At 28 day, HCVRNA was undetectable in 6/10 patients of gr. A and in 4/10 of gr. B; the subjects who were non-responders presented higher viral load at baseline. CONCLUSIONS: Daffy treatment with Alfacon-1 appears to result in a much faster and stronger decline of HCVRNA than daily treatment with interferon alpha-2a, in patients affected by chronic active hepatitis C genotype lb. A higher percentage of subjects treated with Alfacon- 1 presented HCVRNA undetectable at the end of treatment; the response was related to viral load of HCV.

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HEPATITIS C VIRUS GENOTYPES IN PAKISTAN. Arif Q Khan, Akhtar S Chughtai, Faisal Q Khan, M S Nisar, Rizwan Z Abroad, Zafar I Chaudhry, Tariq M Tahir, Tehseen Ahmed, Allama Iqbal Medical Coll Lahore Pakistan, Lahore Pakistan

Hepatitis C virus (HCV) has at least 6 genotypes and more than 30 subtypes. The relative prevalence of different HCV genotypes differs from country to country. Recently HCV genotyping has been shown to be all important predic- tor of response to treatment, with genotype I being less responsive and geno- type Ill more responsive to the currently available treatment with interferon and ribavirin. The objective of this study was to determine the relative preva- lence of different HCV genotypes in our population of patients with acute and chronic hepatitis C. MATERIAL AND METHODS: Retrospective analysis of 525 patients with acute and chronic hepatitis C seen between January 1, 1997 and December 31, 2000 was carried out. Of these 98 patients had acute hepa- titis C and 427 patients had chronic hepatitis C. Liver Biopsy was performed in 149 patients with chronic hepatitis C ( chronic persistent hepatitis 53, chronic active hepatitis 68 and cirrhosis with activity 29). HCV genotype was per- formed in all the patients. RESULTS: The relative prevalence of different HCV genotypes ill acute hepatitis C (98 pts) was genotype III in 68 (69.3%) both II and I i l in 10 (9.8%), Ia in 5(4.7%), Ib in 4 (4.05%) IVin 2 (2.04%) and not type able in 9 (9.1%) patients. In chronic hepatitis C (427 pts) the prevalence of genotype 11I, both II and In, In, Ib and not typeable was in 320(73.6%), 20 (4.6%), 20 (4.6%), 25 (5.8%) and 42 (9.8%) patients respectively. CONCLU- SION: Genotype III is the most prevalent type in both acute and chronic hepatitis C in Pakistan.