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HCV: GENOTYPES, VIRAEMIA AND RESPONSE TO INTERFERON

Author: S. Magrin, R. Simonetti; M. Albanese, C. Fabiano, G. Fiorentino, R. Messineo, D. Guerrera, M. Cutrera, F. Gianguzza, F. Tine, L. Pagliaro. Div.Med.Interna, Ospedale Cervello; Clinica Medica R; Dip. Biol.Cell. e dello Sviluppo, Universita di Palermo;ITALY

Subtype 1b, whose prevalence shows geographical variations, has been associated with severe liver disease (Cirrhosis, HCC). Thus we assessed, by LiPA, HCV types in 262 patients living in Sicily. In table I are shown the results obtained grouped for age, sex and level of disease.

     group   age   sex   liver disease  1b  1a  2a  3  4
      I     62±6   M(75)  HCC           86% 6%  6%  -  2%
     (100)         F(25) cirrhosis
      II    47±8   M(62)  CH (73)       82% 5%  4%  4% 5%
     (100)         F(38) cirrhosis (27)
      III   41±10  M(42)  CH (60)       58% 8% 16% 10% 8%
     (62)          F(20) cirrhosis (2)
  
Table I. In brackets number of patients

Group II (1989-91) and III (1995-96) were consecutively admitted to our Departement for interferon treatment. Non-HCC patients were younger than HCC patients. Group III was younger, showed milder disease and responded better to interferon treatment (primary response rate : 61% vs 49%) than group II. We have also assessed, by bDNA test, pre-treatment HCV viremia that turned out to be lower in group III than in group II (mean genome eq./ml 1.9x10Ø{6} and 7,8 x10Ø{6} respectively in primary responders; 4,3 x10Ø{6} and 5,7 x10Ø{6} respectively in non responders). Moreover direct sequencing of 5'NC amplified region was performed in 152 patient (52 HCC), by dideoxy-termination chain method. Type 3 was found only among patients less than 45 years. Moreover only both non-responders 1b patients non-HCC (12/63=19%) and 1b HCC patients (5/34=15%), all over 45 years, showed the same substitution of nucleotides A or C (-137 and/or -138) with T. Finally 2 of non-responders 1b patients non-HCC over 45 years, showed a new double compensatory substitution on the stem of the 5'NC secondary structure. In conclusion our results show that HCV types prevalence depends on age and severity of liver disease in the same geographical area, and that the above factors (comprised a negative probable relationship of some subtypes) can influence response to interferon treatment. Moreover the type 3 prevalence is probably increasing, may be at expense of type 1b or closely related subtypes. This should be always take into account in evaluating HCV type as a risk factor for HCC or as a predictor response to interferon.

Source: American Association for the Study of Liver Diseases - 1996 Annual Meeting


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