- Email: [email protected]
Anti hepatitis G E2 antibody detection and its relation to serum HGV-RNA in patients with clotting disorders
194
Puprrs red
Virological and biochemical administration are different M. Gimknez-Barcons. Tapias.
Hospital Response
to
Clinic,
chronic
changes hepatitis
induced
by interferon by HCV-lb.
of VHC
was detected
quasispecies
by RT-PCR
assay was 200 copies/ml) by PCR-SSCP Presence (31%)
of RNA
patients
patients
with
normal
evolution
ALT
that
related interferon
values.
did
not
these
results.
of
the viral
of with
complexity
of the
was analysed
SR the RNA
with
throughout
the study.
was observed in 6/19
values
of elevated
the viral the
type
Sequential
by PCR-SSCP
response.
indicative
in I8 patients.
a TR. RNA was undetectable in 5/32 (16%)
complexity
biochemical
changes
ALT
with
ALT
levels.
RNA
in 618 (75%) of patients with a breakthrough episode
quasispecies
confirm
normal
In
levels
(The sensibility
level were normal
with NR, beside the presence
was detected and
with
(NR).
RNA
the complexity
was analysed
of the S’NCR
is
Sustained
in 66 patients
In addition,
I. In the seven patients
and ALT
in:
between
therapy
C
hepatitis
levels
and No Response
and quasispecies
of the HVR-
was undetectable
(TR)
Unit,
Espafia
chronic
ALT
the relationship
C infected
and the evolution RNA
of
Response
we have analysed
and ALT
in
normalisation
(SR), Transient
study
C.
J.C. Saiz. Liver de Barcelona,
administration
by
hepatitis
lahuerce. J.M. SBnchez_
es.
Universitat
interferon
classified
Response this
D
Jim 6nez de ,YntrZod:a?
M.T.
usually
S A
response to interferon in Chronic
correlated Preliminary response
the of
ALT to
quasispecies of
with data
Conclusions:
virological
of
analysis
HCV-lb
showed different patterns of
values
interferon complexity or
type
of
nucleotide
viral
are not
therapy. are not
biochemical
or
sequences always
Sequential necessarily response
treatment.
to
by title
EARLY ANTIVIRAL RESPONSE TO ALPHA INTERFERON THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C. RELATIONSHIP WITH GENOTYPE AND DOSE OF INTERFERON. N Bover l. M Martinot l. V Martins-Amado’. P Mever”. M Pouteau’. .J . P Marc&. . ew ‘Service d’H8patologie et INSERM U24, HBpital Beaujon, Clichy , France ; “Ciba Geigy Ltd, Basel, Switzerland. Obiective; In patients with chronic hepatitis C treated with alpha interferon, an early response is important to obtain an end of treatment or a sustained response. We studied the relationship between the virological response at 1, 2 and 4 weeks after the initiation of alpha interferon therapy and the dose of interferon received and the HCV genotype. Patients We studied 44 patients with chronic active hepatitis C, histologically confirmed (no cirrhosis). They were 36 men and 8 women. They were randomized in 2 groups, to receive 3 million units (MU) (23 patients) or 32MU (21 patientsjof alpha interferon (Hybrid alpha interferon, Ciba Geigy, Switzerland) thrice weekly, during 26 weeks. Serum HCV RNA was quantified with the bDNA assay (Quantiplex. Chiron), befora treatment and 1 week, 2 weeks and 4 weeks after the initiation of alpha interferon therapy. Genotyping was performed with the reverse hybridization assay (Lipa)(lnno-Lipa, Ingen). Basulls; Patients were classified in 2 groups acoordino to aenotvoes: 1b (20 patients) or non 1b (24 patients). The 2 groups were nit diiereni ior sex and pretreatment serum HCV RNA level. An end of treatment response was observed in genotype 1b group and in genotype non 1b group in 33% and 83% respectively (p=O.O3). The decrease of serum HCV RNA was more markedand more rapid in patients with genotype non 1b than lb (‘p=O.O06). Four sustained responders were PCR negative at week 2. Percentage of patients with negative serum HCV RNA by PCR : week 1 week 2 week 4 Genotype 1b (n=20) 11% 15% 27% Genotype non lb (n=24) 38% 52% 86% Conclusion: In patients with chronic hepatitis C, the virological response to alpha interferon theraov aooears earlv (within 2 weeks) in resoonders. The early virological response ‘i6 more rapjd’and more complete in’patients with genotype non 1b. Detectable serum HCV RNA level (a 0.35 lo6 genome/ml) after 2 weeks of treatment was a predictor of no response.
The possibility to reduce hepatitis B morbidity through vaccination of adolescents. I.V.Shakeildian. M.I. Mikhailov. P.A.Khukhlovich. V.V. R omanenko. I.O.Kuznetsova. A.Yu. Esaulkova
ANTI HEPATITIS G E2 ANTIBODY DETECTION AND ITS RELATION TO SERUM HGV-RNA IN PATIENTS WITH CLOTTING DISORDERS
D.I. Ivanovsky Institute of Virology, N.F. Gamaleya Institute of Epidemiology and Microbiology RAMS, Moscow; Sverdlovsky Regional Sanitary and Epidemiology Centre, Ekaterinburg.
L. Shena. A. Soumillion. K. Peerlinck*, C. Verslvpe, R. Schelstraete”. :elinck. M-P. Emondse. G He **. J V VI *. J Des vte -, h Div. Liver & Pancr. D&., ‘iiv. SlA% ?Vasc. IX: D&. Virol., Univ. Hosp. Gasthuisberg, OBl& Transfusion tent&, Rode Kruis &anderen, Leuven, Belgium; and **Boehringer Mannheim, Germany
Hepatitis B (HB) vaccine prophylaxis is currently a problem of great importance in Russia. There was a marked increase in HB incidence cwer the last years (from 18.1 per 100,000 in 1992 to 25.8 in 1996; in the Region of Sverdlovsk from 20.7 to 62.7,respectiveIy) with mostacute hepatitis cases occuring in adolescents and young adults with low prevalence among children (in1996 82.4% of HB patients were 51-29 years of age in Moscow, 76% in the Region of Sverdlovsk). The number of HBV infections due to illegal parentera drug use or sexual contacts with HBV carriers and chronic HB patients was continuously increasing while the occurance of HB infection in hospitals was decreasing -. HBV vaccination of adolescents (to&her with high-risk cateeories) is considered a most reasonable immunisation &tegy for thl< epidemic: Duhng 1996-1997 such an approach was implemented in the city of Verkhnaya Pyshma, Sverdlovsk region, which the HBV incidence had been greater that the regional average over many years with about half the 1995 cases (46.6%0 being adolescents (aged 15 to 19). Screening of the city adolescents and youg populations for HBV markers (HBsAg and anti-HBs) also demonstrated vast involvement of these populations in the HBV epidemics. HBsAg carriage was 1.9% in adolescents aged 12.14 years, 2.2% in individuals 15-17 years of age, 3.6% among young adults aged 1820 years; the respective anti-HBs rates were 12.25, 20.9% and 30.4%. Administration of three cdses of HBV vaccine ( SmithKline Beechaml to 71% of adolescents aged 13-17 years in V.Pyshma resulted in 1.6 fold reduction in HBV incidence in the city one year following the immunisation start ( the reduction among 13-17 year old adolescents b&g 2.5-fold at year I and 7.9fold at year 2), while the regional rate demonstrated a 20% increase. Protective titres of anti-HBs were detected in 85% of subjects at&r two doses and in 94.7% after three doses of the vaccine (32.1% had titres ranging from 100 to 500 IU/I and 47.8% hiaber than 500 W/l). Vaccination of adolescents and vounz adults is therefore the most reasonable vaccination strategy in areas with moderate HBsAg carriage in which these age groups are mainly involved in the epidemics. I
I
,~
-_
~~~~
In a previous study, we determined the prevalence of serum HGVRNA in Belgian hemophiliacs. 15% of 175 patients were serum HGVRNA positive. HGV-RNA was detectable in PBMC in 10% of the cases, three of these patients were serum HGV-RNA negative. ln this study, we determined the prevalence of anti-HGV-E2 antibodies in the same patient population. Anti-E2 as determined by ELISA and was detected in 45 pts (25.7%). Forty of these patients were serum HGVRNA negative. In a retrospective longitudinal study? we have observed in 15 pts, that serum HGV-RNA persisted dunng 1-19 years of follow-up, while anti-E2 was repeatedly negative. Five additional patients who were anti-E2 positive with concomitant detectable HGVRNA they became HGV-RNA negative during follow-up (l-8 years after the first detection of anti-E2 Abs). Two patients had lost anti-E2 Abs 3-6 years after the seroconversion without the re-appearance of serum HGV-RNA. Twenty four of the 26 HGV viremic pts and 43 of 44 pts with detectable anti-E2 were coinfection with HCV. Of the HCVMGV coinfected patients, 62.5% of the HGV viremic pts and 53% of the anti-E2 pos. pts. showed elevated serum ALT levels. Two patients solely infected with HGV had normal serum ALT levels. Conclusions: 1) The prevalence rate of anti-E2 Abs in Belgian hemophiliacs is higher than the prevalence of HGV viremia. 2) Most of the patients clear the virus spon~eously. HGV viremia may persist for more than I9 years. 3) The clearance of the virus is usually associated with seroconversion to anti-E2. 4) Anti-E2 may be lost during years of follow-up without reapearance of HGV.
Puprrs red
Virological and biochemical administration are different M. Gimknez-Barcons. Tapias.
Hospital Response
to
Clinic,
chronic
changes hepatitis
induced
by interferon by HCV-lb.
of VHC
was detected
quasispecies
by RT-PCR
assay was 200 copies/ml) by PCR-SSCP Presence (31%)
of RNA
patients
patients
with
normal
evolution
ALT
that
related interferon
values.
did
not
these
results.
of
the viral
of with
complexity
of the
was analysed
SR the RNA
with
throughout
the study.
was observed in 6/19
values
of elevated
the viral the
type
Sequential
by PCR-SSCP
response.
indicative
in I8 patients.
a TR. RNA was undetectable in 5/32 (16%)
complexity
biochemical
changes
ALT
with
ALT
levels.
RNA
in 618 (75%) of patients with a breakthrough episode
quasispecies
confirm
normal
In
levels
(The sensibility
level were normal
with NR, beside the presence
was detected and
with
(NR).
RNA
the complexity
was analysed
of the S’NCR
is
Sustained
in 66 patients
In addition,
I. In the seven patients
and ALT
in:
between
therapy
C
hepatitis
levels
and No Response
and quasispecies
of the HVR-
was undetectable
(TR)
Unit,
Espafia
chronic
ALT
the relationship
C infected
and the evolution RNA
of
Response
we have analysed
and ALT
in
normalisation
(SR), Transient
study
C.
J.C. Saiz. Liver de Barcelona,
administration
by
hepatitis
lahuerce. J.M. SBnchez_
es.
Universitat
interferon
classified
Response this
D
Jim 6nez de ,YntrZod:a?
M.T.
usually
S A
response to interferon in Chronic
correlated Preliminary response
the of
ALT to
quasispecies of
with data
Conclusions:
virological
of
analysis
HCV-lb
showed different patterns of
values
interferon complexity or
type
of
nucleotide
viral
are not
therapy. are not
biochemical
or
sequences always
Sequential necessarily response
treatment.
to
by title
EARLY ANTIVIRAL RESPONSE TO ALPHA INTERFERON THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C. RELATIONSHIP WITH GENOTYPE AND DOSE OF INTERFERON. N Bover l. M Martinot l. V Martins-Amado’. P Mever”. M Pouteau’. .J . P Marc&. . ew ‘Service d’H8patologie et INSERM U24, HBpital Beaujon, Clichy , France ; “Ciba Geigy Ltd, Basel, Switzerland. Obiective; In patients with chronic hepatitis C treated with alpha interferon, an early response is important to obtain an end of treatment or a sustained response. We studied the relationship between the virological response at 1, 2 and 4 weeks after the initiation of alpha interferon therapy and the dose of interferon received and the HCV genotype. Patients We studied 44 patients with chronic active hepatitis C, histologically confirmed (no cirrhosis). They were 36 men and 8 women. They were randomized in 2 groups, to receive 3 million units (MU) (23 patients) or 32MU (21 patientsjof alpha interferon (Hybrid alpha interferon, Ciba Geigy, Switzerland) thrice weekly, during 26 weeks. Serum HCV RNA was quantified with the bDNA assay (Quantiplex. Chiron), befora treatment and 1 week, 2 weeks and 4 weeks after the initiation of alpha interferon therapy. Genotyping was performed with the reverse hybridization assay (Lipa)(lnno-Lipa, Ingen). Basulls; Patients were classified in 2 groups acoordino to aenotvoes: 1b (20 patients) or non 1b (24 patients). The 2 groups were nit diiereni ior sex and pretreatment serum HCV RNA level. An end of treatment response was observed in genotype 1b group and in genotype non 1b group in 33% and 83% respectively (p=O.O3). The decrease of serum HCV RNA was more markedand more rapid in patients with genotype non 1b than lb (‘p=O.O06). Four sustained responders were PCR negative at week 2. Percentage of patients with negative serum HCV RNA by PCR : week 1 week 2 week 4 Genotype 1b (n=20) 11% 15% 27% Genotype non lb (n=24) 38% 52% 86% Conclusion: In patients with chronic hepatitis C, the virological response to alpha interferon theraov aooears earlv (within 2 weeks) in resoonders. The early virological response ‘i6 more rapjd’and more complete in’patients with genotype non 1b. Detectable serum HCV RNA level (a 0.35 lo6 genome/ml) after 2 weeks of treatment was a predictor of no response.
The possibility to reduce hepatitis B morbidity through vaccination of adolescents. I.V.Shakeildian. M.I. Mikhailov. P.A.Khukhlovich. V.V. R omanenko. I.O.Kuznetsova. A.Yu. Esaulkova
ANTI HEPATITIS G E2 ANTIBODY DETECTION AND ITS RELATION TO SERUM HGV-RNA IN PATIENTS WITH CLOTTING DISORDERS
D.I. Ivanovsky Institute of Virology, N.F. Gamaleya Institute of Epidemiology and Microbiology RAMS, Moscow; Sverdlovsky Regional Sanitary and Epidemiology Centre, Ekaterinburg.
L. Shena. A. Soumillion. K. Peerlinck*, C. Verslvpe, R. Schelstraete”. :elinck. M-P. Emondse. G He **. J V VI *. J Des vte -, h Div. Liver & Pancr. D&., ‘iiv. SlA% ?Vasc. IX: D&. Virol., Univ. Hosp. Gasthuisberg, OBl& Transfusion tent&, Rode Kruis &anderen, Leuven, Belgium; and **Boehringer Mannheim, Germany
Hepatitis B (HB) vaccine prophylaxis is currently a problem of great importance in Russia. There was a marked increase in HB incidence cwer the last years (from 18.1 per 100,000 in 1992 to 25.8 in 1996; in the Region of Sverdlovsk from 20.7 to 62.7,respectiveIy) with mostacute hepatitis cases occuring in adolescents and young adults with low prevalence among children (in1996 82.4% of HB patients were 51-29 years of age in Moscow, 76% in the Region of Sverdlovsk). The number of HBV infections due to illegal parentera drug use or sexual contacts with HBV carriers and chronic HB patients was continuously increasing while the occurance of HB infection in hospitals was decreasing -. HBV vaccination of adolescents (to&her with high-risk cateeories) is considered a most reasonable immunisation &tegy for thl< epidemic: Duhng 1996-1997 such an approach was implemented in the city of Verkhnaya Pyshma, Sverdlovsk region, which the HBV incidence had been greater that the regional average over many years with about half the 1995 cases (46.6%0 being adolescents (aged 15 to 19). Screening of the city adolescents and youg populations for HBV markers (HBsAg and anti-HBs) also demonstrated vast involvement of these populations in the HBV epidemics. HBsAg carriage was 1.9% in adolescents aged 12.14 years, 2.2% in individuals 15-17 years of age, 3.6% among young adults aged 1820 years; the respective anti-HBs rates were 12.25, 20.9% and 30.4%. Administration of three cdses of HBV vaccine ( SmithKline Beechaml to 71% of adolescents aged 13-17 years in V.Pyshma resulted in 1.6 fold reduction in HBV incidence in the city one year following the immunisation start ( the reduction among 13-17 year old adolescents b&g 2.5-fold at year I and 7.9fold at year 2), while the regional rate demonstrated a 20% increase. Protective titres of anti-HBs were detected in 85% of subjects at&r two doses and in 94.7% after three doses of the vaccine (32.1% had titres ranging from 100 to 500 IU/I and 47.8% hiaber than 500 W/l). Vaccination of adolescents and vounz adults is therefore the most reasonable vaccination strategy in areas with moderate HBsAg carriage in which these age groups are mainly involved in the epidemics. I
I
,~
-_
~~~~
In a previous study, we determined the prevalence of serum HGVRNA in Belgian hemophiliacs. 15% of 175 patients were serum HGVRNA positive. HGV-RNA was detectable in PBMC in 10% of the cases, three of these patients were serum HGV-RNA negative. ln this study, we determined the prevalence of anti-HGV-E2 antibodies in the same patient population. Anti-E2 as determined by ELISA and was detected in 45 pts (25.7%). Forty of these patients were serum HGVRNA negative. In a retrospective longitudinal study? we have observed in 15 pts, that serum HGV-RNA persisted dunng 1-19 years of follow-up, while anti-E2 was repeatedly negative. Five additional patients who were anti-E2 positive with concomitant detectable HGVRNA they became HGV-RNA negative during follow-up (l-8 years after the first detection of anti-E2 Abs). Two patients had lost anti-E2 Abs 3-6 years after the seroconversion without the re-appearance of serum HGV-RNA. Twenty four of the 26 HGV viremic pts and 43 of 44 pts with detectable anti-E2 were coinfection with HCV. Of the HCVMGV coinfected patients, 62.5% of the HGV viremic pts and 53% of the anti-E2 pos. pts. showed elevated serum ALT levels. Two patients solely infected with HGV had normal serum ALT levels. Conclusions: 1) The prevalence rate of anti-E2 Abs in Belgian hemophiliacs is higher than the prevalence of HGV viremia. 2) Most of the patients clear the virus spon~eously. HGV viremia may persist for more than I9 years. 3) The clearance of the virus is usually associated with seroconversion to anti-E2. 4) Anti-E2 may be lost during years of follow-up without reapearance of HGV.