4 New ABSTRACTS on Hep C topics

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Eur J Gastroenterol Hepatol. 2011 Sep 12. [Epub ahead of print]

Female patients in fertile age with chronic hepatitis C, easy genotype, and

persistently normal transaminases have a 100% chance to reach a sustained

virological response.

Floreani A, Cazzagon N, Boemo DG, Baldovin T, Baldo V, Egoue J, Antoniazzi S,

Minola E.

Source

aDepartment of Surgical and Gastroenterological Sciences bDepartment of Hygiene

and Public Health, University of Padova, Padova cNational Centre for Health and

Gender Medicine dDepartment of Infectious Disease, Bergamo Hospital, Bergamo,

Italy.

Abstract

BACKGROUND:

Patients with chronic hepatitis C and persistently normal alanine transaminase

levels have recently been included in the guidelines for antiviral treatment.

AIM:

To evaluate the efficacy of PEG-interferon α-2a and weight-based ribavirin

doses in patients with these characteristics in a single Italian centre.

MATERIALS AND METHODS:

Patients with chronic hepatitis C and at least three normal alanine transaminase

values over a 12-month period were offered a treatment with PEG-interferon α-2a

180 mg/week and ribavirin (800 mg/day for weight <60 kg; 1000 mg/day for weight

>60 and <75 kg; 1200 mg/day for weight >75 kg) for 24 weeks (according to

genotype 2 or 3) or for 48 weeks (according to genotype 1 or 4). Each patient at

baseline underwent liver stiffness (LS) examination using Fibroscan. Data were

analysed according to the intention-to-treat criteria.

RESULTS:

A total of 227 patients (55 men, 172 women) were enrolled into the study: 65

(28.6%) had genotype 1, 144 (63.4%) genotype 2, nine (4.0%) genotype 3 and nine

(4.0%) genotype 4. Patients with genotype 2 or 3 (N=153 with easy genotypes)

were allocated in group 1 and those with genotype 1 or 4 (N=74 with difficult

genotypes) in group 2. According to the LS measurement, patients were classified

as follows: 159 (70.0%) presented absent or mild fibrosis (LS=2.5-7.0 kPa), 61

(26.9%) patients had significant fibrosis (LS=7.1-9.5) and seven (3.1%) patients

had severe fibrosis (LS >9.6). Twelve patients (5.3%) dropped out within 4

months because of side-effects, whereas 215 patients completed the study.

Overall, 13 patients were considered nonresponders (5.7%) and six patients

(2.6%) were relapsers to the therapy. The sustained virological response (SVR)

rate was 85.4% and it was higher in 'easy' genotypes (2 or 3) compared with

'difficult' genotypes (1 or 4) (92.2 vs. 74.3%, P<0.001). No statistical

difference was found in the SVR rate between patients presenting absent or mild

fibrosis as against those with significant fibrosis. Multivariate analysis,

including factors correlated with SVR, showed that easy genotype and female sex

are significantly associated with a SVR.

CONCLUSION:

Patients with chronic hepatitis C and persistently normal transaminases have an

85.4% chance to clear the virus with conventional antiviral treatment. Female

patients in fertile age with easy genotypes have a 100% chance to reach a SVR.

PMID: 21915057 [PubMed - as supplied by publisher]

Related citations

--------------------------------------------------------------

Eur J Gastroenterol Hepatol. 2011 Sep 7. [Epub ahead of print]

Efficacy and safety of peginterferon α-2a (40 KD) plus ribavirin in

treatment-naive chronic hepatitis C patients in Central and Eastern Europe.

Urbanek P, Oltman M, Ivanovski L, Rehák V, Messinger D, Tietz A, Husa P.

Source

aDepartment of Internal Medicine, 1st Medical Faculty University Prague

and Central Military hospital Prague, Prague bRemedis Clinic Praha, Praha

cDepartment of Infectious Diseases, Faculty Hospital and Faculty of Medicine,

Masaryk University Brno, Brno, Czech Republic dSt. Cyril and Method's Hospital,

Bratislava, Slovakia eClinic for Infectious Diseases, Clinical Center Skopje,

Skopje, FYR Macedonia fBiometrics, IST GmbH, Mannheim, Germany gRoche, Basel,

Switzerland.

Abstract

OBJECTIVE:

Assess the safety and efficacy of 24 or 48 weeks of treatment with peginterferon

α-2a (40 KD) plus ribavirin in treatment-naive patients with chronic hepatitis

C.

METHODS:

All patients in this open-label multinational study were assigned at the

investigator's discretion to receive peginterferon α-2a (40 KD) 180 µg/week

plus ribavirin (800 mg/day) for a total of 24 weeks or peginterferon α-2a (40

KD) 180 µg/week plus ribavirin (1000/1200 mg/day) for a total of 48 weeks.

Treatment success was defined as sustained virological response [sustained

virological response (SVR); hepatitis C virus RNA less than 50 IU/ml after

completion of untreated follow-up].

RESULTS:

A total of 789 treatment-naive patients were enroled, of whom 91% (138 of 152)

of nongenotype 1 patients and 77% (490 of 637) of genotype 1 patients completed

24 and 48 weeks of treatment, respectively. The overall SVR rate was 58% (459 of

789), and was 70 and 55% in nongenotype 1 and genotype 1 patients, respectively.

Age (per 10-year decrement) and baseline hepatitis C virus RNA level (≤400 000

vs. >4 00 000 IU/ml) were significantly associated with SVR by multiple logistic

regression analysis. The safety profile of peginterferon α-2a (40 KD) plus

ribavirin was similar to that reported in pivotal trials, with no new or

unexpected safety signals.

CONCLUSION:

The combination of peginterferon α-2a (40 KD) plus ribavirin was well tolerated

and produced an overall SVR rate of 58% in treatment-naive patients. This study

confirms that SVR rates achieved in pivotal clinical trials in Western Europe

and the USA can be achieved in routine clinical practice in Central and Eastern

Europe.

PMID: 21904204 [PubMed - as supplied by publisher]

Related citations

--------------------------------------------

J Hepatol. 2011 Sep 7. [Epub ahead of print]

A variant in myeloperoxidase promoter hastens the emergence of hepatocellular

carcinoma in patients with HCV-related cirrhosis.

Nahon P, Sutton A, Rufat P, Charnaux N, Mansouri A, Moreau R, Ganne-Carrié N,

Grando-Lemaire V, N'kontchou G, Trinchet JC, Pessayre D, Beaugrand M.

Source

Service d'Hépatologie, Hôpital Verdier, AP-HP, Bondy; INSERM, U773,

Centre de Recherche Bichat Beaujon CRB3, Université Paris 7, Paris, France.

Abstract

BACKGROUND AND AIMS:

Genetic dimorphisms modulate the activities of several pro- or antioxidant

enzymes, including myeloperoxidase (MPO), catalase (CAT), manganese superoxide

dismutase (SOD2) and glutathione peroxidase 1 (GPx1). We assessed the role of

the G(-463)A-MPO, T(-262)C-CAT, Ala16Val-SOD2 and Pro198Leu-GPx1 variants in

modulating HCC development in patients with HCV-induced cirrhosis.

METHODS:

205 patients with HCV-induced, biopsy-proven cirrhosis but without detectable

HCC at inclusion were prospectively followed-up for HCC development. The

influence of various genotypes on HCC occurrence was assessed with the

Kaplan-Meier method.

RESULTS:

During follow-up (103.2 ± 3.4 months), 84 patients (41%) developed HCC, and 66

died. Whereas the Ala16Val-SOD2 or Pro198Leu-GPx1 dimorphisms did not modulate

the risk, HCC occurrence was increased in patients with either the homozygous

GG-MPO genotype (HR=2.8 [1.7-4.4]; first quartile time to HCC occurrence: 45 vs.

96 months; LogRank<0.0001) or the homozygous CC-CAT genotype (HR=1.74

[1.06-2.82]; first quartile time to HCC occurrence: 55 vs. 96 months;

LogRank=0.02). Compared to patients with neither of these two at risk factors,

patients with only the CC-CAT genotype had a HR of 2.05 [0.9-4.6] (P=0.08) and

patients with only the GG-MPO genotype had a HR of 3.8 [1.5-9.1] (P=0.002),

while patients with both risk factors had an HR of 4.8 [2.2-10.4] (P<0.0001).

However, only the GG-MPO genotype was independently associated with the HCC risk

in multivariate analysis.

CONCLUSIONS:

The high activity-associated GG-MPO genotype increases the rate of HCC

occurrence in patients with HCV-induced cirrhosis.

Copyright © 2011. Published by Elsevier B.V.

PMID: 21907168 [PubMed - as supplied by publisher]

Related citations

------------------------------------

J Infect Dis. 2011 Oct;204(8):1186-90.

Vaccine-induced cross-genotype reactive neutralizing antibodies against

hepatitis C virus.

Meunier JC, Gottwein JM, Houghton M, RS, Emerson SU, Bukh J, Purcell RH.

Source

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious

Diseases, National Institutes of Health, Bethesda, land.

Abstract

We detected cross-reactive neutralizing antibodies (NtAb) against hepatitis C

virus (HCV) in chimpanzees vaccinated with HCV-1 (genotype 1a) recombinant E1/E2

envelope glycoproteins. Five vaccinated chimpanzees, protected following HCV-1

challenge, were initially studied using the heterologous H77 (genotype 1a) HCVpp

assay. All animals had developed NtAb after the second vaccination; 4 animals

had reciprocal titers of ≥200 at the time of challenge. Using genotypes 1a-6a

HCV pseudoparticles (HCVpp) and cell culture-derived HCV (HCVcc) assays,

cross-reactive NtAb were detected against 1a, 4a, 5a, and 6a, with limited

reactivity against 2a and 3a. Our study provides encouragement for the

development of a recombinant envelope-based vaccine against hepatitis C.

PMID: 21917891 [PubMed - in process]

[Guest guest]

Eur J Gastroenterol Hepatol. 2011 Sep 12. [Epub ahead of print]

Female patients in fertile age with chronic hepatitis C, easy genotype, and

persistently normal transaminases have a 100% chance to reach a sustained

virological response.

Floreani A, Cazzagon N, Boemo DG, Baldovin T, Baldo V, Egoue J, Antoniazzi S,

Minola E.

Source

aDepartment of Surgical and Gastroenterological Sciences bDepartment of Hygiene

and Public Health, University of Padova, Padova cNational Centre for Health and

Gender Medicine dDepartment of Infectious Disease, Bergamo Hospital, Bergamo,

Italy.

Abstract

BACKGROUND:

Patients with chronic hepatitis C and persistently normal alanine transaminase

levels have recently been included in the guidelines for antiviral treatment.

AIM:

To evaluate the efficacy of PEG-interferon α-2a and weight-based ribavirin

doses in patients with these characteristics in a single Italian centre.

MATERIALS AND METHODS:

Patients with chronic hepatitis C and at least three normal alanine transaminase

values over a 12-month period were offered a treatment with PEG-interferon α-2a

180 mg/week and ribavirin (800 mg/day for weight <60 kg; 1000 mg/day for weight

>60 and <75 kg; 1200 mg/day for weight >75 kg) for 24 weeks (according to

genotype 2 or 3) or for 48 weeks (according to genotype 1 or 4). Each patient at

baseline underwent liver stiffness (LS) examination using Fibroscan. Data were

analysed according to the intention-to-treat criteria.

RESULTS:

A total of 227 patients (55 men, 172 women) were enrolled into the study: 65

(28.6%) had genotype 1, 144 (63.4%) genotype 2, nine (4.0%) genotype 3 and nine

(4.0%) genotype 4. Patients with genotype 2 or 3 (N=153 with easy genotypes)

were allocated in group 1 and those with genotype 1 or 4 (N=74 with difficult

genotypes) in group 2. According to the LS measurement, patients were classified

as follows: 159 (70.0%) presented absent or mild fibrosis (LS=2.5-7.0 kPa), 61

(26.9%) patients had significant fibrosis (LS=7.1-9.5) and seven (3.1%) patients

had severe fibrosis (LS >9.6). Twelve patients (5.3%) dropped out within 4

months because of side-effects, whereas 215 patients completed the study.

Overall, 13 patients were considered nonresponders (5.7%) and six patients

(2.6%) were relapsers to the therapy. The sustained virological response (SVR)

rate was 85.4% and it was higher in 'easy' genotypes (2 or 3) compared with

'difficult' genotypes (1 or 4) (92.2 vs. 74.3%, P<0.001). No statistical

difference was found in the SVR rate between patients presenting absent or mild

fibrosis as against those with significant fibrosis. Multivariate analysis,

including factors correlated with SVR, showed that easy genotype and female sex

are significantly associated with a SVR.

CONCLUSION:

Patients with chronic hepatitis C and persistently normal transaminases have an

85.4% chance to clear the virus with conventional antiviral treatment. Female

patients in fertile age with easy genotypes have a 100% chance to reach a SVR.

PMID: 21915057 [PubMed - as supplied by publisher]

Related citations

--------------------------------------------------------------

Eur J Gastroenterol Hepatol. 2011 Sep 7. [Epub ahead of print]

Efficacy and safety of peginterferon α-2a (40 KD) plus ribavirin in

treatment-naive chronic hepatitis C patients in Central and Eastern Europe.

Urbanek P, Oltman M, Ivanovski L, Rehák V, Messinger D, Tietz A, Husa P.

Source

aDepartment of Internal Medicine, 1st Medical Faculty University Prague

and Central Military hospital Prague, Prague bRemedis Clinic Praha, Praha

cDepartment of Infectious Diseases, Faculty Hospital and Faculty of Medicine,

Masaryk University Brno, Brno, Czech Republic dSt. Cyril and Method's Hospital,

Bratislava, Slovakia eClinic for Infectious Diseases, Clinical Center Skopje,

Skopje, FYR Macedonia fBiometrics, IST GmbH, Mannheim, Germany gRoche, Basel,

Switzerland.

Abstract

OBJECTIVE:

Assess the safety and efficacy of 24 or 48 weeks of treatment with peginterferon

α-2a (40 KD) plus ribavirin in treatment-naive patients with chronic hepatitis

C.

METHODS:

All patients in this open-label multinational study were assigned at the

investigator's discretion to receive peginterferon α-2a (40 KD) 180 µg/week

plus ribavirin (800 mg/day) for a total of 24 weeks or peginterferon α-2a (40

KD) 180 µg/week plus ribavirin (1000/1200 mg/day) for a total of 48 weeks.

Treatment success was defined as sustained virological response [sustained

virological response (SVR); hepatitis C virus RNA less than 50 IU/ml after

completion of untreated follow-up].

RESULTS:

A total of 789 treatment-naive patients were enroled, of whom 91% (138 of 152)

of nongenotype 1 patients and 77% (490 of 637) of genotype 1 patients completed

24 and 48 weeks of treatment, respectively. The overall SVR rate was 58% (459 of

789), and was 70 and 55% in nongenotype 1 and genotype 1 patients, respectively.

Age (per 10-year decrement) and baseline hepatitis C virus RNA level (≤400 000

vs. >4 00 000 IU/ml) were significantly associated with SVR by multiple logistic

regression analysis. The safety profile of peginterferon α-2a (40 KD) plus

ribavirin was similar to that reported in pivotal trials, with no new or

unexpected safety signals.

CONCLUSION:

The combination of peginterferon α-2a (40 KD) plus ribavirin was well tolerated

and produced an overall SVR rate of 58% in treatment-naive patients. This study

confirms that SVR rates achieved in pivotal clinical trials in Western Europe

and the USA can be achieved in routine clinical practice in Central and Eastern

Europe.

PMID: 21904204 [PubMed - as supplied by publisher]

Related citations

--------------------------------------------

J Hepatol. 2011 Sep 7. [Epub ahead of print]

A variant in myeloperoxidase promoter hastens the emergence of hepatocellular

carcinoma in patients with HCV-related cirrhosis.

Nahon P, Sutton A, Rufat P, Charnaux N, Mansouri A, Moreau R, Ganne-Carrié N,

Grando-Lemaire V, N'kontchou G, Trinchet JC, Pessayre D, Beaugrand M.

Source

Service d'Hépatologie, Hôpital Verdier, AP-HP, Bondy; INSERM, U773,

Centre de Recherche Bichat Beaujon CRB3, Université Paris 7, Paris, France.

Abstract

BACKGROUND AND AIMS:

Genetic dimorphisms modulate the activities of several pro- or antioxidant

enzymes, including myeloperoxidase (MPO), catalase (CAT), manganese superoxide

dismutase (SOD2) and glutathione peroxidase 1 (GPx1). We assessed the role of

the G(-463)A-MPO, T(-262)C-CAT, Ala16Val-SOD2 and Pro198Leu-GPx1 variants in

modulating HCC development in patients with HCV-induced cirrhosis.

METHODS:

205 patients with HCV-induced, biopsy-proven cirrhosis but without detectable

HCC at inclusion were prospectively followed-up for HCC development. The

influence of various genotypes on HCC occurrence was assessed with the

Kaplan-Meier method.

RESULTS:

During follow-up (103.2 ± 3.4 months), 84 patients (41%) developed HCC, and 66

died. Whereas the Ala16Val-SOD2 or Pro198Leu-GPx1 dimorphisms did not modulate

the risk, HCC occurrence was increased in patients with either the homozygous

GG-MPO genotype (HR=2.8 [1.7-4.4]; first quartile time to HCC occurrence: 45 vs.

96 months; LogRank<0.0001) or the homozygous CC-CAT genotype (HR=1.74

[1.06-2.82]; first quartile time to HCC occurrence: 55 vs. 96 months;

LogRank=0.02). Compared to patients with neither of these two at risk factors,

patients with only the CC-CAT genotype had a HR of 2.05 [0.9-4.6] (P=0.08) and

patients with only the GG-MPO genotype had a HR of 3.8 [1.5-9.1] (P=0.002),

while patients with both risk factors had an HR of 4.8 [2.2-10.4] (P<0.0001).

However, only the GG-MPO genotype was independently associated with the HCC risk

in multivariate analysis.

CONCLUSIONS:

The high activity-associated GG-MPO genotype increases the rate of HCC

occurrence in patients with HCV-induced cirrhosis.

Copyright © 2011. Published by Elsevier B.V.

PMID: 21907168 [PubMed - as supplied by publisher]

Related citations

------------------------------------

J Infect Dis. 2011 Oct;204(8):1186-90.

Vaccine-induced cross-genotype reactive neutralizing antibodies against

hepatitis C virus.

Meunier JC, Gottwein JM, Houghton M, RS, Emerson SU, Bukh J, Purcell RH.

Source

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious

Diseases, National Institutes of Health, Bethesda, land.

Abstract

We detected cross-reactive neutralizing antibodies (NtAb) against hepatitis C

virus (HCV) in chimpanzees vaccinated with HCV-1 (genotype 1a) recombinant E1/E2

envelope glycoproteins. Five vaccinated chimpanzees, protected following HCV-1

challenge, were initially studied using the heterologous H77 (genotype 1a) HCVpp

assay. All animals had developed NtAb after the second vaccination; 4 animals

had reciprocal titers of ≥200 at the time of challenge. Using genotypes 1a-6a

HCV pseudoparticles (HCVpp) and cell culture-derived HCV (HCVcc) assays,

cross-reactive NtAb were detected against 1a, 4a, 5a, and 6a, with limited

reactivity against 2a and 3a. Our study provides encouragement for the

development of a recombinant envelope-based vaccine against hepatitis C.

PMID: 21917891 [PubMed - in process]