[en] Background and aims : Patients with genotype 4 (G4) chronic
hepatitis C from the Middle East respond better to treatment than
genotype 1 (G1) patients. There are few data on the response rates
to treatment of G4 patients living in Western Europe. Many G4
patients in Belgium originate from Central Africa, and their
response to treatment seems lower.
Methods : We analysed the data from 2 randomized phase III
studies conducted in Belgium, BerNar-1 and BerNar-2, comparing
the sustained virological response (SVR) to pegylated interferon
and ribavirin of 78 G4 patients (34 Caucasians, 44 Blacks) and 477
G1 patients (455 Caucasians, 12 Blacks), and assessing the predictors
of SVR.
Results : Baseline characteristics of G4 and G1 patients were
similar except mainly for race. Complete early virological response
(cEVR) was similar in G4 (73.2%) and G1 (68.1%). cEVR was
also similar between Black and Caucasian G4 and between Black
and Caucasian G1 patients. Partial early virological response was
similar for G4 and G1. SVR was similar for G4 (51.3%) and G1
(51.8%). There was a trend for a higher SVR in Caucasians than in
Blacks. In multivariate analysis, the only predictors for SVR were
the presence of cirrhosis, HCV viral load, age < 40 vs 40 yrs, and
treatment status (relapsers vs naïve).
Conclusions : G4 patients in Belgium have the same SVR as G1
patients. It is lower than the SVR described in Arab countries,
especially for Black G4 patients. (Acta gastro enterol. belg., 2010, 73,
229-234).
Disciplines :
Gastroenterology & hepatology
Author, co-author :
de Galocsy, C.
Kaufman, L.
Tomasovic, S.
Delwaide, Jean ; Université de Liège - ULiège > Gastro-Entérologie-Hépatologie
Nevens, F.
Language :
English
Title :
Hepatitis C genotype 4 response rate to pegylated interferon and ribavirin treatment in Belgium is similar to genotype 1
Simmonds P., Holmes E.C., Cha T.A., Chan S.W., McOmish F., Irvine B., Beall E., Yap P.L., Kolberg J., Urdea M.S. Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J. Gen. Virol., 1993, 74: 2391-2399.
RAY S.C., ARTHUR R.R., CARELLA A., BUKH J., THOMAS D.L. Genetic epidemiology of hepatitis C virus throughout Egypt. J. Infect. Dis., 2000, 182: 698-707.
XU L. Z., LARZUL D., DELAPORTE E., BRECHOT C., KREMSDORF D. Hepatits C virus genotype 4 is highly prevalent in central Africa (Gabon). J. Gen. Virol., 1994, 75: 2393-2398.
Fattovich G., Ribero M.L., Pantalena M., Diodati G., Almasio P., Nevens F., Tremolada F., Degos F., Rai J., Solinas A., Mura D., Tocco A., Zagni I., Fabris F., Lomonaco L., Noventa F., Realdi G., Schalm S.W., Tagger A. Hepatitis C virus genotypes: distribution and clinical significance in patients with cirrhosis type C seen at tertiary referral centres in Europe. J. Viral. Hepat., 2001, 8: 206-216.
Bourlière M., Barberin J.M., Rotily M., Guagliardo V., Portal I., Lecomte L., Benali S., Boustière C., Perrier H., Jullien M., Lambot G., Loyer R., Lebars O., Daniel R., Khiri H., Halfon P. Epidemiological changes in hepatitis C virus genotypes in France: Evidence in intravenous drug users. J. Viral. Hepat., 2002, 9: 62-70.
Payan C., Roudot-Thoraval F., Marcellin P., Bled N., Duverlie G., Fouchard-Hubert I., Trimoulet P., Couzigou P., Cointe D., Chaput C., Henquell C., Abergel A., Pawlotsky J.M., Hezode C., Coudé M., Blanchi A., Alain S., Loustaud-Ratti V., Chevallier P., Trepo C., Gerolami V., Portal I., Halfon P., Bourlière M., Bogard M., Plouvier E., Laffont C., Agius G., Silvain C., Brodard V., Thiefin G., Buffet-Janvresse C., Riachi G., Grattard F., Bourlet T., Stoll-Keller F., Doffoel M., Izopet J., Barange K., Martinot-Peignoux M., Branger M., Rosenberg A., Sogni P., Chaix M.L., Pol S., Thibault V., Opolon P., Charrois A., Serfaty L., Fouqueray B., Grange J.D., Lefrère J.J., Lunelfabiani F. Changing of hepatitis C virus genotype patterns in France at the beginning of the third millennium: the GEMHEP GenoCII Study. J. Viral. Hepat., 2005, 12: 405-413.
GERARD C., DELWAIDE J., VAIRA D., BASTENS B., SERVAIS B., WAIN E., BATAILLE C., DAENEN G., BELAICHE J., GLEVHE L. Evolution over a 10 year period of the epidemiological profile of 1,726 newly diagnosed HCV patients in Belgium. J. Med. Virol., 2005, 76: 503-510.
DELWAIDE J., REENAERS C., GERARD C., VAIRA D., BASTENS B., SERVAIS B., BEKHTI A., BATAILLE C., WAIN E., de Leeuw P., DAENEN G., MESUREUR T., SENTE J.M., BELAÏCHE J.; GROUPE LIÉGEOIS D'ETUDE DES VIRUS HÉPATOTROPES. HCV genotype 4 in Belgium: three distinct patterns among patients from European and African origin. Eur. J. Gastroenterol. Hepatol., 2006, 18: 707-712.
De Maeght S., Henrion J., Bourgeois N., De Galocsy C., Langlet P., Michielsen P., Reynaert H., Robaeys G., Sprengers D., ORLENT H., ADLER M. A pilot observational survey of hepatitis C in Belgium. Acta Gastroenterol. Belg., 2008, 71: 4-8.
KHUROO M.S., KHUROO M.S., DAHAB S.T. Meta-analysis: a randomized trial of peginterferon plus ribavirin for the initial treatment of chronic hepatitis C genotype 4. Aliment Pharmacol. Ther., 2004, 20: 931-938.
HASAN F., ASKER H., Al-Khaldi J., Siddique I., Al-Ajmi M., Owaid S., Varghese R., Al-Nakib B. Peginterferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4. Am. J. Gastro -enterol., 2004 Sep, 99 (9): 1733-1737.
KAMAL S.M., EL TAWIL A.A., NAKANO T., HE Q., RASENACK J., HAKAM S.A., SALEH W.A., ISMAIL A., AZIZ A.A., MADWAR M.A. Peginterferon-a2b and ribavirin therapy in chronic hepatitis C genotype 4: impact of treatment duration and viral kinetics on sustained virological response. Gut, 2005, 54: 858-866.
El-Zayadi A.R., Attia M., Barakat E.M.F., Badran H.M., Hamdy H., El-Tawil A., El-Nakeeb A., Selim O., Saied A. Response of hepatitis C genotype-4 naive patients to 24 weeks of peginterferon-alpha 2b/ribavirin or induction-dose interferon-alpha 2b/ribavirin/amantadine: a non-randomized controlled study. Am. J. Gastro -enterol., 2005, 100: 2447-2452.
ALFALEH F.Z., HADAD Q., KHUROO M.S., ALJUMAH A., ALGAMEDI A., Alashgar H., Al-Ahdal M.N., Mayet I., Khan M.Q., Kessie G. Peginterferon-a2b plus ribavirin compared wit interferon-a2b plus ribavirin for the initial treatment of chronic hepatitis C in Saudi patients commonly infected with genotype 4. Liver Int., 2004, 24: 568-574.
DIAGO M., HASSANEIN T., RODÉS J., ACKRILL A.M., SEDARATI F. Optimized virologic response in hepatitis C virus genotype 4 with Peginterferon-a2a and ribavirin. Ann. Intern. Med., 2004, 140: 72-73.
ROSSIGNOL J.F., ELFERT A., El-Gohary Y., KEEFFE E.M. Improved virological response in chronic hepatitis C genotype 4 treated with nitazoxa - nide, Peginterferon and ribavirin. Gastroenterology, 2009, 136: 856-862.
Roulot D., Bourcier V., Grando V., Deny P., Baazia Y., Fontaine H., Bailly F., Castera L., De Ledinghen V., Marcellin P., Poupon R., Bourlière M., Zarski Jp., Roudotthoraval F.; Observational Vhc4 Study Group. Epidemio -logical characteristics and response to peginterferon plus ribavirin treatment of hepatitis C virus genotype 4 infection. J. Viral. Hepat., 2007, 14: 460-467.
Evens F., van Vlierberghe H., D'heygere F., Delwaide J., Adler M., Henrion J., Lenaerts A., Hendlizs A., Michielsen P., Bastens B., Brenard R., Laureys A. And The Bernar-1 Study Group. A randomized, open-label, multicenter study evaluating the efficacy of peginterferon alfa-2a versus interferon alfa-2a, in combination with ribavirin, in naïve and relapsed chronic hepatitis C patients. Acta Gastroenterol. Belg., 2010, 73: 223-228.
LANGLET P.H., DHEYGERE F., HENRION J., ADLER M., DELWAIDE J., VAN VLIERBERGHE H., MULKAY J.P., LASSER L., BRENARD R., HORSMANS Y., MICHIELSEN P., LAUREYS A., NEVENS F. A randomised trial of pegylated-interferon-a-2a plus ribavirin with or without amantadine in treatment-naïve or relapsing chronic hepatitis C patients. Aliment Pharmacol. Ther., 2009, 30: 352-363.
DELTENRE P., HENRION J., CANVA V., DHARANCY S., TEXIER F., LOUVET A., DE MAEGHT S., PARIS J.C., MATHURIN P. Evaluation of amantadine in chronic hepatitis C: a metaanalysis. J. Hepatol., 2004, 41: 462-473.
HOWELL C.D., JEFFERS L.S., CASSIDY W., REDDY K.R., HU S., LEE J.S. Peginterferon alfa-2a and Ribavirin for Chronic Hepatitis C Genotype 1 Infections in Black Patients: Safety, Tolerability and Impact on Sustained Virological Response. J. Viral. Hepat., 2006, 13: 371-376.
Conjeevaram H.S., Fried M.W., Jeffers L.J., Terrault N.A., Wiley-Lucas T.E., Afdhal N., Brown R.S., Belle S.H., Hoofnagle J.H., Kleiner D.E., Howell C.D.; VIRAHEP-C STUDY GROUP. Peginterferon and ribavirin treatment in African American and Caucasian American Patients with Hepatitis C Genotype 1. Gastro -enterology, 2006, 131: 470-477.
ROSEN H.R., WESTON S.J., IM K., YANG H., BURTON J.R. Jr., ERLICH H., KLARQUIST J., BELLE S.H.; VIRAHEP-C STUDY GROUP. Selective decrease in hepatitis C virus-specific immunity among African Americans and outcome of antiviral therapy. Hepatology, 2007, 46: 350-358.
Ge Dongliang., Fellay J., Thompson A.J., Simon J.S., Shianna K.V., Urban T.J., Heinzen E.L., Qiu P., Bertelsen A.H., Muir A.J., Sulkowski M., Mchutchinson J.G., GOLDSTEIN D.B. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature, 2009, 461: 399-401.
ELEFSINIOTIS I.S., VEZALI E., MIHAS G., SAROGLOU G. Predictive value of Complete and Partial Early Virological Response on Sustained Virological Response rates of genotype-4 chronic hepatitis C patients treated with PEG-Interferon plus ribavirin. Intervirology, 2009, 52: 247-251.