Peginterferon alpha-2b plus ribavirin vs interferon alpha-2b plus ribavirin for chronic hepatitis C in HIV-coinfected patients

被引:50
作者
Crespo, M.
Sauleda, S.
Esteban, J. I.
Juarez, A.
Ribera, E.
Andreu, A. L.
Falco, V.
Quer, J.
Ocana, I.
Ruiz, I.
Buti, M.
Pahissa, A.
Esteban, R.
Guardia, J.
机构
[1] Hosp Univ Vall Hebron, Liver Unit, Dept Internal Med, Dept Infect Dis, E-08035 Barcelona, Spain
[2] Hosp Univ Vall Hebron, Inst Catala Salut, Ctr Transfusio Banc Teixits, Barcelona, Spain
[3] Hosp Univ Vall Hebron, Dept Med, Liver Unit, Barcelona, Spain
[4] Hosp Univ Vall Hebron, Ctr Invest Bioquim & Biol Mol, Barcelona, Spain
关键词
hyperlactataemia and liver failure; mitochondrial DNA by real-time PCR; mitochondrial toxicity; treatment of chronic hepatitis C;
D O I
10.1111/j.1365-2893.2006.00779.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Treatment of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients is associated with low response rates and high incidence of side effects. One hundred twenty-one hepatitis C virus (HCV)-HIV-co-infected patients were randomized to receive interferon alpha-2b (3 MU thrice weekly; n = 61) or peginterferon alpha-2b (1.5 mu g/kg/week; n = 60), plus ribavirin (800 mg daily), for 24 (genotype 2 or 3) or 48 weeks (genotype 1 or 4). We assessed early virological response at 4, 8 and 12 weeks to predict sustained virological response (SVR). Safety assessment included frequent blood lactate measurement and relative quantitation of mitochondrial DNA (mtDNA) content in peripheral blood mononuclear cells. In intention-to-treat analysis, the SVR rate was higher in the peginterferon group (55% vs 26%: P = 0.002). The difference for HCV genotypes 1 and 4 was 45% vs 14% (P = 0.009) and 50%, vs 27% (P = 0.387), respectively, and for genotype 2 or 3.71% vs 43%, (P = 0.12) Viral response at 4, 8 and 12 weeks of treatment was highly predictive of SVR. Among genotype 3 patients, 17 of 20 (85%) whose HCV RNA was already undetectable at 4 weeks had an SVR after 24 weeks of treatment. Hyperlactataemia occurred in 22 patients and was clinically significant in six, two of whom died. mtDNA decreased significantly 4-12 weeks after the start of treatment in patients developing clinically significant hyperlactataemia. Peginterferon alpha-2b plus ribavirin was more effective than interferon alpha-2b plus ribavirin in HIV-coinfected patients. Frequent monitoring of virological response may be very helpful to optimize treatment compliance, to tailor treatment duration and to minimize side effects.
引用
收藏
页码:228 / 238
页数:11
相关论文
共 44 条
[1]   Short statement of the first European consensus conference on the treatment of chronic hepatitis B and C in HIV co-infected patients [J].
Alberti, A ;
Clumeck, N ;
Collins, S ;
Gerlich, W ;
Lundgren, J ;
Palù, G ;
Reiss, P ;
Thiebaut, R ;
Weiland, O ;
Yazdanpanah, Y ;
Zeuzem, S .
JOURNAL OF HEPATOLOGY, 2005, 42 (05) :615-624
[2]  
[Anonymous], 2002, Gastroenterology, V123, P2082, DOI 10.1053/gast.2002.1232082
[3]  
BALZARINI J, 1991, J BIOL CHEM, V266, P21509
[4]   Prediction of treatment outcome in patients with chronic hepatitis C: Significance of baseline parameters and viral dynamics during therapy [J].
Berg, T ;
Sarrazin, C ;
Herrmann, E ;
Hinrichsen, H ;
Gerlach, T ;
Zachoval, R ;
Wiedenmann, B ;
Hopf, U ;
Zeuzem, S .
HEPATOLOGY, 2003, 37 (03) :600-609
[5]   Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection [J].
Bica, I ;
McGovern, B ;
Dhar, R ;
Stone, D ;
McGowan, K ;
Scheib, R ;
Snydman, DR .
CLINICAL INFECTIOUS DISEASES, 2001, 32 (03) :492-497
[6]   Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients -: A randomized controlled trial [J].
Carrat, F ;
Bani-Sadr, F ;
Pol, S ;
Rosenthal, E ;
Lunel-Fabiani, F ;
Benzekri, A ;
Morand, P ;
Goujard, C ;
Pialoux, G ;
Piroth, L ;
Salmon-Céron, D ;
Degott, C ;
Cacoub, P ;
Perronne, C .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2004, 292 (23) :2839-2848
[7]   Early detection of nonresponse to interferon plus ribavirin combination treatment of chronic hepatitis C [J].
Castro, FJ ;
Esteban, JI ;
Juárez, A ;
Sauleda, S ;
Viladomiu, L ;
Martell, M ;
Moreno, F ;
Allende, H ;
Esteban, R ;
Guardia, J .
JOURNAL OF VIRAL HEPATITIS, 2002, 9 (03) :202-207
[8]   Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons [J].
Chung, RT ;
Andersen, J ;
Volberding, P ;
Robbins, GK ;
Liu, T ;
Sherman, KE ;
Peters, MG ;
Koziel, MJ ;
Bhan, AK ;
Alston, B ;
Colquhoun, D ;
Nevin, T ;
Harb, G ;
van der Horst, C .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (05) :451-459
[9]   Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV-infected patients [J].
Coté, HCF ;
Brumme, ZL ;
Craib, KJP ;
Alexander, CS ;
Wynhoven, B ;
Ting, LL ;
Wong, H ;
Harris, M ;
Harrigan, PR ;
O'Shaughnessy, MV ;
Montaner, JSG .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (11) :811-820
[10]   Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C [J].
Davis, GL ;
Wong, JB ;
McHutchison, JG ;
Manns, MP ;
Harvey, J ;
Albrecht, J .
HEPATOLOGY, 2003, 38 (03) :645-652