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Titolo:
Biochemical response to interferon therapy correlates with interferon sensitivity-determining region in hepatitis C virus genotype 1b infection
Autore:
Yoshioka, K; Kobayashi, M; Orito, E; Watanabe, K; Yano, M; Sameshima, Y; Kusakabe, A; Hirofuji, H; Fuji, A; Kuriki, J; Arao, M; Murase, K; Mizokami, M; Kakumu, S;
Indirizzi:
Nagoya Univ, Sch Med, Dept Internal Med 3, Showa Ku, Nagoya, Aichi 4668550, Japan Nagoya Univ Nagoya Aichi Japan 4668550 a Ku, Nagoya, Aichi 4668550, Japan Nagoya Univ, Sch Med, Dept Internal Med 2, Nagoya, Aichi 4668550, Japan Nagoya Univ Nagoya Aichi Japan 4668550 ed 2, Nagoya, Aichi 4668550, Japan Nagoya First Red Cross Hosp, Dept Internal Med, Nagoya, Aichi, Japan Nagoya First Red Cross Hosp Nagoya Aichi Japan Med, Nagoya, Aichi, Japan Yokkaichi Municipal Hosp, Dept Internal Med, Yokkaichi, Japan Yokkaichi Municipal Hosp Yokkaichi Japan Internal Med, Yokkaichi, Japan Holy Spirit Hosp, Dept Internal Med, Nagoya, Aichi, Japan Holy Spirit Hosp Nagoya Aichi Japan t Internal Med, Nagoya, Aichi, Japan Gamagori Municipal Hosp, Dept Internal Med, Gamagori, Japan Gamagori Municipal Hosp Gamagori Japan pt Internal Med, Gamagori, Japan Inazawa Municipal Hosp, Dept Internal Med, Inazawa, Japan Inazawa Municipal Hosp Inazawa Japan Dept Internal Med, Inazawa, Japan Chubu Rosai Hosp, Dept Internal Med, Nagoya, Aichi, Japan Chubu Rosai Hosp Nagoya Aichi Japan t Internal Med, Nagoya, Aichi, Japan Aichi Med Univ, Dept Internal Med 1, Aichi, Japan Aichi Med Univ Aichi Japan Med Univ, Dept Internal Med 1, Aichi, Japan
Titolo Testata:
JOURNAL OF VIRAL HEPATITIS
fascicolo: 6, volume: 8, anno: 2001,
pagine: 421 - 429
SICI:
1352-0504(200111)8:6<421:BRTITC>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
NON-B-HEPATITIS; RANDOMIZED CONTROLLED TRIAL; NONSTRUCTURAL 5A PROTEIN; POLYMERASE CHAIN-REACTION; AMINO-ACID SUBSTITUTIONS; NON-A; HEPATOCELLULAR-CARCINOMA; ANTIVIRAL ACTIVITY; MOLECULAR-CLONING; NS5A PROTEIN;
Keywords:
biochemical response; genotype 1b; hepatitis C virus; interferon; interferon sensitivity-determining region; phylogenetic tree;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Yoshioka, K Nagoya Univ, Sch Med, Dept Internal Med 3, Showa Ku, 65 Tsuruma Cho, Nagoya, Aichi 4668550, Japan Nagoya Univ 65 Tsuruma Cho Nagoya AichiJapan 4668550 0, Japan
Citazione:
K. Yoshioka et al., "Biochemical response to interferon therapy correlates with interferon sensitivity-determining region in hepatitis C virus genotype 1b infection", J VIRAL HEP, 8(6), 2001, pp. 421-429

Abstract

Biochemical responders maintain normal alanine aminotransferase levels after interferon (IFN) therapy despite persistent presence of hepatitis C virus (HCV) RNA in their sera. There have been few reports on predictive factors for biochemical response. A region associated with sensitivity to IFN wasidentified in the nonstructural protein 5 A of genotype 1b [aa 2209-2248; IFN sensitivity-determining region (ISDR)]. The substitutions in ISDR correlate with sustained response to IFN. In this report, we assessed the association of ISDR with biochemical response. The sequences of ISDR were determined in 62 patients with HCV genotype lb treated by IFN in two randomized controlled trials. 30 patients had wild ISDR (identical to HCV-J), 20 intermediate ISDR (1-3 amino acid substitutions compared with HCV-J), and 12 mutant ISDR (four or more amino acid substitutions). All 12 patients with mutantISDR had a sustained response, while only one of those with wild or intermediate ISDR had a sustained response (P<0.0001). In the 49 patients other than sustained responders, the patients with intermediate ISDR obtained biochemical response significantly more frequently (52.6%, 10/19) than those with wild-type ISDR (20.0%, 6/30) (P<0.05). Multivariate analysis indicated the number of substitutions in ISDR as the most important predictor for biochemical response (discriminant coefficient=1.08, P<0.05) and sustained response (discriminant coefficient=6.13, P<0.0001). In phylogenetic analysis, clustering of sustained responders and biochemical responders was observed. These results demonstrate that the substitutions in ISDR are the most important predictor for biochemical response to IFN in patients infected with genotype lb as well as for sustained response.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 17:02:47