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Predictive factors of virological non-response to interferon-ribavirin combination therapy for patients infected with hepatitis C virus of genotype 1b and high viral load.
J Med Virol. 2006 Jan; 78(1):83-90.JM

Abstract

Patients with high viral load (> or =1.0 x 10(5) IU/ml) of hepatitis C virus (HCV) genotype 1b do not achieve high sustained virological response rates to interferon (IFN)/ribavirin combination therapy. Previous studies suggested that pretreatment amino acid (aa) substitution patterns in the HCV core region could affect virological non-response especially in patients who could not achieve HCV-RNA negativity during treatment. The present study evaluated 167 consecutive Japanese adults with high HCV genotype 1b viral load who received combination therapy for > or =24 weeks. A case-control study matched for age, sex, genotype, and viral load was conducted to investigate the predictive factors for virological non-response, especially absolute virological non-response (patients who could not achieve >2 log decline of HCV RNA from baseline during the initial 24 weeks of therapy). Virological non-response was identified in 26.3% of patients, and 45.5% of these were absolute virological non-responders. Multivariate analysis identified ribavirin dose <11.0 mg/kg, moderate-to-severe hepatocyte steatosis, and substitutions of aa 70 and/or 91 in the core region as significant independent factors associated with virological non-response. The majority of absolute virological non-responders had such substitutions in the core region (95.0%), as well as substitution of glutamine at aa 70 and/or methionine at aa 91 (90.0%). In the present work, such substitutions significantly affected the viral kinetics in virological non-responders. The results suggest that viral, host, and treatment-related factors determine the response to IFN/ribavirin combination therapy in patients with high HCV genotype 1b viral load, and that amino acid substitution patterns in the core region is potentially useful pretreatment predictor of virological non-response.

Authors+Show Affiliations

Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan. akuta-gi@umin.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16299715

Citation

Akuta, Norio, et al. "Predictive Factors of Virological Non-response to Interferon-ribavirin Combination Therapy for Patients Infected With Hepatitis C Virus of Genotype 1b and High Viral Load." Journal of Medical Virology, vol. 78, no. 1, 2006, pp. 83-90.
Akuta N, Suzuki F, Sezaki H, et al. Predictive factors of virological non-response to interferon-ribavirin combination therapy for patients infected with hepatitis C virus of genotype 1b and high viral load. J Med Virol. 2006;78(1):83-90.
Akuta, N., Suzuki, F., Sezaki, H., Suzuki, Y., Hosaka, T., Someya, T., Kobayashi, M., Saitoh, S., Watahiki, S., Sato, J., Kobayashi, M., Arase, Y., Ikeda, K., & Kumada, H. (2006). Predictive factors of virological non-response to interferon-ribavirin combination therapy for patients infected with hepatitis C virus of genotype 1b and high viral load. Journal of Medical Virology, 78(1), 83-90.
Akuta N, et al. Predictive Factors of Virological Non-response to Interferon-ribavirin Combination Therapy for Patients Infected With Hepatitis C Virus of Genotype 1b and High Viral Load. J Med Virol. 2006;78(1):83-90. PubMed PMID: 16299715.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Predictive factors of virological non-response to interferon-ribavirin combination therapy for patients infected with hepatitis C virus of genotype 1b and high viral load. AU - Akuta,Norio, AU - Suzuki,Fumitaka, AU - Sezaki,Hitomi, AU - Suzuki,Yoshiyuki, AU - Hosaka,Tetsuya, AU - Someya,Takashi, AU - Kobayashi,Masahiro, AU - Saitoh,Satoshi, AU - Watahiki,Sachiyo, AU - Sato,Junko, AU - Kobayashi,Mariko, AU - Arase,Yasuji, AU - Ikeda,Kenji, AU - Kumada,Hiromitsu, PY - 2005/11/22/pubmed PY - 2006/4/14/medline PY - 2005/11/22/entrez SP - 83 EP - 90 JF - Journal of medical virology JO - J Med Virol VL - 78 IS - 1 N2 - Patients with high viral load (> or =1.0 x 10(5) IU/ml) of hepatitis C virus (HCV) genotype 1b do not achieve high sustained virological response rates to interferon (IFN)/ribavirin combination therapy. Previous studies suggested that pretreatment amino acid (aa) substitution patterns in the HCV core region could affect virological non-response especially in patients who could not achieve HCV-RNA negativity during treatment. The present study evaluated 167 consecutive Japanese adults with high HCV genotype 1b viral load who received combination therapy for > or =24 weeks. A case-control study matched for age, sex, genotype, and viral load was conducted to investigate the predictive factors for virological non-response, especially absolute virological non-response (patients who could not achieve >2 log decline of HCV RNA from baseline during the initial 24 weeks of therapy). Virological non-response was identified in 26.3% of patients, and 45.5% of these were absolute virological non-responders. Multivariate analysis identified ribavirin dose <11.0 mg/kg, moderate-to-severe hepatocyte steatosis, and substitutions of aa 70 and/or 91 in the core region as significant independent factors associated with virological non-response. The majority of absolute virological non-responders had such substitutions in the core region (95.0%), as well as substitution of glutamine at aa 70 and/or methionine at aa 91 (90.0%). In the present work, such substitutions significantly affected the viral kinetics in virological non-responders. The results suggest that viral, host, and treatment-related factors determine the response to IFN/ribavirin combination therapy in patients with high HCV genotype 1b viral load, and that amino acid substitution patterns in the core region is potentially useful pretreatment predictor of virological non-response. SN - 0146-6615 UR - https://www.unboundmedicine.com/medline/citation/16299715/Predictive_factors_of_virological_non_response_to_interferon_ribavirin_combination_therapy_for_patients_infected_with_hepatitis_C_virus_of_genotype_1b_and_high_viral_load_ L2 - https://doi.org/10.1002/jmv.20507 DB - PRIME DP - Unbound Medicine ER -