Predictive values of amino acid sequences of the core and NS5A regions in antiviral therapy for hepatitis C: A Japanese multi-center study

Hepatology Center, Saiseikai Suita Hospital, 1-2 Kawazonocho, Suita, 564-0013, Japan.
Journal of Gastroenterology (Impact Factor: 4.52). 07/2009; 44(9):952-63. DOI: 10.1007/s00535-009-0087-x
Source: PubMed


Chronic hepatitis C (CHC) genotype 1b patients with high viral load are resistant to peginterferon (PEG-IFN) and ribavirin (RBV) combination therapy, especially older and female patients.
To elucidate the factors affecting early and sustained viral responses (EVR and SVR), 409 genotype 1b patients CHC with high viral loads who had received 48 weeks of PEG-IFN/RBV therapy were enrolled. The amino acid (aa) sequences of the HCV core at positions 70 and 91 and of the interferon sensitivity determining region (ISDR) were analyzed. Host factors, viral factors, and treatment-related factors were subjected to multivariate analysis.
Male gender, low HCV RNA load, high platelet count, two or more aa mutations of ISDR, and wild type of core aa 70 were independent predictive factors for SVR. In patients with over 80% adherences to both PEG-IFN and RBV, male gender, mild fibrosis stage, and wild type of core aa 70 were independent predictors for SVR.
Independent predictive factors for SVR were: no aa substitution at core aa 70, two or more aa mutations in the ISDR, low viral load, high values of platelet count, mild liver fibrosis and male gender.

2 Reads
  • Source
    • "Enomoto and Maekawa reported that mutations both in NS5A-ISDR (interferon sensitivity-determining region) and core 70Q substitution are associated with no early viral response during PEGIFN and RBV combination therapy [25]. Association of core aa70 substitution and mutations in NS5A region is confirmed to be associated with viral response by PEGIFN and RBV combination therapy in a Japanese multicenter cooperative study [26]. The number of mutations in the interferon sensitivity-determining region was shown to be associated with the viral response to PEGIFN and RBV combination treatment not only in Japan [27], but also in Tunisia [28]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A combination therapy with pegylated interferon (PEG-IFN) plus ribavirin (RBV) has made it possible to achieve a sustained virological response (SVR) of 50% in refractory cases with genotype 1b and high levels of plasma HCVRNA. Several factors including virus mutation and host factors such as age, gender, fibrosis of the liver, lipid metabolism, innate immunity, and single nucleotide polymorphism (SNPs) are reported to be correlated to therapeutic effects. However, it is difficult to determine which factor is the most important predictor for an individual patient. Data mining analysis is useful for combining all these together to predict the therapeutic effects. It is important to analyze blood tests and to predict therapeutic effects prior to initiating treatment. Since new anti-HCV agents are under development, it will be necessary in the future to select the patients who have a high possibility of achieving SVR if treatment is performed with standard regimen.
    Full-text · Article · Sep 2010 · Hepatitis research and treatment
  • [Show abstract] [Hide abstract]
    ABSTRACT: The robustness and reliability of conductive polymer materials for multilayer laminate substrate interconnection has evolved from electronic packaging applications in rather benign environments to applications that endure the harshest automotive environments, i.e. underhood and on-engine. This extended abstract serves as an introductory survey of conductive ink/polymer filled microvia materials, process, and reliability development. It characterizes in microstructural detail several conductive ink systems used to fill microvias, describes multilayer laminate substrate fabrication and interconnection approaches along with some related process issues. It highlights the design advantages of these constructions and summarizes results of bare board reliability testing and the requirements for demanding automotive environments. The bulk resistivity of these conductive ink materials range from 35 to 300 (μΩ cm) depending on the degree of contiguity of the metal phases. The adhesion and/or metallurgical bonding to opposing layer-to-layer circuit pads is critical in obtaining suitable reliability and low contact resistance of the interconnection. The utilization of these interconnection methods for mixed density substrate applications as well as multilayer laminate substrate approaches will be briefly discussed
    No preview · Conference Paper · Apr 1998
  • [Show abstract] [Hide abstract]
    ABSTRACT: Summary form only given. Recent research on capacity approaching codes, i.e., low density parity check (LDPC) codes and turbo codes, assumes perfect timing recovery systems. Conventional timing recovery devices tend to experience cycle-slips at low signal-to-noise ratios (SNRs). In our previous work, we developed a cycle-slip detector (CSD) for AWGN channels using the decoder soft information. In this paper, we generalize the method and develop the CSD for channels with intersymbol interference. We investigate the PR4 (1-D2) channel with a rate 4/5 LDPC code. The channel experiences a slowly time-varying phase drift. We use the Mueller and Muller (M&M) synchronizer to track the phase drift. For i.i.d. equally likely binary symbols, the soft information is the symbol a posteriori probability (APP). Both the symbol APPs and the preliminary decisions for the timing recovery algorithm are provided by a forward-only implementation of the BCJR algorithm, with a survival memory length of 6. This paper further investigates an iterative timing recovery scheme with the aid of the CSD.
    No preview · Article · Jan 2002
Show more