Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04
  • 2024-05

    • br Methods CHC patients receiving anti viral therapy

    2018-11-09


    Methods CHC patients receiving anti-viral therapy were consecutively recruited as a prospective follow-up cohort at one tertiary hospital and two core regional hospitals from 2002 to 2012. All the participants received peginterferon alpha-2a or peginterferon alpha-2b plus ribavirin. Patients were excluded if they were co-infected with HIV or hepatitis B virus infection, exhibited alcohol abuse (≥20g daily) or had evidence of HCC before, during or within 6months after antiviral therapy. Patients with or without an SVR, defined as seronegativity of HCV RNA throughout a 24-week post-antiviral treatment follow-up period, were further evaluated for the risk of HCC development. Serum HCV RNA was detected using qualitative real-time polymerase chain reaction (PCR) (COBAS AMPLICOR Hepatitis C Virus Test, ver. 2.0; Roche, Branchburg, NJ, USA, detection limit: 50IU/mL) or quantification branched DNA assay (Versant HCV RNA 3.0, Bayer, Tarrytown, New Jersey, USA; quantification limit: 615IU/mL) if evaluated before 2011. The HCV genotypes were determined using the Okamoto method before 2011 (Okamoto et al., 1993). After 2011, both the HCV RNA and Sulfo-NHS-Biotin were detected using real-time PCR assay (Real Time HCV; Abbott Molecular, Des Plaines IL, USA; detection limit: 12IU/mL) (Vermehren et al., 2011). The definition of cirrhosis was based on liver biopsies, which were performed within 6months before starting antiviral therapy, and liver histology was graded and staged according to the scoring system described by Knodell and Scheuer (Scheuer, 1991). The post-treatment follow-up strategy was based on cirrhotic status and treatment outcome, as previously described (Huang et al., 2014). Briefly, patients were followed every 3months if they were cirrhotic or did not have an SVR and every 6 to 12months if they were non-cirrhotic and had an SVR. The diagnosis of HCC was confirmed by histology or by imaging and laboratory evidence, in accordance with the American Association for the Study of Liver Diseases (Bruix & Sherman, 2011) and Asian Pacific Association for the Study of the Liver (Omata et al., 2010) guidelines. All patients provided written informed consent. The institutional review board at the participating hospital approved the protocols, which conformed to the guidelines of the International Conference on Harmonization for Good Clinical Practice.
    Results
    Discussion Host genetic predispositions are associated with anti-HCV treatment efficacy, (Huang et al., 2012, 2013a, 2013b) HCV-related liver fibrosis, (Huang et al., 2015a; Urabe et al., 2013) clinical outcome (Noureddin et al., 2013) and HCC (Kumar et al., 2011; Abu Dayyeh et al., 2011; Tanabe et al., 2008; Guyot et al., 2013). However, whether host genetic variants play important roles in HCC development after anti-viral therapy is unclear. By testing the candidate SNPs in a large treatment cohort, we demonstrated that MICA rs2596542 genetic variants predicted HCC occurrence, and the influence was restricted to cirrhotic patients who failed antiviral therapy. Interestingly, we demonstrated that high sMICA was also predictive of HCC occurrence in the population. Most importantly, cirrhotic non-responders were at the highest risk for HCC development, with an annual incidence of 23·5%, if phenotype carried the MICA A allele risk and had high pretreatment sMICA levels. Preexisting liver cirrhosis is the most critical factor associated with HCC in CHC patients (Lee et al., 2014; Goto & Kato, 2015). Once cirrhosis has evolved, 1 to 4% of patients develop HCC per year (Goto & Kato, 2015). Although successful HCV eradication could reduce the risk of HCC occurrence by 75%, SVR patients remain at risk of HCC development with an average risk of 1·05% per person-year if they have advanced liver disease (Yu et al., 2006a; Morgan et al., 2013). As shown in the current study and other studies, cirrhosis carries a higher hazard risk ratio than failing viral eradication for HCC development in the treatment cohort (Lee et al., 2014; Goto & Kato, 2015). It is therefore imperative to identity the risk of HCC in patients with cirrhotic background with and without SVR.