Miki Taniguchi

Serum granulysin levels as a predictor of serious telaprevir-induced dermatological reactions.

Telaprevir‐based therapy for chronic hepatitis C patients is effective; however, the high prevalence of dermatological reactions is an outstanding issue. The mechanism and characteristics of such adverse reactions are unclear; moreover, predictive factors remain unknown. Granulysin was recently reported to be upregulated in the blisters of patients with Stevens–Johnson syndrome (SJS). Therefore, we investigated the risk factors for severe telaprevir‐induced dermatological reactions as well as the association between serum granulysin levels and the severity of such reactions.

Efficacy of additional radiofrequency ablation after transcatheter arterial chemoembolization for intermediate hepatocellular carcinoma

For intermediate hepatocellular carcinoma (HCC), transcatheter arterial chemoembolization (TACE) therapy is recommended in the guidelines as a monotherapy, although TACE is a non‐curative therapy. The aims of the present study were to evaluate the efficacy of adding radiofrequency ablation (RFA) to TACE in patients with intermediate HCC, and to identify the factors that were associated with favorable survival in these patients.

Impaired induction of interleukin 28B and expression of interferon λ 4 associated with nonresponse to interferon‐based therapy in chronic hepatitis C

Interferon (IFN) λ plays an important role in innate immunity to protect against hepatitis C viral (HCV) infection. Single nucleotide polymorphisms (SNPs) near IL28B (IFNλ3) are strongly associated with treatment response to IFNα therapy in chronic hepatitis C (CHC) patients. Recently, IFNλ4 related to IL28B‐unfavorable allele was discovered. However, the impact of IFNλs on CHC is unknown. We aimed to investigate the mechanism underlying responsiveness to IFN‐based therapy in CHC associated with SNPs near IL28B.

Evaluation of Interferon Resistance in Newly Established Genotype 1b Hepatitis C Virus Cell Culture System.

Background and Aims: The hepatitis C virus (HCV) genotype 1b is known to exhibit treatment resistance with respect to interferon (IFN) therapy. Substitution of amino acids 70 and 91 in the core region of the 1b genotype is a significant predictor of liver carcinogenesis and poor response to pegylated-IFN-α and ribavirin therapy. However, the molecular mechanism has not yet been clearly elucidated because of limitations of the HCV genotype 1b infectious model. Recently, the TPF1-M170T HCV genotype 1b cell culture system was established, in which the clone successfully replicates and infects Huh-7-derived Huh7-ALS32.50 cells. Therefore, the purpose of this study was to compare IFN resistance in various HCV clones using this system. Methods: HCV core amino acid substitutions R70Q and L91M were introduced to the TPF1-M170T clone and then transfected into Huh7-ALS32.50 cells. To evaluate the production of each virus, intracellular HCV core antigens were measured. Results were confirmed with Western blot analysis using anti-NS5A antibodies, and IFN sensitivity was subsequently measured. Results: Each clone was transfected successfully compared with JFH-1, with a significant difference in intracellular HCV core antigen (p < 0.05), an indicator of continuous HCV replication. Among all clones, L91M showed the highest increase in the HCV core antigen and HCV protein. There was no significant resistance against IFN treatment in core substitutions; however, IFN sensitivity was significantly different between the wildtype core and JFH-1 (p < 0.05). Conclusions: A novel genotype 1b HCV cell culture was constructed with core amino acid substitutions, which demonstrated IFN resistance of genotype 1b. This system will be useful for future analyses into the mechanisms of HCV genotype 1b treatment.