Interleukin-28B genotypes determine response to pegylated-interferon plus ribavirin therapy in patients with hepatitis C virus infection.

We recently reported that the interleukin (IL)-28B major genotype is a predictor of early suppression of the hepatitis C virus (HCV) at 12 weeks in response to pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy. The present study investigated the relationship between IL-28 genotypes and the virological response to PEG-IFN/RBV therapy at 24 and 48 weeks. Genotypes of the IL-28B rs8099917 T>G single nucleotide polymorphism were determined in 177 patients with HCV infection. Among them, 56 patients with HCV1 infection were treated with PEG-IFN/RBV. The frequency of the IL-28B major allele (TT) was 73.8% in patients with HCV serotype 1 and 86.3% in patients with HCV serotype 2. The rate of HCV-RNA positivity was significantly lower at 48 weeks in patients with the IL-28B major allele compared to patients with the IL-28B minor allele (TG or GG). The rate of HCV-RNA positivity at 24 weeks tended to be lower in patients with the IL-28B major allele, but there was no statistical significance (P=0.059). The sustained virological response (SVR) rate was 45.9% in patients with the IL-28B major allele, but 13.3% in patients with the IL-28B minor allele. The SVR correlated with the IL-28B major allele (OR=7.13, P=0.010), early virological response (OR=33.3, P=0.008), HCV-RNA ≤ 6.3 log IU/ml (OR=81.2, P=0.009) and γ-GTP ≤ 47 IU/l (OR=49.4, P=0.027). The IL-28B genotype is a significant pre-treatment predictor of the response to PEG-IFN/RBV therapy at 48 weeks in patients with HCV infection.

Interleukin-28B polymorphisms are associated with an early viral response in patients receiving hepatitis C therapy.

Prediction of the efficacy of pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy against hepatitis C (HCV) infection is valuable for determining its applications. This study investigated the relationship between the early response of HCV to PEG-IFN/RBV therapy and the inter-leukin (IL)-28B genetic polymorphism in patients with HCV infection. The genotypes of IL-28B rs8099917 T>G single nucleotide polymorphism were determined in 144 patients with HCV infection. Among them, 59 were treated with PEG-IFN/RBV. The frequency of IL-28B TT homozygosity was 75.2% in patients with HCV serotype 1 and 84.6% in patients with serotype 2. Multivariate analysis showed that IL-28B TT homozygosity (P=0.014) and the platelets number (P=0.030) was associated with the early suppression of HCV-RNA at 12 weeks after the start of PEG-IFN/RBV therapy. The IL-28B polymorphism was a significant pre-treatment predictor of the response to PEG-IFN/RBV therapy in patients with HCV infection.

Evaluation of transcatheter arterial embolization therapy on hepatocellular carcinomas using contrast-enhanced harmonic power Doppler sonography: comparison with CT, power Doppler sonography, and dynamic MRI.

PURPOSE: The aim of this study was to assess and compare the sensitivity of power Doppler sonography, contrast-enhanced sonography, plain computed tomography (CT), and dynamic magnetic resonance imaging (MRI) for detecting hepatocellular carcinoma (HCC) nodules incompletely treated with transcatheter arterial embolization (TAE). METHODS: A total of 63 unresectable HCC nodules were examined in this study. The HCCs were treated with TAE. All patients underwent plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI 1 week after TAE. The sensitivity of each modality to incompletely treated HCC nodules was compared. Detection of the residual viable HCC on angiography or tumor biopsy was regarded as the gold standard for the diagnosis of incomplete treatment. RESULTS: Twenty-four nodules (38%) were diagnosed as incompletely treated. The sensitivities of plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI to these incompletely treated nodules were 42% (10/24), 46% (11/24), 88% (21/24), and 79% (19/24), respectively. Eighty percent (19 nodules) of the 24 incompletely treated nodules were located within a depth of less than 8 cm. The sensitivities of plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI to these superficial incompletely treated nodules were 37% (7/19), 53% (10/19), 100% (19/19), and 74% (14/19), respectively. In contrast, the sensitivities of each modality to deeply located nodules were 60% (3/5), 20% (1/5), 40% (2/5), and 100% (5/5), respectively. CONCLUSION: Plain CT and power Doppler sonography had a low sensitivity to HCC nodules incompletely treated with TAE. Except for those that were deeply located, contrast-enhanced harmonic sonography showed the highest sensitivity in detecting incompletely treated HCC nodules.

[A case of advanced gastric cancer attaining histological CR of paraaortic lymph node after TS-1/CDDP neoadjuvant chemotherapy].

A 60-year-old male complaining of anemic symptoms went through examinations and was diagnosed with gastric cancer (cardia, type 3', cT2, cN3, cH0, cP0, cM0, cStage IV). Further inspection showed multiple lymph node metastases, including, No. 1, 3, 7, 11, and 16 (paraaortic LNs). Poor prognosis was predicted, yet we tried neoadjuvant chemotherapy (NAC) expecting down staging of the tumor. With the efficacy and safety previously proven, we chose TS-1 + CDDP as NAC regimen. TS-1 (tegafur gimestat otastat potassium, = 80 mg/m2) was administered orally for 21 days, followed by CDDP (cisplatin, = 60 mg/m2) i.v. on day 9. One course was completed without any significant adverse effects. The tumor itself showed PR-MR to the chemotherapy, but all the lymph nodes were expected to attain PR from CT findings. Total gastrectomy, lymph node dissection (D3) with Roux-en-Y reconstruction was performed, and histological re-evaluation was made. Macroscopically, the stomach seemed to be penetrated into serosa by the tumor, i.e., se invasion was suggested, yet histologically no cancerous cells were detected within mp and ss layer. Many of the lymph nodes were replaced with fibrosis, some with normal lymph node structure remained. Definitely no malignant cells were detected throughout all the lymph node specimens (Grade 3). Because pathological CR of paraaortic lymph nodes has never been reported previously, this case shows TS-1 + CDDP as a promising NAC regimen for advanced gastric cancer, in a sense that tumors once diagnosed as inoperable would still have the possibility of CR.

[A case of stomach cancer in which TS-1 neoadjuvant therapy was effective against multiple hepatic metastasis, allowing a radical cure A surgery].

It is believed that multiple hepatic metastases from stomach cancer are highly refractory, and resistant to clinical treatment. In the present study, TS-1 neoadjuvant therapy administered orally in a single course brought about CR in the hepatic metastatic foci and PR in the primary foci, thus enabling grade A radical extirpation in a case of advanced stomach cancer. The patient continued to be treated on an ambulatory basis. His peri- and post-operative courses were satisfactory and the treatment was completed without the development of adverse effects.