Katsuya Higami

Interferon alpha receptor 2 expression by peripheral blood monocytes in patients with a high viral load of hepatitis C virus genotype 1 showing substitution of amino Acid 70 in the core region.

Background/Aim: When patients with chronic hepatitis C (CHC) are treated with interferon (IFN)-based therapy, achieving serum HCV-RNA negativity by week 12 (early viral response, EVR) is an important predictor of a sustained virologic response. The aim of this study was to clarify whether changes in IFN-α receptor 2 (IFNAR-2) expression by peripheral blood monocytes (Mo) and the EVR rate differed between patients with genotype 1b and a high viral load showing substitution of amino acid 70 in the core region of HCV (mutant, n = 20) and patients without this substitution (wild, n = 23). Patients and Methods: Forty-three CHC patients were studied, and received pegylated IFN plus ribavirin. IFNAR-2 expression by Mo was determined using flow cytometry to measure the mean fluorescence intensity (MFI) before and up to 28 days after starting therapy. Results: The EVR rate of the mutant group was significantly lower than that of the wild group (35 vs.70%). The MFI of Mo was significantly higher in the wild group than in the mutant group before and also 3, 7, and 28 days after starting therapy. Conclusions: Mutation of HCV was related to lower IFNAR-2 expression by Mo before and after starting therapy.

Changes of cytokines in cirrhosis patients with advanced hepatocellular carcinoma treated by intra-arterial chemotherapy.

IntroductionTumor necrosis factor (TNF) induces cancer cell-specific apoptosis by binding to a TNF-related apoptosis-inducing ligand. Binding of the Fas ligand on cytotoxic T lymphocytes to the Fas receptor on hepatocytes is also known to induce apoptosis. The aim of this study was to clarify changes of cytokines in patients with liver cirrhosis (LC) and advanced hepatocellular carcinoma (aHCC) receiving intra-arterial combination chemotherapy.MethodsTwenty-one adult Japanese LC patients with aHCC received intra-arterial combination chemotherapy. The serum levels of TNF-alpha, soluble TNF receptor-I (sTNFr-I), soluble Fas ligand (sFas L), and soluble Fas (sFas) were evaluated.ResultsThirteen of the 21 patients (group R) showed an objective response, while the other eight patients (group N) showed no response. The serum level of TNF-alpha was lower after chemotherapy than before chemotherapy in group N, but there was no difference of serum sTNFr-I levels between before and after chemotherapy and there were also no differences between the two groups. The serum sFas levels were higher after chemotherapy than before chemotherapy in group N, while there was no difference among groups.ConclusionsThese results indicate that a high serum TNF-alpha level and a low serum sFas level might be important for successful combined arterial chemotherapy in LC patients with aHCC.

Effects of Mutation Number in Interferon Sensitivity Determining Region on Peripheral Blood CD4-Positive T Cell Subsets (TH1, TH2) in Chronic Hepatitis C Patients With Hepatitis C Virus Genotype 1b a and High Viral Load

Background/aim The number of amino acid (AA) mutations in the interferon sensitivity determining region (ISDR) of NS5A is reported to affect the response to interferon (IFN) therapy in patients with chronic hepatitis C (CHC). The aim of this study was to clarify whether host immunity is influenced by the number of AA mutations in the ISDR.