A multicenter study to clarify the optimal HCV-RNA negative period during combined therapy with pegylated interferon plus ribavirin in patients with chronic hepatitis caused by HCV genotype 2.

OBJECTIVE: A multicenter open trial was performed to clarify the optimal duration of combined pegylated interferon (Peg-IFN) plus ribavirin therapy in patients with chronic hepatitis caused by HCV genotype 2. METHODS: A total of 100 patients seen between 2005 and 2007 received the combination therapy for 4 to 52 weeks. The cutoff value of the HCV-RNA-negative (titers under 1.7 Log IU/mL) period during the therapy to predict sustained virological response (SVR) was determined by ROC curve and multivariate logistic regression analyses. The result was validated in 48 patients between 2008 and 2009. RESULTS: SVR was achieved in 78 patients. Serum HCV-RNA titers decreased to less than 1.7 Log IU/mL at 4 weeks of the therapy in 60 patients. The SVR rate in these patients was 85%, which was significantly higher than that of remaining 40 patients with a SVR rate of 68%. An HCV-RNA-negative period of ≥17 weeks was selected as the cutoff value, which showed a significant odds ratio of 4.77 for SVR. Among the 35 patients who showed a decrease of the serum HCV-RNA of less than 1.7 Log IU/mL between 8 and 16 weeks of therapy, the SVR rate was significantly higher in 16 patients with a serum HCV-RNA-negative period of ≥17 weeks (94%) than in 19 patients in whom the period was less than 17 weeks (63%). Similar results were obtained in the subsequent validation study. CONCLUSION: Prolonged combined Peg-IFN plus ribavirin therapy, with an HCV-RNA-negative period of ≥17 weeks, yielded good therapeutic outcomes in patients with chronic HCV genotype 2 hepatitis.

Protein expression of nuclear receptors in human and murine tissues.

Nuclear receptors (NR) are transcriptional regulators expressed in a variety of tissues and they play important roles in embryonic development, organogenesis and metabolic homeostasis. In order to investigate the tissue-specific expression pattern of NR, mouse anti-human monoclonal antibodies newly generated against various NR. Specificities of the antibodies were confirmed on immunoblotting using overexpressed proteins. Most of the antibodies recognized intrinsic protein. Among 60 monoclonal antibodies generated, 32 were applicable for immunohistochemistry. The expression pattern of NR in human liver and pancreas was confirmed on immunohistochemical staining using these antibodies. The P2 promoter-driven hepatocyte nuclear factor 4alpha (HNF4alpha) isoform and progesterone receptor were expressed in pancreatic alpha-cells, but not beta-cells in the human pancreas, suggesting an unknown role of these NR in diabetes mellitus. These antibodies were also useful for immunohistochemistry of the murine liver and pancreas. Immunoblotting using these antibodies produced similar corresponding bands both in human and mouse tissues. These monoclonal antibodies may serve as powerful tools to detect tissue-specific localization of NR and provide a platform for future studies of NR in human and murine tissues.