A phase II, single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection / 中华肝脏病杂志

Objective@#To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection.@*Methods@#Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval.@*Results@#132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death.@*Conclusion@#Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.

Cladogynos orientalis Zipp. extracts inhibit cell culture-derived hepatitis C virus genotype 2a replication in Huh-7 cells through NS5B inhibition

Objective: To evaluate the potential anti-hepatitis C virus (HCV) activities of Cladogynos orientalis Zipp. ex Span and to investigate the molecular mode of action. Methods: Ethanolic and water extracts from various parts of Cladogynos orientalis were examined for cytotoxicity by MTT assay. Sub-cytotoxic concentrations of the extracts were used for further determining anti-HCV activity using cell culture-derived HCV genotype 2a propagated in HepaRG cell line. Immunofluorescence assay was performed to observe the effect on viruses at the pre-entry step. Mode of action at the post-entry step was investigated for the viral RNA and protein expressions by real time RT-PCR and Western blotting assays, respectively. Results: Although Cladogynos orientalis water extracts exhibited lower cytotoxicity than ethanolic extracts, all ethanolic extracts from roots, stems, and leaves of Cladogynos orientalis exhibited higher anti-HCV activities than water extracts. The highest anti-HCV activity was observed in infected cells treated with the extracts 5 h after absorption. No extracts showed pre-viral entry effect. At the post-viral entry step, only leaf ethanolic extracts inhibited NS5B expression, while all extracts did not inhibit HCV NS3 expression. Conclusions: Cladogynos orientalis ethanolic extracts could be further studied and the major active compound needs to be identified as a promising source for anti-HCV agents.

Cladogynos orientalis Zipp. extracts inhibit cell culture-derived hepatitis C virus genotype 2a replication in Huh-7 cells through NS5B inhibition

Objective: To evaluate the potential anti-hepatitis C virus (HCV) activities of Cladogynos orientalis Zipp. ex Span and to investigate the molecular mode of action. Methods: Ethanolic and water extracts from various parts of Cladogynos orientalis were examined for cytotoxicity by MTT assay. Sub-cytotoxic concentrations of the extracts were used for further determining anti-HCV activity using cell culture-derived HCV genotype 2a propagated in HepaRG cell line. Immunofluorescence assay was performed to observe the effect on viruses at the pre-entry step. Mode of action at the post-entry step was investigated for the viral RNA and protein expressions by real time RT-PCR and Western blotting assays, respectively. Results: Although Cladogynos orientalis water extracts exhibited lower cytotoxicity than ethanolic extracts, all ethanolic extracts from roots, stems, and leaves of Cladogynos orientalis exhibited higher anti-HCV activities than water extracts. The highest anti-HCV activity was observed in infected cells treated with the extracts 5 h after absorption. No extracts showed pre-viral entry effect. At the post-viral entry step, only leaf ethanolic extracts inhibited NS5B expression, while all extracts did not inhibit HCV NS3 expression. Conclusions: Cladogynos orientalis ethanolic extracts could be further studied and the major active compound needs to be identified as a promising source for anti-HCV agents.

Analysis on genetic characteristics of rubella virus isolates from 2011 to 2017 in Shanghai, China / 中华实验和临床病毒学杂志

Objective@#To analyze the molecular epidemiological characteristics of rubella virus wild strains isolated in Shanghai during 2011-2017.@*Methods@#Throat swabs were collected from suspected measles or rubella patients in Shanghai during 2011-2017, which were identified as rubella and excluded measles by laboratory tests. Throat swabs were used to conduct cell culture for rubella virus isolation. After identification by RT-PCR, the nucleic acid of gene E1 of rubella virus was amplified and sequenced, followed by molecular epidemiological analysis.@*Results@#Totally 395 strains of rubella virus were isolated from 684 throat swabs. Compared 377 isolates with the WHO reference strains of all genotypes, phylogenetic tree was constructed based on the amplified 739 nucleotides sequences. These isolates were characterized as two genotypes respectively, 109 strains were defined as genotype 1E which were closer to the WHO reference strain from China (RVi/Shandong.CHN/0.02/), and others were genotype 2B while 5 strains of them were defined as a lineage. Most of the nucleotide mutations were nonsense mutation, and the amino acid sequences were highly conserved. All the genotype 1E rubella viruses except one strain had the same mutation at aa338 site.@*Conclusions@#Two genotypes of rubella virus circulated in Shanghai during 2011-2017.Genotype 1E appeared to be the predominant genotype during 2011-2013, genotype 2B was continuously existing since being found in 2011 and appeared to be the predominant genotype during 2014-2016.

Does the old-fashioned sofosbuvir plus ribavirin treatment in genotype 2 chronic hepatitis C patients still works for Koreans?

No abstract available.

Tratamiento acortado a 16 semanas en paciente con infección por genotipo 2 del virus de hepatitis C: Reporte de un caso y revisión de la literatura / Case Report and Literature Review: Shortened 16 Week Treatment of Patient with Genotype 2 Hepatitis C Infection

Presentamos el caso de una paciente de 46 años con hepatitis C infectada por el genotipo 2 quien recibió tratamiento acortado con dosis bajas de interferón pegilado alfa 2b (1 mcg/k semana SC) y ribavirina (800 mg día oral) durante 16 semanas alcanzando respuesta viral sostenida a las 12 (RVS12) y a las 24 semanas (RVS24). La tolerancia al tratamiento fue muy buena sin presentarse anemia clínicamente significativa o efectos adversos. Se plantea la posibilidad de este tipo de terapia en pacientes con factores relacionados con un buen pronóstico como carga viral baja, poca fibrosis (< F2), respuesta viral rápida (RVR) e IL28B genotipo CC. Esta estrategia puede reducir significativamente los costes relacionados con los nuevos antivirales de acción directa (AAD) tipo sofosbuvir asociado a ribavirina que deben ser administrados durante 12 semanas.

We report the case of a 46-year patient infected with genotype 2 of hepatitis C. The patient received short-course treatment with low doses of pegylated interferon alfa 2b (1 mcg/week SC k) and ribavirin (800 mg/day orally) for 16 weeks. The patient had sustained virologic response at 12 weeks (SVR12) viral and at 24 weeks (SVR24). Tolerance to treatment was very good, and there were no clinically significant signs of anemia or adverse effects. We propose that this type of therapy be considered for patients with factors associated with good prognoses such as low viral loads, low levels of fibrosis (