Alfosbuvir plus Daclatasvir for Treatment of Chronic Hepatitis C Virus Infection in China.

INTRODUCTION: A pan-genotypic and effective treatment regimen for patients with chronic hepatitis C virus (HCV) infection remains an unmet medical need in China. Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. We conducted a phase 3 study to evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV infection. METHODS: All patients received 600 mg alfosbuvir tablets plus 60 mg daclatasvir tablets once daily for 12 weeks. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). A follow-up visit was done at week 4 and 12, and those who achieved SVR12 were followed up at post-treatment week 24. RESULTS: Of the 326 patients who received at least one dose of the study drug, 320 (98.2% [95% confidence interval (CI): 96.5%-99.5%]) achieved sustained virological response at post-treatment week 12 (SVR12), which was superior to the historical SVR12 rate of 88% (p < 0.0001). The SVR12 rates were similar regardless of most baseline characteristics. The most common adverse event (AE) (≥ 10%) was hypercholesterolemia. Serious adverse events (SAEs) were reported in 25 (7.7%) patients, none of which was judged to be related to the study drug. The majority of AEs were mild to moderate in severity. CONCLUSIONS: Alfosbuvir plus daclatasvir for 12 weeks was highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3, or 6, suggesting that this regimen could be a promising option for HCV treatment in China irrespective of genotype. TRIAL REGISTRATION: ClinicalTrial.gov identifier, NCT04070235.

The investigation of glucose metabolism and insulin secretion in subjects of chronic hepatitis B with cirrhosis.

AIMS: To investigate the situations of abnormal glucose metabolism and dysfunction of pancreatic islet beta cells in subjects of chronic hepatitis B (CHB) with cirrhosis. METHODS: 106 hepatitis B virus (HBV) positive subjects with liver cirrhosis as well as with different grade of Child-Pugh and 37 healthy subjects were included in this study. The oral glucose tolerance test (OGTT), C-peptide and insulin release test were detected. Plasma glucose and insulin levels were analyzed periodically for 2 h after oral glucose loading. RESULTS: There was no significant difference in the level of fasting plasma glucose and C-peptide between cirrhosis group and control group (P>0.05). The levels of OGTT 2 h glucose, insulin and C peptide were significantly higher in cirrhosis group than control group (P<0.01). Peak plasma glucose levels were obtained at 60 min in normal group and cirrhosis group. The peak insulin and C-peptide response occurred at 60 min in normal group, whereas it was delayed to 120 min in cirrhosis group. There was a significant difference between two groups in the pattern of plasma glucose levels at corresponding time points (P<0.05). The OGTT 2 h glucose and insulin levels were positively correlated with Child-Pugh Score (r1 = 0.389, r2 = 0.508, P<0.01). CONCLUSION: These findings implied that there was a certain degree of insulin resistance and abnormal glucose metabolism in the patients with liver cirrhosis.

[Immunological parameters on prophase of severe hepatitis B].

OBJECTIVE: To study cellular and humoral immune status on prophase of severe hepatitis B (PSHB). METHODS: 56 cases of PSHB patients, 40 cases of chronic hepatitis B (CHB) patients and 20 cases of healthy volunteers were enrolled for detection of CD3+, CD4+, CD8+ and CD3-/CD19+ (B cells) lymphocyte subsets in peripheral blood by flow cytometry. Serum IgG and complement C3 was detected by immunoturbidimetry and analyzed statistically. RESULTS: Compared with CHB group and healthy control group, percentage of lymphocyte subsets CD8+ were significantly lower in PSHB group (P < 0.01 or P < 0.05). While the percentage of lymphocyte subsets CD4+ and ratio of CD4+/CD8+ in PSHB group was obviously higher than those in CHB group (P < 0.+01 or P < 0.05). In addition, There was no significant difference on the percentage of B cell and level of serum IgG between PSHB group and CHB group (P > 0.05, while the level of serum complement C3 in PSHB group were significantly lower than those in CHB group and healthy control group (P < 0.01, P < 0.05). CONCLUSION: PSHB has a certain degree of cellular immune dysfunction, which characterized by cellular immune function hyperfunction and humoral immune suppression.

[The characteristics of immunocompetent cells in peripheral blood on prophase of severe hepatitis B].

OBJECTIVE: To analyze the characteristics of immunocompetent cells in peripheral blood on prophase of severe hepatitis B (PSHB). METHODS: 48 cases of PSHB patients, 35 cases of chronic hepatitis B (CHB) patients and 20 cases of healthy volunteers were enrolled for detection of CD3+, CD3+/ CD4+, CD3+/CD8+ and CD4+/CD25+/CD45+ lymphocyte subsets in peripheral blood by flow cytometry. The absolute numbers of each lymphocyte subset were calculated and analyzed statistically. Results Compared with CHB group and healthy control group, The absolute numbers of circulating CD3+, CD8+ T cells and CD4+ CD25+ regulatory T cells (Tregs) were significantly lower in PSHB group( P < 0. 01 or P < 0.05). There was no significant difference on the absolute numbers of circulating CD4+ T cells between PSHB group and CHB group (P > 9.05), while the percentage of lymphocyte subsets CD4+ in PSHB group was significantly higher than that in CHB group (P < 0.05). In addition, CD4+/CD8+ ratio in PSHB were significantly higher than those in the CHB group and healthy control group (P < 0.01 or P < 0.05). CONCLUSION: PSHB has a certain degree of cellular immune dysfunction, which characterized by CD4+ T cells dominated and the decline of absolute numbers of CD8+ T cells and CD4+ CD25+ Tregs.