Correlations between serum hepatitis B surface antigen and hepatitis B core antibody titers and liver fibrosis in treatment-naïve CHB patients.

BACKGROUND: Previous studies have revealed that quantitative hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (qAnti-HBc) levels can be used as predictors of treatment response in both interferon-α and nucleoside analogue therapies. Few data have been published regarding the relationship between quantitative HBsAg or Anti-HBc levels and liver fibrosis stages in patients with chronic hepatitis B (CHB). METHODS: We conducted a cross-sectional study of treatment-naïve CHB patients. A total of 624 CHB patients were recruited. We assessed the serum HBsAg and qAnti-HBc levels, HBV DNA levels, HBV genotypes, BCP/PC mutations, histological fibrosis staging by Scheuer classification. RESULTS: In HBeAg (+) patients, the S0-1 subjects had significantly higher serum HBsAg and lower qAnti-HBc levels than the S2-4 subjects (both p < 0.001). A moderate inverse correlation was present between serum HBsAg levels and fibrosis scores (r = -0.381, p < 0.001), and a moderate positive correlation was found between qAnti-HBc levels and fibrosis scores (r = 0.408, p < 0.001). In the HBeAg (-) patients, the S0-1 subjects also had significantly lower qAnti-HBc levels than the S2-4 subjects (p < 0.001); however, no significant difference in the HBsAg levels was observed between the S0-1 and S2-4 subjects (p > 0.05). Serum qAnti-HBc levels showed a moderate positive correlation with fibrosis scores (r = 0.383, p < 0.001), while serum HBsAg levels exhibited a low inverse correlation with fibrosis scores (r = -0.171, p < 0.001). Multiple logistic regression analysis showed that the parameters for predicting significant fibrosis (S ≥ 2) included age, PLT, qAnti-HBc levels, HBV genotype and BCP/PC mutations in HBeAg (+) group, and age, PLT, qAnti-HBc levels in HBeAg (-) group (all p < 0.05). The AUC of qAnti-HBc levels associated with the diagnosis of significant fibrosis abnormalities in HBeAg (+) and HBeAg (-) patients were 0.734 (95%CI 0.689 to 0.778) and 0.707 (95%CI 0.612 to 0.801), respectively. CONCLUSION: Our study found an association between high serum qAnti-HBc levels and significant fibrosis in both HBeAg (+) and HBeAg (-) treatment-naïve CHB patients. However, low serum HBsAg levels were correlated with moderate to severe fibrosis in HBeAg (+) subjects only.

KLF2 inhibits cell growth via regulating HIF-1α/Notch-1 signal pathway in human colorectal cancer HCT116 cells.

The transcription factor Krüppel-like factor 2 (KLF2) has been shown to function as a tumor suppressor and regulate biological processes of cancer cells, such as cell growth, cell apoptosis and angiogenesis. However, the function and mechanism of KLF2 in colorectal cancer (CRC) is still unknown. In the present study, we show that the expression of KLF2 is diminished in a cohort of CRC cell lines. Also, KLF2 overexpression remarkably inhibits HCT116 and SW480 cell survival and proliferation. Moreover, cell death detection ELISA plus assay showed that KLF2 overexpression increased HCT116 cell proliferation. Caspase-3/7 activity also increased in HCT116 cells transfected with PcDNA3.1-KLF2. Further studies showed that KLF2 significantly suppresses the expression of Notch-1 and is dependent on the decline of the HIF-1α level. Most importantly, silencing Notch-1 expression or HIF-1α level both impair the action of KLF2 overexpression in CRC cells. Collectively, we demonstrated that KLF2 mediates CRC cell biological processes including cell growth and apoptosis via regulating the HIF-1α/Notch-1 signal pathway. These results indicated that KLF2 plays an important role in CRC and provided novel insight on the function of KLF2 in tumor progression.

Serum hepatitis B core antibody titer use in screening for significant fibrosis in treatment-naïve patients with chronic hepatitis B.

BACKGROUND: Previous studies have revealed that hepatitis B core antibody (anti-HBc) levels vary throughout the different phases of treatment-naïve chronic hepatitis B (CHB) patients and can be used as a predictor of treatment response in both interferon-α and nucleoside analogue therapies. However, few data have been published regarding the relationship between quantitative anti-HBc (qAnti-HBc) levels and liver fibrosis in patients with CHB. RESULTS: A total of 489 HBeAg-positive (HBeAg (+)) and 135 HBeAg-negative (HBeAg (-)) patients were recruited. In both HBeAg (+) and HBeAg (-) groups, the S0-1/S0 subjects had significantly lower qAnti-HBc levels than the S2-4 subjects (p < 0.05). Multiple logistic regression analysis showed that the parameters for predicting significant fibrosis (S ≥ 2) included age, PLT and qAnti-HBc. In HBeAg (+) subjects, the AUROC of qAnti-HBc for predicting significant fibrosis was 0.734 (95% CI 0.689 to 0.778) and the optimal cut-off was 4.58 log10IU/mL, with a sensitivity of 63.08% and a specificity of 74.83%. In HBeAg (-) subjects, the AUROC was 0.707 (95% CI 0.612 to 0.801) and the optimal cut-off value was 4.37 log10IU/mL, with a sensitivity of 75.53% and a specificity of 56.10%. MATERIALS AND METHODS: From 2012 to 2015, we conducted a cross-sectional study of treatment-naïve CHB patients. Liver biochemistry, hepatitis B virus (HBV) serological markers, HBV DNA, hepatitis B surface antigen (HBsAg) titers and HBV genotype were determined using commercial assays, and serum qAnti-HBc levels were measured using double-sandwich immunoassay. Liver biopsies and serum samples were obtained on the same day. CONCLUSIONS: The present study showed an association between high serum qAnti-HBc levels and significant fibrosis (S ≥ 2) in treatment-naïve CHB patients. Furthermore, we described a serum qAnti-HBc cut-off for predicting significant fibrosis in CHB patients infected with HBV genotype B or C.

DCF intraperitoneal and intravenous dual chemotherapy regimen for advanced gastric cancer: A feasibility study.

Gastric cancer is the fourth most common type of cancer globally and accounts for the second highest cancer-associated mortality rate in the world. Current treatment strategies for gastric cancer include surgery, radiotherapy, chemotherapy and targeted therapy. Intraperitoneal (IP) chemotherapy may increase the IP concentrations of chemotherapy drugs and reduce the systemic toxicity. At present, IP chemotherapy is used to treat patients with advanced gastric cancer, which has a high rate of peritoneal recurrence. The present study evaluated the feasibility of using docetaxel, cisplatin and fluorouracil (DCF) in an IP and intravenous (IV) dual chemotherapy regimen for the treatment of advanced gastric cancer. The treatment-associated adverse reactions and preliminary efficacy were reported. The first dose level utilized the full dose of DCF: Docetaxel, day one, 45 mg/m2 (IP) and day eight, 30 mg/m2 (IV); cisplatin (DDP), day one, 75 mg/m2 (IP); and fluorouracil (FU), days one to five, 750 mg/m2 (continuous IV). A total of six patients were treated at this level and two patients withdrew due to serious adverse reactions. Taking into account that the the tolerated doses used in combination regimens for Eastern populations are lower than that of the corresponding doses for Western populations, the dosages of the three drugs were all reduced by 20% in the application of the second dose level: Docetaxel, day one, 30 mg/m2 (IP) and day eight, 30 mg/m2 (IV); DDP, day two, 60 mg/m2 (IP); and FU, days one to five, 600 mg/m2 (continuous IV). A total of 26 patients were treated at this level. The main adverse reaction was bone marrow suppression, with grade III/IV neutropenia, leukopenia and febrile neutropenia accounting for 61.5, 53.8 and 19.2% of reactions, respectively, and grade III/IV anemia and thrombocytopenia accounting for 19.2 and 15.4% of reactions, respectively. Gastrointestinal adverse reactions primarily consisted of abdominal pain, with grade III/IV abdominal pain accounting for 30.8% of reactions. Only 7.7% of the patients withdrew from the treatment. The median time to progression (TTP) was five months [95% confidence interval (CI), 1.0-9.0 months], and the median overall survival (OS) was nine months (95% CI, 7.4-10.6 months). It was concluded that the DCF regimen with reduced dosage should be applied. IP and IV dual chemotherapy for the treatment of unresectable advanced gastric cancer is tolerated and demonstrated a good initial efficacy. Strategies for mitigating and reducing the adverse gastrointestinal reactions, particularly abdominal pain, may be the focus of future studies.