Efficacy and safety of combined directly acting antivirals for treatment of Chinese chronic hepatitis C patients in a real-world setting

AIM To assess the efficacy and safety of combined directly acting antivirals(DAAs) for the treatment of Chinese chronic hepatitis C(CHC) patients in a real-world setting.METHODS Hospitalized CHC patients who were treated with DAAs at Peking University First Hospital between January 2015 and December 2016 were enrolled. Samples and clinical data were collected at 0 wk, 2 wk, 4 wk, 8 wk, 12 wk, or 24 wk during DAAs treatment and at 4 wk, 12 wk, and 24 wk after the end of treatment. RESULTS Fifty-four patients who underwent DAAs treatment were included in our study, of whom 83.3%(45/54) achieved rapid virological response at 2 wk after treatment initiation(RVR 2) and 94.4%(51/54)achieved sustained virological response at 24 wk after the end of treatment(SVR 24). Serum creatinine and uric acid levels at the end of treatment were significantly increased compared with baseline levels(83.6 ± 17.9 vs 88.8 ± 19.4, P 01 < 0.001; 320.8 ± 76.3 vs 354.5 ± 87.6, P 01 < 0.001), and no significant improvements were observed at 24 w after the end of treatment(83.6 ± 17.9 vs 86.8 ± 19.1, P 02 = 0.039; 320.8 ± 76.3 vs 345.9 ± 89.4, P 02 = 0.001). The total frequency of adverse events(AEs) during treatment was 33.3%(18/54), with major AEs being fatigue(16.7%), headache(7.4%), anorexia(7.4%), and insomnia(5.6%). CONCLUSION Though based in a small cohort of patients, the abnormal changes in renal function indices and relative high frequency of AEs during combined DAAs treatment should be taken as a note of caution.

Thyroid dysfunction in Chinese hepatitis C patients: Prevalence and correlation with TPOAb and CXCL10

AIM: To investigate the relationship among pretreatment serum CXC chemokine ligand 10(CXCL10),thyroid peroxidase antibody(TPOAb) levels and thyroid dysfunction(TD) in Chinese hepatitis C patients.METHODS: One hundred and thirty-nine treatmentnaive genotype 1 chronic hepatitis C patients with no history of TD or treatment with thyroid hormones were enrolled in this study.Patients underwent peginterferon alfa-2a/ribavirin(Peg IFNα-2a/RBV) treatment for 48 wk,followed by detection of clinical factors at each follow-up point.Hepatitis C virus(HCV) antibodies were analyzed using microsomal chemiluminescence,and serum HCV RNA was measured by real-time PCR assay at 0,4,12,24 and 48 wk after the initiation of therapy and 24 wk after the end of therapy.To assess thyroid function,serum thyroid stimulating hormone(TSH),free thyroxine(FT4),free triodothyronine(FT3) and TPOAb/thyroglobulin antibody(TGAb) levels were determined using chemiluminescent immunoassays every 3 mo.Serum CXCL10 levels were determined at baseline.RESULTS: The prevalence of TD was 18.0%.Twentyone(84.0%) out of twenty-five patients exhibited normal thyroid function at week 24 after therapy.The rate of sustained virological response to Peg IFNα-2a/RBV in our study was 59.0%(82/139),independent of thyroid function.Pretreatment serum CXCL10 levels were significantly increased in patients with euthyroidstatus compared with patients with TD(495.2 ± 244.2 pg/m L vs 310.0 ± 163.4 pg/m L,P = 0.012).Patients with TD were more frequently TPOAb-positive than non-TD(NTD) patients(24.2% vs 12.3%,P = 0.047) at baseline.Three of the one hundred and fifteen patients without TPOAb at baseline developed TD at the end of treatment(37.5% vs 2.6%,P = 0.000).Female patients exhibited an increased risk for developing TD compared with male patients(P = 0.014).CONCLUSION: Lower pretreatment serum CXCL10 levels are associated with TD,and TD prevalence increases in female patients and patients who are positive for TPOAb at baseline.

Dysregulation of non-coding RNAs in gastric cancer

Gastric cancer(GC) is one of the most common cancers in the world and a significant threat to the health of patients, especially those from China and Japan. The prognosis for patients with late stage GC receiving the standard of care treatment, including surgery, chemotherapy and radiotherapy, remains poor. Developing novel treatment strategies, identifying new molecules for targeted therapy, and devising screening techniques to detect this cancer in its early stages are needed for GC patients. The discovery of non-coding RNAs(nc RNAs), primarily micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs), helped to elucidate the mechanisms of tumorigenesis, diagnosis and treatment of GC. Recently, significant research has been conducted on non-coding RNAs and how the regulatory dysfunction of these RNAs impacts the tumorigenesis of GC. In this study, we review papers published in the last five years concerning the dysregulation of noncoding RNAs, especially mi RNAs and lnc RNAs, in GC. We summarize instances of aberrant expression of the ncR NAs in GC and their effect on survival-related events, including cell cycle regulation, AKT signaling, apoptosis and drug resistance. Additionally, we evaluate how nc RNA dysregulation affects the metastatic process, including the epithelial-mesenchymal transition, stem cells, transcription factor activity, and oncogene and tumor suppressor expression. Lastly, we determine how ncR NAs affect angiogenesis in the microenvironment of GC. We further discuss the use of ncR NAs as potential biomarkers for use in clinical screening, early diagnosis and prognosis of GC. At present, no ideal ncR NAs have been identified as targets for the treatment of GC.

Identification of Human Hepatocyte Proliferation Related Gene C2orf69

Objective To construct the prokaryotic expression vector p ET-32a(+)-C2orf69 and induce the expression of recombinant proteins in vitro. Then the possible effects of recombinant protein on cell proliferation was observed and rabbit-anti-C2orf69 protein polyclonal antibodies was obtained.Methods Gene fragment of C2orf69 was amplified by PCR and then prokaryotic expression plasmid pE T-32a(+)-C2orf69 was constructed. Recombinant protein C2orf69 expression was identified by SDS-PAGE and Western blot. The white-ear rabbits were immunized with purified recombinant protein C2orf69, and the potency and specificity of polyclonal antibody were evaluated by enzyme-linked immunosorbent assay(ELISA) and Western blot. Also, different liver cells were incubated with recombinant protein C2orf69 in vitro. Results C2orf69 gene fragment was successfully amplified, results of gene sequencing were consistent with the sequence in Gen Bank. Recombinant protein of C2orf69 was successfully induced and expressed. The polyclonal antibody titer was up to 1︰1 280 000 through enzyme-linked immunosorbent assay. Results of cell proliferation showed that the recombinant protein could inhibit the proliferation of different liver cells. Conclusions The recombinant protein C2orf69 could inhibit the proliferation of different liver cells, and we speculated that it may be a widely roled inhibitor of hepatocyte proliferation. Our experiment showed that the proliferation inhibition of cells may be realized by G1 phase extending and S phase shortening.

Dynamic Characteristics of Serum Hepatitis B Surface Antigen in Chinese Chronic Hepatitis B Patients Receiving 7 Years of Entecavir Therapy

Background：The ultimate goal of hepatitis B treatment is hepatitis B surface antigen （HBsAg） seroclearance.Several factors have been suggested to be associated with the rate of HBsAg reduction in antiviral-naive or lamivudine therapy cohorts.However,there are few studies evaluating the factors during long-term entecavir （ETV） therapy.In the present study,we aimed to evaluate the factors to predict the outcome of ETV therapy for 7 years.Methods：A total of 47 chronic hepatitis B （CHB） patients treated with ETV monotherapy were included in this study.Liver biochemistry,hepatitis B virus （HBV） serological markers,serum HBV DNA,and HBsAg titers were tested at baseline,3 months,6 months,and yearly from 1 to 7.The associations between factors and HBsAg reduction were assessed using multivariate tests with repeated measure analysis of variance.Results：At baseline,serum HBsAg levels showed a positive correlation with baseline HBV DNA levels （r =0.625,P 〈 0.001）.The mean HBsAg titers after ETV treatment were significantly lower than the baseline titers （P ranges from 0.025 to 0.000,000,6）.The HBsAg reduction rate during the 1st year was greater compared to after 1 year of treatment （P 〈 0.05）.Multivariate test showed that hepatitis B e antigen （HBeAg） seroclearance and/or HBsAg reduction ≥0.5 log10 IU/ml at 6 months had a high negative predictive value （96.77%） for HBsAg seroclearance （P =0.002,P =0.012,respectively）.Conclusions：The HBsAg reduction rate during the 1st year was greater than that after 1 year of treatment.Further,HBeAg status and HBsAg levels at month 6 are the optimal factors for the early prediction of HBsAg seroclearance after long-term ETV therapy in CHB patients.