Comparison of clinical features and outcomes between HBV-related and non-B non-C hepatocellular carcinoma.

OBJECTIVE: To evaluate the difference between hepatitis B virus related hepatocellular carcinoma (HBV-HCC) and non-HBV non-HCV hepatocellular carcinoma (NBNC-HCC) patients based on clinical features and prognosis. METHODS: A total of 175 patients with HCC were enrolled. Patients' characteristics were extracted from medical records. Among them, 107 patients were positive for HBsAg and negative for HCV-Ab while 68 patients were negative for HBsAg and HCV-Ab. RESULTS: The patients in the NBNC-HCC group were significantly older than those in the HBV-HCC group (P = 0.045). Moreover, vascular invasion was found in 23.4% of HBV-HCC patients, which was significantly higher than that in the NBNC-HCC patients with 10.3% (P = 0.029). Kaplan-Meier analysis revealed that HBV-HCC patients had significantly worse outcomes in terms of overall survival (P = 0.036). Compared with the NBNC-HCC patients, the HBV-HCC patients had a significantly worse disease-free survival (P = 0.0018). The multivariate analysis results indicated that TNM stage (HR = 1.541, 95%CI 1.072-2.412, P = 0.002) and HBV infection (HR = 1.087, 95%CI 1.012-1.655, P = 0.042) were independent risk variables for overall survival. While vascular invasion (HR = 1.562, 95%CI 1.013-2.815, P = 0.042) and HBV infection (HR = 1.650, 95%CI 1.017-2.676, P = 0.037) were independent risk factors associated with disease-free survival. CONCLUSION: Our data revealed that HBV-HCC is more common in young males with vascular invasion, while NBNC-HCC occurs mostly in elderly patients, and overall survival rate is significantly better than that of HBV-HCC. Our study therefore provides evidence that patients with HBV-HCC require closer follow-up due to their poor prognosis.

Health-related quality of life in patients with chronic hepatitis B during antiviral treatment and off-treatment.

INTRODUCTION: Health-related quality of life (HRQoL) has emerged as an important consideration in the care of patients with chronic hepatitis B (CHB). However, whether benefits from the improved HRQoL that occurs after antiviral treatment or drug discontinuation outweigh the risks of viral relapse is an unanswered question. The aim of this study was to evaluate the HRQoL among patients with CHB during antiviral treatment and withdrawal of treatment. PATIENTS AND METHODS: There were 102 patients who met the enrollment criteria with 54 patients in the treatment group and 48 patients in the discontinuation group. Sociodemographic information was collected. The 36-Item Short-Form Health Survey (SF-36), European Quality of Life-5 Dimensions, and Beck Depression Inventory (BDI) were adopted to evaluate life quality and mental health. RESULTS: In the treatment group, SF-36 showed that the physical functions were significantly increased. In the discontination group, the psychological functions showed improvement. A multivariate regression analysis indicated that baseline SF-36 score was a predictor for improvement in HRQoL (odds ratio =1.17, P=0.003) and baseline BDI score was a factor for remission of depression (odds ratio =0.75, P=0.005) after medical intervention. When the cutoff value of SF-36 score was set at 79.5, the sensitivity and specificity to predict improvement in HRQoL were 82.8% and 74.0%, respectively. When the cutoff value of BDI was found as 8.5, the sensitivity and specificity to predict alleviation of depression were 58.6%, and 76.0%, respectively. CONCLUSION: Antiviral treatment benefits the physical health of the patients with CHB, while conferring no obvious improvement in their psychological condition. Improved psychological interventions for patients with CHB, especially for those with lower baseline SF-36 scores and higher BDI scores, may improve their quality of life.

Dynamic Changes in Liver Stiffness Measured by Transient Elastography Predict Clinical Outcomes Among Patients With Chronic Hepatitis B.

OBJECTIVES: We aimed to evaluate the validity of transient elastography in monitoring the antiviral outcomes in patients with chronic hepatitis B. METHODS: This study included 108 patients treated with nucleos(t)ide analogues and 67 patients treated with interferon (IFN). Liver biopsies were evaluated by the METAVIR score. Transient elastography was performed initially at baseline, 48 weeks, and 96 weeks. Liver tissue was obtained before and after 96 weeks of treatment. The area under the receiver operating characteristic curve was used to examine the diagnostic value of transient elastography in predicting and monitoring outcomes of antiviral treatment. RESULTS: The liver stiffness value correlated well with the baseline alanine aminotransferase level (r = 0.33; P < .001) and was significantly different among various stages of liver fibrosis (P < .001). In the nucleos(t)ide analogue group, the mean pretreatment and posttreatment liver stiffness values ± SD were 8.7 ± 3.1 and 5.9 ± 1.6 kPa, respectively (P < .001), and they were 9.2 ± 3.7 and 7.2 ± 1.9 kPa (P < .001) in the IFN group. Although the liver stiffness values at baseline between the groups were similar (P = .45), they were 5.9 ± 1.6 kPa in the nucleos(t)ide analogue group and 7.2 ± 1.9 kPa in the IFN group after 48 weeks of treatment (P < .001). With the decreased magnitude liver stiffness for predicting the improvement in liver fibrosis, the area under the receiver operating characteristic curve was 0.68 (P = .029). When the decreased magnitude of liver stiffness was 4.1 kPa or higher, the sensitivity and specificity for predicting a histologic response were 88.2% and 50.0%. CONCLUSIONS: Our findings suggest that transient elastography is an effective measurement tool for diagnosing and monitoring the histologic response in patients with chronic hepatitis B during antiviral treatment and can help avoid multiple liver biopsies.

Potential effects of telbivudine and entecavir on renal function: a systematic review and meta-analysis.

BACKGROUND: To assess the potential effects of telbivudine (LdT) and entecavir (ETV) on renal function in patients with chronic hepatitis B (CHB), we performed a meta-analysis of the relevant data available on these agents to evaluate their effects on the estimated glomerular filtration rate (eGFR) during treatment. METHODS: The PubMed, EMBASE, Scopus, CNKI (China National Knowledge Infrastructure), Cochrane Library, and WanFang databases were searched for relevant articles appearing in the literature up to July 1, 2015. A total of 6 studies (1960 CHB patients) with 1-year eGFR outcomes were retrieved and analyzed. RESULTS: Generally, the results of the 6 studies analyzed showed that eGFR was improved after LdT treatment, but was decreased after ETV treatment. Using a fixed-effects approach, the change in eGFR was found to be significantly different between LdT and ETV treatment (Z = 3.64; P = 0.0003). Whereas the eGFR was slightly decreased with ETV compared with baseline (-1.45 mL/min/1.73 m(2)), the eGFR was improved with LdT (2.99 mL/min/1.73 m(2)) after 1 year of treatment. An overall test of effect in the meta-analysis showed that the eGFR in LdT-treated patients was significantly improved after 1-year of treatment (Z = 3.71; P = 0.0002). CONCLUSION: This meta-analysis has confirmed that LdT has a renal protective effect whereas ETV does not. However, whether the benefit on renal function outweighs the occurrence of resistance in specific clinical situations is not yet clear.

Activity identification of ribozyme and U1 snRNA chimeric ribozyme against TGFbeta1 in cell-free system and in hepatic stellate cells.

Transforming growth factorbeta1 (TGFbeta1) is known to be intimately involved in many cellular processes. To explore the mechanism of TGFbeta1 in these processes, the non-chimeric hammerhead ribozyme and U1 snRNA chimeric ribozyme against TGFbeta1 were designed to down-regulate TGFbeta1 expression. The activity of non-chimeric ribozyme and U1 snRNA chimeric ribozyme against TGFbeta1 in vitro and in activated hepatic stellate cells (HSCs) was detected. Cleavage reactions of both ribozymes in vitro demonstrated that non-chimeric ribozyme possessed better cleavage activity in vitro than U1 snRNA chimeric ribozyme. The further study showed U1 snRNA chimeric ribozyme inhibited TGFbeta1 expression more efficiently than non-chimeric ribozyme in transfected HSC cells. So it indicates that the U1 snRNA chimeric ribozyme provides an alternative approach for the research on the precise mechanism of TGFbeta1 in many cellular processes and a potential therapeutic candidate for TGFbeta1-related diseases.

[Hammerhead ribozyme-mediated cleavage of transforming growth factor beta1 RNA in a cell-free system and in hepatic stellate cells].

OBJECTIVE: To identify the activity of hammerhead ribozyme against transforming growth factor beta1 (TGFbeta1) in a cell-free system and in activated hepatic stellate cells (HSCs). METHODS: The ribozyme against TGFb1 was designed with computer software. The transcripts of ribozyme, disabled ribozyme and target RNAs were prepared using the RiboMAX large scale RNA production system. The in vitro cleavage reactions were performed through incubation of 32P-labeled target RNAs with ribozyme or disabled ribozyme in different conditions. The eukaryotic expression vector encoding ribozyme and disabled ribozyme were constructed, and then transfected into HSC-T6 cells which exhibited characteristics of activated HSCs. The intracellular activity of the ribozyme was determined by detecting the ribozyme, disabled ribozyme and the TGFbeta1 expression. RESULTS: The ribozyme cleaved target RNAs into anticipated products effectively. As expected, the disabled ribozyme possessed no cleavage activity in vitro. Further study demonstrated that the ribozyme expressed efficiently and inhibited TGFbeta1 expression in activated HSCs, while the disabled ribozyme displayed only a slight effect on TGFbeta1 expression. CONCLUSION: The ribozyme with perfect cleavage activity in the cell-free system used inhibited TGFbeta1 expression effectively in activated HSCs. This ribozyme can provide a potential therapeutic approach for liver fibrosis.

Experimental studies on PNP suicide gene therapy of hepatoma.

To investigate the killing effect of PNP/MeP-dR suicide gene system on hepatoma cells, pcDNA3.0/PNP, an eukaryotic expression vector harboring E. coli PNP gene, was transfected into human hepatoma HepG2 cells by liposome-mediated method. A HepG2 cell line with stable PNP gene expression, HepG2/PNP, was established with presence of G418 selection. The cell growth curves were determined with trypan blue staining. The sensitivity of HepG2/PNP to MeP-dR and bystander effects were assayed by MTT and FCM methods. The enzymatic activity of the product of PNP gene was determined by HPLC method. The cytotoxic effects of MeP-dR on HepG2/PNP cells were obvious (IC50 = 4.5 micromol/L) and all HepG2/PNP cells were killed 4 days after the treatment with 100 micromol/L MeP-dR. In mixed cultures containing increasing percentages of HepG2/PNP cells, total population killing was demonstrated when HepG2/PNP cells accounted for as few as 5% of all HepG2 cells 8 days after the treatment with 100 micromol MeP-dR. High-pressure liquid chromatography (HPLC) demonstrated that the PNP enzyme could convert MeP-dR into 6-MP. PNP/MeP-dR suicide gene system had an advantage over traditional suicide gene systems for hepatoma gene therapy. Our e results suggest that high-level bystander effects of this system result in significant anti-tumor responses to hepatoma gene therapy, especially in vivo.

RNA interference targeting leptin gene effect on hepatic stellate cells.

To construct the specific siRNA expression vectors and investigate their effect on leptin and collagen I in HSC, which provide a new approach to the prevent and treat hepatic fibrosis. The five siRNAs against leptin gene were transcript synthesized intracellularly by expression templates of plasmid vector psiRNA-hH1neo. The recombinant leptin siRNA plasmid vectors could express in eukaryocyte, and then to evaluate them by using enzyme cutting and sequencing. The recombinant plasmids were transfected into HSCs using Lipofectamine methods respectively. The cells were selected after growing in DMEM containing 300 microg/mL G418 for about 4 weeks. Gene expression of leptin and collagen I were showed by Western blot analysis and reverse transcription polymerase chain reaction (RT-PCR). Identification by enzyme cutting and sequencing showed that the leptin siRNA expression vectors were constructed successfully, and leptin siRNA could inhibit the leptin and collagen I gene expression effectively. It was concluded that RNA interference-mediated silencing of leptin gene diminished leptin and collagen I gene expression in HSCs. Furthermore, attenuated the extracellular matrix over-deposition at the same time. Leptin gene is ideal targets of gene therapy for liver fibrosis.