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Hepatitis B [keywords]
- Effects of Dendritic Cells from Hepatitis B Virus Transgenic Mice-Stimulated Autologous Lymphocytes on Hepatitis B Virus Replication: A Study on the Impact of Specific Sensitized Effector Cells on In Vitro Virus Replication. [JOURNAL ARTICLE]
- Viral Immunol 2014 Oct 24.
Abstract The objective of this study was to explore the effects of dendritic cells (DCs) from hepatitis B virus (HBV) transgenic mice-stimulated autologous lymphocytes on in vitro HBV replication. DCs from HBV transgenic mice were induced to maturity by lipopolysaccharide, followed by incubation with hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in vitro. Mature DCs and autologous lymphocytes were co-stimulated to form specific sensitized immune effector cells (IEC), which were then co-cultured with the human hepatoma cell line HepG2.2.15. Changes in morphology and activity of hepatocytes were then observed, as well as analysis of changes in liver enzyme, and HBV DNA and inflammatory cytokine levels in the culture supernatant. Intracellular HBV DNA and covalently closed circular DNA (cccDNA) concentration were measured by real-time polymerase chain reaction. Co-stimulation by mature DCs and IEC showed no impact on the morphology and liver enzyme expression level of HepG2.2.15 cells, but the supernatant HBV DNA and intracellular HBV DNA and cccDNA levels decreased significantly compared with those cells co-cultured with immature DCs. Secretion of inflammatory cytokines in the supernatant showed that when HBV DNA was highly expressed, the concentration of IFN-γ and IL-2 decreased, while IL-10 increased. Contrastingly, when HBV DNA had low expression, the concentration of IFN-γ and IL-2 increased and IL-10 decreased. Co-stimulation of HBV-related antigen-induced mature DCs and autologous lymphocytes showed inhibitory effects on ex vivo HBV replication, and cytokines were suggested to mediate this effect.
- Significance of detecting circulating hepatocellular carcinoma cells in peripheral blood of hepatocellular carcinoma patients by nested reverse transcription-polymerase chain reaction and its clinical value: a retrospective study. [JOURNAL ARTICLE]
- Tumori 2014 Sep-Oct; 100(5):536-540.
Aims and background. Circulating hepatocellular carcinoma cells may be detected by reverse transcription-polymerase chain reaction. We investigated the relationship between circulating hepatocellular carcinoma cells and hepatoma patient survival after different managements and survival periods. Methods and study design. Peripheral vein blood (5 ml) samples were obtained from 113 patients with hepatocellular carcinoma and from 33 control subjects (9 with liver cirrhosis after hepatitis B, 14 with chronic hepatitis B, 10 healthy individuals) between January 1, 2009, and December 31, 2013. To detect circulating hepatocellular carcinoma cells in peripheral blood, alpha-fetoprotein messenger RNA was amplified from total RNA extracted from whole blood by reverse transcription-polymerase chain reaction. Results. Alpha-fetoprotein messenger RNA was detected in 59 blood samples from the hepatocellular carcinoma patients (59/113, 52.2%). In contrast, there were no clinical control subjects whose samples showed detectable alpha-fetoprotein messenger RNA. The presence of alpha-fetoprotein messenger RNA in blood seemed to be correlated with the stage (by TNM classification) of hepatocellular carcinoma, serum alpha-fetoprotein value, and the presence of intrahepatic metastasis, portal vein thrombosis, tumor diameter and/or distant metastasis. In addition, alpha-fetoprotein messenger RNA was detected in the blood of 25 patients showing distant metastasis at extrahepatic organs (100%), in contrast to 32 of 88 cases without metastasis (36.4%). All the patients with hepatocellular carcinoma were followed. Seventeen patients with resection of a T 2 stage hepatocellular carcinoma had a survival of 3.2 years after surgical management, 38 cases with resection of a T3 stage hepatocellular carcinoma had a 1.3-year survival, and only 37 cases with T4 stage disease after different treatments except surgery survived for 0.6 years (P <0.01). Conclusions. The presence of alpha-fetoprotein messenger RNA in peripheral blood may be an indicator of circulating hepatocellular carcinoma cells, which might predict hematogenous spreading metastasis in patients with hepatocellular carcinoma and may be a poor prognostic factor for hepatocellular carcinoma patients.
- Drug use, sexual risk behaviour and sexually transmitted infections among swingers: a cross-sectional study in The Netherlands. [JOURNAL ARTICLE]
- Sex Transm Infect 2014 Oct 23.
Recreational drug use has been found to be associated with high-risk sexual behaviour and with sexually transmitted infections (STI). This study is the first to assess the prevalence of drug use among swingers (heterosexuals who, as a couple, practise mate swapping or group sex, and/or visit sex clubs for couples), and its association with high-risk sexual behaviour and STI.We recruited individuals who self-identified as swingers and visited our STI clinic (from 2009 to 2012, South Limburg, The Netherlands). Participants (n=289; median age 45 years; 49% female) filled in a self-administered questionnaire on their sexual and drug use behaviour while swinging, over the preceding 6 months. We assessed associations between sexual behaviour, drug use and STI diagnoses (Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG), syphilis, HIV and hepatitis B) using logistic regression analyses.Overall, the prevalence of CT and/or NG was 13%. No other STIs were observed. Seventy-nine percent of swingers reported recreational drug use (including alcohol and use of erectile dysfunction drugs); 46% of them reported multiple drug use. Recreational drug use excluding alcohol and erectile dysfunction drugs (reported by 48%) was associated with high-risk behaviours in men and women. Drug use was independently associated with STI in female swingers, especially those who practice group sex.High rates of multiple drug use, as well as risky sexual behaviour and STIs among swingers, warrant paying more attention to this key population in prevention and care, as they are a risk group that is generally under-recognised and underserved in care.
- MicroRNA-26b Inhibits Hepatitis B Virus Transcription and Replication by Targeting the Host Factor CHORDC1. [JOURNAL ARTICLE]
- J Biol Chem 2014 Oct 23.
Hepatitis B virus (HBV) causes acute and chronic hepatitis in humans, and HBV infection is a major threat to global health. HBV replication is regulated by a series of host factors including microRNAs (miRNAs), which are highly conserved small noncoding RNAs that participate in a variety of physiological and pathological processes. Here we report that a chemically synthesized mimic of miR-26b inhibited HBV antigen expression, transcription, and replication, whereas antisense knockdown of endogenous miR-26b enhanced HBV replication in HepG2 cells. Overexpression and knockdown experiments showed that miR-26b significantly decreased HBV enhancer/promoter activities. We identified cysteine and histidine-rich domain containing 1 (CHORDC1) as a novel host factor target of miR-26b. CHORDC1 protein but not mRNA was markedly decreased by miR-26b overexpression via base-pairing with complementary sequences in the 3'UTR of its mRNA. Overexpression and knockdown studies showed that CHORDC1 increased viral antigen expression, transcription, and replication by elevating HBV enhancer/promoter activities. Conversely, HBV infection suppressed miR-26b expression and increased CHORDC1 protein level in human liver cells. Another mature miRNA of the hsa-miR-26 family, miR-26a, had similar function as miR-26b in targeting CHORDC1 and affecting HBV production. These results suggest that suppression of miR-26b expression upregulates its target gene CHORDC1, which increases HBV enhancer/promoter activities and promotes viral transcription, gene expression, and replication. Our study could provide new insights into miRNA expression and the persistence of HBV infection.
- Full-genome sequence of a hepatitis B virus genotype f1b clone from a chronically infected chilean patient. [Journal Article]
- Genome Announc 2014; 2(5)
The hepatitis B virus (HBV) is a DNA virus belonging to the Hepadnaviridae family. Viral isolates have been classified into 10 genotypes, named from A to J, and several subtypes. We report the full-genome sequence from a single molecular clone of HBV genotype F1b, amplified from a chronically infected Chilean patient.
- Cohort Profile: The Bissau HIV Cohort-a cohort of HIV-1, HIV-2 and co-infected patients. [JOURNAL ARTICLE]
- Int J Epidemiol 2014 Oct 22.
The West African country Guinea-Bissau is home to the world's highest prevalence of HIV-2, and its HIV-1 prevalence is rising. Other chronic viral infections like human T-lymphotropic virus type 1 (HTLV-1) and hepatitis B virus are common as well. The Bissau HIV Cohort was started in 2007 to gain new insights into the overall effect of introducing antiretroviral treatment in a treatment-naïve population with concomitant infection with three retroviruses (HIV-1, HIV-2 and HTLV-1) and tuberculosis. The cohort includes patients from the HIV clinic at Hospital Nacional Simão Mendes, the main hospital in Bissau, the capital of the country. From July 2007 to June 2013, 3762 HIV-infected patients (69% HIV-1, 18% HIV-2, 11% HIV-1/2 and 2% HIV type unknown) were included in the world's largest single-centre HIV-2 cohort. Demographic and clinical data are collected at baseline and every 6 months, together with CD4 cell count and routine biochemistry analyses. Plasma and cells are stored in a biobank in Denmark. The Bissau HIV Cohort is administered by the Bissau HIV Cohort study group. Potential collaborators are invited to contact the chair of the cohort study group, Christian Wejse, e-mail: [email@example.com].
- The best method of hepatitis B vaccination in hemodialysis patients? [Journal Article]
- J Renal Inj Prev 2013; 2(4):125-6.
- Sudden deterioration of renal function in a patient with nephrotic syndrome and a very high hepatitis B viral DNA load. [Journal Article]
- J Renal Inj Prev 2012; 1(1):39-41.
- Entecavir has high efficacy and safety in white patients with chronic hepatitis B and comorbidities. [JOURNAL ARTICLE]
- Eur J Gastroenterol Hepatol 2014 Oct 21.
The aim of this study was to evaluate the efficacy and safety of entecavir monotherapy in nucleos(t)ide-naive chronic hepatitis B patients and to analyse the influence of the comorbidity burden on therapy outcome.We retrospectively analysed data from 237 nucleos(t)ide-naive chronic hepatitis B white patients treated with entecavir (0.5 mg/day) at 23 Spanish centres. For the efficacy and safety analyses, patients were grouped according to their baseline comorbidities.The mean age of the cohort was 43 years (range: 19-82 years); 73% were male, 83% were white, and 33% were hepatitis B e antigen (HBeAg) positive. At baseline, the median hepatitis B virus DNA level was 6.20 log10 IU/ml. Of the patients, 18% had cirrhosis, 9.7% had diabetes, 16.3% had hypertension, and 15.7% had obesity; 13.4% of patients had more than one comorbid condition. Virological and biochemical responses at month 36 were obtained independently of the patients' baseline comorbid condition. Of 10 HBeAg-positive patients who discontinued treatment after HBeAg seroconversion, those who had not also cleared HBsAg (six) experienced virological recurrence in a median 5.6 months. There were no treatment discontinuations due to adverse events. Three patients were diagnosed with hepatocellular carcinoma at months 12, 30 and 54, and six experienced hepatic decompensation during follow-up. The median serum creatinine levels did not increase after 36 months of treatment, even in patients with comorbidities.Entecavir is safe, well tolerated, and highly effective, even in patients with comorbid condition(s). Discontinuation of treatment in patients who have not been cleared of HBsAg may lead to virological recurrence.
- Up-Regulated MicroRNA499a by Hepatitis B Virus Induced Hepatocellular Carcinogenesis via Targeting MAPK6. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e111410.
Emerging evidence showed miR499a could not only function as an oncogene but also as a tumor suppressor in various types of cancer, such as melanoma. However, whether miR499a was involved in hepatocarcinogenesis remains unknown. We previously reported that miR499a was up-regulated in HBV-mediated hepatocellular carcinoma (HCC). In this study, we found that HBV could induce the expression of miR499a by promoting its promoter activity. In addition, we reported that miR499a increased cell proliferation and cell migration of HCC cells. MAPK6 was further identified as a target of miR499a, which could also be down-regulated by HBV. Moreover, we demonstrated that MAPK6 could rescue the cell growth induced by miR499a and HBV. These findings indicated that miR499a might play an oncogene role by targeting MAPK6 in the development and progression of HBV-related HCC.