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Hepatitis B [keywords]
- Wnt/beta-catenin signaling pathway in hepatocellular carcinomas cases from Colombia. [Journal Article]
- Ann Hepatol 2015 Jan-Feb; 14(1):64-74.
Background and aim. Hepatocellular carcinoma (HCC) is the most common primary liver cancer diagnosed worldwide. Deregulation of Wnt/beta-catenin pathway has been associated with the development of HCC in a substantial number of cases in Europe and far less in Asia. Nothing is known about this pathway in HCC cases from South America. This study aimed to investigate the frequency of mutations in beta-catenin gene (CTNNB1) and the subcellular localization of beta-catenin in HCC cases from Colombia. Material and methods. We determine by direct sequencing the frequency of mutations in exon 3 of CTNNB1 gene and by immunohistochemistry the subcellular localization of beta-catenin in 54 samples of HCC obtained from three pathology units in Bogota and Medellin cities.
Results.Only three HCC cases (5.6%) were found mutated at residues (G34E, S45P, P44S, T41I) important for phosphorylation and ubiquitination of beta-catenin protein. Strikingly, nuclear or cytoplasmic accumulation of beta-catenin, hallmark of Wnt pathway activation, was found in 42.6% HCC cases (23/54). Interestingly, beta-catenin accumulation was significantly more frequent in young patients and hepatitis B virus-related HCC.
Conclusions.Although, CTNNB1 exon 3 mutations are not frequent in HCC from Colombian patients, our findings indicate that Wnt/beta-catenin signaling is activated in 42.6% of HCC samples. Furthermore, Wnt signaling was demonstrated in HCC cases associated of HBV infection, one of the most important HCC risk factors in Colombia.
- Factors associated with recurrence and survival in liver transplant patients with HCC - a single center retrospective study. [Journal Article]
- Ann Hepatol 2015 Jan-Feb; 14(1):58-63.
Introduction.Hepatocellular carcinoma is the most common primary tumor of the liver and is diagnosed in more than a half million people worldwide each year. This study aims to assess factors associated with the recurrence and survival of patients with hepatocellular carcinoma and liver transplantation in a cohort of patients from Medellín, Colombia. Material and methods. This was a descriptive retrospective study of a consecutive series of liver transplant patients from the Pablo Tobon Uribe Hospital of Medellín from January 2004 to May 2013. Demographic, clinical, imaging, and pathology variables were analyzed.
Results.Three hundred thirty liver transplants were performed during the study period, 54 cases (16.4%) had one or more hepatocellular carcinomas in the explant, and 79.6% of these patients were men. Cirrhotic patients had different etiologies, but most of them were due to alcohol abuse (22.2%), followed by hepatitis B virus infection (20.4 %), and hepatitis C virus infection (18.5%). In the pathology specimen, 51.9% had only one focus of hepatocellular carcinoma, 22.2% had two foci and 12.9% had three tumors. Recurrence of hepatocellular carcinoma occurred in 7.4% patients with an average time of 81 months. During follow-up, 25.9% of the patients died in an average time of 67.9 months (CI95 59.1-80.1 months).
Conclusion.Recurrence and survival of patients with liver transplantation for hepatocellular carcinoma in this study had a similar behavior as that reported in the world literature. The factors associated with these outcomes were vascular invasion, poor tumor differentiation and satellitosis.
- Interferon-based therapy delays but metabolic comorbidity accelerates progression of chronic hepatitis C. [Journal Article]
- Ann Hepatol 2015 Jan-Feb; 14(1):36-45.
Background.We compared mortality and complications of chronic hepatitis C between treated and untreated Mexican patients after long-term follow-up. We used a time-to-event analysis and identified the prognostic factors. Material and methods. Seventy-four patients with chronic hepatitis C were studied. They were ≥ 18 years of age and had a molecular diagnosis of chronic hepatitis C and ≥ 6 months of follow-up. Patients with neoplasia or those infected with human immunodeficiency virus or hepatitis B Virus were excluded. Kaplan-Meier analysis, log-rank test, annualized incidence per 100 person-years, and stepwise discriminant analysis were used to analyse mortality and complications.
Results.The end-point of annualized incidence was lowest in sustained virological responders, intermediate in non-responders, and highest in untreated patients. The absence of treatment impacted adversely on cirrhosis development and the occurrence of portal hypertension and hepatic decompensation/hepatocellular carcinoma (logrank, p < 0.05). Diabetes impacted adversely on liver-related death/liver transplantation among untreated patients. Stepwise discriminant analysis showed that diabetes, high blood pressure, and no retreatment predicted cirrhosis development (eigenvalue ≥ 0.8; p < 0.05). A MELD score ≥ 18 and age ≥ 50 years predicted hepatic decompensation/hepatocellular carcinoma (eigenvalue < 0.8; p < 0.05). APRI ≥ 1.5 predicted mortality/liver transplantation and liver-related death/liver transplantation (eigenvalue < 0.8; p < 0.05).
Conclusions.This is the first long-term study of chronic hepatitis C among Mexican patients. Treated patients showed less progression of liver disease. Treated patients showed less progression of liver disease; and older patients, those with metabolic comorbidities, with MELD score ≥ 18 and APRI ≥ 1.5 exhibited adverse effects.
- European Code Against Cancer: what does the Spanish population know and think about its recommendations? [JOURNAL ARTICLE]
- Eur J Cancer Prev 2014 Dec 22.
The aim of this study was to evaluate the Spanish population's knowledge of and beliefs regarding the European Code Against Cancer (ECAC) recommendations. This was a cross-sectional, observational, multicentric study that used self-administered surveys. Ten individuals, between the ages of 15 and 69 years old, were enrolled by each participating primary care professional in their respective surgery consultations. This study used 2058 individuals who were recruited by 205 professionals from 106 health centres. Their average age was 41.5 years (52.2% women). The majority believe that smoking [94.1%; 95% confidence interval (CI): 93.1-95.2], sun exposure (91%; 95% CI: 89.7-92.3) and alcoholism (72.1%; 95% CI: 70.1-74.1) are factors related to cancer. The least relevant are infection by the hepatitis B virus (25.7%; 95% CI: 23.8-27.7) and having multiple sexual partners (25%; 95% CI: 23.1-26.9). In all, 86.7% (95% CI: 85.2-88.2) had never heard about the ECAC. Patients adequately identify the carcinogenic effect of tobacco, alcohol or sun exposure. Moreover, they inadequately identify having hepatitis B and multiple sexual partners as being related to cancer. A large majority of individuals have not heard of the ECAC, which raises the need to conduct outreach campaigns at an institutional level and/or through scientific associations and activities promoting health education among primary care professionals.
- Genomic predictors for recurrence patterns of hepatocellular carcinoma: model derivation and validation. [Journal Article]
- PLoS Med 2014 Dec; 11(12):e1001770.
Typically observed at 2 y after surgical resection, late recurrence is a major challenge in the management of hepatocellular carcinoma (HCC). We aimed to develop a genomic predictor that can identify patients at high risk for late recurrence and assess its clinical implications.Systematic analysis of gene expression data from human liver undergoing hepatic injury and regeneration revealed a 233-gene signature that was significantly associated with late recurrence of HCC. Using this signature, we developed a prognostic predictor that can identify patients at high risk of late recurrence, and tested and validated the robustness of the predictor in patients (n = 396) who underwent surgery between 1990 and 2011 at four centers (210 recurrences during a median of 3.7 y of follow-up). In multivariate analysis, this signature was the strongest risk factor for late recurrence (hazard ratio, 2.2; 95% confidence interval, 1.3-3.7; p = 0.002). In contrast, our previously developed tumor-derived 65-gene risk score was significantly associated with early recurrence (p = 0.005) but not with late recurrence (p = 0.7). In multivariate analysis, the 65-gene risk score was the strongest risk factor for very early recurrence (<1 y after surgical resection) (hazard ratio, 1.7; 95% confidence interval, 1.1-2.6; p = 0.01). The potential significance of STAT3 activation in late recurrence was predicted by gene network analysis and validated later. We also developed and validated 4- and 20-gene predictors from the full 233-gene predictor. The main limitation of the study is that most of the patients in our study were hepatitis B virus-positive. Further investigations are needed to test our prediction models in patients with different etiologies of HCC, such as hepatitis C virus.Two independently developed predictors reflected well the differences between early and late recurrence of HCC at the molecular level and provided new biomarkers for risk stratification. Please see later in the article for the Editors' Summary.
- Outcomes in hepatitis B surface antigen-positive renal transplant recipients. [Journal Article]
- Nephrology (Carlton) 2015 Jan; 20(1):40-3.
- In Vitro Immunomodulatory Activity of Interferon Alpha on Toll-Like Receptor 9 Signaling Pathway in Chronic Hepatitis B. [JOURNAL ARTICLE]
- J Interferon Cytokine Res 2014 Dec 23.
Interferon alpha (IFN-α) is registered for chronic hepatitis B (CHB) treatment. However, the antiviral mechanism of IFN-α and the biological function of many IFN-α responsive genes have not been fully elucidated. We investigated to determine the regulative effect of IFN-α on toll-like receptor (TLR) 9 signaling in peripheral blood mononuclear cells (PBMCs) from CHB patients in vitro. We examined the changes of expression and function of TLR9 signaling pathway in the PBMCs with different treatment methods and investigated the synergism of IFN-α and TLR9 ligand on antiviral cytokine secretions in vitro. The data showed that, for the TLR9 signaling pathway, IFN-α not only augmented the expressions of TLR9 signal transduction molecules but also activated the TLR9 signal function. This study has clearly demonstrated that the TLR9 ligand could stimulate PBMCs that have been pretreated with IFN-α. Furthermore, the quantity of antiviral cytokines secreted by the pretreated PBMCs was greater than those without pretreatment. The interaction between IFN-α and TLR9 ligand appears to be synergistic. Data revealed IFN-α could influence TLR9 signaling transduction and synergistically improve the immune efficacy of TLR9 ligand against CHB. The present study suggests a potential novel mechanism for the antiviral activity against hepatitis B virus and a new individualized antiviral strategy.
- Glioblastoma multiforme and hepatitis B: do the right thing(s). [Journal Article]
- Eur Rev Med Pharmacol Sci 2014 Dec; 18(23):3629-31.
Hepatitis B virus (HBV) reactivation is a well-known complication related to immunosuppression. Clinical manifestations of HBV relapse range from self-limiting anicteric hepatitis to acute hepatic failure. Temozolomide (TMZ) is an alkylating agent used for the treatment of glioblastoma multiforme (GBM), the most common and deadliest of malignant primary brain tumors.We report the case of a 52-year old man with a history of serological positivity for hepatitis B surface antigen (HBsAg) who was diagnosed with GBM. Since the tumor was multifocal and thus inoperable, the patient received radiotherapy with concomitant TMZ and corticosteroids, without a prophylactic therapy for HBV infection. Acute hepatitis developed five months later the beginning of anticancer therapy. We started antiviral entecavir, which led to a decrease of HBV-DNA titer to 20 IU/ml, allowing the prosecution of the TMZ therapy.Up to now only four other cases of HBV relapse during TMZ therapy have been reported in literature. These cases underline the need of HBV screening and antiviral prophylaxis before starting TMZ administration.
- Therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis B: preclinical studies in the woodchuck. [JOURNAL ARTICLE]
- Med Microbiol Immunol 2014 Dec 23.
Infection with hepatitis B virus (HBV) may lead to subclinical, acute or chronic hepatitis. In the prevaccination era, HBV infections were endemic due to frequent mother to child transmission in large regions of the world. However, there are still estimated 240 million chronic HBV carriers today and ca. 620,000 patients die per year due to HBV-related liver diseases. Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to satisfactory results. Induction of HBV-specific T cells by therapeutic vaccination or immunomodulation may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients with or without therapeutic reduction of viral load did not result in effective immune control of HBV infection, suggesting that combination of antiviral treatment with new formulations of therapeutic vaccines is needed. The woodchuck (Marmota monax) and its HBV-like woodchuck hepatitis virus are a useful preclinical animal model for developing new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments using nucleos(t)ide analogues, with prime-boost vaccination using DNA vaccines, new hepadnaviral antigens or recombinant adenoviral vectors were tested in the woodchuck model. In this review, we summarize these encouraging results obtained with these therapeutic vaccines. In addition, we present potential innovations in immunostimulatory strategies by blocking the interaction of the inhibitory programmed death receptor 1 with its ligand in this animal model.
- The role of Moloney leukemia virus 10 in hepatitis B virus expression in hepatoma cells. [JOURNAL ARTICLE]
- Virus Res 2014 Dec 19.
Recent studies have shown that the Moloney leukemia virus 10 (Mov10), a putative RNA helicase, has very broad and potent antiretroviral activities. Hepatitis B virus (HBV) has a reverse transcription process, but the potential role of Mov10 in HBV replication remains unknown. In this study, Mov10 was demonstrated to affect HBV expression in HepG2 and HepG2.2.15 cell lines. The data showed that the over-expression of exogenous Mov10 resulted in an increase of the HBsAg and HBeAg levels in the culture supernatant and HBV mRNA level in transfected cells at a low dose and resulted in a decrease at a high dose, but HBV DNA in culture supernatant was not affected. The knockdown of endogenous Mov10 expression through siRNA treatment could suppress levels of HBsAg, HBeAg and HBV mRNA, but had no effect on HBV DNA. Above results indicate that an appropriate level of exogenous Mov10 is responsible for HBV replication, that any perturbation in the level of Mov10 could affect HBV replication, while the endogenous Mov10 could promote HBV replication in vitro. The precise mechanisms that underlie the action of Mov10 on HBV still need further investigation.