RESUMEN

INTRODUCTION AND OBJECTIVES: Blood glucose fluctuates severely in the diabetes (DM) and tumor microenvironment. Our previous works have found Hepatitis B virus X protein (HBx) differentially regulated metastasis and apoptosis of hepatoma cells depending on glucose concentration. We here aimed to explore whether HBx played dual roles in the angiogenesis of hepatocellular carcinoma varying on different glucose levels. MATERIALS AND METHODS: We collected conditioned medium from HBx-overexpressing cells cultured with two solubilities of glucose, and then applied to EA.hy926 cells. Alternatively, a co-culture cell system was established with hepatoma cells and EA.hy926 cells. We analyzed the angiogenesis of EA.hy926 cells with CCK8, wound-healing, transwell-migartion and tube formation experiment. ELISA was conducted to detect the secretion levels of angiogenesis-related factors. siRNAs were used to detect the P53-VEGF axis. RESULTS: HBx expressed in hepatoma cells suppressed VEGF secretion, and subsequently inhibited the proliferation, migration and tube formation of EA.hy926 cells in a high glucose condition, while attenuating these in the lower glucose condition. Furthermore, the p53-VEGF axis was required for the dual role of HBx in angiogenesis. Additionally, HBx mainly regulated the nuclear p53. CONCLUSIONS: These data suggest that the dual roles of HBx confer hepatoma cells to remain in a glucose-rich environment and escape from the glucose-low milieu through tumor vessels, promoting liver tumor progression overall. We exclusively revealed the dual role of HBx on the angiogenesis of liver tumors, which may shed new light on the mechanism and management strategy of HBV- and DM-related hepatocellular carcinoma.

Asunto(s)

Carcinoma Hepatocelular , Movimiento Celular , Proliferación Celular , Glucosa , Neoplasias Hepáticas , Neovascularización Patológica , Transducción de Señal , Transactivadores , Proteína p53 Supresora de Tumor , Factor A de Crecimiento Endotelial Vascular , Proteínas Reguladoras y Accesorias Virales , Humanos , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Transactivadores/metabolismo , Transactivadores/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Glucosa/metabolismo , Línea Celular Tumoral , Células Hep G2 , Técnicas de Cocultivo , Virus de la Hepatitis B/genética , Microambiente Tumoral , Angiogénesis

RESUMEN

INTRODUCTION AND OBJECTIVES: The increasing incidence of hepatocellular carcinoma (HCC) in China is an urgent issue, necessitating early diagnosis and treatment. This study aimed to develop personalized predictive models by combining machine learning (ML) technology with a demographic, medical history, and noninvasive biomarker data. These models can enhance the decision-making capabilities of physicians for HCC in hepatitis B virus (HBV)-related cirrhosis patients with low serum alpha-fetoprotein (AFP) levels. PATIENTS AND METHODS: A total of 6,980 patients treated between January 2012 and December 2018 were included. Pre-treatment laboratory tests and clinical data were obtained. The significant risk factors for HCC were identified, and the relative risk of each variable affecting its diagnosis was calculated using ML and univariate regression analysis. The data set was then randomly partitioned into validation (20 %) and training sets (80 %) to develop the ML models. RESULTS: Twelve independent risk factors for HCC were identified using Gaussian naïve Bayes, extreme gradient boosting (XGBoost), random forest, and least absolute shrinkage and selection operation regression models. Multivariate analysis revealed that male sex, age >60 years, alkaline phosphate >150 U/L, AFP >25 ng/mL, carcinoembryonic antigen >5 ng/mL, and fibrinogen >4 g/L were the risk factors, whereas hypertension, calcium <2.25 mmol/L, potassium ≤3.5 mmol/L, direct bilirubin >6.8 µmol/L, hemoglobin <110 g/L, and glutamic-pyruvic transaminase >40 U/L were the protective factors in HCC patients. Based on these factors, a nomogram was constructed, showing an area under the curve (AUC) of 0.746 (sensitivity = 0.710, specificity=0.646), which was significantly higher than AFP AUC of 0.658 (sensitivity = 0.462, specificity=0.766). Compared with several ML algorithms, the XGBoost model had an AUC of 0.832 (sensitivity = 0.745, specificity=0.766) and an independent validation AUC of 0.829 (sensitivity = 0.766, specificity = 0.737), making it the top-performing model in both sets. The external validation results have proven the accuracy of the XGBoost model. CONCLUSIONS: The proposed XGBoost demonstrated a promising ability for individualized prediction of HCC in HBV-related cirrhosis patients with low-level AFP.

Asunto(s)

Carcinoma Hepatocelular , Cirrosis Hepática , Neoplasias Hepáticas , Aprendizaje Automático , alfa-Fetoproteínas , Humanos , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/diagnóstico , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Cirrosis Hepática/sangre , Cirrosis Hepática/virología , Cirrosis Hepática/diagnóstico , Medición de Riesgo , Factores de Riesgo , China/epidemiología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/sangre , Valor Predictivo de las Pruebas , Adulto , Nomogramas , Biomarcadores de Tumor/sangre , Hepatitis B/complicaciones , Hepatitis B/sangre , Hepatitis B/diagnóstico , Anciano , Estudios Retrospectivos

RESUMEN

This study aims to characterize the molecular profile of the hepatitis B virus (HBV) among socially vulnerable immigrants residing in Brazil to investigate the introduction of uncommon HBV strains into the country. Serum samples from 102 immigrants with positive serology for the HBV core antibody (anti-HBc) were tested for the presence of HBV DNA by PCR assays. Among these, 24 were also positive for the HBV surface antigen (HBsAg). The full or partial genome was sequenced to determine genotype by phylogenetic analysis. Participants were from Haiti (79.4%), Guinea-Bissau (11.8%), Venezuela (7.8%), and Colombia (1%). Of the 21 HBV DNA-positive samples, subgenotypes A1 (52.4%), A5 (28.6%), E (9.5%), F2 (4.8%), and F3 (4.8%) were identified. Among the 78 HBsAg-negative participants, four were positive for HBV DNA, resulting in an occult HBV infection rate of 5.1%. Phylogenetic analysis suggested that most strains were likely introduced to Brazil by migration. Importantly, 80% of A5 sequences had the A1762T/G1764A double mutation, linked to an increased risk of hepatocellular carcinoma development. In conclusion, this study is the first report of HBV subgenotype A5 in Brazil, shedding new light on the diversity of HBV strains circulating in the country. Understanding the genetic diversity of HBV in immigrant communities can lead to better prevention and control strategies, benefiting both immigrants and wider society.

Asunto(s)

Carcinoma Hepatocelular , Emigrantes e Inmigrantes , Genotipo , Virus de la Hepatitis B , Hepatitis B , Neoplasias Hepáticas , Mutación , Filogenia , Humanos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Brasil/epidemiología , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/epidemiología , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/epidemiología , Femenino , Masculino , Adulto , Hepatitis B/virología , Hepatitis B/epidemiología , Hepatitis B/genética , Persona de Mediana Edad , ADN Viral/genética , Antígenos de Superficie de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/sangre , África/etnología , África/epidemiología , América Latina/etnología , América Latina/epidemiología

RESUMEN

OBJECTIVES: The primary objective was to evaluate Liver-Related Events (LREs), including hepatic decompensation (ascites, hemorrhagic varices and encephalopathy) and Hepatocellular Carcinoma (HCC), as well as changes in liver stiffness during the follow-up period among patients who achieved a Sustained Virological Response (SVR) after treatment for chronic Hepatitis C Virus (HCV) infection. METHODS: A total of 218 patients with HCV were treated, and those who achieved an SVR were followed up for 3-years. Transient Elastography (TE) using FibroScan® was performed at various time points: before treatment, at the end of treatment, at 6-months post-treatment, at 1-year post-treatment, at 2-years post-treatment, and at 3-years post-treatment. RESULTS: At 6-months post-treatment, a Liver Stiffness Measurement (LSM) cutoff of > 19 KPa was identified, leading to a 14.5-fold increase in the hazard of negative outcomes, including decompensation and/or HCC. The analysis of relative changes in liver stiffness between pre-treatment and 6-months posttreatment revealed that a reduction in LSM of -10 % was associated with a -12 % decrease in the hazard of decompensation and/or HCC, with this trend continuing as the LSM reduction reached -40 %, resulting in a -41 % hazard of decompensation and/or HCC. Conversely, an increase in the relative change during this period, such as an LSM increase of +10 %, led to a + 14 % increase in the hazard of decompensation. In cases where this relative change in LSM was +50 %, the hazard of decompensation increased to +92. CONCLUSION: Transient elastography using FibroScan® can be a good tool for monitoring HCV patients with SVR after treatment to predict LREs in the long term.

Asunto(s)

Antivirales , Carcinoma Hepatocelular , Diagnóstico por Imagen de Elasticidad , Hepatitis C Crónica , Cirrosis Hepática , Neoplasias Hepáticas , Respuesta Virológica Sostenida , Humanos , Diagnóstico por Imagen de Elasticidad/métodos , Masculino , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/virología , Femenino , Persona de Mediana Edad , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico por imagen , Antivirales/uso terapéutico , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/virología , Estudios de Seguimiento , Factores de Tiempo , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/virología , Resultado del Tratamiento , Adulto , Anciano , Valor Predictivo de las Pruebas

Asunto(s)

Carcinoma Hepatocelular , Virus de la Hepatitis B , Neoplasias Hepáticas , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/virología , Guadalupe/epidemiología , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/virología

RESUMEN

Hepatitis B virus (HBV) is a circular, and partially double-stranded DNA virus. Upon infection, the viral genome is translocated into the cell nucleus, generating the covalently closed circular DNA (cccDNA) intermediate, and forming a mini chromosome. HBV HBx is a small protein displaying multiple roles in HBV-infected cells, and in different subcellular locations. In the nucleus, the HBx protein is required to initiate and maintain viral transcription from the viral mini chromosome. In contrast, HBx also functions in the cytoplasm, where it is able to alter multiple cellular functions such as mitochondria metabolism, apoptosis and signal transduction pathways. It has been reported that in cultured cells, at low expression levels, the HBx protein is localized in the nucleus, whereas at high expression levels, it accumulates in the cytoplasm. This dynamic subcellular distribution of HBx might be essential to exert its multiple roles during viral infection. However, the mechanism that regulates different subcellular localizations of the HBx protein is unknown. We have previously taken a bioinformatics approach to investigate whether HBx might be regulated via post-translational modification, and we have proposed that the multiple nucleocytoplasmic functions of HBx might be regulated by an evolutionarily conserved mechanism via phosphorylation. In the current study, phylogenetically conserved amino acids of HBx with a high potential of phosphorylation were targeted for site-directed mutagenesis. Two conserved serine (Ser25 and Ser41), and one conserved threonine (Thr81) amino acids were replaced by either alanine or aspartic acid residues to simulate an unphosphorylated or phosphorylated state, respectively. Human hepatoma cells were transfected with increasing amounts of the HBx DNA constructs, and the cells were analyzed by fluorescence microscopy. Together, our results show that the nucleocytoplasmic distribution of the HBx protein could be regulated by phosphorylation since some of the modified proteins were mainly confined to distinct subcellular compartments. Remarkably, both HBx Ser41A, and HBx Thr81D proteins were predominantly localized within the nuclear compartment throughout the different expression levels of HBx mutants.

Asunto(s)

Carcinoma Hepatocelular/genética , Hepatitis B/genética , Neoplasias Hepáticas/genética , Transactivadores/genética , Proteínas Reguladoras y Accesorias Virales/genética , Secuencia de Aminoácidos/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Secuencia Conservada/genética , Regulación Viral de la Expresión Génica/genética , Genoma Viral/genética , Células Hep G2 , Hepatitis B/patología , Hepatitis B/virología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/patogenicidad , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Fosforilación/genética , Filogenia

RESUMEN

The association of Non-Hodgkin lymphomas and Hepatitis C virus is well documented and antiviral treatments facilitate a virological and hematological response in the majority of HCV related Non-Hodgkin lymphomas. The recent years, direct acting antivirals have made cure possible almost for every HCV patient. Some concerns were raised as regards the frequency and the pattern of recurrence in HCV patients with HCC, treated with these agents. We present a patient with DLBCL, in remission after appropriate treatment, HCV cirrhosis that was cured with the new antivirals and shortly after SVR, he experienced a lethal lymphoma recurrence.

Asunto(s)

Antivirales/uso terapéutico , Hepacivirus/aislamiento & purificación , Neoplasias Hepáticas/tratamiento farmacológico , Hígado/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Biopsia , Humanos , Hígado/virología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/virología , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/virología , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Respuesta Virológica Sostenida

RESUMEN

INTRODUCTION AND OBJECTIVES: Emerging evidence has demonstrated that long noncoding RNAs (lncRNAs) may be closely associated with Hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC). In this study, we investigated the expression and functions of a lncRNA, LINC01189, in HCV-associated HCC. PATIENTS OR MATERIALS AND METHODS: LINC01189 expression was measured in HCC tumors, HCV-infected HCC tumors and HCV-infected HCC cells. LINC01189 was overexpressed in HCV-infected HepG2 cells to measure its function on HCV-correlated cancer proliferation. In HCC cell lines of Huh7 and Hep3B, LINC01189 was upregulated to investigate its effects on cancer cell proliferation and 5-FU chemoresistance. The competing endogenous RNA (ceRNA) target of LINC01189, human microRNA-155-5p (hsa-miR-155-5p) was probed by dual-luciferase assay and qRT-PCR. Hsa-miR-155-5p was upregulated in LINC01189-overexpessed Huh7 and Hep3B cells to investigate their epigenetic correlation on HCC development regulation. RESULTS: LINC01189 is downregulated in HCV-infected HCC tumors and cell lines. LINC01189 overexpression inhibited HCC cancer cell proliferation and 5-FU chemoresistance. Hsa-miR-155-5p was confirmed to be a ceRNA target of LINC01189 in HCC. Upregulating hsa-miR-155-5p reversed the LINC01189-mediated inhibition on HCC proliferation and 5-FU chemoresistance. CONCLUSIONS: LINC01189 downregulation is associated with HCV infection in HCC, and it has tumor-suppressing effects on HCC development through hsa-miR-155-5p.

Asunto(s)

Carcinoma Hepatocelular/genética , Hepatitis C/patología , Neoplasias Hepáticas/genética , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Técnicas de Cultivo de Célula , Proliferación Celular , Resistencia a Antineoplásicos , Células Hep G2 , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/metabolismo , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología

RESUMEN

Hepatocellular carcinoma in patients with hepatitis C in the absence of cirrhosis is uncommon. We demonstrate the importance of morphofunctional magnetic resonance imaging (MRI) with a hepatospecific contrast agent by describing an asymptomatic female patient with HCV, who presented with a nodule detected on ultrasound. She underwent inconclusive computed tomography, presenting no signs of chronic liver disease. MRI with hepatospecific contrast providing functional information combined with the superior tissue contrast inherent to this method stands out for its greater accuracy with the possibility of not resorting to invasive diagnostic methods. With increasing experience and the dissemination of this new diagnostic modality in the medical field, its use and other potential benefits of morphofunctional MRI with hepatospecific contrast agents may be established, benefiting patients with challenging focal liver lesions.

Asunto(s)

Carcinoma Hepatocelular , Hepatitis C , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/virología , Medios de Contraste , Femenino , Hepatitis C/complicaciones , Humanos , Cirrosis Hepática , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/virología , Imagen por Resonancia Magnética

RESUMEN

In this study we investigated the impact of rs2596542A/G single nucleotide polymorphism (SNP) in the major histocompatibility complex class I chain-related sequence A (MICA) gene on HCV-induced hepatocellular carcinoma (HCC) susceptibility in a Brazilian population. In total, 252 HCV-infected patients (98 with HCV-induced HCC and 154 non-malignant HCV-induced liver cirrhosis) were enrolled and 98 healthy control subjects (negative anti-HCV). The MICA rs2596542 SNP genotypes were determined by real-time PCR assay. No differences in MICA genotype frequencies between HCV-induced cirrhosis patients and controls were observed. However, genotype frequencies of rs2596542A/G SNP were statistically different between HCV-induced HCC patients and controls (p = 0.048), and also between HCC and HCV-induced cirrhosis patients (p = 0.039). The highest frequency of the rs2596542AA genotype was observed in HCC patients (31.6%) when compared with HCV-induced cirrhosis patients (18.8%) and healthy controls (19.4%). Also, rs2596542AA genotype carriers have an increased risk for HCC when compared to HCV-induced cirrhosis status [odds ratio (OR) = 1.99; 95% confidence interval (CI) = 1.06-3.74, p = 0.020)] and healthy individuals (OR = 1.92, 95% CI = 1.00-3.70, p = 0.049). Taken together our study suggest that MICA rs2596542 SNP impacts HCV-induced HCC susceptibility suggesting that genetic variants in MICA are of clinical relevance to hepatocarcinogenesis by impacting host immune response in chronic HCV infection.

Asunto(s)

Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virología , Hepatitis C Crónica/complicaciones , Antígenos de Histocompatibilidad Clase I/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virología , Anciano , Brasil , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple

RESUMEN

PURPOSE: Hepatitis B core antibody (HBcAb) positivity is regarded as a sensitive marker for occult and prior hepatitis B virus (HBV) infection. However, the prognosis of patients with HBcAb-positive in non-B, non-C hepatocellular carcinoma (NBNC-HCC) remains unclear. The study aimed to compare the clinicopathological characteristics of patients with HBcAb-positive NBNC-HCC to those with overt HBV (hepatitis B surface antigen positive) HCC. METHODS: 306 HCC patients underwent hepatectomy were divided into two groups: an overt HBV-HCC group and HBcAb-positive NBNC-HCC group. Then patients were analyzed using propensity score matching (PSM) to reduce selection bias. Clinicopathological characteristics and survival outcomes were compared between the two groups. Univariate and multivariate analysis for risk factors were also evaluated. RESULTS: HBcAb-positive NBNC-HCC group showed comparable survival outcomes to the overt HBV-HCC group (3-year overall survival rates 66% vs 62%, 69% vs 53%; 3-year recurrence-free survival rates 49% vs 40%, 47% vs 37%; P > 0.05) before and after PSM. Patients with HBcAb-positive NBNC-HCC were older, had more complications, higher proportions of vascular invasion, and larger tumor sizes but lower proportions of cirrhosis, elevated alanine aminotransferase and prothrombin time. CONCLUSIONS: HBcAb-positive NBNC-HCC group had more advanced tumors, but their prognosis was relatively comparable to that of the other group. Therefore, we believe that screening is also necessary in HBcAb-positive patients for early detection of HCC, especially in the elderly.

Asunto(s)

Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , Virus de la Hepatitis B/aislamiento & purificación , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , Adulto , Anciano , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Femenino , Hepatectomía , Hepatitis B/complicaciones , Anticuerpos contra la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Puntaje de Propensión , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento

RESUMEN

SUMMARY Hepatocellular carcinoma in patients with hepatitis C in the absence of cirrhosis is uncommon. We demonstrate the importance of morphofunctional magnetic resonance imaging (MRI) with a hepatospecific contrast agent by describing an asymptomatic female patient with HCV, who presented with a nodule detected on ultrasound. She underwent inconclusive computed tomography, presenting no signs of chronic liver disease. MRI with hepatospecific contrast providing functional information combined with the superior tissue contrast inherent to this method stands out for its greater accuracy with the possibility of not resorting to invasive diagnostic methods. With increasing experience and the dissemination of this new diagnostic modality in the medical field, its use and other potential benefits of morphofunctional MRI with hepatospecific contrast agents may be established, benefiting patients with challenging focal liver lesions.

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RESUMO O surgimento de carcinoma hepatocelular em pacientes portadores de hepatite C na ausência de cirrose é de ocorrência pouco comum. Demonstramos a importância da ressonância magnética (RM) morfofuncional com contraste hepatoespecífico por meio da descrição de uma paciente do sexo feminino, assintomática, portadora do vírus da hepatite C (VHC), que se apresentou com nódulo detectado na ultrassonografia. Realizou tomografia computadorizada inconclusiva, sem sinais de hepatopatia crônica. A RM com contraste hepatoespecífico, ao proporcionar informações funcionais, somado ao superior contraste tecidual inerente ao método, destaca-se pela maior acurácia, com a possiblidade de não se recorrer a métodos diagnósticos invasivos. Com o acúmulo de experiência e divulgação dessa nova modalidade diagnóstica no meio médico, sua utilização e outros potenciais benefícios da RM morfofuncional com contraste hepatoespecífico podem vir a se estabelecer, beneficiando pacientes com lesões hepáticas focais desafiadoras.

Asunto(s)

Humanos , Femenino , Hepatitis C/complicaciones , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética , Medios de Contraste , Cirrosis Hepática

RESUMEN

Hepatocellular carcinoma (HCC) is a terminal, yet preventable, outcome of untreated infection with hepatitis B virus (HBV). HBV is endemic in many areas of Latin America and the Caribbean, including Haiti. Haitians have the highest incidence of liver cancer among Caribbean immigrants. Unfortunately, many of these patients are not screened, despite current guidelines. As HBV is treatable, screening of high-risk populations is crucial to early intervention and prevention of poor outcomes. We highlight the case of a young Haitian male immigrant who presented with unintentional weight loss and epigastric pain and found to have HCC associated with HBV. Despite chemotherapy, the patient died 15 months after diagnosis. Increased awareness of HBV among patients from high-incidence countries may result in early recognition of this disease and reduced morbidity and mortality from devastating complications.

Asunto(s)

Carcinoma Hepatocelular/virología , Hepatitis B Crónica/complicaciones , Neoplasias Hepáticas/virología , Adulto , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Diagnóstico Diferencial , Resultado Fatal , Haití , Hepatitis B Crónica/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Tamizaje Masivo , Oxaliplatino/uso terapéutico , Guías de Práctica Clínica como Asunto , Sorafenib/uso terapéutico , Tomografía Computarizada por Rayos X , Gemcitabina

RESUMEN

La dermatomiositis (DM) es una miopatía inflamatoria de causa desconocida caracterizada por inflamación muscular, debilidad músculo-esquelética proximal y manifestaciones cutáneas típicas. Se ha asociado a malignidades como un síndrome paraneoplásico. Reportamos el caso de un paciente varón de 33 años, diagnosticado de hepatitis B, VHB crónico inactivo, que presentó lesiones papulares, pruriginosas y descamativas en cara, manos, zona inguinal y pies. Al examen físico se evidenció pápulas de Gottron, signo del heliotropo, debilidad muscular simétrica proximal. Se realizó una biopsia de piel donde se encontraron hallazgos compatibles con DM. Tras una ecografía abdominal se encontró una tumoración hepática, cuyo resultado en biopsia fue de carcinoma hepatocelular moderadamente diferenciado. Posteriormente se le realiza segmentectomía con lo cual síntomas de DM disminuyen. Es un caso infrecuente, y de sumo interés por lo que se decide reportar.

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Dermatomyositis is an idiopathic inflammatory myopathie characterized by proximal skeletal muscle weakness, typical skin manifestations and muscle inflammation. This disease has been associated with malignancies as a paraneoplastic syndrome. We present a patient of thirty-three years diagnosed with hepatitis B, chronic inactive HBV who presents papular, pruritic and desquamative lesions on the face, hands, inguinal area and feet. At the physical examination is evidentiated Gottron's papules, heliotrope sign and proximal symmetric muscular weakness. Findings compatible with DM were found in a skin biopsy. An abdominal ultrasound revealed a liver tumor whereby a biopsy was performed and the result was a moderately differentiated hepatocellular carcinoma. Subsequently, a segmentectomy has been made and consequently the DM symptoms decreased. This case is of great interest and rare reason why we decided to reported it.

Asunto(s)

Adulto , Humanos , Masculino , Virus de la Hepatitis B , Carcinoma Hepatocelular/complicaciones , Hepatitis B Crónica/complicaciones , Dermatomiositis/etiología , Neoplasias Hepáticas/complicaciones , Perú , Piel/patología , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/diagnóstico por imagen , Dermatomiositis/patología , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/diagnóstico por imagen

RESUMEN

OBJECTIVE: The clinical significance of coexistence of HBsAg/anti-HBs in chronic hepatitis B (CHB) patients remains controversial. This study was aimed to assess the association of this serological pattern with hepatocellular carcinoma (HCC) in patients with CHB. METHODS: In this cross-section study, 206 CHB patients with coexistence of HBsAg/anti-HBs and 206 CHB patients with HBsAg alone were included to evaluate the risk of HCC development by logistic regression analysis. In addition, a retrospective cohort of 260 patients with CHB was recruited to estimate the cumulative incidence of HCC by Kaplan-Meier analysis. RESULTS: The serological pattern of coexistence of HBsAg/anti-HBs, with high levels of ("High") HBsAg/low levels of ("Low") anti-HBs, were considered as independent risk factors for HCC. In particular, patients with "High" HBsAg/"High" anti-HBs [odds ratio (OR), 4.295; 95% confidence interval (CI), 1.104-16.699; p = 0.035] and "Low" HBsAg/ "High" anti-HBs (OR, 3.207; 95%CI, 1.299-7.919; p = 0.012) exhibited significantly higher risk for HCC development. However, only "Low" HBsAg /"High" anti-HBs might increase risk of HCC in CHB patients with high HBV load (logrank p < 0.001) in our cohort study. CONCLUSION: The coexistence of "Low" HBsAg /"High" anti-HBs might increase the risk of HCC development in CHB patients with high HBV load, which reflected that the long-term interaction between immune response and virus might lead to the development of HCC. The identification of the patients with poor prognosis will help clinicians to refine the therapeutic decisions and individualize follow-up strategies.

Asunto(s)

Carcinoma Hepatocelular/virología , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Neoplasias Hepáticas/virología , Biomarcadores/sangre , Carcinoma Hepatocelular/sangre , Estudios Transversales , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/sangre , Masculino , Persona de Mediana Edad , Factores de Riesgo , Carga Viral

RESUMEN

INTRODUCTION: HPA polymorphism has been associated with HCV presence and fibrosis progression in chronic hepatitis C. However, it is unknown if there is an association between HPA-1 polymorphism and hepatocellular carcinoma (HCC). Therefore, this study aimed to evaluate HPA-1 polymorphism in the presence of HCC. METHODS: PCR-SSP was used to perform HPA genotyping on 76 HCV-infected patients. RESULTS: There was no association between patients with and without HCC. There was significant difference in HPA-1 genotypic frequency distribution between HCC and F1/F2 fibrosis degree. CONCLUSIONS: The HPA-1a/1b polymorphism appears to be more associated with liver damage progression than with HCC presence.

Asunto(s)

Antígenos de Plaqueta Humana/genética , Carcinoma Hepatocelular/virología , Hepatitis C Crónica/genética , Neoplasias Hepáticas/virología , Carcinoma Hepatocelular/genética , Progresión de la Enfermedad , Femenino , Marcadores Genéticos , Genotipo , Hepatitis C Crónica/virología , Humanos , Integrina beta3 , Neoplasias Hepáticas/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Pronóstico , Factores de Riesgo

Asunto(s)

Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Fusión Génica , Virus de la Hepatitis B/genética , Hepatitis B/genética , Neoplasias Hepáticas/genética , ARN Largo no Codificante/genética , Transactivadores/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/virología , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Hepatitis B/virología , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/virología , Vietnam/epidemiología , Proteínas Reguladoras y Accesorias Virales

RESUMEN

INTRODUCTION AND OBJECTIVES: The hepatitis B virus (HBV) surface antigen (HBsAg) variations suggested having some effects on infection outcome. Due to some controversial issues, the aim of this study was to compare the pattern of HBsAg variation between asymptomatic carriers and HCC/cirrhosis patients. MATERIALS AND METHODS: In this cross-sectional study, 19 HCC/cirrhotic and 26 asymptomatic patients were enrolled. After viral DNA extraction, HBs gene was amplified using an in-house nested-PCR. Then, PCR products were introduced into bi-directional Sanger sequencing. The retrieved sequences were compared with references, to investigate the variation of immunologic sites, major hydrophilic region (MHR) of HBsAg as well as reverse transcriptase (RT), and also to determine genotype/subtype. RESULTS: The analysis of MHR and epitopes on HBsAg showed dozens of substitution, which occurred more prevalently in I110, P120, Y134, G159, S193, Y206, S207, I208, L213 and P214 positions. However, Y134N/F/L (P=0.04) and P120T/S (P=0.009) were significantly detected in MHR and B-cell epitope of HCC/Cirrhotic group. A number of truncation-related mutations were higher in HCC/Cirrhotic group (P>0.001), albeit only C69* stop codon was statistically significant (P=0.003). In RT, some potentially resistant substitutions such as Q215S, V191I and V214A, were revealed. Phylogenetic analysis showed that all of isolates belonged to genotype D, and the major serotype was ayw1. CONCLUSION: The higher frequency of substitutions in MHR and immune epitopes at positions such as Y134 and P120 as well as stop codons such as C69* in HCC/cirrhotic group might candidate them as predictive factors for infection outcome.

Asunto(s)

Carcinoma Hepatocelular/virología , Portador Sano/virología , Farmacorresistencia Viral/genética , Productos del Gen pol/genética , Antígenos de Superficie de la Hepatitis B/genética , Hepatitis B Crónica/virología , Cirrosis Hepática/virología , Neoplasias Hepáticas/virología , Adulto , Infecciones Asintomáticas , ADN Viral/análisis , Epítopos de Linfocito B/genética , Epítopos de Linfocito T/genética , Femenino , Genotipo , Humanos , Evasión Inmune/genética , Masculino , Persona de Mediana Edad , Mutación , Adulto Joven

RESUMEN

Yellow fever virus (YFV) penetrates the skin through the bite of a vector mosquito and spreads to various organs, mainly the liver, where it causes lesions and induces necrosis and apoptosis. We evaluated the mRNA expression of various cytokines and the activation of caspases in HepG2 cells infected with YFV. We observed that interferon-α (IFN-α) expression decreased and IFN-ß, transforming growth factor (TGF)-ß IIIR, interleukin (IL)-6, and IL-8 expression increased in cells infected with genotype 1. In contrast, TNF-α expression increased in cells infected with genotype 2 but not with genotype 1. This provides insights into the role of cytokine regulation in yellow fever.

Asunto(s)

Caspasa 3/metabolismo , Caspasa 7/metabolismo , Citocinas/genética , Neoplasias Hepáticas/genética , Virus de la Fiebre Amarilla/fisiología , Caspasa 3/genética , Caspasa 7/genética , Línea Celular , Citocinas/metabolismo , Células Hep G2 , Interacciones Huésped-Patógeno , Humanos , Interferón gamma/genética , Interferón gamma/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/virología , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Virus de la Fiebre Amarilla/genética

RESUMEN

BACKGROUND & AIMS: Data from Europe and North America have been published regarding the risk of developing hepatocellular carcinoma (HCC) after treatment with direct antiviral agents (DAA). We proposed to evaluate cumulative incidence and associated risk factors for de novo HCC. METHODS: This was a prospective multicentre cohort study from Latin America including 1400 F1-F4-treated patients with DAAs (F3-F4 n = 1017). Cox proportional regression models (hazard ratios, HR and 95% CI) were used to evaluate independent associated variables with HCC. Further adjustment with competing risk regression and propensity score matching was carried out. RESULTS: During a median follow-up of 16 months (IQR 8.9-23.4 months) since DAAs initiation, overall cumulative incidence of HCC was 0.02 (CI 0.01; 0.03) at 12 months and 0.04 (CI 0.03; 0.06) at 24 months. Cumulative incidence of HCC in cirrhotic patients (n = 784) was 0.03 (CI 0.02-0.05) at 12 months and 0.06 (CI 0.04-0.08) at 24 months of follow-up. Failure to achieve SVR was independently associated with de novo HCC with a HR of 4.9 (CI 1.44; 17.32), after adjusting for diabetes mellitus, previous interferon non-responder, Child-Pugh and clinically significant portal hypertension. SVR presented an overall relative risk reduction for de novo HCC of 73% (CI 15%-91%), 17 patients were needed to be treated to prevent one case of de novo HCC in this cohort. CONCLUSIONS: Achieving SVR with DAA regimens was associated with a significant risk reduction in HCC. However, this risk remained high in patients with advanced fibrosis, thus demanding continuous surveillance strategies in this population.

Asunto(s)

Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/epidemiología , Anciano , Carcinoma Hepatocelular/virología , Femenino , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/complicaciones , Humanos , Incidencia , América Latina/epidemiología , Cirrosis Hepática/virología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Respuesta Virológica Sostenida