RESUMO
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.
Assuntos
Antivirais , Carcinoma Hepatocelular , Técnicas de Imagem por Elasticidade , Hepatite C Crônica , Cirrose Hepática , Neoplasias Hepáticas , Resposta Viral Sustentada , Humanos , Técnicas de Imagem por Elasticidade/métodos , Masculino , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/virologia , Feminino , Pessoa de Meia-Idade , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico por imagem , Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/virologia , Seguimentos , Fatores de Tempo , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/virologia , Resultado do Tratamento , Adulto , Idoso , Valor Preditivo dos TestesAssuntos
Carcinoma Hepatocelular , Vírus da Hepatite B , Neoplasias Hepáticas , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Guadalupe/epidemiologia , Vírus da Hepatite B/isolamento & purificação , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologiaRESUMO
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.
Assuntos
Carcinoma Hepatocelular/genética , Hepatite B/genética , Neoplasias Hepáticas/genética , Transativadores/genética , Proteínas Virais Reguladoras e Acessórias/genética , Sequência de Aminoácidos/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Sequência Conservada/genética , Regulação Viral da Expressão Gênica/genética , Genoma Viral/genética , Células Hep G2 , Hepatite B/patologia , Hepatite B/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/patogenicidade , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Fosforilação/genética , FilogeniaRESUMO
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.
Assuntos
Carcinoma Hepatocelular/genética , Hepatite C/patologia , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Técnicas de Cultura de Células , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Células Hep G2 , Hepacivirus , Hepatite C/complicações , Hepatite C/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologiaRESUMO
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.
Assuntos
Antivirais/uso terapêutico , Hepacivirus/isolamento & purificação , Neoplasias Hepáticas/tratamento farmacológico , Fígado/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Biópsia , Humanos , Fígado/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/virologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/virologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Resposta Viral SustentadaRESUMO
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.
Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/virologia , Meios de Contraste , Feminino , Hepatite C/complicações , Humanos , Cirrose Hepática , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/virologia , Imageamento por Ressonância MagnéticaRESUMO
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.
Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Vírus da Hepatite B/isolamento & purificação , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia , Hepatite B/complicações , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
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.
Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Hepatite C Crônica/complicações , Antígenos de Histocompatibilidade Classe I/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Idoso , Brasil , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
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.
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.
Assuntos
Humanos , Feminino , Hepatite C/complicações , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Meios de Contraste , Cirrose HepáticaRESUMO
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.