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1.
PLoS One ; 15(9): e0239462, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956413

RESUMO

This study was performed to determine the clinical significance of adenomatous polyposis coli (APC)-binding protein end-binding 1 (EB1) in hepatocellular carcinoma (HCC) and to characterize its biochemical role in comparison with previous reports. We performed immunohistochemical staining to detect EB1 expression in tissues from 235 patients with HCC and investigated its correlations with clinicopathological features and prognosis. We also investigated the roles of EB1 in cell proliferation, migration, and tumorigenesis in vitro and in vivo by siRNA- and CRISPR/Cas9-mediated modulation of EB1 expression in human HCC cell lines. The results showed that EB1 expression was significantly correlated with several important factors associated with tumor malignancy, including histological differentiation, portal vein invasion status, and intrahepatic metastasis. Patients with high EB1 expression in HCC tissue had poorer overall survival and higher recurrence rates than patients with low EB1 expression. EB1 knockdown and knockout in HCC cells reduced cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. Further, genes encoding Dlk1, HAMP, and SLCO1B3 that were differentially expressed in association with EB1 were identified using RNA microarray analysis. In conclusion, elevated expression of EB1 promotes tumor growth and metastasis of HCC. EB1 may serve as a new biomarker for HCC, and genes coexpressed with EB1 may represent potential targets for therapy.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteínas Associadas aos Microtúbulos/fisiologia , Proteínas de Neoplasias/fisiologia , Adulto , Idoso , Animais , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/genética , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Genes APC , Hepatite Viral Humana/complicações , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/genética , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Associadas aos Microtúbulos/antagonistas & inibidores , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Veia Porta/patologia , Prognóstico , Interferência de RNA , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , RNA Interferente Pequeno/genética , Proteínas Recombinantes/metabolismo , Recidiva , Taxa de Sobrevida , Análise Serial de Tecidos
2.
Ann Parasitol ; 66(2): 135-141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32530590

RESUMO

There is an increasing concern about the co-infection of visceral leishmaniosis (VL) with human immunodeficiency virus (HIV) and/or viral hepatitis B/C. The aim of this study was to determine the prevalence of HIV and viral hepatitis co-infections among VL patients in a hyperendemic area in Eastern Sudan and to assess antibody levels in co-infected patients. This is a retrospective study where the sera of confirmed VL cases and non-VL individuals were analysed. The sera were screened for co-infections using immunochromatographic tests and ELISA for anti-HIV 1+2 antibodies, hepatitis B surface antigen (HBsAg), and anti-hepatitis C virus (HCV). Anti-Leishmania donovani antibodies in the sera of VL alone were assessed and compared to the sera of co-infected patients. Of the 100 screened VL sera, 6 (6%), 0 (0%), and 1 (1%) were positive for HBsAg, anti-HCV, and anti-HIV, respectively. These values were 5 (5%), 0 (0%), and 1 (1%) in the control group. Of note, the HCV screening test (Biorex, UK) showed positive reactivity in 32 (32%) and 17 (17%) sera of VL and control groups, respectively. All reactive sera tested negative in HCV ELISA. Of the 93 VL sera, 75 (80.6%) had strong DAT titers (1:˃102400), 2 (2.1%) demonstrated the lowest DAT titers (1:≤800), and 5 (5.4%) had marginal DAT titers (1:1600). Interestingly, the VL/HIV co-infected serum had a negative antibody titer (1:1600). Of the 6 VL/HBV co-infected sera, 1 (16.7%) and 5 (83.3%) demonstrated moderate (1:12800­1:51600) and strong (1:≥102400) DAT titers, respectively. The strong DAT titers observed in the VL/HBV co-infected sera were comparable to the DAT titers of the VL sera. The VL co-infection with HIV and hepatitis B/C is low in endemic areas in Eastern Sudan but may create a diagnostic difficulty. VL/HIV co-infected patients can have low Leishmania antibodies, thus alternative methodologies (e.g., antigen tests) may help the diagnosis.


Assuntos
Infecções por HIV , Hepatite Viral Humana , Leishmaniose Visceral , Anticorpos/sangue , Infecções por HIV/sangue , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hepatite Viral Humana/sangue , Hepatite Viral Humana/complicações , Hepatite Viral Humana/epidemiologia , Humanos , Leishmaniose Visceral/complicações , Leishmaniose Visceral/epidemiologia , Prevalência , Estudos Retrospectivos , Estudos Soroepidemiológicos , Sudão/epidemiologia
3.
Gastroenterol Clin North Am ; 49(2): 179-189, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32389357

RESUMO

Viral hepatitis (A, B, C, D, and E) is the leading cause of inflammation of liver tissue (hepatitis). The disease burden associated with hepatitis A and E occurs shortly after infection; it is more severe among adults. With hepatitis A and E, the number of incident cases (new acute infections) is important from a public health perspective. Long-term hepatitis has been shown to cause cirrhosis and hepatocellular carcinoma in patients. The disease burden associated with hepatitis B, C, and D appears 10 to 20 years after infection. Thus, the prevalence of these infections is important from a public health perspective.


Assuntos
Saúde Global , Hepatite Viral Humana/epidemiologia , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Feminino , Hepatite Viral Humana/complicações , Hepatite Viral Humana/mortalidade , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino , Prevalência , Saúde Pública , Fatores de Tempo
4.
Obstet Gynecol ; 135(2): 396-400, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31923059

RESUMO

BACKGROUND: Herpes simplex virus (HSV) causes only 2-4% of all acute hepatitis but has high morbidity and mortality. Pregnancy is a risk factor for HSV hepatitis. We describe a case of gestational HSV hepatitis. CASE: A 32-year old woman, gravida 2 para 1, presented at 38 2/7 weeks of gestation with back pain and fetal tachycardia. She became febrile after admission, had spontaneous rupture of membranes, and was delivered by cesarean for malpresentation. Postpartum, she became persistently febrile and developed transaminitis, symptomatic hypotension, and pancytopenia despite antibiotics. Imaging revealed acute liver injury, splenomegaly, pleural effusions, and cardiomyopathy. Serum polymerase chain reaction (PCR) screening identified HSV-1 infection. The patient recovered on acyclovir. There was no evidence of neonatal seroconversion. CONCLUSION: Herpes simplex virus hepatitis causes significant morbidity, and pregnant women are susceptible to severe infections. Pregnant or peripartum women with acute febrile hepatitis require prompt evaluation for HSV with serum PCR screening.


Assuntos
Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Hepatite Viral Humana/complicações , Herpes Simples/complicações , Complicações Infecciosas na Gravidez/diagnóstico , Adulto , Cesárea , Diagnóstico Diferencial , Feminino , Hepatite Viral Humana/diagnóstico , Hepatite Viral Humana/tratamento farmacológico , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico , Humanos , Reação em Cadeia da Polimerase , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Simplexvirus/isolamento & purificação
5.
Sci Rep ; 10(1): 1156, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980687

RESUMO

A concurrent increase in the prevalence of hepatocellular carcinoma (HCC) with that of type 2 diabetes (T2D) and obesity has been reported in the absence of hepatitis B virus surface antigen-negative/hepatitis C virus antibody-negative HCC (NBNC-HCC). However, the prognostic relevance of this association remains unclear. Promoter methylation (PM) of the dihydropyrimidinase-like 3 gene (DPYSL3) has been implicated in virus-related HCC. However, it remains unclear whether T2D influences PM in NBNC-HCC. We determined the influence of T2D on clinicopathological profile and PM of DPYSL3 and CDK2NA in patients with NBNC-HCC who were divided into two groups: non-diabetes (non-DM; n = 46) and diabetes (DM; n = 47). DM was associated with a higher Union for International Cancer Control grade, marginal vascular invasion and tumour cell proliferation irrespective of the duration of T2D as well as higher rates of PM of DPYSL3 than non-DM; however, PM of CDK2NA was similar between both groups. PM of DPYSL3 reduced its expression which inversely correlated with reduced patient survival. In conclusion, T2D is associated with poor prognosis of NBNC-HCC in which a high frequency of PM of DPYSL3 may play a pivotal role in its pathogenesis.


Assuntos
Carcinoma Hepatocelular/genética , Metilação de DNA , Diabetes Mellitus Tipo 2/complicações , Neoplasias Hepáticas/genética , Proteínas Musculares/genética , Regiões Promotoras Genéticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobina A Glicada/análise , Hepatite Viral Humana/complicações , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Obesidade/complicações , Prognóstico , Recidiva
6.
J Gastroenterol Hepatol ; 35(7): 1223-1228, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31749188

RESUMO

BACKGROUND: Hepatitis infection from non-hepatotropic viruses such as dengue virus (DENV) is increasing worldwide. There is increasing recognition of the changing epidemiology and atypical presentations of DENV infection including acute liver failure (ALF). There is paucity of data regarding incidence, disease characteristics, and markers of prognosis in patients who develop DENV-related ALF. METHODS: We aimed to study the incidence, clinical features, laboratory characteristics, and determinants of outcome in patients of DENV presenting with ALF. We reviewed all patients with DENV infection and focused on DENV-related ALF from 2014 to 2017. Diagnosis of DENV and ALF was confirmed by serological tests and standard criteria, respectively. RESULTS: Thirty-six patients (20 men, mean age 32.3) developed ALF among 10 108 patients with DENV infection (0.35%). Twenty-one patients died (58.3%). Although bilirubin, aspartate and alanine aminotransferase, and international normalized ratio were markedly elevated in all patients with DENV ALF, there was no statistically significant difference between survivors and non-survivors. Lactate levels, pH at admission, and model for end-stage liver disease (MELD) score were the only predictors of mortality. Lactate levels were significantly higher in non-survivors (11.5 ± 4.2 mmol/L) than survivors (6.3 ± 3.6 mmol/L) (P < 0.001). MELD score in non-survivors (26.7 ± 10.2) was significantly higher than in survivors (20 ± 7.2) (P = 0.039). Receiver operator characteristic curve showed lactate or pH to be a superior prognostic marker than MELD with an area under the curve of 0.80, 0.79, and 0.70, respectively. CONCLUSION: Dengue hepatitis progressed to ALF in 0.35%. Development of ALF was associated with a high mortality (> 50%). Lactate level, pH, and MELD score at admission were significant determinants of outcome.


Assuntos
Dengue/complicações , Dengue/diagnóstico , Hepatite Viral Humana/complicações , Hepatite Viral Humana/diagnóstico , Falência Hepática Aguda/etiologia , Adulto , Alanina Transaminase/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Dengue/mortalidade , Feminino , Hepatite Viral Humana/mortalidade , Humanos , Concentração de Íons de Hidrogênio , Coeficiente Internacional Normatizado , Lactatos/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Testes Sorológicos , Taxa de Sobrevida
7.
Nutr Clin Pract ; 35(1): 24-29, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31840297

RESUMO

Acute liver failure (ALF) is a rare syndrome resulting from an acute insult to the liver in patients without known underlying chronic liver disease. It is characterized by loss of synthetic function in the form of jaundice and coagulopathy and development of hepatic encephalopathy. Multiorgan failure (MOF) eventually develops, leading to death. Many different etiologies have been identified, with acetaminophen (APAP) overdose and viral hepatitis being the most common causes worldwide. The pathophysiology of ALF can be divided into cause-specific liver injury pathophysiologies and pathophysiology related to occurrence of secondary MOF. In terms of liver injury pathophysiology, APAP toxicity is the most well known. Secondary MOF is often a result of the initial massive proinflammatory response generating a systemic inflammatory response syndrome followed by a compensatory anti-inflammatory response leading to immune cell dysfunction and sepsis. As the liver is a tremendously important metabolic organ involved in energy metabolism, protein synthesis, fat metabolism, and glycemic control, multiple aspects of nutrition also need to be considered as part of the overall pathophysiology of ALF.


Assuntos
Falência Hepática Aguda/epidemiologia , Falência Hepática Aguda/fisiopatologia , Acetaminofen/envenenamento , Analgésicos não Entorpecentes/envenenamento , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Overdose de Drogas/complicações , Overdose de Drogas/epidemiologia , Feminino , Encefalopatia Hepática/etiologia , Hepatite Viral Humana/complicações , Humanos , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/complicações , Masculino , Insuficiência de Múltiplos Órgãos/epidemiologia , Insuficiência de Múltiplos Órgãos/etiologia , Estado Nutricional , Sepse/etiologia
8.
Top Antivir Med ; 27(3): 101-110, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31634861

RESUMO

Among individuals with HIV infection, liver disease remains an important cause of morbidity and mortality, even with the availability of agents that cure hepatitis C infection and suppress hepatitis B replication. The causes of liver disease are multifaceted and continue to evolve as the population ages and new etiologies arise. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis and hepatitis viruses such as A, D, and E have emerged even as hepatitis C has receded. Newer antiretroviral agents may increase risk of weight gain and subsequent fatty infiltration, and prior use of nucleotide-based therapies may continue to impact liver health. Several barriers including economics, social stigma, and psychiatric disease impact identification of liver disease, as well as management and treatment interventions. Hepatocellular carcinoma is emerging as a more common and late-diagnosed complication in those with HIV infection and liver disease.


Assuntos
Infecções por HIV/complicações , Hepatite Viral Humana/complicações , Hepatopatias/etiologia , Fígado/virologia , Antirreumáticos/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Fígado Gorduroso/complicações , Fígado Gorduroso/epidemiologia , Fígado Gorduroso Alcoólico/complicações , Fígado Gorduroso Alcoólico/epidemiologia , Infecções por HIV/epidemiologia , Hepatite A/complicações , Hepatite A/epidemiologia , Hepatite B/complicações , Hepatite B/epidemiologia , Hepatite C/complicações , Hepatite C/epidemiologia , Hepatite D/complicações , Hepatite D/epidemiologia , Hepatite E/complicações , Hepatite E/epidemiologia , Vírus de Hepatite , Hepatite Viral Humana/epidemiologia , Humanos , Fígado/lesões , Hepatopatia Gordurosa não Alcoólica
9.
J Hematol Oncol ; 12(1): 58, 2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182108

RESUMO

Among all malignant tumors that threaten human health, virus-related tumors account for a large proportion. The treatment of these tumors is still an urgent problem to be resolved. The immune system is the "guard" of the human body, resisting the invasion of foreign substances such as viruses. Studies have shown that immunotherapy has clinical significance in the treatment of a variety of tumors. In particular, the emergence of immune checkpoint inhibitors (ICIs) in recent years has opened a new door to cancer therapy. Considering the potential role of ICIs in the treatment of virus-related cancers, we focused on their therapeutic effect in virus-associated cancers and explored whether the therapeutic effect in virus-associated cancers was related to virus infection status. Although there is no clear statistical significance indicates that ICIs are more effective in virus-associated cancers than non-virus infections, the efficacy of checkpoint inhibitors in the treatment of virus-related cancers is promising. We believe that this research provides a good direction for the implementation of individualized precision medicine.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Imunoterapia/métodos , Neoplasias/terapia , Neoplasias/virologia , Animais , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/terapia , Infecções por Vírus Epstein-Barr/virologia , Hepatite Viral Humana/complicações , Hepatite Viral Humana/terapia , Hepatite Viral Humana/virologia , Humanos , Neoplasias/etiologia , Neoplasias/imunologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/terapia , Infecções por Papillomavirus/virologia
10.
Dig Dis Sci ; 64(12): 3642-3651, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31209721

RESUMO

BACKGROUND: Liver stiffness (LS) measured by vibration-controlled transient elastography (VCTE) is influenced by liver fibrosis and hepatic perfusion pressure. VCTE-based controlled attenuation parameter (CAP) is a noninvasive marker for hepatic steatosis (HS). AIMS: To investigate the diagnostic performance of CAP in patients with advanced chronic liver disease (ACLD)/portal hypertension (PHT: hepatic venous pressure gradient (HVPG) ≥ 6 mmHg). METHODS: Eighty-eight patients with LS ≥ 10 kPa and/or HVPG ≥ 6 mmHg who underwent simultaneous liver biopsy, CAP, and HVPG measurement were included. HS was histologically graded according to the modified Brunt classification. RESULTS: Patient characteristics: Mean MELD:11 (standard derivation [SD] ± 4), median HVPG:16 (interquartile range [IQR]10-19) mmHg, median LS:27.4 (IQR 16.2-48.9) kPa, and mean CAP:221 (SD ± 75) dB/m. According to histology, 47 (53.4%) patients had no HS (S0), 28 (31.8%) had S1, 11 (12.5%) had S2, and 2 (2.3%) had S3. The area under the receiver operating characteristic curve (AUROC) of CAP for diagnosing any HS (S0 vs. ≥ S1) was 0.692 (95% confidence interval [95% CI] 0.582-0.802) in the overall cohort, 0.830 (95% CI 0.637-1.0) in patients with HVPG < 10 mmHg, and 0.629 (95% CI 0.497-0.761) in patients with clinically significant portal hypertension (CSPH; HVPG ≥ 10 mmHg; n = 69). Using the established cutoff for any HS (248 dB/m), the sensitivity/specificity of CAP was only 48.8%/76.6%, respectively. In contrast, the AUROC and sensitivity/specificity (cutoff 268 dB/m) for diagnosing HS ≥ S2 were 0.842 (95% CI 0.747-0.936) and 84.6%/81.3%, respectively. CAP correlated with the percentage of steatotic hepatocytes (Spearman's ρ = 0.402; p ≤ 0.001) and showed a weak correlation with liver stiffness (ρ = 0.225; p = 0.035). CONCLUSIONS: The diagnostic performance of CAP for any HS seems to be limited in patients with ACLD, if CSPH is present.


Assuntos
Fígado Gorduroso/diagnóstico por imagem , Hipertensão Portal/diagnóstico por imagem , Hepatopatias/diagnóstico por imagem , Adulto , Idoso , Área Sob a Curva , Doença Crônica , Técnicas de Imagem por Elasticidade , Fígado Gorduroso/complicações , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/patologia , Feminino , Hepatite Viral Humana/complicações , Humanos , Hipertensão Portal/complicações , Fígado/diagnóstico por imagem , Fígado/patologia , Hepatopatias/complicações , Hepatopatias/patologia , Hepatopatias Alcoólicas/complicações , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Curva ROC , Sensibilidade e Especificidade , Índice de Gravidade de Doença
11.
Eur J Gastroenterol Hepatol ; 31(10): 1283-1291, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31206409

RESUMO

BACKGROUND: Recently, stem cells have been used in the treatment of viral hepatitis-induced liver cirrhosis (LC), and stem cell therapy is showing potential therapeutic effects on liver function improvement. The consensus on effects and safety of stem cell therapy has not been reached, thus it is essential for us to conduct a systematic review and meat-analysis to investigate the efficacy and safety of stem cell therapy for viral hepatitis-induced LC. MATERIALS AND METHODS: Medline, Embase, SinoMed and Cochrane Library databases were searched with appropriate keywords through 5 August 2018. We included eight trials involving 467 patients. The pooled weight mean difference (WMD) and 95% confidence interval (CI) were calculated using a fixed or random effects model. Quality assessment and publication bias were also performed. The selected studies were considered for meta-analysis using RevMan V5.3. RESULTS: Compared with traditional therapy group, autologous stem cell transplantation increased the level of albumin (WMD: 2.47, 95% CI: 1.05-3.90, P < 0.001), but decreased the level of total bilirubin (WMD: -2.26, 95% CI: -3.61 to -0.90, P = 0.001), alanine aminotransferase (WMD: -9.16, 95% CI: -16.47 to -1.85, P = 0.01) and prothrombin time (WMD: -3.02, 95% CI: -4.83 to -1.22, P = 0.001). Clinical symptoms such as edema, fatigue, anorexia and abdominal distention were alleviated. Model for End-Stage Liver Disease and Child-Pugh scores were decreased after stem cell therapy. Whereas, there was no statistically significant difference between two groups regarding aspartate aminotransferase, prothrombin time activity, ascites and pleural fluid. No procedure-related complications were found. CONCLUSION: Autologous stem cell transplantation might have beneficial effects on patients with viral hepatitis-induced LC and is relatively safe for these patients. Further high-quality randomized controlled trials are needed.


Assuntos
Hepatite Viral Humana/complicações , Cirrose Hepática/terapia , Transplante de Células-Tronco/métodos , Humanos , Cirrose Hepática/virologia , Modelos Estatísticos , Transplante Autólogo , Resultado do Tratamento
12.
Mol Med Rep ; 19(6): 5237-5250, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059056

RESUMO

This study was conducted to screen prognosis­â€‹associated long­noncoding RNAs (lncRNAs) and a prognosis assessment model in hepatocellular carcinoma (HCC). lncRNA­ and mRNA­sequencing data of early­stage HCC samples were downloaded from The Cancer Genome Atlas database. The samples were divided into training set and validation set. Differentially expressed lncRNAs (DELs) between poor prognosis and good prognosis samples were screened with DEseq and edgeR. Cox regression analysis was conducted to identify prognosis­associated lncRNAs in the training set. A prognosis risk assessment model was established to calculate the risk score for each patient in the training set, and the prognosis prediction function was tested and validated in the validation dataset. The connection between the risk assessment model and clinical features was analyzed. A co­expression network between lncRNAs and corresponding genes was constructed, and functional enrichment was performed for these genes. A total of 81 DELs were screened between poor and good prognosis samples in the training set, and 43 prognosis­associated lncRNAs were observed. Of these DELs, five were used to construct the risk assessment model (RP11­325L7.2, DKFZP434L187, RP11­100L22.4, DLX2­AS1 and RP11­104L21.3). Low­risk samples exhibited longer survival time compared with the high­risk samples. The five lncRNAs exhibited significant differences in expression levels between different prognosis groups. Risk score was an independent prognostic factor for HCC. In the entire set, the low­risk group demonstrated significantly better prognosis compared with the high­risk group, even across all age, sex and alcohol consumption subgroups. 'Nucleoside­triphosphatase regulator activity', 'GTPase regulator activity', 'enzyme binding', 'peroxisome proliferator­activated receptor signaling pathway' and 'fatty acid metabolism' were the most significantly enriched functional terms. The signature lncRNAs screened in this study may have constitute novel strategies and biomarkers that predict the prognosis of HCC, and these may also contribute to a deeper understanding of the mechanisms underlying HCC development.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/metabolismo , Idoso , Área Sob a Curva , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Bases de Dados Genéticas , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatite Viral Humana/complicações , Hepatite Viral Humana/patologia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , RNA Longo não Codificante/genética , Curva ROC , Fatores de Risco
13.
Rev Gastroenterol Peru ; 39(1): 55-63, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31042237

RESUMO

INTRODUCTION: Liver cirrhosis decompensated due to bacterial infections is one of the main diagnoses of admission to hospitalization, taking into account that the risk per se in it is higher than in non-cirrhotic patients, leading to high mortality rates. OBJECTIVE: The present study sought to determine the predictors of infection and mortality in patients with liver cirrhosis, as well as the epidemiological-clinical characteristics of patients with cirrhosis. MATERIAL AND METHODS: Prospective data were collected from hospitalized cirrhotic patients in the Gastroenterology and Internal Medicine Service of the Hospital High Complexity "Virgen de la Puerta", from 2015 to June 2018. RESULTS: The study included 66 patients. The infection frequency was of 37.88%, being more frequent the spontaneous bacterial peritonitis (21.2%) and the total mortality was of 12.12%. When performing binary logistic regression and ROC curve, the MELD value> 13.5 (p=0.003), TP >18.26 (p=0.003) and the Child Pugh C stage were obtained as predictors of mortality (p=0.02, IC 95% EXP(B) 0.13-0.365). The variables that predict absence of mortality were a platelet value ≥74 500 /mm3 (p=0.01) and sodium ≥133 (p=0.019). The predictors of infection, MELD value ≤14.5 (p=0.0004) and sodium level ≥134.5 (AUC 0.696, p=0.028), to predict absence of infection. CONCLUSIONS: High MELD is a predictor of both mortality and infection. Child Pugh C and high values of Prothrombin time are predictors of mortality. The normal sodium level is a predictor of absence of mortality and infection, as well as platelet values discreetly low are predictors of absence of mortality.


Assuntos
Cirrose Hepática/mortalidade , Idoso , Alcoolismo/complicações , Infecções Bacterianas/complicações , Feminino , Hepatite Viral Humana/complicações , Mortalidade Hospitalar , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Peritonite/complicações , Peritonite/microbiologia , Peru , Estudos Prospectivos , Curva ROC , Fatores de Risco , Índice de Gravidade de Doença , Centros de Atenção Terciária
14.
Dtsch Med Wochenschr ; 144(8): 520-527, 2019 04.
Artigo em Alemão | MEDLINE | ID: mdl-30986859

RESUMO

Chronic viral hepatitis can remain unrecognized but may nevertheless lead to liver cirrhosis and hepatocellular carcinoma. Thus, patients with elevated liver enzymes as well as risk groups need to be screened and treated for viral hepatitis. These groups include, in particular, migrants from countries with high HBV or HCV prevalence, persons with previous or current intravenous drug use, and homosexual men. For HBV- or HCV-associated diseases, such as panarteriitis nodosa, cryoglobulinemic vasculitis or B-cell lymphoma, antiviral therapy may lead to remission. Prior to high-dose immunosuppressive therapy, especially with regimes containing rituximab, chronic or resolved HBV infection must be ruled out or antiviral prophylaxis may be required to avoid a potentially fatal HBV reactivation.


Assuntos
Hepatite Crônica/diagnóstico , Hepatite Viral Humana/diagnóstico , Doença Aguda , Hepatite Crônica/complicações , Hepatite Crônica/terapia , Hepatite Viral Humana/complicações , Hepatite Viral Humana/terapia , Humanos
15.
Curr Gastroenterol Rep ; 21(4): 17, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30976932

RESUMO

PURPOSE OF REVIEW: To discuss current knowledge and recent findings regarding the epidemiology of hepatocellular carcinoma (HCC) in the USA. RECENT FINDING: The US incidence rate of HCC is increasing, although the pace may have somewhat slowed since 2010. In 2012, incidence rates of HCC in Hispanics surpassed those of Asians. The recent epidemiological changes in major risk factors for HCC include increasing hepatitis C virus post-sustained virologic response, suppressed hepatitis B virus on nucleoside analogues, and alcoholic and non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease has the greatest proportion of the burden of the main risk factors for HCC in the USA, followed by alcoholic liver disease, and hepatitis C virus and hepatitis B virus infections. This review focuses on current knowledge regarding the recent epidemiological trends in HCC, with an emphasis on future directions.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Neoplasias Hepáticas/epidemiologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Detecção Precoce de Câncer/métodos , Hepatite Viral Humana/complicações , Hepatite Viral Humana/epidemiologia , Humanos , Incidência , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Fatores de Risco , Estados Unidos/epidemiologia
16.
Cient. dent. (Ed. impr.) ; 16(1): 17-25, ene.-abr. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-183377

RESUMO

La enfermedad o disfunción hepática puede deberse a numerosas causas como infecciones adquiridas, patologías congénitas o el abuso de drogas. Cuando esta disfunción y el daño hepático se prolongan a lo largo del tiempo, puede desembocar en una cirrosis hepática, cuadro irreversible y de graves repercusiones para el enfermo. Las dos patologías hepáticas más frecuentes y principales causas de la cirrosis son la hepatitis o inflamación hepática, la cual se puede deber a numerosos factores siendo el más frecuente las infecciones por virus, y la enfermedad hepática alcohólica, provocada por el abuso de alcohol continuado durante un largo período de tiempo. El manejo odontológico de un paciente con alteraciones hepáticas supone un verdadero reto, ya que el hígado juega un papel vital en numerosas funciones metabólicas, como la secreción de bilis o la excreción de bilirrubina procedente del metabolismo de la hemoglobina. Un fallo en la función hepática puede suponer alteraciones en el metabolismo de aminoácidos, amoníaco, proteínas, hidratos de carbono y triglicéridos. Un paciente con patología hepática tendrá un metabolismo alterado de numerosos fármacos empleados habitualmente por el dentista, tendrá un mayor riesgo de hemorragia debido a anomalías en la síntesis de diferentes factores de coagulación, siendo además un paciente con mayor riesgo de infecciones. La gran repercusión de la enfermedad hepática, así como el notable desconocimiento de muchos profesionales odontólogos en su manejo, justifican este artículo donde se talla tanto las generalidades más importantes de esta entidad como sus principales manifestaciones orales y consideraciones en el manejo odontológico


Liver disease or dysfunction may be due to numerous causes such as acquired infections, congenital pathologies or drug abuse. When this dysfunction and liver damage are prolonged overtime, it can lead to hepatic cirrhosis, an irreversible condition and serious repercussions for the patient. The two most frequent liver diseases and major causes of cirrhosis are hepatitis or hepatic inflammation, which may be due to numerous factors being the most frequent virus infections, and alcoholic liver disease, caused by alcohol abuse continued during A long period of time. The dental management of a patient with liver disorders is a real challenge, since the liver plays a vital role in many metabolic functions, such as bile secretion or excretion of bilirubin from hemoglobin metabolism. A failure in liver function can lead to alterations in the metabolismof amino acids, ammonia, proteins, carbohydrates and triglycerides. A patient with liver disease will have an altered metabolism of numerous drugs commonly used by the dentist, will have a greater risk of hemorrhage due to abnormalities in the synthesis of different coagulation factors, being also a patient with a higher risk of infections. The great repercussion of liver disease, as well as the remarkable lack of knowledge of many dental professionals in its management, justify this article where it is detailed both the most important generalities of this entity as its main oral manifestations and considerations in dental management


Assuntos
Humanos , Hepatite Viral Humana/complicações , Hepatite Crônica/complicações , Hepatopatias Alcoólicas/complicações , Doenças da Boca/complicações , Doenças da Boca/terapia , Assistência Odontológica para Doentes Crônicos/métodos , Doenças Dentárias/complicações , Doenças Dentárias/terapia
17.
Ann Transplant ; 24: 162-167, 2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30898994

RESUMO

BACKGROUND The classical cardiovascular risk factors and changes in the circulatory system secondary to end-stage liver disease (ESLD) are associated with an increased risk of cardiac abnormalities (CAs) in patients waiting for liver transplantation (LTx). The aim of this study was to assess the relationship between the etiology of liver disease and the presence of CAs in patients qualified for LTx. MATERIAL AND METHODS The study enrolled patients qualified to LTx due to ESLD at the Clinical Hospital of the Medical University of Warsaw between 2013 and 2016. Out of 396 patients: 65, 157, 117, and 57 had ESLD due to the alcoholic liver disease (ALD), viral infections (VIR), autoimmune disorders (AUTO), and different etiologies (OTHER), respectively. RESULTS An increased frequency of hypertension and diabetes mellitus were observed in ALD and VIR groups, while for hyperlipidemia, the highest rates were observed in ALD and AUTO groups. Significant differences in CAs rates were observed for resting tachycardia, prolonged QT interval, bradycardia, and left ventricular diastolic dysfunction. After adjustment for age, MELD, and Child-Pugh scores, hyperlipidemia (26% vs. 7-15%, p<0.048) was most frequently observed in the AUTO group, while poor aerobic capacity (49% vs. 21-34%, p<0.009) dominated in the OTHER group. CONCLUSIONS The frequency of hyperlipidemia, and poor aerobic capacity were directly related to the etiology of liver disease, while the remaining associations resulted from effects of age, MELD, and Child-Pugh score.


Assuntos
Doenças Cardiovasculares/etiologia , Doença Hepática Terminal/complicações , Transplante de Fígado , Listas de Espera , Adulto , Doenças Autoimunes/complicações , Doenças Autoimunes/cirurgia , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/cirurgia , Feminino , Hepatite Viral Humana/complicações , Hepatite Viral Humana/cirurgia , Humanos , Hiperlipidemias/etiologia , Hepatopatias Alcoólicas/complicações , Hepatopatias Alcoólicas/cirurgia , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Período Perioperatório/efeitos adversos , Fatores de Risco
18.
Immunol Lett ; 208: 11-18, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30831142

RESUMO

Inflammasomes are a set of innate receptors which are the responsible molecules for activation of pro-interleukin (IL)-1ß and IL-18 and induction of inflammation. Due to the key roles of the inflammasomes in the induction of inflammation, it has been hypothesized that the molecules may be the main parts of immune responses against viral infections and the tissue damage. Because some cases of viral hepatitis infections, including hepatitis B and C, are diagnosed as chronic and may be associated with various complications such as liver cirrhosis and hepatocellular carcinoma (HCC), several studies focused on the roles played by the inflammation on the pathogenesis of viral hepatitis. Based on the roles played by inflammasomes in induction of inflammation, it has been hypothesized that inflammasomes may be the main parts of the puzzle of the viral hepatitis complications. This article reviews the roles of the inflammasomes in the pathogenesis of hepatitis B and C viral infections and their complications, liver cirrhosis, and HCC.


Assuntos
Suscetibilidade a Doenças , Hepatite Viral Humana/etiologia , Hepatite Viral Humana/metabolismo , Inflamassomos/metabolismo , Animais , Biomarcadores , Citocinas/metabolismo , Hepacivirus/imunologia , Vírus da Hepatite B/imunologia , Hepatite Viral Humana/complicações , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/imunologia , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo
19.
Semin Liver Dis ; 39(1): 26-42, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30809789

RESUMO

Hepatocellular carcinoma (HCC) is associated with chronic inflammation and fibrosis arising from different etiologies, including hepatitis B and C and alcoholic and nonalcoholic fatty liver diseases. The inflammatory cytokines tumor necrosis factor-α and interleukin-6 and their downstream targets nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and signal transducer and activator of transcription 3 drive inflammation-associated HCC. Further, while adaptive immunity promotes immune surveillance to eradicate early HCC, adaptive immune cells, such as CD8+ T cells, Th17 cells, and B cells, can also stimulate HCC development. Thus, the role of the hepatic immune system in HCC development is a highly complex topic. This review highlights the role of cytokine signals, NF-κB, JNK, innate and adaptive immunity, and hepatic stellate cells in HCC and discusses whether these pathways could be therapeutic targets. The authors will also discuss cholangiocarcinoma and liver metastasis because biliary inflammation and tumor-associated stroma are essential for cholangiocarcinoma development and because primary tumor-derived inflammatory mediators promote the formation of a "premetastasis niche" in the liver.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Apoptose , Carcinogênese , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/imunologia , Feminino , Células Estreladas do Fígado/metabolismo , Hepatite Viral Humana/complicações , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Cirrose Hepática Alcoólica/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/imunologia , Masculino , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Distribuição por Sexo , Fator de Necrose Tumoral alfa/metabolismo
20.
Pediatr Neonatol ; 60(4): 389-395, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30361144

RESUMO

BACKGROUND: This study investigated the prognostic parameters and beneficial effects of repeat plasma exchange in children with acute liver failure (ALF). METHODS: Twenty-three patients under 18 years of age admitted to National Taiwan University Hospital due to ALF from 2003 to 2016 were included in this retrospective analysis. RESULTS: Among the patients, 11 (48%) had native liver recovery (NLR), 9 (39.1%) died without liver transplant, and 3 (12.9%) received liver transplantation. The NLR group showed a lower proportion of idiopathic cases, lower peak ammonia level, higher peak alpha fetoprotein (AFP) level, and they had plasma exchange fewer times than the other groups. Receiver operating characteristic curve analyses yielded optimal cutoff values of plasma exchange (≤6 times), peak ammonia level (<190 µmol/L), and peak AFP level for predicting NLR in children with ALF. CONCLUSION: Pediatric ALF with idiopathic etiology, high peak ammonia level, and low peak AFP level are associated with fewer cases of NLR. Plasma exchange for more than six times probably offers little benefit with regard to patient survival if liver transplantation is not performed promptly.


Assuntos
Falência Hepática Aguda/terapia , Transplante de Fígado , Troca Plasmática , Adolescente , Amônia/metabolismo , Antitireóideos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/complicações , Criança , Pré-Escolar , Feminino , Hemocromatose/complicações , Hepatite Viral Humana/complicações , Degeneração Hepatolenticular/complicações , Humanos , Lactente , Recém-Nascido , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/metabolismo , Linfo-Histiocitose Hemofagocítica/complicações , Masculino , Erros Inatos do Metabolismo/complicações , Mortalidade , Prognóstico , Propiltiouracila/toxicidade , Curva ROC , Recuperação de Função Fisiológica , Estudos Retrospectivos , Taiwan , alfa-Fetoproteínas/metabolismo
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