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1.
Adv Exp Med Biol ; 1179: 1-16, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31741331

RESUMO

Hepatitis B virus (HBV) is a DNA virus, belonging to the Hepadnaviridae family. It is a partially double-stranded DNA virus with a small viral genome (3.2 kb). Chronic HBV infection remains a global public health problem. If left untreated, chronic HBV infection can progress to end-stage liver disease, such as liver cirrhosis and hepatocellular carcinoma (HCC). In recent years, tremendous advances in the field of HBV basic and clinical research have been achieved, ranging from the HBV biological characteristics, immunopathogenesis, and animal models to the development of new therapeutic strategies and new drugs against HBV. In this overview, we begin with a brief history of HBV discovery and treatment milestones. We then briefly summarize the HBV research advances, which will be detailed in the following chapters.


Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B , Hepatite B Crônica , Cirrose Hepática , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/etiologia , Hepatite B/complicações , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/complicações , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Pesquisa/tendências
2.
Zhonghua Gan Zang Bing Za Zhi ; 27(10): 788-792, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31734994

RESUMO

Objective: To investigate whether type 2 diabetes mellitus increases the risk of hepatitis B-related cirrhosis combined with type 2 diabetes mellitus for the occurrence of primary hepatocellular carcinoma, and to compare the effects of different nature of diabetes duration on the risk of different anti-diabetic drugs. Methods: A retrospective case-control study was conducted. (1) 325 cases with hepatitis B-related cirrhosis complicated with primary hepatocellular carcinoma were selected as the study group and 601 patients with hepatitis B cirrhosis as the control group. The relationship between diabetes mellitus and the risk of primary liver cancer was analyzed by multivariate logistic regression analysis. (2) Selected the study group and control group combined with type 2 diabetes mellitus, and used multivariate logistic regression analysis to study the relationship between diabetes-related factors and the risk of primary liver cancer. Results: The incidence of diabetes was 14.2% in the study group and 6.0% in the control group, and the difference was statistically significant between the two groups (P < 0.05). Multivariate logistic regression analysis showed that type 2 diabetes was one of the independent risk factors for primary hepatocellular carcinoma, which had increased the risk of primary hepatocellular carcinoma (adjusted odds ratio (AOR): 1.982, 95% CI: 1.224-3.210). Patients with diabetes > 10 years (adjusted ratio: AOR value 6.011, 95% CI: 1.659-21.777) were at significantly higher risk for primary hepatocellular carcinoma than that of patients with diabetes < 10 years. Metformin (adjusted odds ratio: AOR 0.188, 95% CI: 0.052-0.688) had reduced the risk, while insulin (adjusted odds ratio: AOR 6.682, 95% CI: 1.899-23.510) had increased the risk. Conclusion: Type 2 diabetes mellitus is one of the independent risk factors for primary HCC, which can increase the risk of hepatocellular carcinoma in hepatitis B cirrhosis in relation to the duration of diabetes mellitus. The risk of hepatocellular carcinoma is higher in patients with duration of diabetes > 10 years and metformin reduces the risk.


Assuntos
Carcinoma Hepatocelular/etiologia , Diabetes Mellitus Tipo 2/complicações , Hepatite B/complicações , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Estudos de Casos e Controles , Humanos , Estudos Retrospectivos , Fatores de Risco
4.
Anticancer Res ; 39(10): 5639-5643, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570461

RESUMO

BACKGROUND/AIM: Diabetes mellitus (DM) is known as an important risk factor for hepatocellular carcinoma (HCC). However, surgical outcomes in patients with DM and HCC have not been evaluated in detail. PATIENTS AND METHODS: We retrospectively studied 177 patients with type 2 DM who underwent curative hepatectomy for HCC. Surgical outcomes after curative hepatectomy and prognostic factors were evaluated among 75 patients with DM and/or nonalcoholic steatohepatitis (NASH)-related HCC and 102 patients with DM and viral or alcoholic hepatitis (VAH)-related HCC. RESULTS: The 5-year survival rate and 5-year recurrence-free survival rate were significantly higher in the DM and/or NASH-related HCC group (87% and 51%) than in the DM and VAH-related HCC group (68%: p=0.0001 and 26%: p=0.0002). Multivariate analysis showed DM and/or NASH-related HCC to be significant independent prognostic factors for overall survival and recurrence-free survival. CONCLUSION: Patients with DM and/or NASH-related HCC showed more favorable surgical outcomes after hepatectomy in patients with DM and HCC.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/mortalidade , Hepatopatia Gordurosa não Alcoólica/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
5.
Medicine (Baltimore) ; 98(38): e17275, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31568008

RESUMO

Single nucleotide polymorphisms (SNPs) of the interleukin 28B (IL28B) gene has proven to be associated with the clinical outcome of patients with chronic hepatitis virus B or C (HBV or HCV) infections. However, whether IL28B SNPs have an influence on the risk of hepatocellular carcinoma (HCC) among patients with HBV or HCV infection remains controversial. Therefore, this study aims to determine the association between IL28B polymorphisms and the risk of HCC in individuals with HBV or HCV infection.PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases were used to identify studies meeting the selection requirements using the terms "interleukin 28B", "IFN-lambda-3", "IFNL3", "single nucleotide polymorphisms", "SNPs", "hepatocellular carcinoma", "HCC", "liver cancer".A total of 24 eligible original studies (1 cohort study and 23 case-control studies) involved 20238 individuals (HCC group = 8725 vs control group = 11,513) were included. Both IL28B rs12979860 CC and rs8099917 TT genotypes were significantly associated with a decreased risk of HCC among patients with HBV or HCV infection (OR = 0.71, 95% CI = 0.57-0.88; OR = 0.82, 95% CI = 0.72-0.94, respectively). Egger test and Begg test revealed no' publication bias (P > .05). Sensitivity analyses suggested the robustness of the results in this meta-analysis.Both IL28B rs12979860 CC and rs8099917 TT genotypes are protective factors for the development of HCC among patients with HBV or HCV infection. Future prospective studies examining the impact of IL28B polymorphisms on the risk of HCC and investigating the underlying mechanism for the protective role of IL28B polymorphisms in HCC development are warranted.


Assuntos
Carcinoma Hepatocelular/genética , Predisposição Genética para Doença/genética , Hepatite B/complicações , Hepatite C/complicações , Interferons/genética , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único/genética , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/virologia , Hepacivirus , Hepatite B/genética , Vírus da Hepatite B , Hepatite C/genética , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/virologia
6.
Anticancer Res ; 39(9): 5149-5156, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519627

RESUMO

BACKGROUND: Factors associated with response to lenvatinib have not been clarified in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This study retrospectively analyzed 50 patients treated with lenvatinib as first-line therapy between March 2018 and March 2019. Patients were divided into two groups by the Modified Response Evaluation Criteria in Solid Tumours (mRECIST) (responders and non-responders, whose best overall responses were complete (CR)/partial response (PR) and stable (SD)/progressive disease (PD), respectively). Factors associated with response were assessed, including the relative dose intensity 8 weeks after lenvatinib induction (8W-RDI). RESULTS: The best overall responses were 0/22/14/14 of CR/PR/SD/PD. Multivariate analysis revealed that only 8W-RDI was significantly associated with response. The receiver operating characteristic curve for 8W-RDI in differentiating responders from non-responders revealed a cut-off value of 75%. Patients with 8W-RDI ≥75% experienced a higher response rate and longer progression-free survival than patients with 8W-RDI <75%. CONCLUSION: Our results suggest that maintaining an RDI ≥75% during the initial 8 weeks of lenvatinib treatment has a favorable impact on response.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Curva ROC , Estudos Retrospectivos , Resultado do Tratamento
7.
Medicine (Baltimore) ; 98(32): e16736, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393384

RESUMO

RATIONALE: Laparoscopic right donor hepatectomy has been reported sporadically in several experienced centers for selected donors. This report introduced a case of a donor with an independent right posterior segmental portal branching from the main portal vein. PATIENT CONCERNS: A 47-year-old woman volunteered to donate her right liver to her 48-year-old husband. DIAGNOSES: The recipient has been diagnosed as hepatocellular carcinoma meeting the Milan criteria and hepatitis B virus related cirrhosis. INTERVENTIONS: The parenchymal transection was performed by ultrasonic aspirator and Hem-o-Lok clips. The right hepatic artery, right hepatic duct, and the anterior and posterior branches of right portal vein were meticulously dissected, clamped, and transected. The right hepatic vein was transected by vascular stapler. A Y-graft of the recipient's own portal confluence was reconstructed with the donor's separate right anterior and posterior portal veins. OUTCOMES: The donor's operation time was 420 minutes and the warm ischemia time was about 9 minutes. Blood loss was less than 600 ml without transfusion. The donor was discharged at the 10th postoperative day without any complications. LESSONS: Laparoscopic right hepatectomy for donors with anomalous portal vein branching and subsequent inflow reconstruction for adult living donor liver transplantation is safe and feasible in highly experienced center.


Assuntos
Hepatectomia/métodos , Transplante de Fígado/métodos , Doadores Vivos , Veia Porta/anatomia & histologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatite B/complicações , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Duração da Cirurgia , Isquemia Quente
8.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(6): 633-640, 2019 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-31270040

RESUMO

OBJECTIVE: To compare the efficacy and safety of different antiviral and antifibrotic regimens in patients with chronic hepatitis B (CHB) and hepatic fibrosis and the incidence of hepatocellular carcinoma (HCC) associated with these therapies. METHODS: A total of 840 patients with CHB and concurrent hepatic fibrosis, who received antiviral therapy in Nanfang Hospital between June, 2010 and June, 2018, were enrolled in this follow-up cohort study. The patients were assigned to 3 cohorts matched for gender, age (difference≤5 years), HBeAg status and liver stiffness measurement (LSM) for treatment with one of the 3 antiviral drugs, namely entecavir, tenofovir dipivoxil and adefovir dipivoxil; each cohort was divided into 2 groups, with one of the groups having a combined treatment with Fufang Biejiaruangan tablet. The cumulative negative conversion rate of HBV DNA, normalization rate of ALT, hepatic fibrosis regression and the incidence of HCC were compared among the 3 cohorts and across the 6 groups at 144 weeks. RESULTS: A total of 749 patients were available to follow-up at 144 weeks. Compared with the baseline data, the cumulative negative conversion rate of HBV DNA increased gradually and the abnormal rate of ALT decreased significantly over time during the treatment in all the 6 groups (all P < 0.001). Compared with the any of the antiviral drugs used alone, the combined treatments all resulted in significantly better antifibrotic effects (χETV cohort2=11.345, χTDF cohort2=10.160, χADV cohort2=6.358; all P < 0.05). At 144 weeks, the incidence of HCC were 2.2%, 1.7%, 1.7% and 3.3% in enecavir group, enecavir with Biejiaruangan tablet group, adefovir group, and adefovir with Biejiaruangan tablet group, respectively, showing no significant difference between the two cohorts (4 groups; χ2=6.813, P=0.138). None of the patients in the 2 groups with tenofovir treatment had HCC by the end of the observation. CONCLUSIONS: Antiviral therapy combined with antifibrotic therapy can effectively reverse hepatic fibrosis and reduce the incidence of HCC in patients with CHB; among the 3 antiviral drugs, tenofovir dipivoxil can be a better option for reducing the incidence of HCC in these patients.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Cirrose Hepática , Neoplasias Hepáticas , Antivirais , Carcinoma Hepatocelular/etiologia , DNA Viral , Seguimentos , Antígenos E da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Estudos Prospectivos
9.
Anticancer Res ; 39(7): 3855-3862, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262913

RESUMO

BACKGROUND: We examined treatment the efficacy and data on long-term outcomes in real-world Japanese patients infected with hepatitis C virus (HCV) genotype 2 treated with 12-week sofosbuvir/ribavirin combination therapy. PATIENTS AND METHODS: In a total of 86 patients who were treated with sofosbuvir/ribavirin, sustained virological response (SVR) rates and long-term-outcomes were retrospectively analyzed. RESULTS: The adherence to this combination therapy was 98.8%. The rates of SVR at week 24 (SVR24) achieved with this treatment according to the 'intention-to-treat' and 'per-protocol' analyses were 89.5% and 96.2%, respectively. Two patients who experienced relapse did not have any previously reported resistance-associated substitutions in the HCV non-structural protein 5B (NS5B) polymerase region. We did not observe any patients who experienced late relapse but did observe that 50% and 1.3% of patients with and without a previous history of hepatocellular carcinoma (HCC), respectively, developed HCC after achieving SVR24 (with a mean follow-up period of 2.7±0.8 years). CONCLUSION: Patients with SVR should be carefully followed-up to screen for the occurrence of HCC, although it is infrequent.


Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Idoso , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/virologia , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/virologia , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , Resultado do Tratamento
10.
Eur J Epidemiol ; 34(8): 753-763, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152367

RESUMO

Current experimental and epidemiological studies provide inconsistent evidence toward the association between tea consumption and cancer incidence. We investigated whether tea consumption was associated with the incidence of all cancers and six leading types of cancer (lung cancer, stomach cancer, colorectal cancer, liver cancer, female breast cancer and cervix uteri cancer) among 455,981 participants aged 30-79 years in the prospective cohort China Kadoorie Biobank. Tea consumption was assessed at baseline (2004-2008) with an interviewer-administered questionnaire. Cancer cases were identified by linkage to the national health insurance system. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In the present population, daily tea consumers were more likely to be current smokers and daily alcohol consumers. 22,652 incident cancers occurred during 10.1 years follow-up (5.04 cases/1000 person-years). When we restricted analyses to non-smokers and non-excessive alcohol consumers to minimize confounding, tea consumption was not associated with all cancers (daily consumers who added tea leaves > 4.0 g/day vs. less-than-weekly consumers: HR, 1.03; 95%CI, 0.93-1.13), lung cancer (HR, 1.08; CI, 0.84-1.40), colorectal cancer (HR, 1.08; CI, 0.81-1.45) and liver cancer (HR, 1.08; CI, 0.75-1.55), yet might be associated with increased risk of stomach cancer (HR, 1.46; CI, 1.07-1.99). In both less-than-daily and daily tea consumers, all cancer risk increased with the amount of tobacco smoked or alcohol consumed. Our findings suggest tea consumption may not provide preventive effect against cancer incidence.


Assuntos
Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Cafeína/efeitos adversos , Neoplasias/epidemiologia , Neoplasias/etiologia , Medição de Risco/métodos , Chá/efeitos adversos , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , China/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Feminino , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , População Rural , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia , Fumar Tabaco/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etiologia
11.
Gut ; 68(11): 2019-2031, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31227589

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC) is heterogeneous, especially in multifocal tumours, which decreases the efficacy of clinical treatments. Understanding tumour heterogeneity is critical when developing novel treatment strategies. However, a comprehensive investigation of tumour heterogeneity in HCC is lacking, and the available evidence regarding tumour heterogeneity has not led to improvements in clinical practice. DESIGN: We harvested 42 samples from eight HCC patients and evaluated tumour heterogeneity using whole-exome sequencing, RNA sequencing, mass spectrometry-based proteomics and metabolomics, cytometry by time-of-flight, and single-cell analysis. Immunohistochemistry and quantitative polymerase chain reactions were performed to confirm the expression levels of genes. Three independent cohorts were further used to validate the findings. RESULTS: Tumour heterogeneity is considerable with regard to the genomes, transcriptomes, proteomes, and metabolomes of lesions and tumours. The immune status of the HCC microenvironment was relatively less heterogenous. Targeting local immunity could be a suitable intervention with balanced precision and practicability. By clustering immune cells in the HCC microenvironment, we identified three distinctive HCC subtypes with immunocompetent, immunodeficient, and immunosuppressive features. We further revealed the specific metabolic features and cytokine/chemokine expression levels of the different subtypes. Determining the expression levels of CD45 and Foxp3 using immunohistochemistry facilitated the correct classification of HCC patients and the prediction of their prognosis. CONCLUSION: There is comprehensive intratumoral and intertumoral heterogeneity in all dimensions of HCC. Based on the results, we propose a novel immunophenotypic classification of HCCs that facilitates prognostic prediction and may support decision making with regard to the choice of therapy.


Assuntos
Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imunofenotipagem , Antígenos Comuns de Leucócito/metabolismo , Neoplasias Hepáticas/metabolismo , Microambiente Tumoral
12.
World J Surg Oncol ; 17(1): 75, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039803

RESUMO

BACKGROUND: The Toronto hepatocellular carcinoma (HCC) risk index (THRI) was developed to predict HCC in patients with cirrhosis. This study aimed to validate the THRI in a 10-year Asian cohort. METHODS: A total of 2836 patients with cirrhosis at the First Affiliated Hospital of Soochow University between January 2008 and May 2018 were evaluated. Based on the THRI value at diagnosis, patients were divided into three groups (< 120, low-risk; 120-240, intermediate-risk; > 240, high-risk). Student's t test and Fisher's exact test were applied to compare parameters between the HCC group and the non-HCC group. The receiver operator characteristic (ROC) curve was drafted to identify the value of the THRI in predicting HCC. Logistic regression was utilized to assess the relationship between the development of HCC and THRI values. The incidence of HCC was calculated for the three groups using the Kaplan-Meier method, and curves were compared using the log-rank test. RESULTS: Of 520 patients enrolled in this study, 76 patients developed HCC. Patients who developed HCC had a higher THRI score than those who did not develop HCC (279.5 ± 57.1 vs. 232.3 ± 67.6, respectively, p < 0.001). The area under the ROC curve for the THRI to predict HCC was 0.707 ([95% CI 0.645-0.769], p < 0.001), with a sensitivity of 0.842 and a specificity of 0.486 when the cutoff THRI value was 226. Compared to the low-risk group, the high-risk group presented higher odds of developing HCC (adjusting odds ratio 1.026 [95% CI 1.002-1.051], p = 0.036). Differences existed in the cumulative incidence of HCC among the three risk groups (log-rank, p < 0.001). The 5-year cumulative HCC incidence of the low-risk group, intermediate-risk group, and high-risk group was 0%, 13%, and 34%, respectively. CONCLUSION: This study validated THRI values for predicting HCC in Asians with cirrhosis, which presented a fine sensitivity to identify the high-risk population of HCC for secondary prevention.


Assuntos
Carcinoma Hepatocelular/etiologia , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Testes de Função Hepática , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
13.
BMC Cancer ; 19(1): 511, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142283

RESUMO

BACKGROUND: It has been proved that nucleos(t) ide analogues (NAs) therapy could improve underlying liver disease and reduce the incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, the difference of effectiveness in reducing HCC occurrence between tenofovir (TDF) and enticavir (ETV), two first-line NAs drugs, is still little known. This meta analysis aims to assess the efficacy in reducing incidence of HCC comparing tenofovir monotherapy with entecavir monotherapy among chronic hepatitis B (CHB) patients by analyzing their long-term clinical outcomes. METHODS: Databases including PubMed, Embase, Cochrane Central Register of Controlled Trial, and ISI Web of Science were fully investigated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For the included articles, two of the authors independently extracted and confirmed relevant data. Review Manager software (RevMan 5.3) was using for meta analysis. RESULTS: Seven articles with 3698 patients were finally included in this research, 1574 in tenofovir group and 2124 in entecavir group. For meta analysis, the incidence of HCC was significantly lower among the tenofovir group than entecavir group [rate ratio (95% CI) of 0.66 (0.49, 0.89), P = 0.008], while there was no statistical significance in incidence of death or transplantation [rate ratio (95% CI) of 0.78 (0.55, 1.13), P = 0.19], encephalopathy [risk ratio (95% CI) of 0.72 (0.45, 1.13), P = 0.15] or variceal bleeding [risk ratio (95% CI) of 0.71 (0.34, 1.50), P = 0.37] between the two groups. CONCLUSION: There is a better effect of tenofovir in reducing HCC incidence than entecavir, which indicates tenofovir should be used more widely while treating chronic hepatitis B patients. However before applying, randomized controlled trial and large prospective cohort study should be performed in the future.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Tenofovir/uso terapêutico , Adulto , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/prevenção & controle , Ensaios Clínicos Controlados como Assunto , Feminino , Guanina/uso terapêutico , Hepatite B Crônica/complicações , Humanos , Incidência , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos
14.
J Exp Clin Cancer Res ; 38(1): 229, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142329

RESUMO

BACKGROUND: The study examines the expression and function of hypoxia-inducible gene 2 (HIG2) in hepatocellular carcinoma (HCC) tissues and cells. METHODS: Forty patients with HCC were included in the study. Bioinformatic analysis was used to analyze the clinical relevance of HIG2 expression in HCC tissue samples. Immunohistochemistry was employed to determine the expression of target proteins in tumor tissues. Hepatic HepG2 and SMMC-7721 cells were transfected with HIG2-targeting siRNA with Lipofectamine 2000. qRT-PCR was carried out to determine gene expression levels, while Western blotting was used to determine protein expression. A CCK-8 assay was performed to detect proliferation of cells, while migration and invasion of cells were studied by Transwell assay. Flow cytometry was carried out to detect surface markers and effector molecules in Nature killercells, as well as the killing effect of NK cells. RESULTS: HIG2 expression was upregulated in HCC. Silencing of HIG2 suppressed HCC cell migration and invasion. The killing effect of NK cells on HCC cells was enhanced after HIG2 was silenced in HCC cells. Conditioned media from HIG2-silenced SMMC-7721 cells inhibited the phenotype and function of NK cells. HCC cells with silenced expression of HIG2 modulated the activity of NK cells via STAT3. HIG2 promoted the evasion of HCC cells from killing by NK cells through upregulation of IL-10 expression. CONCLUSION: The study demonstrates that HIG2 activates the STAT3 signaling pathway in NK cells by promoting IL-10 release by HCC cells, thereby inhibiting the killing activity of NK cells, and subsequently promoting the recurrence and metastasis of HCC.


Assuntos
Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/metabolismo , Interleucina-10/metabolismo , Células Matadoras Naturais/fisiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/genética , Transdução de Sinais , Evasão Tumoral/imunologia , Adulto , Animais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Expressão Gênica , Inativação Gênica , Células Hep G2 , Xenoenxertos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , RNA Interferente Pequeno/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Evasão Tumoral/genética
15.
Am Soc Clin Oncol Educ Book ; 39: 248-260, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31099615

RESUMO

The incidence and death rates of hepatocellular carcinoma (HCC) are rising. For more than a decade, the multikinase inhibitor sorafenib was the only U.S. Food and Drug Administration (FDA)-approved systemic therapy for HCC. However, since 2017, five additional agents have been approved in the first- or second-line setting. Although this represents an incredible victory for the field, there are no clear guidelines for agent selection on the basis of either patient or tumor characteristics. Here, we review the available systemic therapy options for advanced HCC and reported clinical data for each. We outline each agent's unique toxicity profile, potential impact on patient quality of life, monitoring recommendations, and supportive strategies. Last, we review molecular and immunologic classifications of HCC as well as preclinical data that may serve as a basis for future biomarker enriched clinical trials to enable precision oncology care in HCC.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Animais , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Ensaios Clínicos como Assunto , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Metástase Neoplásica , Estadiamento de Neoplasias , Medicina de Precisão , Prognóstico , Resultado do Tratamento
16.
Zhonghua Wai Ke Za Zhi ; 57(6): 408-411, 2019 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-31142063

RESUMO

Liver resection is the mainstay of treatment for patients with hepatocellular carcinoma (HCC). Most of HCC patients are associated with varied degrees of liver cirrhosis.Severity of liver cirrhosis adversely affects the outcomes of liver resection, and also plays a vital role in making an appropriate surgical strategy for HCC.In current surgical practice for HCC, liver function and functional reserve are the focus of preoperative evaluation. Liver cirrhosis is still widely regarded as an one-stage entity. The pathological severity of liver cirrhosis is largely ignored. As neither liver function nor functional reserve can reflect the pathological severity of liver cirrhosis when liver function is at the stage of compensation. Preoperative evaluation on the severity of cirrhosis has not been established in a surgical setting.Thus, there is an urgent need to stage the severity of cirrhosis in surgical practice in order to make more precise surgical modalities for individual patients.This article mainly introduces the ongoing research progress in staging the severity of liver cirrhosis while treating HCC at Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and emphasizes the importance of staging the severity of cirrhosis in surgical treatment of HCC.


Assuntos
Carcinoma Hepatocelular/cirurgia , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Neoplasias Hepáticas/cirurgia , Fígado/fisiopatologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Hepatectomia , Humanos , Fígado/patologia , Fígado/cirurgia , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Índice de Gravidade de Doença
17.
Expert Opin Drug Saf ; 18(7): 603-610, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067134

RESUMO

INTRODUCTION: Concerns were raised about a high occurrence of hepatocellular carcinoma (HCC) after successful treatment of chronic hepatitis C (CHC) by direct-acting antivirals (DAAs). AREAS COVERED: The authors summarize the clinical studies reporting the occurrence rate and risk factors of HCC after DAAs in CHC. EXPERT OPINION: The recent introduction of all-oral DAAs has substantially changed the scenario of CHC, achieving a sustained virological response (SVR) in >90% of cases. Earlier concerns raised about an increasing incidence of HCC post-DAAs were flawed by large heterogeneity of patients, the limited number of well-designed prospective studies (only nine, up to date) and the inclusion of a large number of patients with advanced liver disease, previously excluded from interferon-based studies. Current data on DAAs have shown a lower risk of HCC development; however, they were unable to identify patients at greater risk for HCC occurrence after SVR. Surveillance strategy, likely lifelong, is mandatory in these patients according to general expert opinion.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Neoplasias Hepáticas/epidemiologia , Carcinoma Hepatocelular/etiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Incidência , Neoplasias Hepáticas/etiologia , Projetos de Pesquisa , Fatores de Risco , Resposta Viral Sustentada , Resultado do Tratamento
18.
Br J Biomed Sci ; 76(2): 64-69, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31025604

RESUMO

BACKGROUND: Hepatitis C virus (HCV) related liver cirrhosis occurs in about 20% of chronically infected patients over a duration of 10-20 years, and within 5 years approximately 10-20% of these cirrhotic patients will develop hepatocellular carcinoma (HCC). Previous studies report that the X-ray repair cross-complementing group1 gene (XRCC1) is important in the risk of HCC development; however, results obtained from these studies are conflicting rather than conclusive. We hypothesised an association between single nucleotide polymorphisms (SNPs) in XRCC1 with the HCC risk on a background of chronic hepatitis C. MATERIALS AND METHODS: We recruited 210 subjects, 70 with HCC, 70 with cirrhosis and 70 healthy controls. Two SNPs [c.1254C>T(rs2293035) and c.1517G>C(rs139599857)] in XRCC1 were genotyped using created restriction site-polymerase chain reaction (CRS-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS: The TT genotype, CT genotype and T-allele in c.1254C>T (rs2293035) were linked to risk of HCC compared to the CC genotype: OR 3.58 [confidence interval (CI) 95%: 1.19-10.7] p = 0.019; OR 2.16 (CI 95%: 1.04-4.47) p = 0.037 and OR 2.10 (CI 95%: 1.2-3.3) p = 0.006, respectively. Regarding c.1517G>C (rs139599857), the CC genotype, GC genotype and C-allele were linked with higher risk of developing HCC compared to GG genotype: OR 4.77 (CI 95%: 1.3-16.9), p = 0.016; OR 3.02 (CI 95%: 1.46-6.2), p = 0.002 and OR 2.4 (CI 95%: 1.4-4.0), p = 0.001, respectively. CONCLUSION: We conclude that the T-allele of c.1254C>T (rs2293035) and the C allele of c.1517G>C (rs139599857) genetic variants may be associated with increased HCC risk among chronic hepatitis C patients.


Assuntos
Carcinoma Hepatocelular/genética , Hepatite C Crônica/genética , Neoplasias Hepáticas/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Alelos , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
19.
Genome Biol ; 20(1): 84, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-31027518

RESUMO

BACKGROUND: Circular RNAs are a class of regulatory RNA transcripts, which are ubiquitously expressed in eukaryotes. In the current study, we evaluate the function of a novel circRNA derived from the ß-catenin gene locus, circß-catenin. RESULTS: Circß-catenin is predominantly localized in the cytoplasm and displays resistance to RNase-R treatment. We find that circß-catenin is highly expressed in liver cancer tissues when compared to adjacent normal tissues. Silencing of circß-catenin significantly suppresses malignant phenotypes in vitro and in vivo, and knockdown of this circRNA reduces the protein level of ß-catenin without affecting its mRNA level. We show that circß-catenin affects a wide spectrum of Wnt pathway-related genes, and furthermore, circß-catenin produces a novel 370-amino acid ß-catenin isoform that uses the start codon as the linear ß-catenin mRNA transcript and translation is terminated at a new stop codon created by circularization. We find that this novel isoform can stabilize full-length ß-catenin by antagonizing GSK3ß-induced ß-catenin phosphorylation and degradation, leading to activation of the Wnt pathway. CONCLUSIONS: Our findings illustrate a non-canonical function of circRNA in modulating liver cancer cell growth through the Wnt pathway, which can provide novel mechanistic insights into the underlying mechanisms of hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/etiologia , RNA/metabolismo , Via de Sinalização Wnt , beta Catenina/genética , Animais , Carcinogênese , Linhagem Celular Tumoral , Movimento Celular , Técnicas de Silenciamento de Genes , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Camundongos Nus , Metástase Neoplásica
20.
BMC Cancer ; 19(1): 363, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30991968

RESUMO

BACKGROUND: Hepatoma arterial-embolization prognostic (HAP) score and its modifications (modified HAP [mHAP] and mHAP-II), consisting of some or all of the following factors of tumor size, number, alpha-fetoprotein, bilirubin, and serum albumin, have been found to predict outcomes after trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We investigated the feasibility of using HAP-related risk scores for dynamic risk assessment during repeated TACE. METHODS: A total of 619 HCC patients treated with TACE from two institutions between 2003 and 2010 were included. RESULTS: Patients with A-B class risk scores showed significantly better survival than those with C-D class risk scores at the first (median 43.7 vs. 21.5 months for mHAP-II, 35.2 vs. 10.2 months for mHAP, and 39.8 vs. 18.6 months for HAP; all P < 0.001) and the second rounds of TACE (38.6 vs. 17.2 months for mHAP-II, 30.0 vs. 8.5 months for mHAP, and 32.6 vs. 17.3 months for HAP; all P < 0.001). Sequential assessment of risk scores at the second TACE round was applied for patients with A-B class risk scores at the first TACE round, which further identified two subgroups of A-B and C-D class risk scores with different outcomes (median survival 40.6 vs. 19.6 months for mHAP-II, 31.2 vs. 16.9 months for mHAP, and 35.8 vs. 21.0 months for HAP; all P < 0.001). Compared with mHAP and HAP, mHAP-II showed the highest likelihood ratio (22.61 vs. 14.67 and 13.97, respectively), highest linear trend (24.43 vs. 19.67 and 14.19, respectively), and lowest Akaike information criteria value (1432.51 vs. 3412.29 and 2296.98, respectively). CONCLUSIONS: All HAP-related risk scores dynamically predicted outcomes during repeated TACE. Sequential risk assessment using mHAP-II best identified optimal candidates for repeated TACE.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Idoso , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Gerenciamento Clínico , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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