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1.
Medicine (Baltimore) ; 99(48): e23384, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33235113

RESUMO

Hepatitis C virus (HCV) infection is very common in maintenance hemodialysis patients, causing high morbidity and mortality. This study aimed to evaluate the effectiveness and adverse events of direct-acting antivirals (DAAs) in maintenance hemodialysis patients complicated with chronic hepatitis C in real-world clinical practice.In this retrospective observational study, hemodialysis patients with chronic hepatitis C infection in the Third Central Hospital of Tianjin outpatient were screened, and appropriate treatment plans were selected accordingly. Totally 25 patients diagnosed with chronic hepatitis C and treated with DAAs for 12 weeks or 24 weeks were included. The sustained virologic response (SVR) rate obtained 12 weeks post-treatment (SVR12) was evaluated. Laboratory indexes and adverse reactions during the treatment process were also assessed.A total of 25 cases met the eligibility criteria and provided informed consent. Except for 1 patient who discontinued the treatment due to gastrointestinal bleeding, the remaining 24 cases completed the treatment cycle with 100% rapid virologic response (RVR) and 100% SVR12, with no serious adverse reactions recorded.Maintenance hemodialysis patients complicated with chronic hepatitis C in Chinese real-world setting tolerate DAAs very well, with a viral response rate reaching 100%.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Diálise Renal , Insuficiência Renal Crônica/complicações , Alanina Transaminase , Amidas/administração & dosagem , Amidas/efeitos adversos , Antivirais/efeitos adversos , Aspartato Aminotransferases , Benzofuranos/administração & dosagem , Benzofuranos/efeitos adversos , Carbamatos/administração & dosagem , Carbamatos/efeitos adversos , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Quimioterapia Combinada , Feminino , Genótipo , Hemoglobinas/análise , Hepacivirus/genética , Hepatite C Crônica/complicações , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Isoquinolinas/administração & dosagem , Isoquinolinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Quinoxalinas/administração & dosagem , Quinoxalinas/efeitos adversos , RNA Viral/sangue , Insuficiência Renal Crônica/terapia , Estudos Retrospectivos , Sofosbuvir/administração & dosagem , Sofosbuvir/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Carga Viral
3.
PLoS One ; 15(10): e0241002, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33085694

RESUMO

BACKGROUND: We examined serum kynurenine levels in patients with chronic hepatitis C virus infection, and the relationship between serum kynurenine and prognosis in patients with hepatocellular carcinoma (HCC) and chronic hepatitis C. METHODS: We retrospectively analyzed 604 patients with HCC diagnosed between January 1999 and December 2015, and 288 patients without HCC who were seen at the National Hospital Organization Nagasaki Medical Center between October 2014 and November 2017. The association between serum kynurenine and prognosis was evaluated using the Cox's proportional hazards regression analysis. RESULTS: Patients with HCC had significantly higher values of serum kynurenine than patients without HCC (median: 557.1 vs. 464.2 ng/mL, p<0.001). Five-year survival rates of HCC patients with serum kynurenine ≥900 (n = 65), 600-899 (n = 194), and <600 ng/mL (n = 345) were 30.6%, 47.4%, and 61.4%, respectively (p = 0.001, log-rank test). Multivariate analysis identified serum kynurenine as an independent predictor for prognosis of HCC patients. The hazard ratio of serum kynurenine ≥900, and 600-899 compared with serum kynurenine <600 ng/mL were 1.91 (p<0.001) and 1.37 (p = 0.015), respectively. CONCLUSIONS: A high level of serum kynurenine correlated with poor prognosis of HCC. Serum kynurenine levels may be a novel biomarker to predict the prognosis of patients with HCC. The development of drugs that inhibit kynurenine production is expected to help improve the prognosis of patients with HCC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/mortalidade , Hepatite C Crônica/sangue , Cinurenina/sangue , Neoplasias Hepáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/virologia , Feminino , Hepatite C Crônica/complicações , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
4.
Zhonghua Gan Zang Bing Za Zhi ; 28(10): 827-830, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33105926

RESUMO

The occult progression of chronic hepatitis C (CHC) is one of the main causes of liver cirrhosis and hepatocellular carcinoma (HCC). Recently, antiviral treatment of CHC has achieved great progress with the advent of direct-acting antiviral drugs (DAA), especially for special populations including advanced liver disease and HCC. However, DAA and HCC-related issues have also become one of the important concerns of current CHC treatment. This article summarizes the recent research progresses made in the diagnosis and treatment of HCV-related HCC.


Assuntos
Antivirais , Carcinoma Hepatocelular , Hepatite C Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/virologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/virologia
5.
PLoS One ; 15(10): e0241199, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33125400

RESUMO

INTRODUCTION: Liver fibrosis is a result of continuous damage to the liver combined with accumulation of the extracellular matrix and is characteristic of most chronic liver diseases such as hepatitis C virus (HCV) infection. METHODS: This study evaluated interleukin 10 (IL10) expression in the liver and plasma of 45 HCV patients and its association with the pathogenesis and progression of liver fibrosis. The expression of transforming growth factor beta (TGFB1) was also assessed. Patients were divided into three groups according to the METAVIR classification (F0-F1, F2 and F3-F4); there was also a control group (n = 8). RESULTS: In the control group, high intrahepatic IL10 mRNA expression showed a positive association with F0-F1 fibrosis, no inflammation, low concentrations of liver enzymes and a high viral load; conversely, low intrahepatic IL10 mRNA expression showed a negative association with fibrosis progression. Intrahepatic TGFB1 mRNA expression was greater in the HCV group than in the control group, and regarding different disease phases, its expression increased as fibrosis evolved to more severe forms. CONCLUSION: Intrahepatic IL10 mRNA expression decreases with persistent fibrosis, probably due to the production of TGF-ß1, a potent antimitotic and fibrogenic cytokine. IL10 restricts and decreases the immune response and limits the fibrogenic response; however, a decrease in IL10 favors persistent inflammatory infiltrate, resulting in severe fibrosis.


Assuntos
Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Interleucina-10/metabolismo , Cirrose Hepática/patologia , Fígado/patologia , Fator de Crescimento Transformador beta1/metabolismo , Estudos de Casos e Controles , Feminino , Hepatite C Crônica/virologia , Humanos , Interleucina-10/genética , Fígado/metabolismo , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta1/genética , Carga Viral
10.
JAMA Netw Open ; 3(9): e2015626, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32870314

RESUMO

Importance: Deep learning, a family of machine learning models that use artificial neural networks, has achieved great success at predicting outcomes in nonmedical domains. Objective: To examine whether deep learning recurrent neural network (RNN) models that use raw longitudinal data extracted directly from electronic health records outperform conventional regression models in predicting the risk of developing hepatocellular carcinoma (HCC). Design, Setting, and Participants: This prognostic study included 48 151 patients with hepatitis C virus (HCV)-related cirrhosis in the national Veterans Health Administration who had at least 3 years of follow-up after the diagnosis of cirrhosis. Patients were identified by having at least 1 positive HCV RNA test between January 1, 2000, to January 1, 2016, and were followed up from the diagnosis of cirrhosis to January 1, 2019, for the development of incident HCC. A total of 3 models predicting HCC during a 3-year period were developed and compared, as follows: (1) logistic regression (LR) with cross-sectional inputs (cross-sectional LR); (2) LR with longitudinal inputs (longitudinal LR); and (3) RNN with longitudinal inputs. Data analysis was conducted from April 2018 to August 2020. Exposures: Development of HCC. Main Outcomes and Measures: Area under the receiver operating characteristic curve, area under the precision-recall curve, and Brier score. Results: During a mean (SD) follow-up of 11.6 (5.0) years, 10 741 of 48 151 patients (22.3%) developed HCC (annual incidence, 3.1%), and a total of 52 983 samples (51 948 [98.0%] from men) were collected. Patients who developed HCC within 3 years were older than patients who did not (mean [SD] age, 58.2 [6.6] years vs 56.9 [6.9] years). RNN models had superior mean (SD) area under the receiver operating characteristic curve (0.759 [0.009]) and mean (SD) Brier score (0.136 [0.003]) than cross-sectional LR (0.689 [0.009] and 0.149 [0.003], respectively) and longitudinal LR (0.682 [0.007] and 0.150 [0.003], respectively) models. Using the RNN model, the samples with the mean (SD) highest 51% (1.5%) of HCC risk, in which 80% of all HCCs occurred, or the mean (SD) highest 66% (1.2%) of HCC risk, in which 90% of all HCCs occurred, could potentially be targeted. Among samples from patients who achieved sustained virologic response, the performance of the RNN models was even better (mean [SD] area under receiver operating characteristic curve, 0.806 [0.025]; mean [SD] Brier score, 0.117 [0.007]). Conclusions and Relevance: In this study, deep learning RNN models outperformed conventional LR models, suggesting that RNN models could be used to identify patients with HCV-related cirrhosis with a high risk of developing HCC for risk-based HCC outreach and surveillance strategies.


Assuntos
Carcinoma Hepatocelular , Aprendizado Profundo/estatística & dados numéricos , Hepatite C Crônica , Cirrose Hepática , Neoplasias Hepáticas , Área Sob a Curva , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Indicadores de Doenças Crônicas , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/terapia , Humanos , Incidência , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Prognóstico , Medição de Risco/métodos , Resposta Viral Sustentada , Serviços de Saúde para Veteranos Militares/estatística & dados numéricos
11.
Indian J Gastroenterol ; 39(3): 253-260, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32833144

RESUMO

BACKGROUND: Liver fibrosis is a frequent complication of chronic hepatitis C virus (HCV) infection. Its evaluation is very important for the prognosis of these patients. The aim of this study was to evaluate the possibility of exploiting the platelet to lymphocyte ratio and the neutrophil to lymphocyte ratio as non-invasive predictive markers of liver fibrosis. METHODS: We recruited 120 patients with chronic HCV infection. They were subjected to various clinical investigations to assess the severity of fibrosis. Transient elastography and some serological tests were performed, and the platelet to lymphocyte ratio and the neutrophil to lymphocyte ratio were estimated. RESULTS: Sixty-four patients had F4 fibrosis (defined by elastography) and their platelet to lymphocyte ratio (69.92 ± 26.47) was lower than in patients with non-F4 fibrosis (95.19 ± 48.15) (p = 0.001). The neutrophil to lymphocyte ratio was also estimated, but the difference between the 2 groups of patients was not significant statistically (p = 0.07). CONCLUSION: The platelet to lymphocyte ratio can be used as a predictive biomarker of liver fibrosis, unlike the neutrophil to lymphocyte ratio which is not predictive of this HCV-related chronic hepatitis complication. More studies are needed to validate this hypothesis.


Assuntos
Hepatite C Crônica/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Contagem de Linfócitos , Contagem de Plaquetas , Idoso , Biomarcadores/sangue , Técnicas de Imagem por Elasticidade/métodos , Feminino , Humanos , Contagem de Leucócitos , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neutrófilos , Valor Preditivo dos Testes
12.
PLoS One ; 15(8): e0237475, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790728

RESUMO

BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) exert high anti-HCV activity and are expected to show anti-inflammatory effects associated with HCV elimination. Furthermore, hepatocellular carcinoma (HCC) is known to dedifferentiate from hypovascular tumors, such as dysplastic nodules or well-differentiated HCC, to hypervascular tumors. We therefore explored whether or not DAAs can suppress the growth and hypervascularization of hypovascular tumors. METHODS: We enrolled 481 patients with HCV genotype 1 infection who were treated with Daclatasvir and Asunaprevir therapy. Of these, 29 patients had 33 hypovascular tumors, which were confirmed by contrast-enhanced MRI or CT before therapy. We prospectively analyzed the cumulative incidence of HCC, i.e. the growth or hypervascularization of hypovascular tumors, and compared the HCC development rates between patients with hypovascular tumors and those without any tumors. RESULTS: The mean size of the hypovascular tumors was 11.3 mm. Twenty seven of 29 patients who achieved an SVR had 31 nodules, 19 of 31 nodules (61.3%) showed tumor growth or hypervascularization, and 12 (38.7%) nodules showed no change or improvement. The cumulative incidence rates of tumor growth or hypervascularization were 19.4% at 1 year, 36.0% at 2 years, 56.6% at 3 years, and 65.3% at 4 years. Among the patients who achieved a sustained virologic response, the cumulative HCC development rates of patients with hypovascular tumors was significantly higher than in those without any tumors. A Cox proportional hazard analysis showed that a history of HCC therapy, the presence of a hypovascular tumor, and AFP >4.6 ng/mL at the end of treatment were independent risk factors for HCC development. CONCLUSION: Hypovascular tumors developed into HCC at a high rate despite the elimination of HCV by DAAs. As patients with hypovascular tumors were shown to have a high risk of HCC development, they should undergo strict HCC surveillance.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/epidemiologia , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Imidazóis/uso terapêutico , Incidência , Isoquinolinas/uso terapêutico , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada , alfa-Fetoproteínas/análise
13.
Medicine (Baltimore) ; 99(30): e21270, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791706

RESUMO

In a hepatitis C virus (HCV)/HIV-positive Brazilian cohort, evaluate the safety and efficacy of HCV DAAs, the frequency of resistance substitutions in the HCV NS5A and NS5B genes and identify predictors of treatment failure.Retrospective multicenter study of HCV/HIV patients treated with sofosbuvir (SOF)-based regimens at 10 reference centers in Brazil.Clinical and virological data were collected. Genetic diversity in the NS5A and NS5B genes was assessed by direct nucleotide sequencing. The primary outcome was sustained virological response (SVR) 12 weeks after DAA completion.Of 643 HCV/HIV patients analyzed, 74.7% were male, median CD4+ T cell count was 617 cells/mm, 90% had an undetectable HIV viral load. HCV genotype 1 was detected in 80.2%, and 60% were taking at least 1 medication other than antiretroviral drugs during their DAA therapy. Cirrhosis was present in 42%. An SOF/daclatasvir (DCV) regimen was used in most patients (98%). The frequency of NS5A polymorphisms associated with clinically relevant resistance to DCV was 2%; no relevant NS5B variants were identified. The SVR12 rate was 92.8% in an intention to treat (ITT) analysis and 96% in a modified ITT (m-ITT) analysis. AE occurred in 1.6% of patients. By multivariate analysis, therapeutic failure was associated, in the m-ITT analysis, with concomitant use of anticonvulsant drugs (P = .001), age (P = .04), and female gender (P = .04).SOF/DCV regimens were associated with a high SVR rate in an HCV/HIV population. The use of concurrent anticonvulsant drugs and DAAs decreases the chances of achieving an SVR.


Assuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Adulto , Coinfecção/tratamento farmacológico , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resposta Viral Sustentada
14.
J Surg Oncol ; 122(8): 1543-1552, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32856301

RESUMO

OBJECTIVE: To investigate the postoperative recurrence of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after liver resection in patients with and without the achievement of sustained virologic response (SVR) through the administration of direct-acting antivirals (DAA). METHODS: Among 28 patients with HCC detected after DAA-SVR (DAA group) and 197 patients with HCC who did not receive treatment for HCV infection or who did not achieve an SVR (control group) between January 2000 and July 2019, we performed propensity score matching (PSM) to avoid confounding differences between the two groups. RESULTS: After PSM, 28 patients in each group were selected for analysis. The DAA-SVR patients showed improved liver function at operation and at recurrence in comparison to the control group. The disease-free survival rate at 3 years after surgery was 69% in the DAA group and 35% in the control group, respectively (P = .021). In the DAA group, all three patients with recurrence met the Milan criteria and could be managed by curative treatments and none died of liver failure during the follow-up period. CONCLUSIONS: SVR status suppresses postoperative recurrence of HCV-related HCC detected after DAA-SVR. Improved liver function may contribute to the successful treatment and prevention of liver failure.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Hepacivirus/efeitos dos fármacos , Hepatectomia/mortalidade , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Seguimentos , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/virologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resposta Viral Sustentada
15.
J Surg Oncol ; 122(8): 1553-1568, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32862430

RESUMO

BACKGROUND: Inflammation plays an important role in the progression and prognosis of hepatocellular carcinoma (HCC). Our aim is to explore the prognostic value of preoperative and postoperative peripheral lymphocyte differences and to develop a dynamic prognosis nomogram in hepatitis B virus-related HCC patients. METHODS: Important indicators related to overall survival (OS) are screened out by Cox proportional hazard models. The receiver operating characteristic curves, decision curve analysis curves, net reclassification improvement, and integrated discrimination improvement were used to evaluate the performance of the model. RESULTS: Lymphocyte (L) difference was an independent risk factor. It was further verified that the performance of the nomogram was significantly improved after the L difference was incorporated into the nomogram. The nomogram generated had the area under curves of 0.779, 0.775, and 0.793 at 3, 5, and 7 years after surgery, respectively. Our nomogram models showed significantly better performance in predicting the HCC prognosis compared to other models. And online webserver and scoring system table was built based on the proposed nomogram for convenient clinical use. CONCLUSIONS: It is newly found that L difference is an effective predictor of OS, and the nomogram based on this indicator can accurately predict the prognosis of HCC patients.


Assuntos
Carcinoma Hepatocelular/patologia , Hepacivirus/isolamento & purificação , Hepatectomia/mortalidade , Hepatite C Crônica/complicações , Neoplasias Hepáticas/patologia , Linfócitos/patologia , Recidiva Local de Neoplasia/patologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Feminino , Seguimentos , Hepatite C Crônica/virologia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/virologia , Nomogramas , Prognóstico , Taxa de Sobrevida
16.
Aliment Pharmacol Ther ; 52(5): 866-876, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32697871

RESUMO

BACKGROUND: A strong association between chronic hepatitis C (CHC) and hepatic steatosis has been reported. However, the influence of steatohepatitis on hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) elimination remains unclear. AIM: To evaluate the development of HCC after HCV cure using a new steatohepatitis-related biomarker. METHODS: This cohort study analysed the prospective database of 290 CHC patients without a history of HCC who achieved HCV elimination by direct-acting antivirals. We calculated the FibroScan-aspartate aminotransferase (FAST) score 12 weeks after the end of treatment (pw12). The risk of HCC was analysed using the multivariable Cox proportional hazard model. RESULTS: HCV genotype (GT)1 was most prevalent at 72.4%, followed by GT2 (26.6%). Median follow-up period was 4.2 years (IQR 3.1-4.5). The cumulative HCC incidence for a FAST score ≥ 0.35 was significantly higher than that for a FAST score < 0.35 (log-rank test: P < 0.001). The annual HCC incidence rate for a FAST score ≥ 0.35 was significantly higher than that for a FAST score < 0.35, in patients with liver stiffness measurement (LSM) ≥10 kPa (adjusted hazard ratio [HR] 4.41, 95% confidence interval [CI] 1.30-15.0, P = 0.018). After adjusting for variables, including age, albumin, alpha-fetoprotein, the patatin-like phospholipase domain-containing the 3 (PNPLA3) rs738409 genotype, and pw12 fibrosis markers with FIB-4, non-alcoholic fatty liver disease fibrosis score, and LSM, FAST score ≥ 0.35 was associated with the development of HCC (adjusted HR 4.42, 95% CI 1.02-19.9, P = 0.043). CONCLUSIONS: Steatohepatitis-related biomarkers with the FAST score are helpful for predicting the development of HCC after HCV elimination.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/diagnóstico , Fígado Gorduroso/diagnóstico , Hepacivirus/fisiologia , Hepatite C Crônica/diagnóstico , Neoplasias Hepáticas/diagnóstico , Adulto , Idoso , Antivirais/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Transformação Celular Viral , Estudos de Coortes , Progressão da Doença , Fígado Gorduroso/sangue , Fígado Gorduroso/genética , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Indução de Remissão , Estudos Retrospectivos , alfa-Fetoproteínas/genética
17.
Am J Med ; 133(11): e641-e658, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32603791

RESUMO

BACKGROUND: The opioid epidemic has been associated with an increase in hepatitis C virus (HCV) infections. Federally qualified health centers (FQHCs) have a high burden of hepatitis C disease and could serve as venues to enhance testing and treatment. METHODS: We estimated clinical outcomes and the cost-effectiveness of hepatitis C testing and treatment at US FQHCs using individual-based simulation modeling. We used individual-level data from 57 FQHCs to model 9 strategies, including permutations of HCV antibody testing modality, person initiating testing, and testing approach. Outcomes included life expectancy, quality-adjusted life-years (QALY), hepatitis C cases identified, treated and cured; and incremental cost-effectiveness ratios. RESULTS: Compared with current practice (risk-based with laboratory-based testing), routine rapid point-of-care testing initiated and performed by a counselor identified 68% more cases after (nonreflex) RNA testing in the first month of the intervention and led to a 17% reduction in cirrhosis cases and a 22% reduction in liver deaths among those with cirrhosis over a lifetime. Routine rapid testing initiated by a counselor or a clinician provided better outcomes at either lower total cost or at lower cost per QALY gained, when compared with all other strategies. Findings were most influenced by the proportion of patients informed of their anti-HCV test results. CONCLUSIONS: Routine anti-HCV testing followed by prompt RNA testing for positives is recommended at FQHCs to identify infections. If using dedicated staff or point-of-care testing is not feasible, then measures to improve immediate patient knowledge of antibody status should be considered.


Assuntos
Antivirais/uso terapêutico , Centros Comunitários de Saúde , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/prevenção & controle , Adulto , Antivirais/economia , Análise Custo-Benefício , Conselheiros , Feminino , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/complicações , Hepatite C Crônica/economia , Humanos , Expectativa de Vida , Cirrose Hepática/economia , Cirrose Hepática/etiologia , Cirrose Hepática/mortalidade , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Epidemia de Opioides , Oregon , Testes Imediatos/economia , Anos de Vida Ajustados por Qualidade de Vida , RNA Viral/sangue , Testes Sorológicos/economia , Estados Unidos , United States Health Resources and Services Administration
18.
Lancet Gastroenterol Hepatol ; 5(9): 839-849, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32682494

RESUMO

BACKGROUND: Glecaprevir-pibrentasvir results in high rates of sustained virological response in patients with chronic hepatitis C virus (HCV) genotype 1-6 infection. Data for glecaprevir-pibrentasvir in non-Japanese Asian patients have been minimal. The aim of these studies was to assess the efficacy and safety of glecaprevir-pibrentasvir in treatment-naive and treatment-experienced Asian patients with chronic HCV genotype 1-6 infection without cirrhosis (VOYAGE-1) and with compensated cirrhosis (VOYAGE-2). METHODS: We did two phase 3 studies in treatment-naive and treatment-experienced patients with chronic HCV genotype 1-6 infection. VOYAGE-1 was a randomised, double-blind, placebo-controlled study that recruited patients without cirrhosis at 47 sites across China, South Korea, and Singapore. Randomisation was 2:1 with a fixed block size of three and stratified by geographical region and HCV genotype. Investigators, study site personnel, the study sponsor, and patients were masked to treatment allocation. VOYAGE-2 was a single-arm, open-label study that recruited patients with compensated cirrhosis at 34 sites across China and South Korea. Glecaprevir (300 mg) and pibrentasvir (120 mg) or placebo (VOYAGE-1, 2:1 ratio), administered as three tablets daily, was given for 8 weeks in patients without cirrhosis and for 12 weeks in those with cirrhosis (and for 16 weeks in treatment-experienced patients with genotype 3). The primary efficacy endpoint was the proportion of patients with a sustained virological response, defined as HCV RNA below the lower limit of quantification 12 weeks after the last dose of glecaprevir-pibrentasvir. We analysed efficacy and safety in all patients who received at least one dose of the study drug. These trials are registered with ClinicalTrials.gov, NCT03222583 (VOYAGE-1) and NCT03235349 (VOYAGE-2); both trials have been completed. This Article reports the results of the primary analysis for each study, undertaken when all patients who received glecaprevir-pibrentasvir (during the double-blind period in VOYAGE-1) had been followed up for 12 weeks following their last dose of study drug. Data from the double-blind period for placebo patients in VOYAGE-1 are also summarised. FINDINGS: Between Oct 4, 2017, and April 20, 2018, 546 patients with chronic HCV without cirrhosis were randomly assigned to treatment (363 to glecaprevir-pibrentasvir, 183 to placebo) in VOYAGE-1. One patient withdrew consent and did not receive treatment with glecaprevir-pibrentasvir. 352 of 362 patients who received glecaprevir-pibrentasvir achieved SVR12 (97·2% [95% CI 95·5-98·9]). Of 160 patients with compensated cirrhosis who were enrolled in VOYAGE-2 between Sept 29, 2017, and June 14, 2018, 159 of 160 achieved SVR12 (99·4%, 95% CI 98·2-100·0). 20 patients with HCV genotype 3b across both trials received glecaprevir-pibrentasvir; six of these patients were among the 11 patients who did not achieve SVR12. Upper respiratory tract infection was the most common adverse event (35 [10%] of 362 receiving glecaprevir-pibrentasvir and 18 [10%] of 183 receiving placebo in VOYAGE-1; 19 [12%] of 160 in VOYAGE-2). For patients receiving glecaprevir-pibrentasvir, serious adverse events occurred in three (<1%) of 362 patients in VOYAGE-1 and five (3%) of 160 patients in VOYAGE-2. Grade 3-4 adverse events in patients receiving glecaprevir-pibrentasvir occurred in five (1%) of 362 patients in VOYAGE-1 and six (4%) of 160 patients in VOYAGE-2; each type of event was experienced by at most one patient within a study. One patient with cirrhosis discontinued study drug because of an adverse event. INTERPRETATION: Glecaprevir-pibrentasvir showed high efficacy and an acceptable safety profile in these studies although responses were less common in the few patients with HCV genotype 3b. The results support the use of glecaprevir-pibrentasvir in these Asian populations. FUNDING: AbbVie.


Assuntos
Benzimidazóis/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Pirrolidinas/uso terapêutico , Quinoxalinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Ásia/epidemiologia , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Estudos de Casos e Controles , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Prevalência , Pirrolidinas/administração & dosagem , Pirrolidinas/efeitos adversos , Quinoxalinas/administração & dosagem , Quinoxalinas/efeitos adversos , Infecções Respiratórias/induzido quimicamente , Infecções Respiratórias/epidemiologia , Segurança , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resposta Viral Sustentada , Resultado do Tratamento
19.
Am J Gastroenterol ; 115(10): 1650-1656, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32516202

RESUMO

INTRODUCTION: Both transient elastography (TE)-based and non-TE-based criteria exist for detection of varices needing treatment (VNT) in patients with asymptomatic advanced chronic liver disease (CLD). However, their performance in clinical settings at different risk thresholds of detection of VNT and in regions where elastography is not widely available is unknown. We aimed to validate existing noninvasive criteria in our patients with CLD and identify best TE- and non-TE-based criteria for VNT screening at usual risk thresholds. METHODS: Patients with compensated advanced CLD (cACLD) who underwent esophagogastroduodenoscopy and TE within 3 months were included. Diagnostic performance of Baveno VI, expanded Baveno VI, platelet-model for end-stage liver disease, and platelet-albumin (Rete Sicilia Selezione Terapia-hepatitis C virus) criteria were estimated. Decision curve analysis was conducted for different predictors across range of threshold probabilities. A repeat analysis including all patients with compensated CLD (cACLD and non-cACLD) was performed to simulate absence of TE. RESULTS: A total of 1,657 patients (cACLD, 895; non-cACLD, 762) related to hepatitis B virus (38.2%), hepatitis C virus (33.4%), nonalcoholic steatohepatitis (14.7%), and alcohol (11.8%) were included. Baveno VI identified maximum VNT (97.3%) and had best negative predictive value (96.9%), followed by platelet-albumin criteria. Expanded Baveno VI and platelet-model for end-stage liver disease had intermediate performance. At threshold probability of 5%, Baveno VI criteria showed maximum net benefit, and platelet-albumin criteria was next best, with need for 95 additional elastographies to detect 1 additional VNT. Similar results were obtained on including all patients with compensated CLD irrespective of TE. DISCUSSION: Baveno VI criteria maximizes VNT yield at 5% threshold probability. An acceptable alternative is the platelet-albumin criteria in resource-limited settings.


Assuntos
Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas/diagnóstico , Cirrose Hepática/diagnóstico por imagem , Adulto , Grupo com Ancestrais do Continente Asiático , Técnicas de Apoio para a Decisão , Doença Hepática Terminal , Endoscopia do Sistema Digestório , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/terapia , Feminino , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Humanos , Índia , Fígado/diagnóstico por imagem , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Cirrose Hepática/metabolismo , Cirrose Hepática Alcoólica/sangue , Cirrose Hepática Alcoólica/complicações , Cirrose Hepática Alcoólica/diagnóstico por imagem , Cirrose Hepática Alcoólica/metabolismo , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Contagem de Plaquetas , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Albumina Sérica/metabolismo , Índice de Gravidade de Doença , Adulto Jovem
20.
New Microbiol ; 43(2): 99-102, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32510160

RESUMO

Cryptococcus species is still a very common opportunistic infection in AIDS patients. However, it is increasingly responsible for disease in otherwise immunocompromised individuals, such as transplant recipients and the heterogeneous group of patients with underlying immunologic diseases, hematologic disorders and organ failure syndromes. Clinical presentation, prognosis, and outcomes are difficult to define given these varied host groups, and tailoring treatments to fit the necessities of each patient is likewise challenging. Our patient was on treatment with steroids and direct-acting antiviral agents (DAAs) for a chronic HCV-related hepatitis, worsened by cryoglobulinemia, membranoproliferative glomerulonephritis and a lowgrade B cells lymphoma. We report a case of systemic cryptococcal infection in an immunosenescent, HIV-negative patient.


Assuntos
Criptococose/diagnóstico , Hepatite C Crônica/complicações , Imunossenescência , Antivirais , Criptococose/virologia , Soronegatividade para HIV , Hepatite/virologia , Hepatite C Crônica/microbiologia , Humanos
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