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1.
N Engl J Med ; 382(11): 1018-1028, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32160663

RESUMO

BACKGROUND: More information is needed about the long-term effects of low-dose aspirin (≤160 mg) on incident hepatocellular carcinoma, liver-related mortality, and gastrointestinal bleeding in persons with chronic hepatitis B or hepatitis C virus infection. METHODS: Using nationwide Swedish registries, we identified all adults who received a diagnosis of chronic hepatitis B or hepatitis C from 2005 through 2015 and who did not have a history of aspirin use (50,275 patients). Patients who were starting to take low-dose aspirin (14,205 patients) were identified by their first filled prescriptions for 90 or more consecutive doses of aspirin. We constructed a propensity score and applied inverse probability of treatment weighting to balance baseline characteristics between groups. Using Cox proportional-hazards regression modeling, we estimated the risk of hepatocellular carcinoma and liver-related mortality, accounting for competing events. RESULTS: With a median of 7.9 years of follow-up, the estimated cumulative incidence of hepatocellular carcinoma was 4.0% among aspirin users and 8.3% among nonusers of aspirin (difference, -4.3 percentage points; 95% confidence interval [CI], -5.0 to -3.6; adjusted hazard ratio, 0.69; 95% CI, 0.62 to 0.76). This inverse association appeared to be duration-dependent; as compared with short-term use (3 months to <1 year), the adjusted hazard ratios were 0.90 (95% CI, 0.76 to 1.06) for 1 to less than 3 years of use, 0.66 (95% CI, 0.56 to 0.78) for 3 to less than 5 years of use, and 0.57 (95% CI, 0.42 to 0.70) for 5 or more years of use. Ten-year liver-related mortality was 11.0% among aspirin users and 17.9% among nonusers (difference, -6.9 percentage points [95% CI, -8.1 to -5.7]; adjusted hazard ratio, 0.73 [95% CI, 0.67 to 0.81]). However, the 10-year risk of gastrointestinal bleeding did not differ significantly between users and nonusers of aspirin (7.8% and 6.9%, respectively; difference, 0.9 percentage points; 95% CI, -0.6 to 2.4). CONCLUSIONS: In a nationwide study of patients with chronic viral hepatitis in Sweden, use of low-dose aspirin was associated with a significantly lower risk of hepatocellular carcinoma and lower liver-related mortality than no use of aspirin, without a significantly higher risk of gastrointestinal bleeding. (Funded by the National Institutes of Health and others.).


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Carcinoma Hepatocelular/mortalidade , Hemorragia Gastrointestinal/induzido quimicamente , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Neoplasias Hepáticas/mortalidade , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Risco , Suécia/epidemiologia
2.
Int J Infect Dis ; 92: 184-188, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31978574

RESUMO

BACKGROUND: There are scant data regarding hepatitis C (HCV) virologic response to directly acting antiviral agents (DAAs) in chronic hepatitis B (HBV) and HCV coinfected persons. HCV treatment response in those with spontaneously cleared HBV infection is unknown. METHODS: All HCV infected persons treated with a DAA regimen in ERCHIVES were identified and categorized into HBV/HCV-coinfected (HBsAg, HBV DNA or both positive), HCV-monoinfected, and resolved HBV (isolated HBcAb+). SVR rates were determined and compared for all groups. Logistic regression model was used to determine factors associated with SVR. RESULTS: Among 115 HCV/HBV-coinfected, 38,570 HCV-monoinfected persons, and 13,096 persons with resolved HBV, 31.6% of HCV/HBV-coinfected, 24.6% of HCV-monoinfected and 26.4% with resolved HBV had cirrhosis at baseline. SVR was achieved in 90.4% of HCV/HBV-coinfected, 83.4% of HCV-monoinfected and 84.5% of those with resolved HBV infection (P = 0.04 HCV/HBV vs. HCV monoinfected). In a logistic regression model, those with HCV/HBV were more likely to achieve SVR compared with HCV monoinfected (OR 2.25, 95% CI 1.17, 4.31). For HCV/HBV coinfected, the SVR rates dropped numerically with increasing severity of liver fibrosis (P-value non-significant). Factors associated with a lower likelihood of attaining SVR included cirrhosis at baseline (OR 0.85, 95% CI 0.80, 0.92), diabetes (OR 0.93, 95% CI 0.87, 0.99) and higher pre-treatment HCV RNA (OR 0.86, 95% CI 0.84, 0.87). CONCLUSION: HBV/HCV-coinfected persons have higher overall SVR rates with newer DAA regimens. Though not statistically significant, the virologic response is graded, with decreasing SVR rates with increasing degree of liver fibrosis as determined by the FIB-4 scores.


Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Feminino , Hepacivirus/genética , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade
3.
Rev Soc Bras Med Trop ; 53: e20190210, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31994660

RESUMO

INTRODUCTION: Hepatitis C virus (HCV) infection is involved in the pathogenesis of autoimmune and rheumatic disorders. Although the human platelet antigens (HPA) polymorphism are associated with HCV persistence, they have not been investigated in rheumatological manifestations (RM). This study focused on verifying associations between allele and genotype HPA and RM in patients with chronic hepatitis C. METHODS: Patients (159) with chronic hepatitis C of both genders were analyzed. RESULTS: Women showed association between HPA-3 polymorphisms and RM. CONCLUSIONS: An unprecedented strong association between rheumatological manifestations and HPA-3 polymorphism, possibly predisposing women to complications during the disease course, was observed.


Assuntos
Antígenos de Plaquetas Humanas/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Polimorfismo Genético/genética , Doenças Reumáticas/sangue , Doenças Reumáticas/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Antígenos de Plaquetas Humanas/sangue , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
4.
Curr Diabetes Rev ; 16(2): 165-170, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31146663

RESUMO

Background /Introduction: A high prevalence of type 2 diabetes mellitus (T2DM) was seen in association with hepatitis C virus infection; moreover, risk of development of T2DM is increased about 11 folds in patients with risk factors for metabolic syndrome in the presence of chronic hepatitis C virus (HCV) infection. There is a few available data on the effect of HCV eradication by the new direct-acting antiviral drugs (DAAs) on the glycemic control; hence the aim of our study is to evaluate the glycated haemoglobin (HbA1c) level changes in type 2 diabetic chronic HCV non cirrhotic treatment-naïve Egyptian patients after eradication with sofosbuvir (SOV) plus daclatasvir (DCV). PATIENTS AND METHODS: A prospective observational cross-sectional study, included 128 type 2 diabetic HCV patients with easy to treat criteria (non cirrhotic treatment-naïve patients with the following liver biochemical markers; total serum bilirubin ≤ 1.2 mg/dl, serum albumin ≥ 3.5 g/dl, INR≤ 1.2 and Platelet count≥ 150.000/mm3); according to the protocol of the Egyptian National Committee for Controlling HCV and the guidelines of the European Association for the Study of the Liver. HbA1c was done for all patients enrolled in the study before starting antiviral treatment, at the end of treatment and 3 months (12 weeks) after the end of treatment to patients who achieved sustained virological response (SVR) 12 only. RESULTS: According to their antidiabetic medications, patients were classified to Group I: 70 patients taking oral hypoglycemic drugs, Group II: 58 patients taking insulin therapy +/- oral hypoglycemic drugs. Regarding the glycemic profile, a statistically significant decrease of mean HbA1c % values was found in the studied patients (n=128), over the period of the study with p-value < 0.05. For better evaluation of improvement of glycemic control, we used a composite endpoint given by the reduction of HbA1c % (of a minimum of 0.5%). The endpoint was reached to 79% (101 patients) of all studied patients 3 months after the end of treatment. 75.7% (53 patients) reached the endpoint in group I, while 82.75 % (48 patients) of group II reached the endpoint 3 months after the end of treatment. CONCLUSION: This study supports the idea that HCV eradication leads to a reduction in HbA1c in patients with diabetes, which could delay the onset and progression of microvascular diabetes complications.


Assuntos
Antivirais/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Hemoglobina A Glicada/análise , Hepatite C Crônica/tratamento farmacológico , Imidazóis/uso terapêutico , Sofosbuvir/uso terapêutico , Glicemia/análise , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Quimioterapia Combinada , Egito , Feminino , Hepatite C Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento
5.
Georgian Med News ; (295): 101-105, 2019 Oct.
Artigo em Russo | MEDLINE | ID: mdl-31804208

RESUMO

The aim of the study was to investigate the influence of Hp on clinical and biochemical course of chronic hepatitis C (CHC). The study included 150 patients with a confirmed diagnosis of chronic hepatitis C, who for various reasons did not receive specific antiviral therapy. Helicobacter pylori (Нр) was determined using a quick urease test (CLO-test) and a coprological test (CITO TEST, manufactured by Pharmasco LLC), interleukin (IL) levels: IL-1ß, IL-6, tumor necrosis factor α (TNF-α) and neopterin by ELISA. Two groups were formed: the 1st (n=52) - patients with chronic hepatitis C infected with Hp and the 2nd (n=98) - patients with chronic hepatitis C without Hp. It was found that in patients with chronic hepatitis C infected with HP, dyspeptic syndrome (94.2% versus 52.0%, p<0.05), pain and severity in the right hypochondrium (65.4% versus 20.4%, p<0.05); and periodic itching of the skin (57.7% versus 12.4%, p<0.05) were significantly more often recorded, compared with patients with chronic hepatitis C without HP. Levels of total bilirubin, alkaline phosphatase and gammaglutamyltranspeptidase are significantly higher in patients with chronic hepatitis C combined with Hp, compared with patients without Hp (p<0.05), which indicates the predominance of cholestasis syndrome in them. Also, in patients with chronic hepatitis C combined with Hp, higher levels of hepatic enzyme activity (AlAT, AsAT) were detected compared with patients with chronic hepatitis C without Hp (82.3% versus 22.9%, respectively; p<0.001). More pronounced disregulatory changes in the cytokine link of the immune system, characterized by an increase in the levels of proinflammatory cytokines: IL-1ß, IL-6, TNF-α and neopterin were registered in patients with chronic hepatitis C infected with Hp, than in patients without Hp. High levels of hepatic enzyme activity (AlAT, AsAT, GGTP), as well as the predominance of cholestasis syndrome in patients with chronic hepatitis C combined with Hp, require the development of a comprehensive eradication therapy of Hp considering the results of clinical and laboratory features of the course of CHC.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Hepatite C Crônica , Citocinas/metabolismo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/metabolismo , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/metabolismo , Humanos
6.
Orv Hetil ; 160(40): 1591-1602, 2019 Oct.
Artigo em Húngaro | MEDLINE | ID: mdl-31565976

RESUMO

Introduction: Liver cirrhosis (20-25%), hepatocellular carcinoma (1.5-3%), insulin resistance (30-40%) and type 2 diabetes (25-30%) are common complications in patients with chronic hepatitis C virus (HCV) infection; however, data are missing from Hungary. Aim: To determine the prevalence of diabetes and insulin resistance in Hungarian HCV patients; to evaluate treatment-induced metabolic changes in relation to diabetes/insulin resistance and virological response and to perform a sustained follow-up for hepatocellular carcinoma detection. Method: We enrolled 150 Hungarian HCV genotype 1 patients (mean age: 48.55 ± 8.55 years, male/female ratio: 45/55%) from 2007-2012. We analysed their baseline, week 12, and end of therapeutic follow-up (24 weeks after interferon-based therapy completion) laboratory data. We performed a 5-year follow-up (2012-2017). Results: The prevalence of insulin sensitivity, insulin resistance and diabetes was 37.4%, 35.3% and 27.3%, respectively. Insulin resistant and diabetic patients showed a decrease in fasting glucose from baseline to end of follow-up (5.47 ± 0.66 vs. 5.08 ± 0.60, p<0.001; 7.90 ± 2.67 vs. 7.04 ± 2.75, p = 0.006), as did both the sustained responder and non-responder groups. Treatment efficacy rate was poor in diabetic vs. insulin sensitive and insulin resistant groups (17% vs. 46% and 40%); insulin sensitivity was not a predictor of virological response. Three participants with diabetes were diagnosed with hepatocellular carcinoma during follow-up by regular ultrasound examinations. Conclusion: Hungarian HCV patients showed high prevalence of diabetes and insulin resistance, though antiviral therapy caused favourable changes in their carbohydrate metabolism. Antiviral therapy was less effective in diabetic patients. Follow-up ultrasound examinations are required for hepatocellular carcinoma in HCV patients, especially those with diabetes. Orv Hetil. 2019; 160(40): 1591-1602.


Assuntos
Antivirais/uso terapêutico , Glicemia/metabolismo , Carcinoma Hepatocelular/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/terapia , Resistência à Insulina , Neoplasias Hepáticas/complicações , Adulto , Idoso , Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Hungria/epidemiologia , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência
7.
An Bras Dermatol ; 94(4): 479-481, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644627

RESUMO

A 63-year-old black female patient with blisters and exulcerations on the face, neck, upper limbs, and subsequent evolution with hypochromic sclerotic areas and alopecia, is reported. Chronic hepatitis C and presence of high levels of porphyrins in urine were demonstrated. There was complete remission with the use of hydroxychloroquine, photoprotection, and treatment of hepatitis. Significant sclerodermoid involvement of the skin as a manifestation of porphyria cutanea tarda secondary to hepatitis C emphasizes the importance of diagnostic suspicion regarding skin manifestation in order to indicate the appropriate therapy, and to minimize the hepatic morbidity.


Assuntos
Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Porfiria Cutânea Tardia/etiologia , Porfiria Cutânea Tardia/patologia , Esclerodermia Localizada/etiologia , Esclerodermia Localizada/patologia , Alopecia/etiologia , Feminino , Hepatite C Crônica/terapia , Humanos , Pessoa de Meia-Idade , Porfiria Cutânea Tardia/terapia , Esclerodermia Localizada/terapia , Resultado do Tratamento
8.
BMC Infect Dis ; 19(1): 834, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601174

RESUMO

BACKGROUND: Tenofovir alafenamide (TAF)-containing combinations were introduced in Switzerland after October 2016 and are recommended over tenofovir disoproxil fumarate (TDF) in patients with osteoporosis or impaired renal function. METHODS: We included all participants of the Swiss HIV Cohort Study on TDF-containing antiretroviral therapy with follow-up visits after January 2016. We determined the proportion of switches from TDF to TAF overall, and among patients with risk factors for TDF toxicity, including osteoporosis, impaired renal function or marked proteinuria. We used multivariable logistic regression to explore predictors of switching from TDF to TAF. RESULTS: We included 5'012 patients, of whom 652 (13.0%) had risk factors for TDF toxicity. A switch from TDF to TAF was undertaken in 2'796 (55.8%) individuals overall, and in 465 (71.3%) with risk factors. Predictors of switching to TAF were male sex (adjusted odds ratio 1.27, 95% confidence interval 1.07-1.50), age > 50 years (1.43, 1.23-1.66) and the presence of risk factors for TDF toxicity (2.21, 1.77-2.75). In contrast, patients with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based single-pill regimen (0.11, 0.09-0.13), those treated in non-tertiary care centers (0.56, 0.46-0.70), as well as those with CD4 cell counts below 500/µL (0.77, 0.66-0.90) and with chronic hepatitis C infection (0.66, 0.54-0.80) were most likely to stay on TDF. CONCLUSIONS: Over 50% of patients on TDF-containing therapy, including the majority of patients at risk for TDF toxicity, were switched to TAF within two years of its introduction in Switzerland. Individuals on NNRTI-based single-pill regimens were most likely to remain on TDF.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adenina/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Interações de Medicamentos , Feminino , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Suíça , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico
9.
Medicine (Baltimore) ; 98(39): e17300, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574855

RESUMO

We investigated associations between inflammatory marker levels and hepatitis C virus (HCV)-related compensated liver cirrhosis risk in patients with chronic hepatitis C (CHC) infection in China. We used a case-control design and data from the records of 110 Chinese patients with CHC and cirrhosis for the study; 458 CHC patients who did not have a diagnosis of cirrhosis were matched to the case group by age and sex characteristics. We also investigated fatty liver disease risk factors. The group of patients with CHC infection and cirrhosis had lower platelet-to-lymphocyte ratio (PLR) values (60.63 [44.09, 89.31]) compared with the control group patients (80.24 [57.85, 111.08]). The results indicated that the group of patients with cirrhosis had higher 4-factor fibrosis index and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) values compared with the group of patients with CHC-only (1.66 [0.98, 2.60] vs 0.71 [0.45, 1.17], respectively; P < .001 and 2.12 [0.97, 4.25] vs 0.99 [0.51, 2.01], respectively; P < .001). Compared with the control group, the AST/alanine aminotransferase ratio (AAR) values in the group of patients with cirrhosis were significantly higher (P < .001). Logistic regression analysis that included model adjustment for demographic characteristics and other factors that could affect cirrhosis risk revealed that greater 1/PLR values were associated with an increased odds of having cirrhosis (adjusted odds ratio [AOR], 95% confidence interval [CI] 0.991 [0.985-0.996]); APRI and AAR values were also independent predictors of the presence of compensated cirrhosis. We found that compared with the patients with CHC-only, the triglyceride, cholesterol, and low-density lipoprotein cholesterol levels in the patients with both CHC and fatty liver disease were significantly higher. The multivariate analysis of the risk of fatty liver development in patients with CHC infection found that cholesterol level was a statistically significant risk factor (AOR [95% CI] 1.380 [1.089-1.750], P = .008). Increased 1/PLR, APRI, and AAR values were associated with increased risks for development of cirrhosis in this population of Chinese patients with CHC infection. Higher cholesterol levels increased the risk of development of fatty liver disease in patients with CHC.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Hepatite C Crônica , Cirrose Hepática , Biomarcadores/sangue , Estudos de Casos e Controles , China/epidemiologia , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/epidemiologia , Feminino , Hepacivirus/isolamento & purificação , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Humanos , Lipoproteínas/sangue , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Contagem de Linfócitos/métodos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas/métodos , Fatores de Risco
10.
Gastroenterol. hepatol. (Ed. impr.) ; 42(8): 465-475, oct. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-183882

RESUMO

Objetivo: Determinar la comorbilidad y las potenciales interacciones-farmacológicas (IFs) entre los antivirales de acción-directa pangenotípicos (AADp) y la medicación-concomitante asociada a los pacientes con hepatitis C crónica (HCC) en práctica clínica habitual en España. Métodos: Diseño observacional retrospectivo. Se incluyeron pacientes ≥18 años con diagnóstico de HCC, en tratamiento antiviral y visitados durante el año 2017. Se diferenciaron 2 grupos en función de la edad (<50 y ≥50 años). Las variables recogidas fueron: edad, género, comorbilidad general/específica, medicación-concomitante y potenciales IFs (www.hep-druginteractions.org). Los AADp analizados fueron: a) sofosbuvir/velpatasvir (SOF/VEL); b) glecaprevir/pibrentasvir; y c) sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). Análisis-estadístico bivariante: p<0,05. Resultados: Se reclutaron 3.430 pacientes, edad-media de 56,9 años y el 60,3% varones. El promedio del índice Charlson fue 0,8 puntos. Distribución por rangos de edad: 18-49 (28,9%) y ≥50 años (71,1%). El promedio de medicamentos fue: 3,1 (DE: 2,6) por paciente. El porcentaje total de potenciales IFs fue: 8,6% débil, 40,5% clínicamente significativas y 10,0% medicación contraindicada. Estas interacciones fueron mayores en los pacientes ≥50 años (8,6%; 43,8% y 12,4%, respectivamente, p<0,001). Para todas las edades SOF/VEL en comparación con glecaprevir/pibrentasvir y SOF/VEL/VOX presentó un menor porcentaje de interacciones-débiles (1,3% vs. 6,6% y 5,9%, p<0,001); interacciones clínicamente-significativas (53,4%, vs. 77,4% y 66,3%, p<0,001) y medicación-contraindicada (1,7% vs. 8,3% y 10,7%, p<0,001). Conclusiones: Los sujetos con HCC presentan una elevada comorbilidad y consumo de medicación concomitante, especialmente en pacientes mayores, circunstancia que repercute en una mayor exposición a potenciales IFs. Aunque la tasa de IFs fue considerable con las 3 combinaciones analizadas, SOF/VEL mostró una menor proporción clínicamente relevante


Objective: To determine the comorbidity and potential for drug-drug interactions (DDIs) among pangenotypic direct-acting-antivirals (pDAAs) and the concomitant medications associated with chronic hepatitis C (CHC) patients in routine clinical practice in Spain. Methods: Retrospective observational study. Included patients were ≥18 years, diagnosed with CHC, on antiviral treatment and required medical attention during 2017. Two groups were differentiated according to age ranges (<50 and ≥50 years). The variables collected were: age, gender, general/specific comorbidity, concomitant medication and potential DDIs (www.hep-druginteractions.org). The pDAAs analysed were: a) Sofosbuvir/Velpatasvir (SOF/VEL), b) Glecaprevir/Pibrentasvir (GLE/PIB) and c) Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX). Bivariate statistical analysis, P<.05. Results: 3,430 patients with a mean age of 56.9 years and 60.3% males were enrolled. The average Charlson index was 0.8. Age range distribution: 18-49 years (28.9%) and ≥50 years (71.1%). The average number of medications per patient/year was 3.1 (SD 2.6). The total percentage of potential DDIs was: 8.6% minor DDIs, 40.5% clinically significant DDIs and 10.0% contraindicated medication. These DDIs were greater in patients ≥50 years (8.6%, 43.8% and 12.4%, respectively, P<.001). For all ages, SOF/VEL showed a lower percentage of: minor interactions (1.3% vs. 6.6% and 5.9%, P<.001); clinically significant interactions (53.4%, vs. 77.4% and 66.3%, P<.001) and contraindicated medication (1.7% vs. 8.3% and 10.7%, P<.001) compared to GLE/PIB and SOF/VEL/VOX, respectively. Conclusions: Patients with CHC present high comorbidity and concomitant medication use, particularly elderly patients, thus implying a greater exposure to potential DDIs. Although the DDI rate was considerable with the three combinations analysed, SOF/VEL showed a lower number of clinically significant interactions


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Antivirais , Comorbidade , Interações de Medicamentos , Espanha/epidemiologia , Estudos Retrospectivos , Análise Estatística , Estudos Longitudinais
11.
Trans Am Clin Climatol Assoc ; 130: 104-118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31516174

RESUMO

The modern age of viral hepatitis began in the early 1960s with the serendipitous discovery of the Australia antigen, a protein that was later shown to represent the envelope of the hepatitis B virus leading to its designation as the hepatitis B surface antigen. This was the first marker for any hepatitis virus and became not only a diagnostic assay, but also a mandatory blood donor screening test and the basis for the first generation hepatitis B vaccine. Prospective studies of transfusion recipients then showed that hepatitis B virus accounted for only 25% of cases of post-transfusion hepatitis (PTH). Discovery of the hepatitis A virus in 1975 revealed that none of the non-B PTH cases were due to hepatitis A virus infection resulting in the designation of this predominant form of PTH as non-A, non-B hepatitis. Using pedigreed patient samples and the chimp model, it was shown even before the advent of molecular biology that the non-A, non-B agent was small and lipid enveloped suggesting it might be a flavivirus. This was confirmed when the agent was cloned by Houghton and colleagues at the Chiron Corporation in 1987 and renamed the hepatitis C virus (HCV). In 1990 a donor screening assay for HCV was introduced nationwide and by 1997 PTH had virtually disappeared with rates now mathematically estimated to be one case per 2 million transfusions, compared to a 30% incidence before 1970. Clinical and molecular studies of HCV have shown that it results in persistent infection in 75% to 85% of cases due to its high replication rate, its existence as a quasispecies with a high mutation rate and the ability of HCV proteins to blunt and ultimately exhaust the HCV immune response. Although HCV infection is clinically and histologically mild in most patients, it can lead to progressive fibrosis over the course of decades in 30% to 40% and culminate in cirrhosis and end-stage liver disease. HCV can also cause hepatocellular carcinoma, generally on the background of cirrhosis with an incidence of 1% to 3% per year in this setting. After 2 decades of difficult and prolonged treatments with interferon-based regimens that resulted in cure rates of less than 50%, successive generations of HCV specific direct-acting antivirals were introduced that now result in cure rates of 95% to 100% across all genotypes after only 8 to 12 weeks of nontoxic oral therapy. This unprecedented efficacy has led to speculation that HCV infection might be eradicated even in the absence of a vaccine, but there are many impediments to global eradication including ascertainment of silent carriers, access to medication, and high drug cost. Nonetheless, we are in a new era of HCV control and optimism abounds.


Assuntos
Hepatite C Crônica/história , Antivirais/uso terapêutico , Transfusão de Sangue , Carcinoma Hepatocelular/etiologia , Hepacivirus , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/transmissão , Hepatite Viral Humana/história , História do Século XX , História do Século XXI , História Antiga , Humanos , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia
12.
Biochemistry (Mosc) ; 84(8): 941-953, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31522676

RESUMO

Transforming growth factor beta (TGF-ß) acts as a tumor-suppressing cytokine in healthy tissues and non-malignant tumors. Yet, in malignancy, TGF-ß can exert the opposite effects that can promote proliferation of cancer cells. C-Kit plays a prominent role in stem cell activation and liver regeneration after injury. However, little is known about the cross-talk between TGF-ß and C-Kit and its role in the progression of hepatocellular carcinoma (HCC). Here, we studied the effect of increasing doses of TGF-ß1 on CD44+CD90+ liver stem cells (LSCs) and C-Kit gene expression in malignant and adjacent non-malignant liver tissues excised from 32 HCC patients. The percentage of LSCs in malignant tumors was two times higher compared to their counterparts from the non-malignant tissues. When treated with increasing doses of TGF-ß1, proliferation of both malignant and non-malignant LSCs was progressively suppressed, but low TGF-ß1 dose failed to suppress the growth of malignant LSCs. Moreover, C-Kit exons 9 and 11 were expressed in malignant LSCs, but not in their non-malignant counterparts. Analysis of C-Kit detected mutations in exon 9 (but not in exon 11) in some malignant liver cells resulting in the changes in the amino acid sequence and dysregulation of protein structure and function. Interestingly, in malignant liver cells, mutations in exon 9 were associated with high-viremia hepatitis C virus (HCV), and expression of this exon was not suppressed by the TGF-ß1 treatment at all doses. To our knowledge, this is the first report that mutations in the C-Kit gene in HCC patients are associated with high- viremia HCV. Our study emphasizes the need for investigation of the TGF-ß1 level and C-Kit mutations in patients with chronic HCV for HCC prevention and better therapy management.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Hepacivirus , Hepatite C Crônica/genética , Hepatite C Crônica/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Fator de Crescimento Transformador beta1/farmacologia , Idoso , Carcinoma Hepatocelular/etiologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Farmacorresistência Viral Múltipla , Éxons/genética , Feminino , Expressão Gênica , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Receptores de Hialuronatos/metabolismo , Fígado/patologia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Mutação , Células-Tronco Neoplásicas/metabolismo , Antígenos Thy-1/metabolismo , Viremia
13.
Am J Case Rep ; 20: 1394-1397, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31541071

RESUMO

BACKGROUND Rituximab is a chimeric monoclonal antibody to CD20 that is used to treat vasculitis, B-cell lymphoproliferative disorders, and B-cell non-Hodgkin lymphoma (NHL). A report is presented of a case of rituximab-induced acute thrombocytopenia (RIAT) in a woman with splenic marginal zone lymphoma (SMZL) and chronic hepatitis C virus (HCV) infection. CASE REPORT A 46-year-old woman with SMZL complicated by chronic HCV infection presented with worsening B symptoms of fever, night sweats, and loss of weight. The patient had a history of recreational drug use. Intravenous treatment with rituximab (dose, 375 mg/m²) commenced with close monitoring in hospital. On the following day, the complete blood count (CBC) showed that her platelet count had dropped from her admission level of 167,000/µl to 7,000/µl, with no change in hemoglobin or white blood cell (WBC) levels. A diagnosis of RIAT was made. The patient was managed conservatively and monitored for the development of potential clinical complications. CONCLUSIONS RIAT is a rare complication of treatment with rituximab and may be poorly recognized. Further studies are needed to determine the incidence and causes of thrombocytopenia in patients treated with rituximab and the possible association with chronic viral infections, including HCV.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Rituximab/efeitos adversos , Trombocitopenia/induzido quimicamente , Feminino , Hepatite C Crônica/complicações , Humanos , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Esplênicas/tratamento farmacológico
14.
Rev. clín. esp. (Ed. impr.) ; 219(6): 293-302, ago.-sept. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-186570

RESUMO

Introducción: Se desconoce la asociación entre ateromatosis subclínica e infección crónica por el virus de la hepatitis C (VHC), relevante ahora que los antivirales mejoran la supervivencia en los pacientes infectados. Objetivos: Conocer si el VHC es factor de riesgo independiente de ateromatosis subclínica y analizar las modificaciones del perfil lipídico según niveles de ARN viral y fibrosis hepática. Pacientes y métodos: Estudio observacional y transversal; incluye 102 pacientes VHC positivos y 102 sujetos VHC negativos con paridad de sexo y edad, sin antecedentes de enfermedad cardiovascular, renal ni diabetes. La ateromatosis (presencia de placas de ateroma) y el grosor íntima-media carotídeo (GIMc) se evaluó mediante ecografía de arterias carótidas y femorales. Resultados: La presencia de ateromatosis en cualquier territorio vascular fue mayor en pacientes VHC que en sujetos no infectados (58,8% frente a 28,4%, p<0,001). En el análisis multivariante, los factores significativamente asociados con ateromatosis incluyeron infección por VHC (OR=14,37 [5,5-37,3]; p<0,001), edad (OR=1,12 [1,1-1,2]; p<0,001), sexo masculino (OR=4,32 [1,9-9,5]; p<0,001) y el coeficiente triglicéridos/colesterol HDL (TG/HDL-indicador indirecto de insulinorresistencia) (OR=1,34 [1,1-1,6]; p=0,007). Los pacientes VHC con placas de ateroma presentaban mayor coeficiente TG/HDL, sin diferencias significativas en cuanto a la carga viral ni grado de fibrosis hepática con un perfil lipídico de «bajo riesgo». Conclusiones: La infección VHC es factor de riesgo independiente de ateromatosis subclínica. La ecografía arterial sistémica en esta población mejora la evaluación del riesgo cardiovascular más allá de las alteraciones del perfil lipídico y del cálculo de riesgo por tablas SCORE


Background: The association between subclinical atheromatosis and chronic hepatitis C virus (HCV) infection is unknown but is relevant now that antivirals are improving the survival of patients with the infection. Objectives: To determine whether HCV is an independent risk factor for subclinical atheromatosis and to analyse the changes in lipid profiles according to viral RNA levels and hepatic fibrosis. Patients and methods: We conducted an observational, cross-sectional study that included 102 HCV-positive patients and 102 HCV-negative patients with parity in terms of sex and age, with no history of cardiovascular or kidney disease or diabetes. Atheromatosis (the presence of atheromatous plaques) and the carotid intima-media thickness (CIMT) were assessed using ultrasonography of the carotid and femoral arteries. Results: There was a greater presence of atheromatosis in any vascular territory in HCV-positive patients than in the patients without infection (58.8% vs. 28.4%, p<.0001). In the multivariate analysis, the factors significantly associated with atheromatosis included HCV infection (OR, 14.37 [5.5-37.3]; p<.001), age (OR, 1.12 [1.1-1.2]; p<.001), male sex (OR, 4.32 [1.9-9.5]; p<.001) and the triglyceride/HDL cholesterol coefficient (TG/HDL-indirect indicator of insulin resistance) (OR, 1.34 [1.1-1.6]; p=.007). The HCV-positive patients with atheromatous plaques had a higher TG/HDL coefficient but no significant differences in terms of the viral load or degree of hepatic fibrosis and with a 'low risk' lipid profile. Conclusions: HCV infection is an independent risk factor for subclinical atheromatosis. Systemic arterial ultrasonography for this population improves the cardiovascular risk assessment beyond lipid profile abnormalities and the risk calculation using SCORE tables


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Hepatite C Crônica/complicações , Cirrose Hepática/epidemiologia , Lipídeos/sangue , Doenças das Artérias Carótidas/epidemiologia , Placa Aterosclerótica/epidemiologia , Estudos Transversais , Estudos de Casos e Controles , Espessura Intima-Media Carotídea/estatística & dados numéricos , Doenças Assintomáticas/epidemiologia
16.
Expert Rev Gastroenterol Hepatol ; 13(9): 839-848, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31392907

RESUMO

Introduction: Over 70 million people are infected with hepatitis C virus (HCV), increasing the risk of cirrhosis and hepatocellular carcinoma. Areas covered: Since the approval of the first interferon-free direct-acting antiviral (DAA) therapy in 2011, a number of DAAs have been approved, and HCV is now considered curable. Until recently, however, there were no clear guidelines on how to re-treat patients who fail DAA therapy. Current protease inhibitors (PIs) are generally unaffected by earlier resistance-associated variants (RAVs), but many NS5A inhibitors continue to have overlapping resistance profiles, and NS5A RAVs can persist even in the absence of DAAs. Expert opinion: Fortunately, RAVs affecting NS5B polymerase inhibitors are rare, making sofosbuvir a safe choice as the backbone of re-treatment therapies. Recent re-treatment guidelines that take into account genotype, fibrosis, treatment history, and RAV suggest that >90% of patients with prior treatment failures can be successfully re-treated with sofosbuvir/velpatasvir, sofosbuvir/velpatasvir/voxilaprevir or glecaprevir/pibrentasvir.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Antivirais/efeitos adversos , Humanos , Falha de Tratamento
17.
Int J Mol Sci ; 20(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370326

RESUMO

Two polymorphisms in the promoter region of macrophage migration inhibitory factor (MIF) - rs755622 and rs5844572 - exhibit prognostic relevance in inflammatory diseases. The aim of this study was to investigate a correlation between these MIF promoter polymorphisms and the severity of hepatitis C virus (HCV)-induced liver fibrosis. Our analysis included two independent patient cohorts with HCV-induced liver fibrosis (504 and 443 patients, respectively). The genotype of the single nucleotide polymorphism (SNP) -173 G/C and the repeat number of the microsatellite polymorphism -794 CATT5-8 were determined in DNA samples and correlated with fibrosis severity. In the first cohort, homozygous carriers of the C allele in the rs755622 had lower fibrosis stages compared to heterozygous carriers or wild types (1.25 vs. 2.0 vs. 2.0; p = 0.03). Additionally, ≥7 microsatellite repeats were associated with lower fibrosis stages (

Assuntos
Carcinoma Hepatocelular/genética , Predisposição Genética para Doença , Hepatite C Crônica/genética , Oxirredutases Intramoleculares/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Fatores Inibidores da Migração de Macrófagos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/virologia , Estudos de Coortes , Técnicas de Imagem por Elasticidade , Feminino , Expressão Gênica , Frequência do Gene , Hepacivirus/patogenicidade , Hepacivirus/fisiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico por imagem , Hepatite C Crônica/virologia , Heterozigoto , Homozigoto , Humanos , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/virologia , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Polimorfismo Genético , Regiões Promotoras Genéticas , Índice de Gravidade de Doença
18.
Acta Med Indones ; 51(2): 128-136, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31383827

RESUMO

BACKGROUND: HIV infection in HCV-infected patients accelerates disease progression and reduces the success rate of Peg-IFN/RBV treatment. HCV mutation in NS5A-ISDR/PKR-BD region improved the outcome in HCV monoinfection treated with Peg-IFN/RBV. SNP-IL28B polymorphism is predicted to have an effect on HCV quasispecies evolution. However, the role of NS5A mutation and SNP IL-28B in HIV-HCV coinfection is still unclear. The aim of the study is to determine the role of HCV NS5A-ISDR/PKR-BD mutation and SNP IL-28 polymorphism on the successfulness of Peg-IFN/RBV therapy in HCV-HIV coinfection. METHODS: prospective cohort was performed in this study. Plasma sample were obtained from 30 and 8 patients with HCV-HIV coinfection and HCV monoinfection, respectively. PCR nucleotide sequencing was performed after RNA virus extraction and cDNA synthesis. Protein secondary structure and prediction of mutation function were analyzed using PredictProtein (PP) program. RESULTS: sixteen HCV-HIV coinfected patients and none from eight HCV patients achieved sustained virological response (SVR). ≥1 non-neutral mutation was found in 24/30 HCV-HIV coinfection and more frequent in SVR group (14 patients). ≥1 non-neutral mutation were found statistically significant for overall SVR achievement (p<0.05) in all patients regardless of coinfection or monoinfection status. Of the 27 HCV-HIV coinfected patients with CC-gene, 21 subjects had non-neutral mutation. The structure which was expected as NS5A binding site structure was different from consensus (wild type) in SVR group, while the structure was similar to consensus in non-SVR group. CONCLUSION: having ≥1 non-neutral mutation was associated with SVR achievement in Peg-IFN/RBV therapy, regardless of monoinfection and coinfection status.


Assuntos
Infecções por HIV/complicações , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Interferons/genética , Proteínas não Estruturais Virais/genética , Adulto , Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação , Polietilenoglicóis , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Ribavirina/uso terapêutico , Resposta Viral Sustentada
19.
Acta Med Indones ; 51(2): 137-144, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31383828

RESUMO

BACKGROUND: increased serum alpha fetoprotein (AFP) levels are often found in patients with advanced hepatocellular carcinoma (HCC). Cluster Differentiation 44 (CD44) and CD90 are stem cell biomarkers that have been assumed as the early HCC markers and associated with onset and progressivity of HCC. The study related to HCC stem cell has not been available in Indonesia. The present study aimed to evaluate the expression of cancer stem cell markers (CD44, CD90) and AFP levels in patients with advanced liver disease. METHODS: an observational study was conducted in 41 patients with chronic hepatitis B and/or C infection, liver cirrhosis, and HCC at dr. Saiful Anwar General Hospital. CD44 and CD90 expressions were measured with flow cytometry, and AFP serum levels with ELISA. Data on patient characteristics were evaluated using bivariate and multivariate statistical analysis (One-way ANOVA, Mann-Whitney, Chi-Square, Kruskal-Wallis). Data of CD44, CD90 and AFP were analyzed using Kruskal Wallis test with a significance value of p<0.05, and diagnostic power was analyzed using receiver operating characteristic (ROC). RESULTS: the subjects of our study were 16 patients with chronic hepatitis, 15 patients with liver cirrhosis, and 10 patients with HCC. There was a significant difference regarding CD44+CD90+ and AFP among those three groups (p=0.001; p=0.000) specifically in chronic hepatitis compared to liver cirrhosis (p=0.002; p=0.000) and HCC (p=0.002; p=0.000) respectively. ROC analysis showed the best diagnostic power for the combination of CD44+CD90+ and AFP (AUC=0.981; p=0.000). CONCLUSION: there are higher expressions of CD44+CD90+ and serum AFP levels in patients with HCC compared to the other two groups (those with chronic hepatitis and liver cirrhosis). The combination of both parameters has the best diagnostic power of HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Receptores de Hialuronatos/sangue , Neoplasias Hepáticas/patologia , Células-Tronco Neoplásicas/patologia , Antígenos Thy-1/sangue , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Estudos Transversais , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Células-Tronco Neoplásicas/metabolismo , Valor Preditivo dos Testes , Curva ROC
20.
Transplant Proc ; 51(7): 2482-2485, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31405736

RESUMO

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a global health problem, and the need for liver transplants is ever-growing. For optimal surgical success, risk factors must be identified and HCV viral load must be reduced to a minimum to avoid complications. In this study, we aimed to investigate the role of HCV viral load on the post-transplant biliary complications. METHOD: Between 2004 and 2018, the cases of 114 liver transplant recipients with HCV infection were retrospectively reviewed. Data collection included demographic variables, preoperative and postoperative amount of serum HCV RNA copies, preoperative diagnosis of hepatocellular carcinoma (HCC), and postoperative biliary complications in the early and late period. After missing values were excluded, the remaining 97 patients were divided into 2 groups according to preoperative HCV RNA status (Group A: HCV RNA [+] and Group B: HCV RNA [-]). RESULTS: Demographic parameters were similar among both groups. There were 67 patients in Group A and 30 patients in Group B. The overall rate of biliary complications was higher in Group A without statistical significance (20% [n = 14] vs 13% [n = 4], respectively, P = .573). Biliary stricture occurrence in the late period was also higher in Group A. In HCC (+) patients (n = 26), biliary complications were significantly higher compared to HCC (-) patients (34% vs 12%, P = .018). However, in patients with biliary complications, the rate of multiple duct anastomoses was higher with no statistical significance (45% vs 26%, respectively, P = .14). CONCLUSION: The biliary complications on patient survival has been previously established, and this is mostly evident in those patients with viral etiology and hepatocellular carcinoma. As was also suggested in our study, hepatocellular carcinoma and positive viral status should be considered as predisposing factors for postoperative biliary complications after liver transplantation. However, the rate of multiple duct anastomoses should also be taken into consideration. New standards of antiviral medications and bridge therapy for HCC may improve transplant outcomes.


Assuntos
Carcinoma Hepatocelular/complicações , Hepatite C Crônica/virologia , Neoplasias Hepáticas/complicações , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Feminino , Hepacivirus , Hepatite C Crônica/complicações , Humanos , Incidência , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Carga Viral
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