RESUMO
Risk of hepatocellular carcinoma (HCC) in hepatitis C virus cirrhotic patients treated with direct-acting antiviral agents (DAA) is still debating. We investigated it in a large cohort. The cohort comprised 1045 cirrhotic patients who completed treatment with DAA, with a median follow-up of 17.3 months after end of treatment (EOT), including 943 patients without history of HCC and 102 previously treated for HCC. The majority were men (59.9%), with compensated cirrhosis (88.8%), genotype 1b (44.7%). Univariate, multivariate analysis and Kaplan-Meier curves were performed to detect predictors of HCC in patients with and without reduction in alpha-fetoprotein (AFP) during treatment. SVR12 was 95.6%. HCC developed in 95 (9.9%), including 54 of 943 (5.7%) occurrent and 41 of 102 (39%) recurrent tumours. De novo were more often unifocal (P = 0.01) and curable (P = 0.03). AFP decreased from 16.1 ± 36.2 mg/dL (baseline) to 11.4 ± 55 mg/dL (EOT). At univariate analysis, predictors were a previous HCC, older age, higher model for end-stage liver disease, prolonged INR, lower platelets, baseline and EOT AFP, virological failure and no reduction in AFP during treatment. Kaplan-Meier curves showed lower incidence of HCC in patients showing any reduction in AFP (P = 0.001). Those with AFP <6 ng/mL had the lowest risk (P = 0.0002). At logistic regression, platelets (P = 0.009, OR 0.99 CI: 0.99-1.00), previous HCC (P < 0.000 01, OR: 10.76, 95% CI: 5.89-19.34) and no reduction in AFP during treatment (P = 0.0005, OR: 2.98, CI: 1.60-5.54) were independent predictors of HCC. In conclusion, risk of HCC after DAA treatment remains substantial. It is higher among patients with previous HCC, low platelets and without reduction in AFP during treatment.
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Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Fibrose/complicações , Fibrose/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , alfa-Fetoproteínas/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medição de Risco , Soro/química , Soro/virologia , Resposta Viral SustentadaRESUMO
BACKGROUND & AIMS: The proportion of HCV-infected patients over age 65 years in Western countries is increasing. This growth and the advent of new antiviral therapy bring into the question the real-world efficacy and safety of the combination of sofosbuvir (SOF) and simeprevir (SMV) plus a flat dose of 800 mg/d ribavirin (RBV) in elderly patients with cirrhosis compared to younger patients. METHODS: Retrospective observational multicentre real-life investigation study of SOF/SMV/RBV for a duration of 12 weeks in HCV genotype 1-infected patients with cirrhosis. RESULTS: Of the 270 patients enrolled in this study, with compensated cirrhosis, 133 (49.2%) were ≥65 years of age. Sustained virological response at 12 weeks (SVR12) was achieved by 94.2% (129/137) of those aged <65 years and 97.7% (130/133) of those ≥65 years. Diabetes was the most common comorbidity in patients ≥65 years compared to younger patients (26.3% vs 12.4% P<.003). The most common adverse event (AE) in elderly patients was a grade 2 anaemia (35.3% vs 19.9% P<.004). CONCLUSIONS: Sofosbuvir/simeprevir plus a daily flat dose of RBV 800 mg for 12 weeks was highly effective and safe in genotype 1 elderly patients with compensated cirrhosis.
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Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Ribavirina/administração & dosagem , Simeprevir/administração & dosagem , Sofosbuvir/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/etiologia , Antivirais/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Hepacivirus/genética , Humanos , Itália , Cirrose Hepática/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Ribavirina/efeitos adversos , Simeprevir/efeitos adversos , Sofosbuvir/efeitos adversos , Resposta Viral SustentadaRESUMO
BACKGROUND & AIMS: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. METHODS: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N=200) and whenever possible at baseline (N=70). RESULTS: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P<.001). Interestingly, 57.1% of DAA IFN-free non-responders had a misclassified genotype, and 3/4 sofosbuvir breakthroughs showed the major-RAS-S282T, while RAS-L159F was frequently found in sofosbuvir relapsers (18.2%). Notably, 9.0% of patients showed also extra target RASs, and 47.4% of patients treated with ≥2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. CONCLUSIONS: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.
Assuntos
Antivirais/uso terapêutico , Farmacorresistência Viral/genética , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Proteínas não Estruturais Virais/genética , Idoso , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Humanos , Interferons/uso terapêutico , Itália , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva , Ribavirina/uso terapêutico , Análise de Sequência de DNA , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Falha de TratamentoRESUMO
BACKGROUND: Liver transplantation (LT) is a well-established procedure for hepatocellular carcinoma (HCC) within the Milan criteria. Yttrium-90 microspheres radioembolization (Y90-RE) has shown to be an effective and safe treatment of primary liver tumors. We retrospectively evaluate the efficacy of the Y90-RE in patients with HCC prior to LT. METHODS: From January 2002 to December 2015, 365 patients were transplanted at the San Camillo Hospital Center. One hundred forty-three patients were transplanted for HCC, and in 22 cases the patients were treated with Y90-RE before LT. RESULTS: Three patients were treated with Y90-RE within the Milan criteria, and 19 patients were out of criteria before Y90-RE. Four patients had an increasing MELD score between Y90-RE and LT. On the other hand, alpha-fetoprotein decreases after Y90-RE treatment in all cases. No patient death was observed in Y90-RE procedure or at LT. In 78.9 % of cases, a successful downstaging was observed, and in 100 % of cases bridging was achieved. From Y90-RE treatment overall survival was 43.9 months. From LT, overall mean survival was 30.2 months with a free survival of 29.6 months. The overall survival after LT analysis between the patients treated with Y90-RE and patients without was not significant (p = 0.113). Free survival analysis was not significant (p = 0.897) between the two populations. CONCLUSIONS: We successfully performed LT in patients after Y90-RE treatment both as bridging and downstaging for HCC and obtained a similar overall and free survival of LT for HCC within Milan criteria. Y90-RE becomes a real option to provide curative therapy for patients who traditionally are not considered eligible for surgery.
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Embolização Terapêutica/métodos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Feminino , Humanos , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Estudos RetrospectivosRESUMO
Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV-based all-oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60 mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 ± 8.2 years; 93% had genotype 1 HCV and 31% had biopsy-proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End-Stage Liver Disease (MELD) score was 13.0 ± 6.0, and the proportion with Child-Turcotte-Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3 × 6 log10 IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n = 77), DCV+SMV (n = 18), and DCV+SMV+SOF (n = 2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV-based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV-based all-oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Imidazóis/uso terapêutico , Simeprevir/uso terapêutico , Sofosbuvir/uso terapêutico , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Carbamatos , Ensaios de Uso Compassivo , Quimioterapia Combinada/métodos , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Hepatopatias/cirurgia , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pirrolidinas , Recidiva , Estudos Retrospectivos , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Ribavirina/uso terapêutico , Simeprevir/administração & dosagem , Simeprevir/efeitos adversos , Sofosbuvir/administração & dosagem , Sofosbuvir/efeitos adversos , Resultado do Tratamento , Valina/análogos & derivadosRESUMO
Rituximab is a chimeric anti-CD20 monoclonal antibody that is a widely used for the treatment of B cells non-Hodgkin lymphoma. The use of chemotherapy regimens containing rituximab in HCV-positive patients with non-Hodgkin lymphoma has been associated with liver dysfunction, but no cases of cholestatic hepatitis C were described. To our knowledge, this is the first case of cholestatic hepatitis C in an HCV-positive patient with diffuse large B-cell lymphoma describes in the literature. We discuss the pathogenetic mechanisms underlying this severe form of hepatitis and describe its evolution after antiviral treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Colestase/induzido quimicamente , Hepacivirus/efeitos dos fármacos , Hepatite C/induzido quimicamente , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab/efeitos adversos , Ativação Viral/efeitos dos fármacos , Idoso , Antivirais/uso terapêutico , Biópsia , Colestase/diagnóstico , Colestase/tratamento farmacológico , Colestase/virologia , Hepacivirus/patogenicidade , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Humanos , Masculino , Fatores de Tempo , Resultado do TratamentoRESUMO
UNLABELLED: BACKGROUND AND RATIONALE OF THE STUDY: Effect of Long-term nucleoside/nucleotide (NUC) on hepatocellular carcinoma (HCC) incidence in a population of HBeAg-negative genotype D patients has not been adequately studied in real-life cohorts. Our aim was to evaluate the impact of liver fibrosis and other variables on HCC incidence in this population of patients. Of 745 patients with chronic hepatitis B (CHB), 306 HBeAg-negative genotype D were selected and included in this study. All patients received treatment with NUC for at least 18 months. Patients with CHB or compensated cirrhosis were included. Patients with HCC diagnosed before or during the first 18 months of NUC therapy were excluded. RESULTS: HCC was diagnosed in 2 CHB patients (1.0%) and 23 cirrhosis patients (20%) (OR = 24.41, 95% CI 5.40 < OR < 153.2; p < 0.0001). Multivariate analysis revealed that HCC risk was independently associated with age ≥ 60 years (OR = 6.45, 95% CI 1.22 to 34.0; p = 0.02) and liver cirrhosis (OR = 12.1, 95% CI 1.39 to 106.2; p = 0.02), but not with virological response (VR), and previous resistance to NUC, or rescue therapy. Multivariate analysis in cirrhosis patients revealed that only age ≥ 60 years was an independent risk factor associated with HCC (p = 0.003). CONCLUSIONS: Liver cirrhosis and age ≥ 60 years are the stronger risk factors for HCC in genotype D HBeA-gnegative patients. Previous resistance to NUC in patients that achieved a VR after rescue therapy was not a predictive factor regarding HCC. VR does not appear to significantly reduce the overall incidence of HCC when a patient has already progressed to liver cirrhosis.
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Antivirais/uso terapêutico , Carcinoma Hepatocelular/etiologia , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/etiologia , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Idoso , Estudos de Coortes , DNA Viral/genética , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/imunologia , Humanos , Lamivudina/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Organofosfonatos/uso terapêutico , Estudos Retrospectivos , Telbivudina , Tenofovir , Timidina/análogos & derivados , Timidina/uso terapêutico , Carga ViralRESUMO
BACKGROUND: The impact of viral subtype on the rate of sustained virological response (SVR) to antiviral therapy in patients chronically infected with hepatitis C genotype 1 subtype 1a and 1b has not been extensively investigated. The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and 1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus ribavirin. METHODS: For 48 weeks, 388 "naïve"genotype 1 patients were treated weekly with PEG-IFN α-2a or PEG-INF α-2b combined with daily ribavirin (1000-1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were compared after 4 (rapid virological response, RVR), 12 (early virological response, EVR), and 48 (end treatment virological response, ETR) weeks of treatment as well as 24 weeks after the last treatment (sustained virological response, SVR). RESULTS: The rate of SVR was higher in subtype 1a patients than subtype 1b patients (55% vs. 43%; p < 0.02). Multiple logistic regression analysis showed that infection with genotype 1a (odds ratio(OR) : 1.8; 95% confidence interval (CI): 1.4 to 4.1), age < 50 years (OR:7.0; 95% CI 1.1 to 21.2), alanine aminotransferase level (ALT)<100 IU/ml (OR:2.1; 95% CI: 1.3 to3.5), HCV-RNA < 5.6 log10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR. CONCLUSION: Dual antiviral therapy is more effective against HCV subtype 1a than against subtype 1b and this difference is independent of other factors that may favour viral clearance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01342003.
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Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Alanina Transaminase/sangue , Biópsia , Quimioterapia Combinada , Feminino , Genótipo , Hepatite C Crônica/patologia , Humanos , Interferon alfa-2 , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: Porphyria cutanea tarda (PCT) is the most common type of porphyria. The strong association between PCT and hepatitis C virus (HCV) infection is well established. Although antiviral treatment of chronic hepatitis C may improve PCT in some cases, de novo onset of PCT has been observed in patients under- going peginterferon/ribavirin treatment. We present a rare case of a genotype 3 HCV-positive liver transplant recipient who developed PCT during antiviral treatment and discuss its probable etiopathogenesis. CASE PRESENTATION: A genotype 3 HCV-positive liver transplant recipient, a 42-year-old man, was treated with peginterferon alfa-2a (180 µg/week) combined with ribavirin (1,200 mg/day) for recurrence of HCV infection after liver transplantation. He presented with hyperferritinemia but tested negative for genetic hemochromatosis (C282Y and H63D mutations). During antiviral therapy, he developed skin lesions on his hands characterized by vesicles and erosions consistent with PCT. PCT was confirmed by skin biopsy and elevated urinary uroporphyrin levels (1,469 mg/24 h). He was treated with chloroquine (200 mg) twice weekly, resulting in gradual regression of the skin lesions. Antiviral treatment was stopped after 48 weeks, and the patient achieved a sustained virological response. In conclusion, we report an extremely rare case of PCT in a genotype 3 HCV-positive liver transplant patient treated with antiviral therapy. We believe that the combination of HCV genotype 3 infection; hemolysis due to ribavirin treatment; and increased plasma levels of cytokines, such as IL-6 and TNFα, could have altered the patient's iron metabolism and thus caused PCT.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Falência Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Polietilenoglicóis/uso terapêutico , Porfiria Cutânea Tardia/etiologia , Ribavirina/uso terapêutico , Adulto , Antivirais/efeitos adversos , Biópsia , Cloroquina/uso terapêutico , Quimioterapia Combinada , Genótipo , Hemólise/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Humanos , Distúrbios do Metabolismo do Ferro/etiologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Falência Hepática/diagnóstico , Falência Hepática/virologia , Masculino , Porfiria Cutânea Tardia/diagnóstico , Porfiria Cutânea Tardia/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Recidiva , Ribavirina/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: In patients with chronic hepatitis C virus (HCV) genotype 2 or 3, 24 weeks' treatment with pegylated interferon alfa (PEG-IFN-alpha) and ribavirin induces a sustained virological response (SVR) in almost 80% of cases. Evidence suggests that a similar response rate may be obtained with shorter treatment periods, especially in patients with a rapid virological response (RVR). The aim of this study was to compare the efficacy of 12 or 24 weeks of treatment in patients with chronic HCV genotype 2 or 3 and to identify patients suitable for 12 weeks treatment. METHODS: Two hundred and ten patients received PEG-IFN-alpha-2a (180 ug/week) and ribavirin (800-1200 mg/day) for 4 weeks. Patients with a RVR (HCV RNA not detectable) were randomized (1:1) to either 12 (group A1) or 24 (group A2) weeks of combination therapy. Patients without a RVR continued with 24-weeks' combination therapy (group B). HCV RNA was monitored at weeks 4, 8, 12, and 24, and at week 24 post-treatment. RESULTS: At study end, end of treatment response (ETR) was observed in 62 (86%) patients of group A1 and in 55 (77%) patients of group A2 (p < 0.05) Relapse rate was 3% each in groups A1 and A2, and 6% in group B. Among patients with a HCVRNA test 24 weeks after the end of treatment, SVR was observed in 60 (83%) of group A1 patients and in 53 (75%) of group A2 patients. Rapid virological response, low baseline HCV RNA levels, elevated alanine aminotransferase levels and low fibrosis score, were the strongest covariates associated with SVR, independent of HCV genotype. No baseline characteristic was associated with relapse. CONCLUSION: In HCV patients with genotype 2 or 3, 12-week combination therapy is as efficacious as 24-week therapy and several independent covariates were predictive of SVR. TRIAL REGISTRATION: Trial number ISRCTN29259563.
Assuntos
Antivirais/administração & dosagem , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Idoso , Esquema de Medicação , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Interferon alfa-2 , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Recidiva , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The once-daily oral combination of daclatasvir (DCV) and sofosbuvir (SOF), with or without ribavirin (RBV), is effective and well tolerated in patients with hepatitis C virus (HCV). However, further field-practice studies are necessary to investigate the effectiveness and safety of the DCV+SOF combination in diverse subpopulations of patients with HCV, including those who are more challenging to treat such as patients with a genotype 3 (G3) infection. The aim of this retrospective, multicenter, field-practice study was to investigate the therapeutic efficacy and safety of the oral combination of DCV and SOF, with or without RBV (DCV+SOF±RBV), in a large unselected cohort of patients with chronic HCV infection (CHC). PATIENTS AND METHODS: Consecutive patients received DCV+SOF±RBV for 12 or 24 weeks. The efficacy endpoint was sustained virological response at 12 weeks after the end of treatment (SVR12). Safety factors were also considered. RESULTS: A total of 620 patients were included in this study; the predominant genotype was G3 (55.3%). Of the total sample, 248 (40%) patients were treated with DCV+SOF+RBV and 372 (60%) did not receive RBV. The majority of patients assessed at week 12 (98%, 596/608) achieved SVR12. Among G3 patients, 98.8% (335/339) achieved SVR12. The most common adverse event was elevated bilirubin (30.6%), recorded in 4.9% of cases as a grade 3-4 adverse event. CONCLUSION: This study shows the high pan-genotypic effectiveness and safety of the DCV+SOF±RBV combination in a large, unselected sample of CHC patients with G1-4, including a wide proportion of G3 CHC patients.
RESUMO
BACKGROUND/AIMS: To evaluate, in clinical practice, the efficacy and safety of combined antiviral treatment in hepatitis C virus (HCV) carriers with normal alanine aminotransferase (ALT) levels. METHODS: Eighty-eight HCV carriers with persistently normal ALT levels were enrolled. All patients received peginterferon (PEG-IFN) alpha-2a 180 microg once weekly plus ribavirin (RBV) 800 mg/day for 24 weeks (HCV-2 and -3) or 1000-1200 mg/day for 48 weeks (HCV-1). RESULTS: Rapid virological response (RVR) was seen in 66/88 patients (75%): 19/32 HCV-1 (59%), 40/46 HCV-2 (87%) and 7/10 HCV-3 patients. Younger patients, leaner subjects and patients with non-1 genotype or lower baseline HCV RNA levels were more likely to achieve an RVR. Sustained virological response (SVR) was seen in 69/88 patients (78%): 20/32 HCV-1 patients (62%), 41/46 HCV-2 patients (89%) and 8/10 (80%) HCV-3 patients. The overall SVR rate was 88% in patients with RVR (58/66) and 50% in those without RVR. CONCLUSIONS: The combination of PEG-IFN alpha-2a and RBV produces, in patients with normal ALT, virological response rates that are comparable or even higher than those obtained in patients with elevated ALT levels. Thus, we suggest that in selected cases immediate therapy might be preferred to a 'wait-and-see' policy.
Assuntos
Alanina Transaminase/sangue , Antivirais/administração & dosagem , Portador Sadio/tratamento farmacológico , Hepatite C/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Portador Sadio/patologia , Portador Sadio/virologia , Quimioterapia Combinada , Feminino , Hepatite C/patologia , Hepatite C/virologia , Humanos , Interferon alfa-2 , Fígado/patologia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Proteínas RecombinantesRESUMO
BACKGROUND: Sarcopenia has been associated with poor outcomes in patients with cirrhosis and solid tumours. OBJECTIVE: Analyse the influence of sarcopenia on survival and treatment duration in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. METHODS: We conducted a multicentre, retrospective study on 96 patients with advanced HCC treated with sorafenib, all with available abdominal computed tomography (CT) scan within 30 days from treatment start. Anthropometric, laboratory, treatment and follow-up data were collected. Sarcopenia was defined by reduced skeletal muscle index calculated from an L3 section CT image. RESULTS: Sarcopenia was present in 49% of patients. Patients were divided into two groups according to sarcopenia: age was significantly higher in the sarcopenic group (SG) (66 years (31-87) versus 72 years (30-84), p = 0.04], with no difference in other baseline characteristics. The SG showed shorter overall survival (OS) (39 (95% confidence interval (CI) 26-50) versus 61 (95% CI 47-77) weeks (p = 0,01)) and shorter time on treatment (12.3 (95% CI 8-19) versus 25.9 (95% CI 15-33) weeks (p = 0.0044)). At multivariate analysis, sarcopenia was independently associated to reduced OS (p = 0.03) and reduced time on treatment (p = 0.001). CONCLUSION: Sarcopenia is present in almost half of patients with advanced HCC, and is associated with reduced survival and reduced duration of oral chemotherapy.
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Antivirais/administração & dosagem , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Cirrose Hepática/etiologia , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Feminino , Humanos , MasculinoRESUMO
Patients infected with human immunodeficiency virus (HIV) are at increased risk for subclinical atherosclerosis. Whether increased cardiac adiposity may be related to HIV subclinical atherosclerosis is still unexplored. The objective of this study was to evaluate whether echocardiographically determined subepicardial adipose tissue, an index of cardiac adiposity, is related to carotid intima-media thickness (IMT), an index of subclinical atherosclerosis, in HIV-infected patients receiving highly active antiretroviral therapy. Echocardiographic epicardial fat thickness and ultrasonographic IMT were measured in 103 consecutive HIV-infected Caucasian subjects receiving highly active antiretroviral therapy. Echocardiographic subepicardial adipose tissue showed an excellent correlation with IMT (r = 0.92, p <0.01). Multiple regression analysis showed that IMT was best predicted by epicardial fat thickness (r(2) = 0.81, p <0.01). In conclusion, this study suggests, for the first time, that epicardial adipose tissue, an index of cardiac adiposity, may be significantly related to subclinical atherosclerosis in HIV-infected patients.
Assuntos
Tecido Adiposo/patologia , Doenças das Artérias Carótidas/etiologia , Artéria Carótida Primitiva/patologia , Pericárdio/patologia , Túnica Íntima/patologia , Túnica Média/patologia , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/virologia , Adiposidade , Adolescente , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Pressão Sanguínea , Índice de Massa Corporal , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/patologia , Doenças das Artérias Carótidas/virologia , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/fisiopatologia , Artéria Carótida Primitiva/virologia , Ecocardiografia , Feminino , Infecções por HIV/complicações , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pericárdio/diagnóstico por imagem , Pericárdio/virologia , Valor Preditivo dos Testes , Análise de Regressão , Resultado do Tratamento , Túnica Íntima/diagnóstico por imagem , Túnica Íntima/virologia , Túnica Média/diagnóstico por imagem , Túnica Média/virologia , Relação Cintura-QuadrilRESUMO
We describe one patient suffering from hepatocellular carcinoma who presented with a right atrial metastatic tumour as a result of invasion of the inferior vena cava and extension into the right atrium. Two-dimensional echocardiography disclosed the right atrium tumour and SonoVue contrast agent echocardiography was employed to assess the local extension of the mass and to exclude an important obstruction due to a mass in the right ventricular inflow. Surgical management in the presence of metastatic right atrial tumour thrombus is described in the literature with poor results and this type of treatment should be reserved only for selected cases in which acute and severe cardiovascular distress due to obstruction of right ventricular inflow is present.
Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Ecocardiografia Tridimensional , Neoplasias Cardíacas/diagnóstico por imagem , Idoso , Ecocardiografia Tridimensional/métodos , Átrios do Coração/diagnóstico por imagem , Neoplasias Cardíacas/secundário , Humanos , MasculinoRESUMO
BACKGROUND: Right-sided endocarditis occurs predominantly in intravenous drug users, in patients with pacemaker or central venous lines and in patients with congenital heart disease. The vast majority of cases involve the tricuspid valve. Eustachian valve endocarditis is an uncommon disease with similar signs and symptoms of the tricuspid valve endocarditis. A series of only 16 cases of eustachian valve endocarditis are reported in the literature. CASE PRESENTATION: We present a case of a 25-year old woman with intravenous drug abuse who had a staphylococcus aureus tricuspid valve endocarditis associated to eustachian valve endocarditis. Transthoracic echocardiography, as first line examination, showed the vegetations on tricuspid and eustachian valve. CONCLUSION: Our case describe an unusual location of right side endocarditis in a intravenous drug abuser. In our case, in accord with other cases described in the literature, transthoracic echocardiography disclosed eustachian valve endocarditis. Antimicrobial management is not altered by the recognition of eustachian valve endocarditis. Antibiotic treatment and duration of eustachian endocarditis depends on the isolated organism and is similar to antibiotic therapy used in native valve endocarditis.
Assuntos
Endocardite/diagnóstico por imagem , Endocardite/microbiologia , Infecções Estafilocócicas/diagnóstico por imagem , Infecções Estafilocócicas/microbiologia , Abuso de Substâncias por Via Intravenosa/microbiologia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/microbiologia , Adulto , Endocardite/etiologia , Feminino , Humanos , Doenças Raras/diagnóstico por imagem , UltrassonografiaRESUMO
HIV-related pulmonary hypertension (HIV-PH) is a cardiovascular complication of HIV infection that has been recognized in the last years with increasing frequency. HIV-related pulmonary hypertension is a clinical disorder which carries a bad prognosis. While a direct HIV infection of the pulmonary vessels in the pathogenesis of this disorder was not demonstrated, currently a multifactorial pathogenesis of this disease could be hypothesized. Echocardiography has been found to be the most useful screening imaging modality for the diagnosis of HIV-PH, with a high predictive negative value and a low positive predictive value. For this reason Doppler echocardiography is not the gold standard in the diagnosis of HIV-PH. The treatment of HIV-PH is complex and controversial. To date, no study determining the agent of choice for the treatment of this disease exists. Different studies have shown variable results in patiens with HIV-PH treated with highly active antiretroviral therapy (HAART) but only HAART seems not to be effective in lowering pulmonary hypertension in these patients, and in some patients, HIV-PH develops in spite of a previous HAART. It seems reasonable in HIV-PH patients that a treatment with oral vasodilator drugs can improve the adherence of a long-lasting and complex antiretroviral therapy.
Assuntos
Infecções por HIV/complicações , Hipertensão Pulmonar/etiologia , Citocinas , Ecocardiografia , Endotelina-1 , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/imunologia , Prognóstico , Análise de SobrevidaAssuntos
Infecções Oculares Bacterianas , Linfoma de Zona Marginal Tipo Células B/microbiologia , Neoplasias Orbitárias/microbiologia , Psitacose/microbiologia , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Chlamydophila psittaci/isolamento & purificação , Infecções Oculares Virais , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/virologia , Neoplasias Orbitárias/tratamento farmacológico , Neoplasias Orbitárias/virologia , Psitacose/tratamento farmacológicoRESUMO
BACKGROUND: We evaluated efficacy and safety of sofosbuvir and daclatasvir±ribavirin in liver transplant recipients with severe recurrent hepatitis C. METHODS: Patients included in an international compassionate use programme for treatment with sofosbuvir and daclatasvir±ribavirin for 24 weeks were prospectively studied. Serum hepatitis C virus RNA was measured at treatment weeks 4, 12, and 24 and during follow-up at weeks 4, 8, and 12. RESULTS: Twelve patients (3 with fibrosing cholestatic hepatitis and 9 with cirrhosis; median model for end-stage liver disease score 20) received sofosbuvir 400mg/day+daclatasvir 60mg/day, and 6 patients (50%) also received ribavirin 200-800mg/day. Nine patients completed 24 weeks of treatment (75%), and all had undetectable hepatitis C virus RNA at week 24; 3 patients died (25%, liver failure, gastrointestinal bleeding and sepsis); 4 patients experienced severe liver disease-related adverse events. Post-treatment hepatitis C virus RNA was available for 5 patients (week 8, n=2; week 4, n=3) and was undetectable in all cases. Mean Child-Pugh score and albumin level improved significantly at week 24. No changes in immunosuppressant doses were needed. CONCLUSION: All-oral sofosbuvir plus daclatasvir combination shows high virological efficacy in liver transplant recipients and does not interact with immunosuppressants. All adverse events were unrelated to study drugs. These data strongly suggest that this combination must be initiated before decompensation.