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1.
Nutrients ; 13(7)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34371806

RESUMO

BACKGROUND AND AIM: Sarcopenia is considered an important risk factor for morbidity and mortality in liver cirrhosis. Beta-hydroxy-beta-methylbutyrate (HMB) has the potential to increase muscle mass and performance by stimulating protein synthesis and reducing muscle catabolism. The present study aimed at evaluating the effect of HMB supplementation on muscle mass and function in patients with liver cirrhosis. Changes in frailty during the study were also estimated, and the safety of HMB supplementation was verified. METHODS: This is a randomized, single-blind, placebo-controlled pilot trial. Twenty-four patients (14 HMB and 10 placebo) affected by liver cirrhosis were enrolled in the study. Each patient received dedicated counseling, which included nutrition and physical activity recommendations for chronic liver disease patients. Patients were randomized to receive 3 g/day of HMB or placebo (sorbitol powder) for 12 consecutive weeks. A diet interview, anthropometry, electrical bioimpedance analysis (BIA), quadriceps ultrasound, physical performance battery, Liver Frailty Index (LFI), and cognitive tests were completed at enrolment (T0), at 12 weeks (T1), and 24 weeks after enrolment (T2). RESULTS: At baseline, the two groups were similar in demography, severity of liver disease, muscle mass, muscle function, and cognitive tests. LFI at baseline was higher in patients in the HMB group vs. those in the placebo group (4.1 ± 0.4 vs. 3.4 ± 0.6, p < 0.01). After treatment, a statistically significant increase in muscle function was seen in the HMB group (chair stand test: 14.2 ± 5 s vs. 11.7 ± 2.6 s, p < 0.05; six-minute walk test: 361.8 ± 68 m vs. 409.4 ± 58 m, p < 0.05). Quadriceps muscle mass measured by ultrasound also increased (4.9 ± 1.8 vs. 5.4 ± 1.8 mm, p < 0.05) after HMB, while LFI decreased (4.1 ± 0.4 vs. 3.7 ± 0.4, p < 0.05). HMB was well tolerated by patients, and no adverse events were documented. CONCLUSIONS: Our study suggests the efficacy of 12-week beta-hydroxy-beta-methylbutyrate supplementation in promoting improvements in muscle performance in compensated cirrhotic patients. LFI was also ameliorated. Further studies with a greater number of patients are required to reinforce this hypothesis.


Assuntos
Suplementos Nutricionais , Cirrose Hepática/terapia , Força Muscular/efeitos dos fármacos , Sarcopenia/prevenção & controle , Valeratos/administração & dosagem , Antropometria , Impedância Elétrica , Exercício Físico/fisiologia , Feminino , Fragilidade/etiologia , Fragilidade/prevenção & controle , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Projetos Piloto , Sarcopenia/etiologia , Método Simples-Cego , Resultado do Tratamento
2.
Sci Rep ; 11(1): 15184, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312420

RESUMO

This study aimed to ascertain, for the first time, whether serum magnesium (Mg) concentration is affected by the presence of hepatocellular carcinoma (HCC). We retrospectively enrolled consecutive cirrhotic patients with a diagnosis of HCC (n = 130) or without subsequent evidence of HCC during surveillance (n = 161). Serum levels of Mg were significantly (P < 0.001) lower in patients with HCC than in those without (median [interquartile range]: 1.80 [1.62-1.90] mg/dl vs. 1.90 [1.72-2.08] mg/dl). On multivariate logistic regression, low serum Mg was associated with the presence of HCC (OR 0.047, 95% CI 0.015-0.164; P < 0.0001), independently from factors that can influence magnesaemia and HCC development. In a subset of 94 patients with HCC, a linear mixed effects model adjusted for confounders showed that serum Mg at diagnosis of HCC was lower than before diagnosis of the tumor (ß = 0.117, 95% CI 0.039-0.194, P = 0.0035) and compared to after locoregional treatment of HCC (ß = 0.079, 95% CI 0.010-0.149, P = 0.0259), with two thirds of patients experiencing these changes of serum Mg over time. We hypothesize that most HCCs, like other cancers, may be avid for Mg and behave like a Mg trap, disturbing the body's Mg balance and resulting in lowering of serum Mg levels.

3.
Interact Cardiovasc Thorac Surg ; 33(2): 188-194, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-33984125

RESUMO

OBJECTIVES: Sutureless aortic valve prostheses have been introduced to facilitate the implant process, speed up the operating time and improve haemodynamic performance. The goal of this study was to assess the potential advantages of using sutureless prostheses during minimally invasive aortic valve replacement in a large multicentre population. METHODS: From 2011 to 2019, a total of 3402 patients in 11 hospitals underwent isolated aortic valve replacement with minimal access approaches using a bioprosthesis. A total of 475 patients received sutureless valves; 2927 received standard valves. The primary outcome was the incidence of 30-day deaths. Secondary outcomes were the occurrence of major complications following procedures performed with sutureless or standard bioprostheses. Propensity matched comparisons was performed based on a multivariable logistic regression model. RESULTS: The annual number of sutureless valve implants increased over the years. The matching procedure paired 430 sutureless with 860 standard aortic valve replacements. A total of 0.7% and 2.1% patients with sutureless and standard prostheses, respectively, died within 30 days (P = 0.076). Cross-clamp times [48 (40-62) vs 63 min (48-74); P = 0.001] and need for blood transfusions (27.4% vs 33.5%; P = 0.022) were lower in patients with sutureless valves. No difference in permanent pacemaker insertions was observed in the overall population (3.3% vs 4.4% in the standard and sutureless groups; P = 0.221) and in the matched groups (3.6% vs 4.7% in the standard and sutureless groups; P = 0.364). CONCLUSIONS: The use of sutureless prostheses is advantageous and facilitates the adoption of a minimally invasive approach, reducing cardiac arrest time and the number of blood transfusions. No increased risk of permanent pacemaker insertion was observed.

4.
Expert Opin Drug Saf ; 20(7): 839-843, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33881366

RESUMO

Background: Treatment of chronic Hepatitis C with directly acting antivirals (DAAs) can bring to sustained virologic response (SVR) in approximately 95% of patients. Efficacy and safety of DAAs in aging patients has not been widely analyzed. We aimed to determine safety and efficacy of DAA-based regimens in a cohort of elderly patients in a real-life setting.Research Design and Methods: We retrospectively investigated safety and efficacy of DAAs in HCV patients of 80 years or older treated in three Hepatology Units.Results and Expert opinion: During the study period, 170 patients older than 80 years received DAAs. Their mean age was 82,3 years. The predominant HCV genotype was 1 (100 patients, 59%). Among the 93 cirrhotic patients (54,7%), 18 had CPT score > A5. Different DAAs regimens were used. Concomitant drugs were common: 163 patients (95,8%) taking at least one drug. In 11 patients, usual therapy had to be changed to start antiviral treatment. Two serious adverse events occurred. Four patients terminated treatment prematurely. In total, 45 patients (26,5%) testified mild side effects. HCV-RNA undetectability at week 12 of treatment follow-up was achieved in 168/170 patients. DAA treatment in HCV patients of 80 years or older is efficacious and safe. Drug-drug interaction should be judiciously evaluated before starting therapy.


Assuntos
Antivirais/administração & dosagem , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Estudos de Coortes , Interações Medicamentosas , Feminino , Seguimentos , Genótipo , Hepacivirus/isolamento & purificação , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Masculino , Estudos Retrospectivos , Resposta Viral Sustentada
5.
Artigo em Inglês | MEDLINE | ID: mdl-33691045

RESUMO

Reoperations for a dysfunctional mechanical aortic valve prosthesis are usually performed with a repeat sternotomy. Reopening the chest may be associated with a heart structure tear, bleeding, excessive transfusion, and a possible unfavorable outcome. Experience performing a redo aortic valve replacement with a minimally invasive approach and avoiding lysis of the pericardial adhesions is growing. We describe a redo aortic valve replacement procedure performed because of subvalvular pannus formation in a patient with a mechanical prosthesis. A partial J-shaped hemisternotomy at the 3rd intercostal space was performed; the ascending aorta was exposed and the valve was replaced with a sutureless bioprosthesis. The video tutorial shows the surgical approach, cardiopulmonary bypass solutions, and sutureless valve deployment.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Bioprótese , Próteses Valvulares Cardíacas , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Esternotomia/métodos , Procedimentos Cirúrgicos sem Sutura/métodos , Implante de Prótese de Valva Cardíaca/métodos , Humanos
6.
J Card Surg ; 36(2): 618-623, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33403735

RESUMO

OBJECTIVE: The use of minimally invasive or transcatheter interventions rather than standard full sternotomy operations to treat tricuspid valve (TV) disease is increasing. The debate however is still open regarding venous drainage management during cardiopulmonary bypass (CPB) and wheatear or not superior and inferior vena cava should be occluded during the opening of the right atrium to avoid air entrance in the venous line. The aim of the present study is to report operative outcomes and midterm follow-up results of minimally invasive TV surgery performed without caval occlusion. METHODS: A retrospective outcome evaluation from institutional records was performed with prospective data entry. Considered were consecutive patients who underwent right mini-thoracotomy TV surgery isolated or combined with mitral valve surgery during the period from June 2013 to February 2020. A telephone and echocardiographic follow-up was performed. RESULTS: During the study period, 68 consecutive patients underwent minimally invasive TV surgery without occlusion of cava veins. The mean age was 69 ± 14 years and 48 (70%) were female. All operations were performed safely without air-lock during CPB. A perioperative cerebral stroke occurred in one patient. The survival at a 5- and 8-year follow-up was 100% and 79%, respectively. No severe tricuspid regurgitation was evident at echocardiographic follow-up. CONCLUSION: Our results show that performing tricuspid surgery without caval occlusion is safe. The air was captured by the active vacuum drainage system without causing damage. Midterm follow-up data confirm that a minimally invasive approach does not alter the quality of surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Tricúspide , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos Prospectivos , Estudos Retrospectivos , Toracotomia , Resultado do Tratamento , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/cirurgia
7.
Liver Int ; 41(1): 70-75, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33064930

RESUMO

Sustained virological response (SVR) obtained with interferon (IFN) or with direct-acting antivirals (DAAs) is commonly followed by response of hepatitis C virus (HCV)-associated mixed cryoglobulinemia vasculitis (MCV), but relapse of MCV despite SVR has been reported in several patients after DAAs and rarely after IFN. Since relapses could have been overlooked in studies with IFN, we retrospectively compared the outcomes of MCV in SVR patients treated with DAAs (n = 70) or IFN (n = 39) followed-up, respectively, for 30.5 (range 11-51) or 48 months. Groups were comparable for demographics and clinics and response rates of MCV were similar (92% and 86%); however, DAA-treated patients less efficiently reduced cryoglobulins (P = .006) and circulating B-cell clones (P = .004), and had more frequently relapses of MCV (18% vs 3%, P = .028) and need for rituximab therapy (P = .01). Although largely inferior on an intention-to-treat basis, IFN may be superior to DAAs on clinico-immunological outcomes possibly owing to its antiproliferative activity.


Assuntos
Crioglobulinemia , Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Crioglobulinemia/tratamento farmacológico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferons/uso terapêutico , Recidiva , Estudos Retrospectivos
8.
Pathologica ; 112(2): 102-104, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32760053

RESUMO

Small hepatic veins Budd-Chiari syndrome is a rare disorder characterized by hepatic venous outflow obstruction limited to the small intrahepatic veins, with normal appearance of the large hepatic veins at imaging. In this case only a liver biopsy can demonstrate the presence of a small vessels outflow block. Paroxysmal nocturnal haemoglobinuria (PNH) is one of the most severe acquired thrombophilic state and represents one of the main aetiological factors of Budd-Chiari syndrome. In patient affected by PNH with liver impairment and/or ascites, Budd-Chiari syndrome must be always taken into consideration and, if necessary, a liver biopsy performed to exclude the small hepatic veins involvement. We report a case of small hepatic veins Budd-Chiari syndrome secondary to paroxysmal nocturnal haemoglobinuria.

9.
Clin Transl Gastroenterol ; 11(2): e00116, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32463622

RESUMO

OBJECTIVES: To investigate whether blood total lysosomal acid lipase activity (BT-LAL) levels are uniquely associated with the noncirrhotic and cirrhotic stages of nonalcoholic fatty liver disease (NAFLD) and with protection from NAFLD in metabolically/genetically predisposed subjects and a normal liver. To clarify which enzyme-carrying circulating cells are involved in reduced BT-LAL of NAFLD. METHODS: In a cross-sectional study, BT-LAL was measured by a fluorigenic method in patients with NAFLD (n = 118), alcoholic (n = 116), and hepatitis C virus-related disease (n = 49), in 103 controls with normal liver and in 58 liver transplant recipients. Intracellular platelet and leukocyte LAL was measured in 14 controls and 28 patients with NAFLD. RESULTS: Compared with controls, (i) BT-LAL and LAL in platelets, but not in leukocytes, were progressively reduced in noncirrhotic NAFLD and in nonalcoholic steatohepatitis-related cirrhosis; (ii) platelet and leukocyte counts did not differ in patients with noncirrhotic NAFLD; and (iii) BT-LAL did not differ in alcoholic and hepatitis C virus noncirrhotic patients. BT-LAL progressively increased in controls with metabolic syndrome features according to their PNPLA3 rs738409 steatosis-associated variant status (II vs IM vs MM), and their BT-LAL was higher than that of noncirrhotic NAFLD, only when carriers of the PNPLA3 unfavorable alleles were considered. Liver transplant recipients with de novo NAFLD compared with those without de novo NAFLD had lower BT-LAL. DISCUSSION: LAL in blood and platelets is progressively and uniquely reduced in NAFLD according to disease severity. High BT-LAL is associated with protection from NAFLD occurrence in subjects with metabolic and genetic predisposition. Low LAL in platelets and blood could play a pathogenetic role in NAFLD.


Assuntos
Plaquetas/metabolismo , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Esterol Esterase/sangue , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Fígado/patologia , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Medição de Risco/métodos , Índice de Gravidade de Doença , Esterol Esterase/metabolismo
11.
Ann Hepatol ; 18(3): 434-438, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31023614

RESUMO

INTRODUCTION AND AIM: Cirrhotic patients with hepatitis C virus genotype 3 infection show unsatisfactory outcomes after 12 weeks' treatment with direct antiviral agents. The National Italian Drug Agency allows 24 weeks of therapy in difficult-to-treat patients, including genotype 3 cirrhotics. Aim of this study was to evaluate efficacy and safety of a 24-week course of sofosbuvir plus daclatasvir±ribavirin in this population. MATERIALS AND METHODS: 106 consecutive cirrhotics (70.8% males, mean age 55.3±7.6 years) in 8 tertiary hepatology centers received sofosbuvir plus daclatasvir for 24 weeks. Ribavirin was administered in 85 (80.2%) based expected tolerability, at a mean dose of 964±202mg/day. Baseline Child-Pugh class was A 91.5%, B 6.6%, C 1.9%; mean baseline MELD was 8.5±2.7. RESULTS: All patients completed 12-week follow-up post-treatment, and 104 (98.1%) obtained sustained virological response (100% in ribavirin -treated patients vs. 90.4% without ribavirin; p=0.04). No worsening in renal and liver function was observed, no serious adverse events occurred. Two virological failures showed resistance associated variants (Y93H and S282T). CONCLUSION: An extended 24-week treatment with sofosbuvir plus daclatasvir+ribavirin obtained 100% efficacy in genotype 3 hepatitis C cirrhosis, with very limited side effects. The role of ribavirin seems crucial in this setting and should be administered if clinically feasible.


Assuntos
Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Imidazóis/administração & dosagem , Cirrose Hepática/virologia , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Adulto , Idoso , Antivirais/uso terapêutico , Estudos de Coortes , Intervalos de Confiança , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Perfil Genético , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/genética , Humanos , Itália , Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento
12.
Appl Clin Genet ; 12: 1-10, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30666147

RESUMO

Background: Alcoholic cirrhosis represents 1% of all cause-of-deaths worldwide. Its incidence is higher in males and results from the combination of environmental and genetic factors. Among all the genetic determinants of alcoholic cirrhosis, the patatin-like phospholipase domain protein 3 (PNPLA3) rs738409 represents the most widely validated determinant. Recent cross-sectional studies on alcohol abusers identified transmembrane-6 superfamily member 2 (TM6SF2) rs58542926, membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs641738, and cluster of differentiation 14 (CD14) rs2569190 as new genetic risk factors for alcoholic cirrhosis. We aimed to develop a gene-based risk score to predict the incidence of alcoholic cirrhosis in males with at-risk alcohol consumption. Materials and methods: A total of 416 male at-risk alcohol drinkers were retrospectively examined. The association between alcoholic cirrhosis incidence and PNPLA3, CD14, TM6SF2, and MBOAT7 variants was tested. Age at onset of at-risk alcohol consumption, age, and body mass index (BMI) were included as covariates to determine the prediction score for alcoholic cirrhosis incidence by evaluating time-dependent receiver operating characteristic curves. Results: We found that PNPLA3, CD14, and TM6SF2 were associated with alcoholic cirrhosis prevalence. PNPLA3 and CD14 were also associated with its incidence. The best predictive score formula was (age at onset of at-risk alcohol consumption × 0.1) + (number of CD14 allele T) + (number of PNPLA3 allele M) + (BMI × 0.1). A threshold of 7.27 was identified as cutoff for the predictive risk of alcoholic cirrhosis development in 36 years from the onset of at-risk alcohol consumption with 70.1% sensitivity and 78.7% specificity. Conclusion: We developed the first score for alcoholic cirrhosis prediction that combines clinical and genetic factors.

13.
Liver Int ; 39(4): 628-632, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30690862

RESUMO

BACKGROUND & AIMS: Hepatitis C virus (HCV)-related mixed cryoglobulinaemia vasculitis (MCV) is characterized by the expansion of rheumatoid factor-producing B-cell clones. The aim of this study was to assess whether B-cell clones may persist in these patients after the clearance of the virus with antiviral therapy, and whether their persistence influences clinical outcomes. METHODS: Forty-five HCV-cured MCV patients were followed up for a median of 18.5 (range 9-38) months after the clearance of HCV. Circulating B-cell clones were detected using flow cytometry either by the skewing of kappa/lambda ratio or by the expression of a VH 1-69-encoded idiotype. RESULTS: The clinical response of vasculitis was 78% complete, 18% partial and 4% null. However, cryoglobulins remained detectable in 42% of patients for more than 12 months. Circulating B-cell clones were detected in 18 of 45 patients, and in 17 of them persisted through the follow-up; nine of the latter patients cleared cryoglobulins and had complete response of vasculitis. Several months later, two of these patients had relapse of MCV. CONCLUSIONS: B-cell clones persist in MCV patients long after HCV infection has been cleared but halt the production of pathogenic antibody. These 'dormant' cells may be reactivated by events that perturb B-cell homeostasis and can give rise to the relapse of cryoglobulinaemic vasculitis.


Assuntos
Linfócitos B/imunologia , Crioglobulinemia/imunologia , Hepatite C/complicações , Vasculite/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Células Clonais/imunologia , Crioglobulinemia/virologia , Feminino , Citometria de Fluxo , Hepatite C/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Vasculite/virologia
14.
Aliment Pharmacol Ther ; 48(10): 1146-1155, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30294870

RESUMO

BACKGROUND: Microbial translocation from the gut lumen has been involved in the pathogenesis of liver damage in hepatitis C virus (HCV) infection. AIM: To investigate the impact of direct-acting antiviral treatment on microbial translocation and T-cell activation, in patients with hepatitis C-related liver disease. METHODS: We enrolled two groups of HCV-infected patients undergoing direct-acting antiviral treatment: patients with fibrosis ≥F3 according to Metavir (Group ≥F3); patients with hepatitis C recurrence after liver transplantation and Metavir ≥F2 (Group Liver Transplantation + ≥F2). All patients were treated with direct-acting antivirals based on ongoing guidelines. Surrogate biomarkers of microbial translocation (plasma concentrations of soluble-CD14, lipopolysaccharide-binding protein and intestinal fatty acid-binding protein) were evaluated at baseline, at first month, at the end of treatment and 3 months later. T-cell activation was measured by expression of CD38+ HLA-DR at the same time points, only in Group ≥F3. RESULTS: There were 32 patients in Group ≥F3 and 13 in Group LT + ≥F2. At baseline, levels of soluble-CD14 and lipopolysaccharide-binding protein were significantly higher in both groups vs healthy controls. Baseline soluble-CD14 correlated with glutamic-oxalacetic transaminase (r = 0.384, P = 0.009) and glutamic-pyruvic transaminase (r = 0.293, P = 0.05). A significant decrease in plasma levels of surrogate microbial translocation biomarkers was observed during and after treatment in the two groups although values were not normalised. In Group ≥F3, CD38+ HLADR+ T-cell expression was significantly decreased by direct-acting antiviral treatment. Relapsers (9%) showed higher soluble-CD14 levels at baseline. CONCLUSION: Surrogate microbial translocation markers and T cell activation are increased in HCV-infected patients with liver fibrosis and decrease during direct-acting antiviral treatment.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/sangue , Hepatite C Crônica/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Adulto , Idoso , Alanina Transaminase/sangue , Antivirais/farmacologia , Biomarcadores/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , Hepacivirus/fisiologia , Hepatite C Crônica/diagnóstico , Humanos , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/tendências , Transplante de Fígado/efeitos adversos , Transplante de Fígado/tendências , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
15.
J Viral Hepat ; 25(12): 1493-1500, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30112854

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.


Assuntos
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 Sustentada
16.
BMC Infect Dis ; 18(1): 223, 2018 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-29769038

RESUMO

BACKGROUND: Management of chronic hepatitis C (CHC) has significantly accelerated in the last few years. Currently, second generation direct acting antivirals (DAAs) promise clearance of infection in most of patients. Here we present the results of the first analysis carried out on data of Lazio clinical network for DAAs. METHODS: The study was designed as a multicenter cohort: a) to assess the evolution of treatment during the first 24 months of the activity of the Clinical Network; b) to report overall efficacy of treatments; c) to analyze potential factors associated with lack of virological response at 12 weeks after therapy (SVR12); d) to evaluate the variation of ALT at baseline and 12 weeks after therapy in those who achieved SVR12 in comparison to those who did not. Analyses of efficacy were carried out with multilevel mixed effect logistic regression model. ALT temporal variation was assessed by mixed effect model mixed models with random intercept at patient's level and random slope at the level of the time; i.e. either before or after therapy. RESULTS: Between 30 December 2014 and 31 December 2016 5279 patients started a DAA treatment; of those, 5127 (in 14 clinical centers) had completed the 12-week follow-up. Overall proportion of SVR12 was 93.41% (N = 4780) with no heterogeneity between the 14 clinical centers. Interruption as the consequence of severe side effect was very low (only 23 patients). Unadjusted analysis indicates that proportion of SVR12 significantly changes according to patient's baseline characteristics, however after adjusting for potential confounders only adherence to current guidelines, stage of liver diseases, gender, transplant and HIV status were independently associated with the response to therapy. Analysis of ALT temporal variation showed that ALT level normalized in most, but not, all patients who achieved SVR12. CONCLUSION: Our study confirmed the extraordinary efficacy of DAAs outside clinical trials. The advantage of DAAs was particularly significant for those patients who were previously considered as difficult-to-treat and did not have treatment options before DAAs era. Intervention based on network of select centers and prioritization of patients according to diseases severity was successful. Further studies are needed to establish whether clearance of HCV after DAAs therapy can arrest or even revert liver fibrosis in non-cirrhotic patients and/or improve life quality and expectancy in those who achieve SVR12 with cirrhosis.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Terapias em Estudo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Quimioterapia Combinada , Drogas em Investigação/uso terapêutico , Feminino , Seguimentos , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Terapias em Estudo/métodos
17.
Ann Hepatol ; 17(1): 110-118, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29311396

RESUMO

Prognostic ability of BCLC-B Subclassification in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization Background and aims. A subclassification system for intermediate hepatocellular carcinoma (HCC) was recently proposed to optimize treatment allocation. The aim of this study was to assess the prognostic ability of that substaging proposal. PATIENTS AND METHODS: This is a retrospective multicenter cohort study including patients with intermediate HCC treated with transarterial chemoembolization (TACE). Predictors of survival were identified using the Cox proportional regression model. RESULTS: 289 Barcelona Clinic Liver Cancer (BCLC) B patients were included. Median overall survival of the whole cohort was 23 months (C.I. 95% 20.2- 25.8). Child A status (H.R. 1.35, C.I. 95% 1.02-1.78) and tumour burden beyond the up-to-seven criterion (H.R. 1.39, C.I. 95% 1.07- 1.80) were independent prognostic factors for overall survival on multivariate analysis. Analysis of the substages showed that median survival was 33.0 months for B1 stage (n = 81), 20.8 months for B2 stage (n = 106), 16.1 months for B3 stage (n = 24), 22.2 months for B4 stage (n = 42) and 15.0 months for quasi-C stage (n = 36). Regarding the discriminatory ability of the substaging proposal, the log rank test showed a significant survival difference for B1vs. B4 (p = 0.003) and B1 vs. Quasi-C (p = 0.039) and a trend for B1 vs. B2 (p = 0.05) and B1 vs. B3 (p = 0.05). CONCLUSIONS: Apart from substage B1, BCLC-B subclassification does not discriminate perfectly patients treated with TACE. Also some patients in substage B4 can benefit from TACE.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Técnicas de Apoio para a Decisão , Neoplasias Hepáticas/terapia , Estadiamento de Neoplasias/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Feminino , Humanos , Itália , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
18.
J Gastroenterol Hepatol ; 33(3): 704-709, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28753738

RESUMO

BACKGROUND AND AIM: Spleen and liver stiffness (LS) measured by acoustic radiation force impulse (ARFI) imaging has been shown to be useful in identifying patients with portal hypertension. The study aims to establish if the modification of portal pressure induced by a transjugular intrahepatic portosystemic shunt (TIPS) parallels the modification of spleen or LS measured by ARFI in order to understand if ARFI may be used to monitor the modification of portal pressure in patients with cirrhosis. METHODS: Thirty-eight patients with severe portal hypertension underwent LS and spleen stiffness (SS) before TIPS and 1 week after TIPS. Portal atrial gradient (PAG) was measured before and after the shunt opening. RESULTS: Portal atrial gradient decreased significantly from 19.5 to 6 mmHg (P < 0.001). SS decreased significantly after TIPS (pre-TIPS 3.7 m/s vs post-TIPS 3. 1 m/s; P < 0.001), and LS was also significantly modified by TIPS (pre-TIPS 2.8 m/s vs post-TIPS 2.4 m/s; P = 0.003). PAG and SS values measured before and after TIPS were significantly correlated (r = 0.56; P < 0.001); on the other hand, PAG and LS were not (r = 0.19; P = 0.27). Two patients developed a persistent hepatic encephalopathy refractory to medical treatment and were submitted to the reduction of the stent diameter. The modification of SS was parallel to the modification of PAG. CONCLUSION: Spleen stiffness is superior to LS in detecting the modification of portal pressure induced by TIPS. This makes SS a potential non-invasive method to monitor the modification of portal hypertension. Further investigations are needed to establish applicability and clinical utility of this promising tool in the treatment of portal hypertension.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hipertensão Portal/diagnóstico por imagem , Hipertensão Portal/fisiopatologia , Pressão na Veia Porta , Derivação Portossistêmica Transjugular Intra-Hepática , Baço/diagnóstico por imagem , Elasticidade , Feminino , Humanos , Hipertensão Portal/etiologia , Fígado/diagnóstico por imagem , Cirrose Hepática , Masculino , Pessoa de Meia-Idade
19.
Hepatology ; 64(5): 1473-1482, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27483451

RESUMO

Hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) vasculitis commonly regresses upon virus eradication, but conventional therapy with pegylated interferon and ribavirin yields approximately 40% sustained virologic responses (SVR). We prospectively evaluated the efficacy and safety of sofosbuvir-based direct-acting antiviral therapy, individually tailored according to the latest guidelines, in a cohort of 44 consecutive patients with HCV-associated MC. In two patients MC had evolved into an indolent lymphoma with monoclonal B-cell lymphocytosis. All patients had negative HCV viremia at week 12 (SVR12) and at week 24 (SVR24) posttreatment, at which time all had a clinical response of vasculitis. The mean (±standard deviation) Birmingham Vasculitis Activity Score decreased from 5.41 (±3.53) at baseline to 2.35 (±2.25) (P < 0.001) at week 4 on treatment to 1.39 (±1.48) (P < 0.001) at SVR12 and to 1.27 (±1.68) (P < 0.001) at SVR24. The mean cryocrit value fell from 7.2 (±15.4)% at baseline to 2.9 (±7.4)% (P < 0.01) at SVR12 and to 1.8 (±5.1)% (P < 0.001) at SVR24. Intriguingly, in the 2 patients with MC and lymphoma there was a partial clinical response of vasculitis and ∼50% decrease of cryocrit, although none experienced a significant decrease of monoclonal B-cell lymphocytosis. Adverse events occurred in 59% of patients and were generally mild, with the exception of 1 patient with ribavirin-related anemia requiring blood transfusion. CONCLUSION: Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for HCV-associated MC patients; the overall 100% rate of clinical response of vasculitis, on an intention-to-treat basis, opens the perspective for curing the large majority of these so far difficult-to-treat patients. (Hepatology 2016;64:1473-1482).


Assuntos
Antivirais/uso terapêutico , Crioglobulinemia/tratamento farmacológico , Crioglobulinemia/virologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Sofosbuvir/uso terapêutico , Vasculite/tratamento farmacológico , Vasculite/virologia , Idoso , Linfócitos B , Feminino , Hepacivirus , Humanos , Masculino , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Ribavirina , Resultado do Tratamento
20.
Rev Recent Clin Trials ; 11(3): 213-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27515958

RESUMO

The gut-liver axis model has often explained liver disease physiopathology. Among the latter we can mention Non-Alcoholic Liver Steatosis (NAFLD), Liver Steatohepatitis (NASH), liver cirrhosis. In this frame an altered Intestinal Permeability (IP) is the gate for antigenic/toxic substances from gut lumen until target organs such as liver in NAFLD. Altered intestinal permeability was discovered almost forty years ago as consequence of acute and chronic alcohol ingestion. Alcohol Liver Disease (ALD) is a systemic pathology whose beginning and end belong to the intestine. Several recent evidences from the literature show how gut microbiota composition can be altered by alcohol, affects IP and can be modulated by several nonpharmacological and pharmacological agents, becoming the target for ALD treatment. In this review we describe the definition of ALD, gut microbiota composition in healthy and ALD, definition and role of IP in ALD physiopathology and emerging evidences on gut microbiota modulation in ALD treatment from preliminary clinical and non-clinical studies.


Assuntos
Microbioma Gastrointestinal/fisiologia , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/microbiologia , Humanos , Hepatopatias Alcoólicas/fisiopatologia
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