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BACKGROUND: Medical treatment of inflammatory bowel disease (IBD) has evolved significantly, and treatment with immunomodulators is recommended. These medications may alter the patient's immune response and increase the risk of opportunistic infections. Our aim was to evaluate the prevalence and the incidence of acute or chronic HEV infection in IBD patients under immunomodulatory treatment. PATIENTS AND METHODS: We conducted a retrospective, multicenter, observational study between 2017 and 2018. IBD outpatients hospitalized for the infusion of immunomodulators were included in 16 French centers. During their daily hospitalization, blood samples were drawn for HEV serology (IgM and IgG) and HEV RNA detection. RESULTS: A total of 488 patients were included, of which 327 (67%) patients had Crohn's disease and 161 (33%) ulcerative colitis. HEV IgM was detected in 3 patients, but HEV RNA was undetectable in all patients. The HEV IgG seroprevalence rate was 14.2%. IgG-positive patients were older at sampling (p = 0.01) and IBD diagnosis (p = 0.03), had higher seafood consumption (p = 0.01) and higher doses of azathioprine (p = 0.03). Ileal and upper digestive tract involvement was more frequent in IgG-positive patients (p = 0.009), and ileocolic involvement was more frequent in IgG-negative patients (p = 0.01). Under multivariate analysis, age > 50 years [OR: 2.21 (1.26, to 3.85), p = 0.004] was associated with previous HEV infection. CONCLUSION: Systematic screening for HEV infection is not needed among IBD patients on immunomodulatory medications. However, in the event of abnormal liver test findings, HEV should be part of the classic diagnostic assessment.
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BACKGROUND: Alcohol-related cirrhosis is a frequent and difficult-to-treat disease. Despite the low hepatic metabolism of baclofen, data on its use in this subgroup are scarce. The French multicenter Observatory of patients treated with Baclofen for Alcohol DEpendence real-life cohort assessed: (a) prescription modalities of baclofen in liver units; (b) safety profile of baclofen; and (c) declared alcohol intake, biological markers of excessive alcohol intake and hepatic function at 12 months. METHODS: All consecutive patients with cirrhosis who received baclofen to reduce alcohol consumption or maintain abstinence were prospectively included. Psychosocial management was always associated. Clinical and biological data were collected every 3 months for 1 year. RESULTS: Between November 2013 and December 2016, 71 in- or outpatients were included from 10 liver units. Of the patients, 25% had ascites. After 12 months, 52 patients (73%) were still being followed, and 41 (57.7%) were still receiving baclofen at a mean dosage of 75 mg/day (r30-210). The overall declared consumption decreased from 100.2 to 14.7 g/day (P < 0.0001), and 29 patients (40.8%) reached abstinence. Significant improvement in the usual biomarkers of excessive alcohol intake (AST, GGT and MCV) and liver function (Prothrombin ratio (PTr), albumin levels) were observed. The usual side effects such as drowsiness were frequent (22%) but no serious adverse events (AEs) or overt encephalopathy related to baclofen was reported. CONCLUSION: In this 1-year follow-up series, baclofen was combined with psychosocial treatment in patients with cirrhosis and was well tolerated. This treatment was associated with a significant decrease in declared alcohol consumption as well as improvement in hepatic function.
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Alcoolismo , Reabilitação Psiquiátrica , Humanos , Baclofeno/uso terapêutico , Cirrose Hepática Alcoólica/complicações , Alcoolismo/psicologia , Consumo de Bebidas Alcoólicas/psicologia , Cirrose Hepática/complicaçõesRESUMO
Background and study aims Prognostic and risk factors for upper gastrointestinal bleeding (UGIB) might have changed overtime because of the increased use of direct oral anticoagulants and improved gastroenterological care. This study was undertaken to assess the outcomes of UGIB in light of these new determinants by establishing a new national, multicenter cohort 10 years after the first. Methods Consecutive outpatients and inpatients with UGIB symptoms consulting at 46 French general hospitals were prospectively included between November 2017 and October 2018. They were followed for at least for 6 weeks to assess 6-week rebleeding and mortality rates and factors associated with each event. Results Among the 2498 enrolled patients (mean age 68.5 [16.3] years, 67.1â% men), 74.5â% were outpatients and 21â% had cirrhosis. Median Charlson score was 2 (IQR 1-4) and Rockall score was 5 (IQR 3-6). Within 24 hours, 83.4â% of the patients underwent endoscopy. The main causes of bleeding were peptic ulcers (44.9â%) and portal hypertension (18.9â%). The early in-hospital rebleeding rate was 10.5â%. The 6-week mortality rate was 12.5â%. Predictors significantly associated with 6-week mortality were initial transfusion (OR 1.54; 95â%CI 1.04-2.28), Charlson score >â4 (OR 1.80; 95â%CI 1.31-2.48), Rockall score >â5 (OR 1.98; 95â%CI 1.39-2.80), being an inpatient (OR 2.45; 95â%CI 1.76-3.41) and rebleeding (OR 2.6; 95â%CI 1.85-3.64). Anticoagulant therapy was not associated with dreaded outcomes. Conclusions The 6-week mortality rate remained high after UGIB, especially for inpatients. Predictors of mortality underlined the weight of comorbidities on outcomes.
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INTRODUCTION AND AIM: Data on the efficacy and tolerance of interferon-free treatment in chronic hepatitis C (CHC) in elderly patients are limited in phase II-III trials. MATERIAL AND METHODS: A prospective cohort of adult patients with CHC treated in French general hospitals. RESULTS: Data from 1,123 patients, distributed into four age groups, were analyzed. Of these, 278 were > 64 years old (fourth quartile) and 133 were > 73 years old (tenth decile). Elderly patients weighed less, were more frequently treatment-experienced women infected with genotype 1b or 2, while they less frequently had genotype 3 or HIV coinfection, but had more frequent comorbidities and drug consumption. Half of the patients had cirrhosis, whatever their ages. The main treatment regimens were sofosbuvir/ledipasvir (37.8%), sofosbuvir/daclatasvir (31.8%), sofosbuvir/simeprevir (16.9%), sofosbuvir/ribavirin (7.8%); ribavirin was given to 24% of patients. The overall sustained virological response (SVR) rate was 91.0 % (95% CI: 89.292.5%) with no difference according to age. Logistic regression of the independent predictors of SVR were albumin, hepatocellular carcinoma and treatment regimen, but not age. The rate of severe adverse events (66 in 59/1062 [5.6%] patients) tended to be greater in patients older than 64 years of age (21/261,8.1%), but the only independent predictors of SAE by logistic regression were cirrhosis and baseline hemoglobin. Patient-reported overall tolerance was excellent in all age groups, and patient-reported fatigue decreased during and after treatment, independent of age. CONCLUSIONS: The high efficacy and tolerance of interferon-free regimens is confirmed in elderly patients in real-life conditions.
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Antivirais/uso terapêutico , DNA Viral/análise , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Fatores Etários , Idoso , Benzimidazóis/uso terapêutico , Carbamatos , Quimioterapia Combinada , Feminino , Fluorenos/uso terapêutico , Seguimentos , França/epidemiologia , Genótipo , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Imidazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Estudos Prospectivos , Pirrolidinas , Ribavirina/uso terapêutico , Simeprevir/uso terapêutico , Sofosbuvir/uso terapêutico , Taxa de Sobrevida/tendências , Resultado do Tratamento , Valina/análogos & derivadosRESUMO
BACKGROUND AND AIMS: According to clinical trials, the treatment of patients with chronic hepatitis C (CHC) with second-generation direct acting antiviral agents (DAAs) is highly efficient and well tolerated. The goal of this study was to investigate the effectiveness and safety of various combinations of these drugs during their first 2 years of use in the real-world practice of French general hospitals. METHODS: Data from patients treated with all-oral DAAs in 24 French non-academic hospital centers from March 1, 2014 to January 1, 2016, were prospectively recorded. The sustained virological response 12-24 weeks after treatment (SVR 12-24) was estimated and severe adverse events (SAE) were evaluated and their predictive factors were determined using logistic regression. RESULTS: Data from 1123 patients were analyzed. The population was 69% genotype (G) 1, 13% G3, 11.5% G4, 5% G2, 49% with cirrhosis and 55% treatment-experienced. The treatment regimens were sofosbuvir/ledipasvir (38%), sofosbuvir/daclatasvir (32%), sofosbuvir/simeprevir (17%), ombitasvir+paritaprevir+ritonavir (5%) (with dasabuvir 3.5%), and sofosbuvir/ribavirin (8%). Ribavirin was given to 24% of patients. The SVR 12-24 was 91.0% (95% CI: 89.2-92.5%). Sofosbuvir-ribavirin was less effective than other regimens. The independent predictors of SVR 12-24 by logistic regression were body weight, albumin, previous hepatocellular carcinoma and treatment regimen (sofosbuvir/ribavirin vs. others). Sixty-four severe adverse events (SAE) were observed in 59 [5.6%] patients, and were independently predicted by cirrhosis and baseline hemoglobin. Serum creatinine increased during treatment (mean 8.5%, [P<10-5]), satisfying criteria for acute kidney injury in 62 patients (7.3%). Patient-reported overall tolerance was excellent, and patient-reported fatigue decreased during and after treatment. CONCLUSIONS: Second generation DAAs combinations are as effective and well tolerated in a « real-world ¼ population as in clinical trials. Further studies are needed on renal tolerance.
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Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Quimioterapia Combinada , Feminino , França , Hospitais Gerais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND & AIMS: There is debate over the effects of long-term oral fluoroquinolone therapy in patients with advanced cirrhosis. We performed a randomized controlled trial to evaluate the effects of long-term treatment with the fluoroquinolone norfloxacin on survival of patients with cirrhosis. METHODS: We performed a double-blind trial of 291 patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy. The study was performed at 18 clinical sites in France from April 2010 through November 2014. Patients were randomly assigned to groups given 400 mg norfloxacin (n = 144) or placebo (n = 147) once daily for 6 months. Patients were evaluated monthly for the first 6 months and at 9 months and 12 months thereafter. The primary outcome was 6-month mortality, estimated by the Kaplan-Meier method, censoring spontaneous bacterial peritonitis, liver transplantation, or loss during follow-up. RESULTS: The Kaplan-Meier estimate for 6-month mortality was 14.8% for patients receiving norfloxacin and 19.7% for patients receiving placebo (P = .21). In competing risk analysis that took liver transplantation into account, the cumulative incidence of death at 6 months was significantly lower in the norfloxacin group than in the placebo group (subdistribution hazard ratio, 0.59; 95% confidence interval, 0.35-0.99). The subdistribution hazard ratio for death at 6 months with norfloxacin vs placebo was 0.35 (95% confidence interval, 0.13-0.93) in patients with ascites fluid protein concentrations <15 g/L and 1.39 (95% confidence interval, 0.42-4.57) in patients with ascites fluid protein concentrations ≥15 g/L. Norfloxacin significantly decreased the incidence of any and Gram-negative bacterial infections without increasing infections caused by Clostridium difficile or multiresistant bacteria. CONCLUSIONS: In a randomized controlled trial of patients with advanced cirrhosis without recent fluoroquinolone therapy, norfloxacin did not reduce 6-month mortality, estimated by the Kaplan-Meier method. Norfloxacin, however, appears to increase survival of patients with low ascites fluid protein concentrations. ClinicalTrials.gov ID: NCT01037959.
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Antibacterianos/administração & dosagem , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/mortalidade , Norfloxacino/administração & dosagem , Ascite/etiologia , Ascite/mortalidade , Método Duplo-Cego , Feminino , França/epidemiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/mortalidade , Humanos , Incidência , Estimativa de Kaplan-Meier , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: Epidemiological data is lacking on primary Budd-Chiari syndrome (BCS) in France. METHODS: Two approaches were used: (1) A nationwide survey in specialized liver units for French adults. (2) A query of the French database of discharge diagnoses screening to identify incident cases in adults. BCS associated with cancer, alcoholic/viral cirrhosis, or occurring after liver transplantation were classified as secondary. RESULTS: Approach (1) 178 primary BCS were identified (prevalence 4.04 per million inhabitants (pmi)), of which 30 were incident (incidence 0.68â¯pmi). Mean age was 40⯱â¯14â¯yrs. Risk factors included myeloproliferative neoplasms (MPN) (48%), oral contraceptives (35%) and factor V Leiden (16%). None were identified in 21% of patients, ≥2 risk factors in 25%. BMI was higher in the group without any risk factor (25.7â¯kg/m2 vs 23.7â¯kg/m2, pâ¯<â¯0.001). Approach (2) 110 incident primary BCS were admitted to French hospitals (incidence 2.17â¯pmi). MPN was less common (30%) and inflammatory local factors predominated (39%). CONCLUSION: The entity of primary BCS as recorded in French liver units is 3 times less common than the entity recorded as nonmalignant hepatic vein obstruction in the hospital discharge database. The former entity is mostly related to MPN whereas the latter with abdominal inflammatory diseases.
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Síndrome de Budd-Chiari/epidemiologia , Adulto , Síndrome de Budd-Chiari/classificação , Síndrome de Budd-Chiari/etiologia , Bases de Dados Factuais , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
The current standard-of-care treatments for chronic hepatitis C, based on a bitherapy that combines peginterferon alpha-2a or -2b and ribavirin for all genotypes, and on a triple therapy with the addition of an antiprotease specifically for genotype 1, are associated with a limited adherence that decreases their efficacy. The main factors limiting adherence are difficulties in taking the treatment and side effects that worsen the quality of life of the patients. Programs of therapeutic education are essential to improve adherence, quality of life, likelihood of viral suppression, improvement of liver disease, and decrease of late complications. Therapeutic education should be understood as an acquisition of decisional, technical, and social competency with the purpose of making the patient able to make health choices, realize their own life plans, and use health care resources in the best manner. The patient should be placed in the center of an organization, comprising various care workers who include social service professionals and medical staff. For hepatitis C, therapeutic education may be separated into three phases: a first phase corresponding to the educative diagnosis; a second phase corresponding to support during treatment; and the third phase corresponding to support after treatment. Therapeutic education is performed using various instruments and methods specifically adapted to the needs and expectations of individual patients. Upcoming treatments for hepatitis C, with evidence for high efficacy, few side effects, and shorter duration, will certainly change the landscape of adherence and the management of therapeutic education.
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Acitretina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Naftalenos/efeitos adversos , Retinoides/efeitos adversos , Acitretina/administração & dosagem , Adapaleno , Administração Cutânea , Feminino , Humanos , Pessoa de Meia-Idade , Naftalenos/administração & dosagem , Retinoides/administração & dosagemRESUMO
OBJECTIVE: Adult primary human hepatocytes (PHHs) support the complete infection cycle of natural HCV from patients' sera. The molecular details underlying sera infectivity towards these cells remain largely unknown. Therefore, we sought to gain a deeper comprehension of these features in the most physiologically relevant culture system. DESIGN: Using kinetic experiments, we defined the optimal conditions to infect PHH and explored the link between cell organisation and permissivity. Based on their infectivity, about 120 sera were classified in three groups. Concentration of 52 analytes was measured in 79 selected sera using multiplexed immunobead-based analyte profiling. RESULTS: PHH permissivity towards HCV infection negatively correlated with cell polarisation and formation of functional bile canaliculi. PHH supported HCV replication for at least 2â weeks with de novo virus production. Depending on their reactivity, sera could be classified in three groups of high, intermediate or low infectivity toward PHH. Infectivity could not be predicted based on the donors' clinical characteristics, viral load or genotype. Interestingly, highly infectious sera displayed a specific cytokine profile with low levels of most of the 52 tested analytes. Among them, 24 cytokines/growth factors could impact hepatocyte biology and infection efficiency. CONCLUSIONS: We identified critical factors leading to efficient PHH infection by HCV sera in vitro. Overall, we showed that this cellular model provides a useful tool for studying the mechanism of HCV infection in its natural host cell, selecting highly infectious isolates, and determining the potency of drugs towards various HCV strains.
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Hepacivirus/patogenicidade , Hepatócitos/virologia , Adulto , Biomarcadores/metabolismo , Técnicas de Cultura de Células/métodos , Linhagem Celular , Células Cultivadas , Citocinas/metabolismo , Hepacivirus/metabolismo , Hepatócitos/fisiologia , Humanos , Cinética , Modelos Imunológicos , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Soro/virologiaRESUMO
BACKGROUND: Rare cases of acute hepatitis have been reported following injection, overdose, and even during the use of buprenorphine (BPN) at therapeutic doses, especially in carriers of hepatitis C virus (HCV). OBJECTIVES: To report a case of acute hepatitis and renal failure related to intranasal BPN misuse in a HCV-negative patient and to analyze cases reported to the French postmarketing surveillance system (PMSS) of drugs and in the literature. METHODS: All cases of hepatitis related to BPN reported to PMSS between January 1996 and December 2012 were analyzed. RESULTS: A 42-year-old man with a history of intranasal BPN misuse (8 mg/d) for at least 10 years was admitted for flu-like symptoms and abdominal pain. At admission, the patient consumed alcohol, cannabis, and tobacco. Acute hepatitis and acute renal failure were diagnosed . Clinical signs and biological parameters resolved within 26 days. An objective causality assessment revealed that an adverse drug reaction (ADR) was possible. In the French PMSS database, 41 cases of suspected BPN-induced hepatitis are reported. In 36.6% of cases, BPN was misused by the intravenous route. In the literature, 16 cases of acute hepatitis related to BPN with or without renal failure are reported. In all cases, patients were HCV carriers. The primary mechanism of BPN-induced hepatitis is a mitochondrial dysfunction, exacerbated by cofactors (HCV, alcohol, and medications). CONCLUSION: Intranasal misuse of BPN is increasingly frequent. We report here the first documented case of acute hepatitis and renal failure related to intranasal BPN misuse in a patient negative for HCV infection.
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Injúria Renal Aguda/induzido quimicamente , Analgésicos Opioides/efeitos adversos , Buprenorfina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Hepatite/etiologia , Falência Hepática Aguda/induzido quimicamente , Administração Intranasal , Adulto , Analgésicos Opioides/administração & dosagem , Buprenorfina/administração & dosagem , Monitoramento de Medicamentos , França , Humanos , Masculino , Uso Indevido de Medicamentos sob PrescriçãoRESUMO
UNLABELLED: Differentiating 'inactive carriers' (ICs) of hepatitis B virus (HBV) from hepatitis B e antigen-negative (HBeAg[-]) patients in remission is challenging. We investigated whether serum-based monitoring of hepatitis B surface antigen (HBsAg) and HBV-DNA in asymptomatic HBeAg(-) patients could distinguish these groups. DESIGN: 129 HBeAg(-) chronic hepatitis B (CHB) patients (HBV genotypes A-E) with normal alanine aminotransferase (ALT) levels at baseline were classified after 1 year of follow-up as either IC (HBV-DNA ≤2000 IU/mL) or 'active carrier' (AC, HBV-DNA >2000 IU/mL) if they exhibited normal ALT throughout, or classified as 'reactivation patient' (RP) if they exhibited marked, transient increases in ALT and HBV-DNA. RESULTS: There were 64%, 18%, and 19% patients in the IC, AC, and RP groups, respectively. Combined HBsAg and HBV-DNA cutoffs (>1000 IU/mL and >200 IU/mL, respectively) differentiated RPs with 92% sensitivity and negative predictive value (NPV) of 96%. HBsAg sero-clearance was associated with baseline HBsAg <1000 IU/mL, annual decrease of ≥0.3 log IU/mL (NPV 95%: PPV 89%) and IFNL3 genotype CC. CONCLUSION: Applying combined HBsAg and HBV-DNA cutoffs to baseline measurements accurately differentiated RPs. These results suggest that HBsAg should be included in the monitoring of asymptomatic HBeAg(-) CHB patients.
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DNA Viral/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Soro/virologia , Ativação Viral , Adolescente , Adulto , Alanina Transaminase/sangue , Doenças Assintomáticas , Biomarcadores/sangue , Portador Sadio/epidemiologia , Portador Sadio/virologia , DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemAssuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Doença Aguda , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Crizotinibe , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , RecidivaRESUMO
AIM: To study the efficacy and factors associated with a sustained virological response (SVR) in chronic hepatitis C (CHC) relapsing patients. METHODS: Out of 1228 CHC patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV), 165 (13%) had a relapse. Among these, 62 patients were retreated with PEG-IFN-α2a or -α2b and RBV. Clinical, biological, virological and histological data were collected. Initial doses and treatment modifications were recorded. The efficacy of retreatment and predictive factors for SVR were analyzed. RESULTS: An SVR was achieved in 42% of patients. SVR was higher in young (< 50 years) (61%) than old patients (27%) (P = 0.007), and in genotype 2 or 3 (57%) than in genotype 1 or 4 (28%) patients (P = 0.023). Prolonging therapy for at least 24 wk more than the previous course was associated with higher SVR rates (53% vs 28%, P = 0.04). Also, a better SVR rate was observed with RBV dose/body weight > 15.2 mg/kg per day (70% vs 35%, P = 0.04). In logistic regression, predictors of a response were age (P = 0.018), genotype (P = 0.048) and initial RBV dose/body weight (P = 0.022). None of the patients without a complete early virological response achieved an SVR (negative predictive value = 100%). CONCLUSION: Retreatment with PEG-IFN/RBV is eff-ective in genotype 2 or 3 relapsers, especially in young patients. A high dose of RBV seems to be important for the retreatment response.
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Antivirais/administração & dosagem , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Ribavirina/administração & dosagem , Adulto , Fatores Etários , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Recidiva , Carga ViralRESUMO
BACKGROUND & AIMS: Polymorphisms in the region of the interleukin (IL)28B gene have been associated with pegylated-interferon (PEG-IFN) and ribavirin treatment response mainly in genotype 1 HCV infections. However, there are few data on HCV genotype 4 (HCV-4) infection. We evaluated, in a unique well-characterized cohort of HCV-4 patients, the association of IL28B polymorphism with response to treatment or liver disease severity. METHODS: This study included 164 HCV-4 patients from different ethnic groups (Egyptian, European, and Sub-Saharan African). Among these patients, 82 were studied for response and 160 for disease severity. Free DNA extracted from all the 164 patient's serum samples was analyzed by direct sequencing of the SNP rs12979860 of IL28B. Genetic and bio-clinical features from patients having sustained virological response (43 SVR patients) and from those who did not respond to treatment or had a relapse after the end of the treatment (39 NR patients) were compared. IL28B polymorphism was compared between the 78 patients with mild fibrosis (Metavir score F0-F1) and the 82 with advanced fibrosis (F2-F4). RESULTS: Our data showed a better treatment response rate of the C allele of the IL28B gene SNP rs12979860 (p=0.0008). The response rates were 81.8%, 46.5%, and 29.4% for genotype CC, CT, and TT, respectively. No significant relationship was found between rs12979860 and the severity of the disease. CONCLUSIONS: The SNP rs12979860 is strongly associated with SVR in patients infected with HCV-4, but not with liver disease severity. Analysis of IL28B genotype might be used to guide treatment for these patients.
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Antivirais/administração & dosagem , Farmacorresistência Viral/genética , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Interleucinas/genética , Adulto , Idoso , Estudos de Coortes , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Humanos , Interferon-alfa/administração & dosagem , Interferons , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Medicina de Precisão/métodos , Estudos Retrospectivos , Ribavirina/administração & dosagem , Índice de Gravidade de Doença , Carga Viral/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND/AIMS: Accuracy of transient elastography (TE) in hepatitis B virus (HBV) infection has not been well established. We aimed to compare the performances of TE for the assessment of liver fibrosis in patients with chronic HBV or hepatitis C virus (HCV) infection. A secondary analysis was performed to assess whether or not alanine aminotransferase (ALT) levels would impact on the accuracy of TE. METHODS: This cross-sectional study, carried out in a single centre, included treatment-naïve patients with compensated chronic HBV or HCV infection, consecutively admitted between 2006 and 2008 for a liver biopsy and TE measurement on the same day. RESULTS: A total of 202 HBV patients and 363 HCV subjects were evaluated. Overall diagnostic accuracy of TE in the HBV group was comparable to that observed in HCV patients [area under the receiver-operating characteristics (AUROCs) 0.867 ± 0.026 vs. 0.868 ± 0.019 for predicting F ≥ 2, P = 0.975; 0.902 ± 0.029 vs. 0.894 ± 0.020 for F ≥ 3, P = 0.820; and 0.935 ± 0.024 vs. 0.947 ± 0.027 for F4, P = 0.740 respectively]. TE exhibited comparable accuracies, sensitivities, specificities, predictive values and likelihood ratios in HBV and HCV groups. AUROC analysis showed no influence of ALT levels on the performance of TE in HBV individuals. ALT-specific cut-off values did not exhibit significantly higher diagnostic performances for predicting fibrosis in HBV patients with elevated ALT. CONCLUSIONS: In HBV patients, TE measurement accurately predicts the absence or presence of significant fibrosis, advanced fibrosis or cirrhosis and shows similar performances as compared to HCV patients. The use of TE cut-off values adjusted to ALT level did not improve performances for estimating liver fibrosis in HBV patients.
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Alanina Transaminase/sangue , Técnicas de Imagem por Elasticidade/métodos , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Cirrose Hepática/diagnóstico , Adulto , Biópsia , Estudos Transversais , França , Humanos , Cirrose Hepática/etiologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROCRESUMO
BACKGROUND: An increasing proportion of patients with hepatocellular carcinoma are older than 75 years. Previous studies suggested that ageing does not adversely impact survival but they have the drawback of being retrospective and spanning a prolonged period of time. GOALS: Evaluate management and prognosis of hepatocellular carcinoma in elderly. PATIENTS AND METHODS: A multidisciplinary oncology meeting prospectively evaluated all patients with hepatocellular carcinoma. Management were standardised according to European and American guidelines. Forty patients older than 75 years were matched with younger patients for tumour extension and liver function. Both groups were compared for the type of treatment and survival. RESULTS: Male/female ratio was 1.2 as compared to 7 in controls. Cirrhosis was related mostly to hepatitis C virus in elderly, and equally to hepatitis C or B virus and alcohol in controls. Curative treatments were recommended in 55% of elderly and 75% of controls. Treatment actually performed was curative in 25% in elderly as compared to 63% in controls. Median survival (30 months) was identical in both groups. CONCLUSION: Despite more restricted access to curative treatments, survival of elderly patients with hepatocellular carcinoma is comparable to that of younger patients.
Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Cuidados Paliativos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Ablação por Cateter , Feminino , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/complicações , Cirrose Hepática/virologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Transplante de Fígado , Masculino , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) currently represents the major cause of liver-related death in patients with hepatitis C virus (HCV)-related cirrhosis. We assessed the influence of combination therapy on the risk of HCC, liver-related complications (ascites, variceal bleeding), and liver-related death (or liver transplantation). METHODS: Three hundred seven chronic hepatitis C patients with bridging fibrosis (n=127) or cirrhosis (n=180) were evaluated by Cox regression analysis. Sustained virological response (SVR) was defined as undetectable serum HCV RNA at 24 weeks after treatment. RESULTS: SVR developed in 33% of patients. The SVR rates were not different between patients with bridging fibrosis (37%) and those with cirrhosis (30%), p=0.186. During a median follow-up of 3.5 years (range 1-18 years) after the last treatment, the incidence rates per 100 person-years of HCC, liver-related complications, and liver-related death, were 1.24, 0.62, and 0.61 among SVR patients, respectively, and 5.85, 4.16, and 3.76 among non-SVR patients, respectively (log-rank test, p<0.001). According to multivariate analysis, non-SVR was an independent predictor of HCC (HR 3.06; 95% CI=1.12-8.39), liver-related complications (HR 4.73; 95% CI: 1.09-20.57), and liver-related death (HR 3.71; 95% CI=1.05-13.05). CONCLUSIONS: SVR is achieved in one-third of patients with HCV-related cirrhosis treated with peginterferon and ribavirin. SVR has a strong independent positive influence on the incidence of HCC and on the prognosis of these patients.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Idoso , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Ensaios Clínicos como Assunto , Feminino , Seguimentos , Genótipo , Hepacivirus/genética , Hepatite C/epidemiologia , Humanos , Incidência , Interferon alfa-2 , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , RNA Viral/sangue , RNA Viral/genética , Proteínas Recombinantes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
UNLABELLED: A sustained virologic response (SVR) in patients with chronic hepatitis C receiving pegylated interferon (PEG-IFN) plus ribavirin is defined as undetectable serum HCV-RNA at 24 weeks (W+24) posttreatment follow-up. Viral load outcome in patients with virological relapse (VR) has not been explored. This study evaluated whether the assessment of serum HCV-RNA 12 weeks (W+12) after the end of treatment was as relevant as W+24 to evaluate SVR in 573 patients who received combination PEG-IFN and ribavirin and had a virological response at the end of treatment. Serum HCV-RNA was measured, using a new assay based on transcription-mediated amplification (TMA) with a lowest detection limit of 5-10 IU/mL, at W+12 and W+24 after the end of treatment. VR was defined as reappearance of detectable HCV-RNA at W+24 posttreatment follow-up. The positive predictive value (PPV) of undetectable serum HCV-RNA at W+12 was evaluated to identify patients with SVR, and the viral load outcome was measured in relapse patients. At the W+24 posttreatment follow-up, 408 (71%) patients had an SVR, 181 (71.2%) were treated with PEG-IFNalpha-2a and ribavirin, and 227 (71.1%) were treated with PEG-IFNalpha-2b and ribavirin. At W+12, serum HCV-RNA was undetectable in 409 patients, and 408 patients were SVR (PPV 99.7%, 95% confidence interval 99.1-100). In relapse patients, serum HCV-RNA levels were 5.623 +/- 0.748, 4.979 +/- 0.870, and 5.216 +/- 0.758 log(10) IU/mL at baseline, W+12, and W+24, respectively. CONCLUSION: Our results show that the assessment of serum HCV-RNA 12 weeks after the end of treatment, using the highly sensitive TMA assay (PPV 99.7%), is as relevant as after 24 weeks to predict SVR and make decisions on the management of treated patients, suggesting a new definition for SVR.
Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Quimioterapia Combinada , Feminino , Seguimentos , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Proteínas Recombinantes , RecidivaRESUMO
BACKGROUND: The aim of this study was to assess the influence of hepatitis B virus (HBV) genotypes on serum hepatitis B surface antigen (HBsAg) kinetics in hepatitis B e antigen (HBeAg)-negative patients treated with pegylated interferon-alpha2a (PEG-IFN-alpha2a). METHODS: A total of 48 consecutive patients treated with PEG-IFN-alpha2a (180 microg/week) for 48 weeks were assessed. HBV genotype was determined. Serum HBV DNA and HBsAg were assessed at baseline, during treatment (weeks 12, 24 and 48) and during follow-up (weeks 72 and 96). RESULTS: The distribution of HBV genotype was A 27%, B 17%, C 12%, D 29% and E 14%. Mean +/-sd pretreatment serum HBV DNA (6.9 +/-1.5 log(10) copies/ml) was not different between genotypes and decreased under treatment in all genotypes without significant difference. Mean +/-sd pretreatment serum HBsAg (3.6 +/-0.6 log(10) IU/ml) was significantly different between genotypes (P<0.001), with high levels in genotypes A and C, intermediate levels in genotypes D and E, and low levels in genotype B (4.0 +/-0.3, 4.1 +/-0.7, 3.6 +/-0.5, 3.6 +/-0.4 and 2.7 +/-0.6 log(10) IU/ml, respectively). Serum HBsAg decreased under treatment in all genotypes with a significant difference. At the end of treatment, mean +/-sd decrease was high in genotype A, intermediate in genotypes B and D, and low in genotypes C and E (1.3 +/-1.6, 0.7 +/-0.7, 0.6 +/-0.9, 0.4 +/-1.0 and 0.4 +/-0.9 log(10) IU/ml, respectively; P<0.001). During follow-up, serum HBsAg continued to decrease in genotypes A and D, whereas rebound was observed in genotypes B, C and E. CONCLUSIONS: HBV genotype has a strong influence on serum HBsAg kinetics during PEG-IFN-alpha2a therapy in HBeAg-negative patients.