RESUMO
BACKGROUND & AIMS: As many as 70% of individuals with chronic hepatitis C (CHC) are managed solely in primary care. The aims of this study were to determine the prevalence of elevated liver stiffness measurement (LSM) in a cohort of community managed patients with CHC and to evaluate predictors of advanced liver disease and liver-related events. METHODS: A prospective cohort of adult patients with CHC were recruited from 21 primary care practices throughout Victoria, Australia. Inclusion criteria included the presence of CHC for >6â¯months, no recent (<18â¯months) specialist input and no history of hepatocellular carcinoma. Clinical assessment, LSM and phlebotomy were carried out in primary care. A hospital cohort was recruited for comparison. Participants were followed longitudinally and monitored for liver-related events. RESULTS: Over 26â¯months, 780 community patients were recruited and included in the analysis. The median LSM was 6.9â¯kPa in the community, with 16.5% of patients at risk of advanced fibrosis (LSM ≥12.5â¯kPa); of these 8.5% had no laboratory features of advanced liver disease. The proportion at risk of cirrhosis was no different between the community and hospital cohorts (pâ¯=â¯0.169). At-risk alcohol consumption, advancing age, elevated body mass index and alanine aminotransferase were independent predictors of elevated LSM. Over a median follow-up of 15.2â¯months, liver-related events occurred in 9.3% of those with an LSM ≥12.5â¯kPa. An LSM of 24â¯kPa had the highest predictive power for liver-related events (hazard ratio152; pâ¯<0.001). CONCLUSION: The prevalence of advanced fibrosis, as determined by LSM, in primary care managed CHC is significant and comparable to a hospital cohort. Furthermore, this study supports the use of LSM as a community screening tool in a CHC population and indicates a possible role in predicting liver-related events. LAY SUMMARY: The prevalence of advanced liver disease in primary care managed hepatitis C is unknown. Our data suggests that rates of advanced fibrosis in the community are significant (16.5%), often underdiagnosed and comparable to rates seen in specialist referral centres. Liver stiffness measurement is a feasible community screening tool prior to hepatitis C therapy and can predict liver-related adverse events.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Técnicas de Imagem por Elasticidade , Hepatite C Crônica/complicações , Cirrose Hepática , Neoplasias Hepáticas/diagnóstico , Fígado/patologia , Atenção Primária à Saúde/métodos , Adulto , Austrália/epidemiologia , Estudos de Coortes , Técnicas de Imagem por Elasticidade/métodos , Técnicas de Imagem por Elasticidade/estatística & dados numéricos , Feminino , Hepatite C Crônica/epidemiologia , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos ProspectivosRESUMO
OBJECTIVES: To determine the factors associated with survival of patients with hepatocellular carcinoma (HCC) and the effect of HCC surveillance on survival. DESIGN, SETTING AND PARTICIPANTS: Prospective population-based cohort study of patients newly diagnosed with HCC in seven tertiary hospitals in Melbourne, 1 July 2012 - 30 June 2013. MAIN OUTCOME MEASURES: Overall survival (maximum follow-up, 24 months); factors associated with HCC surveillance participation and survival. RESULTS: 272 people were diagnosed with incident HCC during the study period; the most common risk factors were hepatitis C virus infection (41%), alcohol-related liver disease (39%), and hepatitis B virus infection (22%). Only 40% of patients participated in HCC surveillance at the time of diagnosis; participation was significantly higher among patients with smaller median tumour size (participants, 2.8 cm; non-participants, 6.0 cm; P < 0.001) and earlier Barcelona Clinic Liver Cancer (BCLC) stage disease (A/B, 59%; C/D, 25%; P < 0.001). Participation was higher among patients with compensated cirrhosis or hepatitis C infections; it was lower among those with alcohol-related liver disease or decompensated liver disease. Median overall survival time was 20.8 months; mean survival time was 18.1 months (95% CI, 16.6-19.6 months). Participation in HCC surveillance was associated with significantly lower mortality (adjusted hazard ratio [aHR], 0.60; 95% CI, 0.38-0.93; P = 0.021), as were curative therapies (aHR, 0.33; 95% CI, 0.19-0.58). Conversely, higher Child-Pugh class, alpha-fetoprotein levels over 400 kU/L, and later BCLC disease stages were each associated with higher mortality. CONCLUSIONS: Survival for patients with HCC is poor, but may be improved by surveillance, associated with the identification of earlier stage tumours, enabling curative therapies to be initiated.
Assuntos
Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Humanos , Incidência , Hepatopatias Alcoólicas/complicações , Hepatopatias Alcoólicas/epidemiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Vitória/epidemiologiaRESUMO
UNLABELLED: Hepatocellular carcinoma (HCC) incidence is rising rapidly in many developed countries. Primary epidemiological data have invariably been derived from cancer registries that are heterogeneous in data quality and registration methodology; many registries have not adopted current clinical diagnostic criteria for HCC and still rely on histology for classification. We performed the first population-based study in Australia using current diagnostic criteria, hypothesizing that HCC incidence may be higher than reported. Incident cases of HCC (defined by American Association for the Study of Liver Diseases diagnostic criteria or histology) were prospectively identified over a 12-month period (2012-2013) from the population of Melbourne, Australia. Cases were captured from multiple sources: admissions to any of Melbourne's seven tertiary hospitals; attendances at outpatients; and radiology, pathology, and pharmacy services. Our cohort was compared to the Victorian Cancer Registry (VCR) cohort (mandatory notified cases) for the same population and period, and incidence rates were compared for both cohorts. There were 272 incident cases (79% male; median age: 65 years) identified. Cirrhosis was present in 83% of patients, with hepatitis C virus infection (41%), alcohol (39%), and hepatitis B virus infection (22%) the commonest etiologies present. Age-standardized HCC incidence (per 100,000, Australian Standard Population) was 10.3 (95% confidence interval [CI]: 9.0-11.7) for males and 2.3 (95% CI: 1.8 to 3.0) for females. The VCR reported significantly lower rates of HCC: 5.3 (95% CI: 4.4 to 6.4) and 1.0 (95% CI: 0.7 to 1.5) per 100,000 males and females respectively (P < 0.0001). CONCLUSIONS: HCC incidence in Melbourne is 2-fold higher than reported by cancer registry data owing to under-reporting of clinical diagnoses. Adoption of current diagnostic criteria and additional capture sources will improve registry completeness. Chronic viral hepatitis and alcohol remain leading causes of cirrhosis and HCC.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Sistema de Registros , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/terapia , Estudos de Coortes , Intervalos de Confiança , Feminino , Humanos , Incidência , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Distribuição de Poisson , Prognóstico , Distribuição por Sexo , Estatísticas não Paramétricas , Vitória/epidemiologiaRESUMO
BACKGROUND AND AIM: Disease recurs frequently after Crohn's disease resection. The role of serological antimicrobial antibodies in predicting recurrence or as a marker of recurrence has not been well defined. METHODS: A total of 169 patients (523 samples) were prospectively studied, with testing peri-operatively, and 6, 12 and 18 months postoperatively. Colonoscopy was performed at 18 months postoperatively. Serologic antibody presence (perinuclear anti-neutrophil cytoplasmic antibody [pANCA], anti-Saccharomyces cerevisiae antibodies [ASCA] IgA/IgG, anti-OmpC, anti-CBir1, anti-A4-Fla2, anti-Fla-X) and titer were tested. Quartile sum score (range 6-24), logistic regression analysis, and correlation with phenotype, smoking status, and endoscopic outcome were assessed. RESULTS: Patients with ≥ 2 previous resections were more likely to be anti-OmpC positive (94% vs 55%, ≥ 2 vs < 2, P = 0.001). Recurrence at 18 months was associated with anti-Fla-X positivity at baseline (49% vs 29%; positive vs negative, P = 0.033) and 12 months (52% vs 31%, P = 0.04). Patients positive (n = 28) for all four antibacterial antibodies (anti-CBir1, anti-OmpC, anti-A4-Fla2, and anti-Fla-X) at baseline were more likely to experience recurrence at 18 months than patients negative (n = 32) for all four antibodies (82% vs 18%, P = 0.034; odds ratio 6.4, 95% confidence interval 1.16-34.9). The baseline quartile sum score for all six antimicrobial antibodies was higher in patients with severe recurrence (Rutgeert's i3-i4) at 18 months, adjusted for clinical risk factors (odds ratio 1.16, 95% confidence interval 1.01-1.34, P = 0.039). Smoking affected antibody status. CONCLUSIONS: Anti-Fla-X and presence of all anti-bacterial antibodies identifies patients at higher risk of early postoperative Crohn's disease recurrence. Serologic screening pre-operatively may help identify patients at increased risk of recurrence.
Assuntos
Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Adulto , Anticorpos Anticitoplasma de Neutrófilos/sangue , Anticorpos Antibacterianos/sangue , Biomarcadores/sangue , Colonoscopia , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Período Perioperatório , Porinas/imunologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Risco , Saccharomyces cerevisiae/imunologia , Fumar/efeitos adversosRESUMO
BACKGROUND: Most patients with Crohn's disease need an intestinal resection, but a majority will subsequently experience disease recurrence and require further surgery. This study aimed to identify the optimal strategy to prevent postoperative disease recurrence. METHODS: In this randomised trial, consecutive patients from 17 centres in Australia and New Zealand undergoing intestinal resection of all macroscopic Crohn's disease, with an endoscopically accessible anastomosis, received 3 months of metronidazole therapy. Patients at high risk of recurrence also received a thiopurine, or adalimumab if they were intolerant to thiopurines. Patients were randomly assigned to parallel groups: colonoscopy at 6 months (active care) or no colonoscopy (standard care). We used computer-generated block randomisation to allocate patients in each centre to active or standard care in a 2:1 ratio. For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped-up to thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. The primary endpoint was endoscopic recurrence at 18 months. Patients and treating physicians were aware of the patient's study group and treatment, but central reading of the endoscopic findings was undertaken blind to the study group and treatment. Analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00989560. FINDINGS: Between Oct 13, 2009, and Sept 28, 2011, 174 (83% high risk across both active and standard care groups) patients were enrolled and received at least one dose of study drug. Of 122 patients in the active care group, 47 (39%) stepped-up treatment. At 18 months, endoscopic recurrence occurred in 60 (49%) patients in the active care group and 35 (67%) patients in the standard care group (p=0.03). Complete mucosal normality was maintained in 27 (22%) of 122 patients in the active care group versus four (8%) in the standard care group (p=0.03). In the active care arm, of those with 6 months recurrence who stepped up treatment, 18 (38%) of 47 patients were in remission 12 months later; conversely, of those in remission at 6 months who did not change therapy recurrence occurred in 31 (41%) of 75 patients 12 months later. Smoking (odds ratio [OR] 2.4, 95% CI 1.2-4.8, p=0.02) and the presence of two or more clinical risk factors including smoking (OR 2.8, 95% CI 1.01-7.7, p=0.05) increased the risk of endoscopic recurrence. The incidence and type of adverse and severe adverse events did not differ significantly between patients in the active care and standard care groups (100 [82%] of 122 vs 45 [87%] of 52; p=0.51) and (33 [27%] of 122 vs 18 [35%] of 52; p=0.36), respectively. INTERPRETATION: Treatment according to clinical risk of recurrence, with early colonoscopy and treatment step-up for recurrence, is better than conventional drug therapy alone for prevention of postoperative Crohn's disease recurrence. Selective immune suppression, adjusted for early recurrence, rather than routine use, leads to disease control in most patients. Clinical risk factors predict recurrence, but patients at low risk also need monitoring. Early remission does not preclude the need for ongoing monitoring. FUNDING: AbbVie, Gutsy Group, Gandel Philanthropy, Angior Foundation, Crohn's Colitis Australia, and the National Health and Medical Research Council.
Assuntos
Doença de Crohn/terapia , Adalimumab , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Azatioprina/uso terapêutico , Colonoscopia , Doença de Crohn/patologia , Doença de Crohn/cirurgia , Feminino , Humanos , Masculino , Mercaptopurina/uso terapêutico , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Crohn's disease (CD) usually recurs after intestinal resection; postoperative endoscopic monitoring and tailored treatment can reduce the chance of recurrence. We investigated whether monitoring levels of fecal calprotectin (FC) can substitute for endoscopic analysis of the mucosa. METHODS: We analyzed data collected from 135 participants in a prospective, randomized, controlled trial, performed at 17 hospitals in Australia and 1 hospital in New Zealand, that assessed the ability of endoscopic evaluations and step-up treatment to prevent CD recurrence after surgery. Levels of FC, serum levels of C-reactive protein (CRP), and Crohn's disease activity index (CDAI) scores were measured before surgery and then at 6, 12, and 18 months after resection of all macroscopic Crohn's disease. Ileocolonoscopies were performed at 6 months after surgery in 90 patients and at 18 months after surgery in all patients. RESULTS: Levels of FC were measured in 319 samples from 135 patients. The median FC level decreased from 1347 µg/g before surgery to 166 µg/g at 6 months after surgery, but was higher in patients with disease recurrence (based on endoscopic analysis; Rutgeerts score, ≥i2) than in patients in remission (275 vs 72 µg/g, respectively; P < .001). Combined 6- and 18-month levels of FC correlated with the presence (r = 0.42; P < .001) and severity (r = 0.44; P < .001) of CD recurrence, but the CRP level and CDAI score did not. Levels of FC greater than 100 µg/g indicated endoscopic recurrence with 89% sensitivity and 58% specificity, and a negative predictive value (NPV) of 91%; this means that colonoscopy could have been avoided in 47% of patients. Six months after surgery, FC levels less than 51 µg/g in patients in endoscopic remission predicted maintenance of remission (NPV, 79%). In patients with endoscopic recurrence at 6 months who stepped-up treatment, FC levels decreased from 324 µg/g at 6 months to 180 µg/g at 12 months and 109 µg/g at 18 months. CONCLUSIONS: In this analysis of data from a prospective clinical trial, FC measurement has sufficient sensitivity and NPV values to monitor for CD recurrence after intestinal resection. Its predictive value might be used to identify patients most likely to relapse. After treatment for recurrence, the FC level can be used to monitor response to treatment. It predicts which patients will have disease recurrence with greater accuracy than CRP level or CDAI score.
Assuntos
Doença de Crohn/cirurgia , Fezes/química , Complexo Antígeno L1 Leucocitário/metabolismo , Adulto , Austrália , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Colonoscopia , Doença de Crohn/diagnóstico , Doença de Crohn/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Valor Preditivo dos Testes , Estudos Prospectivos , Recidiva , Indução de Remissão , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Sorafenib is an oral multikinase inhibitor that improves survival in advanced hepatocellular carcinoma (HCC). In the absence of alternative therapies, sorafenib is often continued despite advancing liver disease or tumour progression. Real world studies are important to better characterise outcomes in these populations. Our aim was to review patterns of sorafenib use across eight Australian tertiary hospitals, defining variables associated with clinical outcomes. MATERIAL AND METHODS: Retrospective cohort study of medical records of 320 patients treated with sorafenib for HCC. Baseline clinical parameters, dosage, adverse effects, and survival from initiation of treatment were collected. Time to radiological progression and 3-month alpha-fetoprotein (AFP) levels were available for a subset of patients. RESULTS: Adverse effects occurred in 79% of patients, requiring dose reduction in 31% of patients. Multivariate analysis identified an increased rate of mortality with Child-Pugh C (HR 5.52, p = 0.012), ECOG performance status 2-3 (HR 2.84, p = 0.001), and extrahepatic metastases (HR 1.54, p = 0.04), and decreased rate of mortality with an AFP reduction of at least 20% at 3 months (HR 0.38, p = 0.001). An increased rate of radiological progression was associated with ECOG performance status 2-3 (HR 2.34, p = 0.041), whilst a decreased rate of radiological progression was associated with development of on-treatment diarrhoea (HR 0.55, p = 0.015). CONCLUSIONS: Survival in patients with Child-Pugh C liver function or advanced functional impairment treated with sorafenib is poor and thus routine use of this agent in these patients does not appear justified, particularly given the high rate of adverse effects. AFP concentration on therapy may help identify favourable response to treatment.
Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Sorafenibe , Resultado do Tratamento , alfa-Fetoproteínas/análiseRESUMO
BACKGROUND AND AIM: The glycoprotein CD147 has a role in tumor progression, is readily detectable in the circulation, and is abundantly expressed in hepatocellular carcinoma (HCC). Advanced HCC patients are a heterogeneous group with some individuals having dismal survival. The aim of this study was to examine circulating soluble CD147 levels as a prognostic marker in HCC patients. METHODS: CD147 was measured in 277 patients (110 HCC, 115 chronic liver disease, and 52 non-liver disease). Clinical data included etiology, tumor progression, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment response. Patients with HCC were stratified into two groups based upon the 75th percentile of CD147 levels (24 ng/mL). RESULTS: CD147 in HCC correlated inversely with poor survival (P = 0.031). Increased CD147 predicted poor survival in BCLC stages C and D (P = 0.045), and CD147 levels >24 ng/mL predicted a significantly diminished 90-day and 180-day survival time (hazard ratio [HR] = 6.1; 95% confidence interval [CI]: 2.1-63.2; P = 0.0045 and HR = 2.8; 95% CI: 1.2-12.6; P = 0.028, respectively). In BCLC stage C, CD147 predicted prognosis; levels >24 ng/mL were associated with a median survival of 1.5 months compared with 6.5 months with CD147 levels ≤24 ng/mL (P = 0.03). CD147 also identified patients with a poor prognosis independent from treatment frequency, modality, and tumor size. CONCLUSIONS: Circulating CD147 is an independent marker of survival in advanced HCC. CD147 requires further evaluation as a potential new prognostic measure in HCC to identify patients with advanced disease who have a poor prognosis.
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Basigina/sangue , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Idoso , Carcinoma Hepatocelular/mortalidade , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Taxa de Sobrevida , Fatores de TempoRESUMO
BACKGROUND: Tumor associated macrophages are present in hepatocellular carcinoma (HCC) and associated with a poor prognosis. The aim of the present study was to investigate the levels and dynamics of soluble (s)CD163, a specific macrophage activation marker, in patients with HCC. METHODS: In a cohort from Australia, we studied 109 HCC patients, 116 patients with chronic liver disease (CLD), and 52 healthy controls. We examined associations between baseline sCD163 and parameters of HCC severity as well as overall and progression-free survival. In a cohort of 42 Danish HCC patients, we measured sCD163 at baseline and 1, 4 and 12 weeks after ablative treatment. RESULTS: In the Australian cohort, median sCD163 was similarly increased in HCC (5.6[interquartile range 3.5-8.0] mg/L) and CLD (6.1[3.6-9.6] mg/L) patients as compared to controls (2.0[1.5-2.7] mg/L, p < 0.001). sCD163 correlated with Child-Pugh and MELD scores in both HCC and CLD patients. Patients with high sCD163 levels had shorter progression-free survival (p < 0.001), but not overall survival (p = 0.15). In the Danish cohort, patients with HCC progression at 12 weeks had an increase in sCD163. There was no association between sCD163 and HCC size, number, vascular invasion or metastasis in any of the cohorts. CONCLUSIONS: We confirmed increased sCD163 levels in CLD and HCC patients associated with Child-Pugh and MELD scores and portal hypertension, but not with HCC size and number, or metastasis. As a novel finding, baseline sCD163 appeared to predict a rapid HCC progression, as sCD163 increased during follow-up in HCC patients who showed progression.
Assuntos
Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Ativação de Macrófagos/fisiologia , Receptores de Superfície Celular/sangue , Idoso , Austrália , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Estudos de Casos e Controles , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Hepatopatias/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Direct-acting antiviral therapy for hepatitis C virus (HCV) infection is safe and effective, but there are little data among people who have recently injected drugs. This study evaluated the efficacy, and safety of paritaprevir/ritonavir, ombitasvir, dasabuvir with or without ribavirin for chronic HCV genotype (G) 1 among people with recent injecting drug use and/or receiving OST. METHODS: D3FEAT is an international open-label study that recruited treatment-naïve participants with recent injecting drug use (previous 6 months) and/or receiving OST with chronic HCV G1 infection between June 2016 and February 2017 in seven countries. Participants received paritaprevir/ritonavir, ombitasvir, dasabuvir with (G1a) or without ribavirin (G1b) administered twice daily in a one-week electronic blister pack (records timing of each dose) for 12 weeks. The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (SVR12). RESULTS: Among 87 participants (median age 48 years), 23% were female, 8% had cirrhosis, and 90% had G1a. Overall, 71% were receiving OST, 61% injected in the previous six months, 45% injected in the previous month, and 15% injected > daily. Treatment completion was 97% (84 of 87). There were no virological breakthroughs, but three discontinuations (loss to follow-up, n = 1; non-adherence, n = 1; incarceration, n = 1). SVR was 91% (79 of 87, 95% CI, 83%-96%). Five participants who completed treatment did not have SVR (loss to follow-up, n = 1; death, n = 1; virologic relapse, n = 3). Drug use prior to and during treatment did not impact SVR12. Treatment-related adverse events were observed in 46 (53%) patients (six grade 3, no grade 4). Five (6%) patients had at least one serious adverse event (two possibly/probably related to therapy; nausea and myoclonus). Two cases of reinfection were observed. CONCLUSION: Paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin for 12 weeks is effective among people with HCV genotype 1 with recent injecting drug use and/or receiving OST.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Tratamento de Substituição de Opiáceos/métodos , Abuso de Substâncias por Via Intravenosa/tratamento farmacológico , Abuso de Substâncias por Via Intravenosa/epidemiologia , 2-Naftilamina , Adulto , Anilidas/uso terapêutico , Antivirais/efeitos adversos , Carbamatos/uso terapêutico , Ciclopropanos , Esquema de Medicação , Quimioterapia Combinada , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Lactamas Macrocíclicas , Compostos Macrocíclicos/uso terapêutico , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Tratamento de Substituição de Opiáceos/estatística & dados numéricos , Prolina/análogos & derivados , Pesquisa Qualitativa , RNA Viral/análise , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico , Abuso de Substâncias por Via Intravenosa/virologia , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada , Resultado do Tratamento , Uracila/análogos & derivados , Uracila/uso terapêutico , ValinaRESUMO
BACKGROUND: Anti-TNF prevents postoperative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence. METHODS: As part of a study of postoperative Crohn's disease management, some patients undergoing resection received prophylactic postoperative adalimumab. In these patients, serum and fecal adalimumab concentration and serum anti-adalimumab antibodies [AAAs] were measured at 6, 12 and 18 months postoperatively. Levels of Crohn's disease activity index [CDAI], C-reactive protein [CRP] and fecal calprotectin [FC] were assessed at 6 and 18 months postoperatively. Body mass index and smoking status were recorded. A colonoscopy was performed at 6 and/or 18 months. RESULTS: Fifty-two patients [32 on monotherapy and 20 on combination therapy with thiopurine] were studied. Adalimumab concentration did not differ significantly between patients in endoscopic remission vs recurrence [Rutgeerts ≥ i2] [9.98µg/mL vs 8.43 µg/mL, p = 0.387]. Patients on adalimumab monotherapy had a significantly lower adalimumab concentration [7.89 µg/mL] than patients on combination therapy [11.725 µg/mL] [p = 0.001], and were significantly more likely to have measurable AAA [31% vs 17%, p = 0.001]. Adalimumab concentrations were lower in patients with detectable AAA compared with those without [3.59 µg/mL vs 12.0 µg/mL, p < 0.001]. Adalimumab was not detected in fecal samples. Adalimumab serum concentrations were lower in obese patients compared with in non-obese patients [p = 0.046]. CONCLUSION: Adalimumab concentration in patients treated with adalimumab to prevent symptomatic endoscopic recurrence postoperatively is, for most patients, well within the therapeutic window, and is not significantly lower in patients who develop recurrence compared with in those who remain in remission. Mechanisms of anti-TNF failure to prevent postoperative recurrence remain to be determined in these patients.
Assuntos
Adalimumab/sangue , Anti-Inflamatórios/sangue , Doença de Crohn/tratamento farmacológico , Prevenção Secundária , Adalimumab/imunologia , Adalimumab/farmacocinética , Adalimumab/uso terapêutico , Adulto , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Anticorpos/sangue , Doença de Crohn/sangue , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Monitoramento de Medicamentos , Fezes/química , Feminino , Humanos , Imunossupressores/uso terapêutico , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Período Pós-Operatório , Recidiva , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto JovemRESUMO
BACKGROUND: Despite revised guidelines that no longer exclude people who inject drugs (PWID) from treatment for hepatitis C virus (HCV) infection, many clinicians are reluctant to treat recent PWID. This study aimed to evaluate the efficacy of sofosbuvir and velpatasvir therapy in people with chronic HCV infection and recent injection drug use. METHODS: In this open-label, single-arm phase 4 trial (SIMPLIFY), we recruited participants with recent injection drug use (past 6 months) and chronic HCV genotype 1-6 infection from seven countries (19 sites). Participants received oral sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks. Therapy was given in 1-week electronic blister packs to record the time and date of each dose. The primary endpoint was the proportion of patients with sustained virological response 12 weeks after completion of treatment (SVR12; defined as HCV RNA <12 IU/mL), analysed in all patients who received at least one dose. This study is registered with ClinicalTrials.gov, number NCT02336139, and follow-up is ongoing to evaluate the secondary endpoint of HCV reinfection. FINDINGS: Between March 29, and Oct 31, 2016, we enrolled 103 participants; 29 (28%) of whom were female, nine (9%) had cirrhosis, 36 (35%) had HCV genotype 1, five (5%) had genotype 2, 60 (58%) had genotype 3, and two (2%) had genotype 4. 61 (59%) participants were receiving opioid substitution therapy during the study, 76 (74%) injected in the past month, and 27 (26%) injected at least daily in the past month. 100 (97%) of 103 participants completed treatment; two people were lost to follow-up and one person died from an overdose. There were no virological failures. 97 (94%, 95% CI 88-98) of 103 people achieved SVR12. Three participants with an end-of-treatment response did not have a SVR; two were lost to follow-up and one had reinfection. Drug use before and during treatment did not affect SVR12. Treatment-related adverse events were seen in 48 (47%) patients (one grade 3, no grade 4). Seven (7%) patients had at least one serious adverse event; only one such event (rhabdomyolysis, resolved) was possibly related to the therapy. One case of HCV reinfection was observed. INTERPRETATION: HCV treatment should be offered to PWID, irrespective of ongoing drug use. Recent injection drug use should not be used as a reason to withhold reimbursement of HCV therapy. FUNDING: Gilead Sciences.
Assuntos
Antivirais/uso terapêutico , Carbamatos/uso terapêutico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Sofosbuvir/uso terapêutico , Abuso de Substâncias por Via Intravenosa/complicações , Administração Oral , Adulto , Antivirais/efeitos adversos , Carbamatos/efeitos adversos , Esquema de Medicação , Embalagem de Medicamentos , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Sofosbuvir/efeitos adversos , Resposta Viral SustentadaRESUMO
OBJECTIVE: The evaluation of a new model of care for older people with complex health care needs that aimed to reduce their use of acute hospital services. METHOD: Older people (over 55 years) with complex health care needs, who had made three or more presentations to a hospital emergency department (ED) in the previous 12 months, or who were identified by community health care agencies as being at risk of making frequent ED presentations, were recruited to the project. The participants were allocated a "care facilitator" who provided assistance in identifying and accessing required health care services, as well as education in aspects of self management. Data for the patients who had been participants on the project for a minimum of 90 days (n=231) were analysed for their use of acute hospital services (ED presentations, admissions and hospital bed-days) for the period 12-months pre-recruitment and post-recruitment. A similar analysis on the use of hospital services was conducted on the data of patients who were eligible and who had been offered participation, but who had declined (comparator group; n=85). RESULTS: Post recruitment, the recruited patients displayed a 20.8% reduction in ED presentations, a 27.9% reduction in hospital admissions, and a 19.2% reduction in bed-days. By comparison, the patients who declined recruitment displayed a 5.2% increase in ED presentations, a 4.4% reduction in hospital admissions, and a 15.3% increase in inpatient bed-days over a similar timeframe. CONCLUSION: A model of care that facilitates access to community health services and provides coordination between existing services reduces hospital demand.
Assuntos
Administração de Caso , Prestação Integrada de Cuidados de Saúde , Serviço Hospitalar de Emergência/estatística & dados numéricos , Idoso Fragilizado , Necessidades e Demandas de Serviços de Saúde , Serviços de Saúde para Idosos/organização & administração , Hospitalização/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Modelos Organizacionais , VitóriaRESUMO
An estimated 210,000 people were living with hepatitis C virus (HCV) infection in Australia at the end of 2001, and the number of people developing cirrhosis was projected to increase 4-fold by 2020. Eighty percent of prevalent and 90% of incident HCV infections are related to injection drug use. Current injection drug use was an exclusion criterion for access to government-funded treatment for HCV infection until May 2001. Despite the removal of this barrier to treatment access for current injection drug users (IDUs), the number of IDUs receiving treatment remains extremely low. Treatment outcomes among IDUs with chronic HCV infection treated at 2 public hospital-based hepatitis clinics are presented. These data demonstrate that IDUs who continue to inject infrequently during treatment for HCV infection can achieve a sustained virological response. Further studies are under way to examine outcomes of treatment for HCV among clients undergoing treatment for drug dependency who have chronic HCV infection and among current IDUs with acute and newly acquired HCV infection.
Assuntos
Hepatite C Crônica/epidemiologia , Hepatite C Crônica/terapia , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Antivirais/uso terapêutico , Austrália/epidemiologia , Feminino , Hepatite C Crônica/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Centros de Tratamento de Abuso de Substâncias/estatística & dados numéricos , Abuso de Substâncias por Via Intravenosa/terapia , Resultado do TratamentoRESUMO
RATIONALE: Methadone is a long-acting mu-opioid and is an effective treatment for heroin addiction. Opioids depress respiration, and patients receiving methadone maintenance treatment (MMT) have higher mortality than the general population. Few studies have investigated ventilatory responses to both hypercapnia and hypoxia in these patients. STUDY OBJECTIVES: We measured hypercapnic ventilatory response (HCVR) and hypoxic ventilatory response (HVR) and investigated possible factors associated with both in clinically stable patients receiving MMT. DESIGN AND SETTING: Patients receiving long-term, stable doses of methadone recruited from a statewide MMT program, and normal, non-opioid-using subjects matched for age, sex, height, and body mass index were studied with HCVR and HVR. RESULTS: Fifty MMT patients and 20 normal subjects were studied, and significantly decreased HCVR and increased HVR were found in MMT patients compared to normal subjects (HCVR [mean +/- SD], l.27 +/- 0.61 L/min/mm Hg vs 1.64 +/- 0.57 L/min/mm Hg [p = 0.01]; HVR, 2.14 +/- 1.58 L/min/% arterial oxygen saturation measured by pulse oximetry [Sp(O2)] vs 1.12 +/- 0.7 L/min/% Sp(O2) [p = 0.008]). Respiratory rate and not tidal volume changes were the major physiologic responses contributing to both HCVR and HVR differences between the groups. Variables associated with HCVR in the MMT patients are as follows: obstructive sleep apnea/hypopnea index (t = 5.1, p = 0.00001), Pa(CO2) (t = - 3.6, p = 0.001), body height (t = 2.6, p = 0.01) and alveolar-arterial oxygen pressure gradient (t = 2.5, p = 0.02). Variables associated with HVR in MMT patients are body height (t = 3.2, p = 0.002) and Pa(CO2) (t = - 2.8, p = 0.008). CONCLUSIONS: Stable long-term MMT patients have blunted central and elevated peripheral chemoreceptor responses. The mechanisms and clinical significance of these findings need further investigation.
Assuntos
Hipercapnia/induzido quimicamente , Hipóxia/induzido quimicamente , Metadona/efeitos adversos , Entorpecentes/efeitos adversos , Ventilação Pulmonar/efeitos dos fármacos , Adulto , Feminino , Dependência de Heroína/tratamento farmacológico , Humanos , Hipercapnia/fisiopatologia , Hipóxia/fisiopatologia , Masculino , Ventilação Pulmonar/fisiologia , Insuficiência Respiratória/induzido quimicamente , Insuficiência Respiratória/fisiopatologiaRESUMO
STUDY OBJECTIVES: Methadone, a long-acting mu-opioid agonist, is an effective treatment for heroin addiction. Our previous data show that 6 of 10 methadone maintenance treatment (MMT) patients had central sleep apnea (CSA). This study aims to confirm these results and to investigate the pathogenesis of the CSA. METHODS: Twenty-five male and 25 female MMT patients and 20 age-, sex-, and body mass index (BMI)-matched normal subjects were tested with polysomnography, blood toxicology, and ventilatory responses to hypoxia and hypercapnia. Resting cardiorespiratory tests were performed in the MMT group RESULTS: MMT patients and normal subjects were 35 +/- 9 years old (mean +/- SD), and BMI values were 27 +/- 6 kg/m2 and 27 +/- 5 kg/m2, respectively. Thirty percent of MMT patients had a central apnea index (CAI) > 5, and 20% had a CAI > 10. All normal subjects had a CAI < 1, and no difference was found in obstructive apnea-hypopnea index between the two groups. Methadone blood concentration was the only significant variable (t = 2.33, p = 0.025) associated with CAI and explains 12% of the variance. Awake Pa(CO2), antidepressant use, reduced ventilatory response to hypercapnia, and widened awake alveolar-arterial oxygen pressure gradient together explain a further 17% of the CAI variance. CONCLUSIONS: Thirty percent of stable MMT patients have CSA, a minority of which can be explained by blood methadone concentration. Other physiologic variables may also play a role in the pathogenesis of CSA in MMT patients, and further research is indicated in this area.
Assuntos
Dependência de Heroína/tratamento farmacológico , Metadona/efeitos adversos , Entorpecentes/efeitos adversos , Apneia do Sono Tipo Central/induzido quimicamente , Apneia do Sono Tipo Central/diagnóstico , Adulto , Feminino , Humanos , Hipercapnia/diagnóstico , Hipóxia/diagnóstico , Masculino , PolissonografiaRESUMO
INTRODUCTION: Patients with Crohn's disease have poorer health-related quality of life [HRQoL] than healthy individuals, even when in remission. Although HRQoL improves in patients who achieve drug-induced or surgically induced remission, the effects of surgery overall have not been well characterised. METHODS: In a randomised trial, patients undergoing intestinal resection of all macroscopically diseased bowel were treated with postoperative drug therapy to prevent disease recurrence. All patients were followed prospectively for 18 months. C-reactive protein [CRP], Crohn's Disease Activity Index [CDAI], and faecal calprotectin [FC] were measured preoperatively and at 6, 12, and 18 months. HRQoL was assessed with a general [SF36] and disease-specific [IBDQ] questionnaires at the same time points. RESULTS: A total of 174 patients were included. HRQoL was poor preoperatively but improved significantly [p < 0.001] at 6 months postoperatively. This improvement was sustained at 18 months. Females and smokers had a poorer HRQoL when compared with males and non-smokers, respectively. Persistent endoscopic remission, intensification of drug treatment at 6 months, and anti-tumour necrosis factor therapy were not associated with HRQoL outcomes different from those when these factors were not present. There was a significant inverse correlation between CDAI, [but not endoscopic recurrence, CRP, or FC] on HRQoL. CONCLUSION: Intestinal resection of all macroscopic Crohn's disease in patients treated with postoperative prophylactic drug therapy is associated with significant and sustained improvement in HRQoL irrespective of type of drug treatment or endoscopic recurrence. HRQoL is lower in female patients and smokers. A higher CDAI, but not direct measures of active disease or type of drug therapy, is associated with a lower HRQoL.
Assuntos
Doença de Crohn/cirurgia , Qualidade de Vida , Adalimumab/uso terapêutico , Adulto , Anti-Inflamatórios , Proteína C-Reativa/metabolismo , Ceco/cirurgia , Colectomia , Colonoscopia , Fezes/química , Feminino , Seguimentos , Humanos , Íleo/cirurgia , Imunossupressores/uso terapêutico , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Indução de Remissão , Índice de Gravidade de Doença , Fatores Sexuais , Fumar/efeitos adversos , Inquéritos e Questionários , Fatores de Tempo , Conduta Expectante , Adulto JovemRESUMO
Six opiate-dependent drug users presented to the local emergency department within a 10-day period with symptoms of severe opioid withdrawal immediately following intravenous use of recently acquired street 'heroin'. The withdrawal picture was similar to that described in patients undergoing rapid opioid detoxification, suggesting that the substance injected was contaminated with an opiate antagonist. A number of potential compounds are discussed, including naltrexone and buprenorphine, and recommendations for the medical management of severe opiate withdrawal within an emergency setting are outlined. [Lubman DI, Koutsogiannis Z, Kronborg I. Emergency management of inadvertent accelerated opiate withdrawal in dependent opiate users.
Assuntos
Buprenorfina/uso terapêutico , Serviços Médicos de Emergência , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Entorpecentes/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/reabilitação , Abuso de Substâncias por Via Intravenosa/reabilitação , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/etiologia , Adulto , Feminino , Humanos , Inativação Metabólica , Masculino , Índice de Gravidade de DoençaRESUMO
AIMS: To evaluate the efficacy, safety and adherence to hepatitis C (HCV) therapy in patients attending tertiary hepatitis clinics who are receiving opioid replacement therapy. DESIGN: A non-randomized, open-label study. Participants were treated with pegylated interferon alpha-2a and weight-based ribavirin for 24 weeks (genotype non-1, n = 31) or 48 weeks (genotype 1, n = 22). SETTING: Four tertiary hospital hepatitis clinics in Australia. PARTICIPANTS: Fifty-three patients with chronic HCV who were receiving opioid replacement therapy. MEASUREMENTS: Patients were monitored for virological response, adverse events and adherence. They were also screened for psychiatric illness prior to and throughout the study utilizing two validated instruments: the Mini International Neuropsychiatric Interview (MINI) and Beck Depression Interview (BDI)-II. FINDINGS: The overall sustained virological response (SVR) rate was 57% (71% genotype non-1 versus 36% genotype 1), and was similar in active injectors (63%) and non-injectors (53%). The psychological profile of patients based on validated instruments did not change on therapy. The pattern and frequency of adverse effects were comparable to non-opioid replacement patients. Eighty-five per cent of patients were adherent to therapy by 80/80/80 criteria and only two patients who had an end-of-treatment response relapsed, one of whom was not an active injector. CONCLUSIONS: Patients on opioid replacement therapy, even if they continue to inject actively, can achieve comparable sustained virological response rates to other populations with pegylated interferon alpha-2a and ribavirin therapy, suffer no excess rates of adverse effects or psychological complications and have good adherence to therapy.