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1.
Clin Oncol (R Coll Radiol) ; 32(7): 423-432, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32093876

RESUMO

AIMS: To evaluate the safety and efficacy of liver stereotactic body radiotherapy (SBRT) in the treatment of unresectable hepatocellular carcinomas (HCC) measuring >5 cm. MATERIALS AND METHODS: Between November 2013 and February 2016, 13 patients with unresectable HCC (>5 cm), ineligible for other local treatments, with a Child-Pugh score (CPS) ≤ B7, were enrolled into a single-institution phase II study. SBRT was delivered by volumetric-modulated arc radiotherapy. Radiological response was reported using modified Response Evaluation Criteria in Solid Tumours criteria and toxicities graded by Common Terminology Criteria for Adverse Events v4 criteria. RESULTS: Sixteen hepatomas (median size 7.5 cm, range 5.1-9.7 cm) were treated in 13 patients. The baseline CPS was A5/6 in nine patients (69%) and B7 in four patients (31%). Five patients (38%) received previous liver-directed treatment. The median prescribed dose was 45 Gy (range 40-45 Gy) in five fractions. The median follow-up was 17.7 months. The 1-year local control rate was 92%. The median overall survival was 17.7 months and the 1-year overall survival was 62%. The median time to local progression was not reached. Five patients (39%) had an increase in CPS by two or more points at 3 months. Overall, there were 10 grade 3 acute toxicities occurring in seven patients, of which six were haematological. Quality of life remained clinically stable or improved at 3 months in 61.5% and 53.8% of patients based on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 Global Health Score and Functional Assessment of Cancer Therapy - Hepatobiliary version 4 score, respectively. CONCLUSIONS: In our cohort, SBRT to unresectable large HCC tumours provided excellent local control with acceptable toxicities. Regional recurrence remained the major cause of failure. Further studies are warranted to examine the role for SBRT in combination with other modalities to maximise disease control in the liver.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Progressão da Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Prospectivos , Qualidade de Vida
2.
Int J Drug Policy ; 74: 52-61, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31525640

RESUMO

BACKGROUND: Colonization and colonial systems have led to the overrepresentation of Indigenous people impacted by substance use and HCV infection in Canada. It is critical to ensure Indigenous people's equitable access to new direct acting antiviral HCV treatments (DAAs). Identifying culturally-safe, healing-centered approaches that support the wellbeing of Indigenous people living with HCV is an essential step toward this goal. We listened to the stories and perspectives of HCV-affected Indigenous people and HCV treatment providers with the aim of providing pragmatic recommendations for decolonizing HCV care. METHODS: Forty-five semi-structured interviews were carried out with Indigenous participants affected by HCV from the Cedar Project (n = 20, British Columbia (BC)) and the Canadian Coinfection Cohort (n = 25, BC; Ontario (ON); Saskatchewan (SK)). In addition, 10 HCV treatment providers were interviewed (n = 4 BC, n = 4 ON, n = 2 SK). Interpretive description identified themes to inform clinical approaches and public health HCV care. Themes and related recommendations were validated by Indigenous health experts and Indigenous participants prior to coding and re-contextualization. RESULTS: Taken together, participants' stories and perceptions were interpreted to coalesce into three overarching and interdependent themes representing their recommendations. First: treatment providers must understand and accept colonization as a determinant of health and wellness among HCV-affected Indigenous people, including ongoing cycles of child apprehension and discrimination within the healthcare system. Second: consistently safe attitudes and actions create trust within HCV treatment provider-patient relationships and open opportunities for engagement into care. Third: treatment providers who identify, build, and strengthen circles of care will have greater success engaging HCV-affected Indigenous people who have used drugs into care. CONCLUSION: There are several pragmatic ways to integrate Truth and Reconciliation as well as Indigenous concepts of whole-person wellness into the HCV cascade of care. By doing so, HCV treatment providers have an opportunity to create greater equity and support long-term wellness of Indigenous patients.


Assuntos
Antivirais/administração & dosagem , Acessibilidade aos Serviços de Saúde , Serviços de Saúde do Indígena/organização & administração , Hepatite C/terapia , Povos Indígenas , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Idoso , Canadá , Cidades , Estudos de Coortes , Feminino , Hepatite C/epidemiologia , Hepatite C/etnologia , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Substâncias/etnologia
5.
J Viral Hepat ; 24(8): 624-630, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28130810

RESUMO

We evaluated the shift in the characteristics of people who received interferon-based hepatitis C virus (HCV) treatments and those who received recently introduced direct-acting antivirals (DAAs) in British Columbia (BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon-based treatments including pegylated interferon/ribavirin (PegIFN/RBV) with/without boceprevir or telaprevir, DAAs with RBV or PegIFN/RBV, and newer interferon-free DAAs. Of 11 886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon-free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or PegIFN/RBV. Compared to those receiving interferon-based treatment, people with HIV co-infection (adjusted odds ratio [aOR]: 2.96, 95% CI: 2.31-3.81), cirrhosis (aOR: 1.77, 95% CI: 1.45-2.15), decompensated cirrhosis (aOR: 1.72, 95% CI: 1.31-2.28), diabetes (aOR: 1.30, 95% CI: 1.10-1.54), a history of injection drug use (aOR: 1.34, 95% CI: 1.09-1.65) and opioid substitution therapy (aOR: 1.30, 95% CI: 1.01-1.67) were more likely to receive interferon-free DAAs. Socio-economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58-0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV-co-infected), although gaps remain for the socio-economically marginalized populations.


Assuntos
Antivirais/uso terapêutico , Disparidades em Assistência à Saúde , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Oligopeptídeos/uso terapêutico , Prolina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Colúmbia Britânica , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prolina/uso terapêutico , Ribavirina/uso terapêutico , Adulto Jovem
6.
Curr Oncol ; 23(3): e196-220, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27330357

RESUMO

BACKGROUND: The incidence of hepatocellular carcinoma (hcc) and the complexity of its diagnosis and treatment are increasing. We estimated trends in net health care utilization, costs of care attributable to hcc in Ontario, and rate ratios of resource use at various stages of care. METHODS: This population-based retrospective cohort study identified hcc patients and non-cancer control subjects, and health care resource utilization between 2002 and 2009. Generalized estimating equations were then used to estimate net health care utilization (hcc patients vs. the matched control subjects) and net costs of care attributable to hcc. Generalized linear models were used to analyze rate ratios of resource use. RESULTS: We identified 2832 hcc patients and 2808 matched control subjects. In comparison with the control subjects, hcc patients generally used a greater number of health care services. Overall, the mean net cost of care per 30 patient-days (2013 Canadian dollars) attributable to outpatient visits and hospitalizations was highest in the pre-diagnosis (1 year before diagnosis), initial (1st year after diagnosis), and end-of-life (last 6 months before death, short-term survivors) phases. Mean net homecare costs were highest in the end-of-life phase (long-term survivors). In the end-of-life phase (short-term survivors), mean net costs attributable to outpatient visits and total services significantly increased to $14,220 from $1,547 and to $33,121 from $14,450 (2008-2009 and 2002-2003 respectively). CONCLUSIONS: In hcc, our study found increasing resource use and net costs of care, particularly in the end-of-life phase among short-term survivors. Our findings offer a basis for resource allocation decisions in the area of cancer prevention and control.

7.
J Viral Hepat ; 23(3): 227-31, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26572686

RESUMO

Faldaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in HCV genotype 1-infected patients who failed peginterferon and ribavirin (PegIFN/RBV) treatment during one of three prior faldaprevir trials. Patients who received placebo plus PegIFN/RBV and had virological failure during a prior trial were enrolled and treated in two cohorts: prior relapsers (n = 43) and prior nonresponders (null responders, partial responders and patients with breakthrough; n = 75). Both cohorts received faldaprevir 240 mg once daily plus PegIFN/RBV for 24 weeks. Prior relapsers with early treatment success (ETS; HCV RNA <25 IU/mL detectable or undetectable at week 4 and <25 IU/mL undetectable at week 8) stopped treatment at week 24. Others received PegIFN/RBV through week 48. The primary efficacy endpoint was sustained virological response (HCV RNA <25 IU/mL undetectable) 12 weeks post treatment (SVR12). More prior nonresponders than prior relapsers had baseline HCV RNA ≥ 800,000 IU/mL (80% vs 58%) and a non-CC IL28B genotype (91% vs 70%). Rates of SVR12 (95% CI) were 95.3% (89.1, 100.0) among prior relapsers and 54.7% (43.4, 65.9) among prior nonresponders; corresponding ETS rates were 97.7% and 65.3%. Adverse events led to faldaprevir discontinuations in 3% of patients. The most common Division of AIDS Grade ≥ 2 adverse events were anaemia (13%), nausea (10%) and hyperbilirubinaemia (9%). In conclusion, faldaprevir plus PegIFN/RBV achieved clinically meaningful SVR12 rates in patients who failed PegIFN/RBV in a prior trial, with response rates higher among prior relapsers than among prior nonresponders. The adverse event profile was consistent with the known safety profile of faldaprevir.


Assuntos
Antivirais/administração & dosagem , Hepacivirus/classificação , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Oligopeptídeos/administração & dosagem , Ribavirina/administração & dosagem , Terapia de Salvação/métodos , Tiazóis/administração & dosagem , Adulto , Idoso , Ácidos Aminoisobutíricos , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Leucina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Prolina/análogos & derivados , Quinolinas , Resultado do Tratamento
8.
Br J Sports Med ; 49(2): 76-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25115810

RESUMO

Over 100 000 solid organ transplants are performed worldwide each year and this has a significant impact on physical function and quality of life. However, the capacity for exercise in solid-organ recipients is reduced. Regular physical activity improves most of the indices of fitness in these patients but, with few exceptions, they do not reach the values seen in healthy controls. The reason for the 40-60% reduction in maximal exercise capacity is not clear; the disease process, need for life long immunosuppression and sedentary lifestyle all contribute. The interaction between exercise and immunosuppressing medication merits research as does the specifics of the exercise prescription for these patients. This paper reviews important features of this rapidly expanding group of patients and suggests clinical considerations in the application of exercise in this population.


Assuntos
Exercício Físico/fisiologia , Transplantados , Traumatismos em Atletas/etiologia , Traumatismos em Atletas/terapia , Suplementos Nutricionais , Tolerância ao Exercício/fisiologia , Humanos , Tolerância Imunológica/fisiologia , Imunossupressores/efeitos adversos , Músculo Esquelético/fisiologia , Aptidão Física/fisiologia , Qualidade de Vida
9.
Aliment Pharmacol Ther ; 38(1): 16-27, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23710734

RESUMO

BACKGROUND: Adherence to therapeutic regimens affects the efficacy of peginterferon alfa (P) and ribavirin (R) therapy in patients with chronic hepatitis C virus genotype 1. AIM: To determine if medication adherence impacts efficacy [sustained virological response (SVR)] with triple therapy that includes boceprevir (BOC) plus P/R. METHODS: Adherence was determined in two Phase 3 clinical studies with BOC: SPRINT-2 (previously untreated patients) and RESPOND-2 (patients who failed previous therapy with P/R). Adherence to the assigned duration of the dosing regimen and adherence to the three times a day (t.d.s.) dosing interval of 7-9 h for BOC were assessed by the recording of data from patients' dosing diaries and by the amount of study drug dispensed and returned. RESULTS: Most patients (63-71%) adhered to ≥80% of their assigned treatment duration and achieved SVR rates of 86-90%. In contrast, patients who adhered to <80% of their assigned treatment duration achieved SVR rates of 8-32% (P < 0.0001), particularly low in patients who failed previous therapy (SVR = 8-15%). Different rates of adherence (<60% to >80%) to the t.d.s. dosing interval (7-9 h) with BOC did not influence the SVR rates (SVR = 60-83%) with the exception of patients who failed previous treatment and adhered to <60% of the t.d.s. dosing interval with BOC (SVR = 48-50%; P = 0.005). CONCLUSIONS: The achievement of an SVR is more dependent on adherence to the assigned duration of treatment than adherence to the t.d.s. dosing interval with boceprevir. Adherence to >60% of t.d.s. dosing with boceprevir is important in patients who failed previous therapy.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Adesão à Medicação , Polietilenoglicóis/uso terapêutico , Prolina/análogos & derivados , Ribavirina/uso terapêutico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Genótipo , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Prolina/uso terapêutico , RNA Viral/genética , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Carga Viral
10.
JIMD Rep ; 8: 139-44, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23430530

RESUMO

BACKGROUND: Transplantation in patients with inborn errors of metabolism (IEM) may be used as rescue therapy for acute decompensation, organ replacement, or disease-modifying therapy. We sought to quantify the use of transplantation in adults with IEM. METHODS: A 10-question online survey was sent through the email list of adult IEM physicians maintained by the Society for the Study of Inborn Errors of Metabolism and posted on the website of the Society of Inherited Metabolic Diseases. RESULTS: Thirteen centers from five continents responded. These centers, ranging in size from <50 adult patients (three centers) to >500 (two centers), reported 57 adult patients who had undergone transplantation. 29/57 (51 %) came from the two largest centers and 27/57(47 %) were renal transplants for Fabry disease (FD). Only seven transplants were identified as being done for acute decompensation. Eight of thirteen centers had not had patients with IEM passed over on the transplant list but four of these eight had not referred a patient for transplantation. 4/13 centers had patients passed over on the transplant list and reasons cited included: (a) transplant team not comfortable with underlying disease, (b) cognitive impairment in patient raised concerns about compliance, (c) multisystem disease makes single organ transplantation inappropriate, and (d) not at enough risk of life-threatening decompensation. CONCLUSIONS: Excluding renal transplantation for FD, there is low use of transplantation in adults with IEM. Some barriers to transplantation reported by adult centers could be improved with development of educational and management modules for both transplant and metabolic programs.

11.
Transpl Infect Dis ; 14(5): 519-25, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22571389

RESUMO

BACKGROUND: Solid organ transplant (SOT) recipients are at risk for Pneumocystis pneumonia (PCP), especially in the first year post transplant. Although trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis substantially decreases this risk, there is little data or consensus on optimal duration of prophylaxis. Consequently, there is lack of standardization of prophylaxis duration (3 months to lifelong, depending on organ group) in SOT programs. METHODS: We performed a retrospective chart review of all cases of confirmed PCP, in adult kidney, pancreas, liver, and lung transplant recipients from 2001 to 2011 in our SOT program. RESULTS: Of 1241 patients followed in our clinic (657 kidney, 44 kidney/pancreas, 436 liver, and 104 lung or heart/lung), a total of 14 PCP cases were identified in 2 kidney, 1 kidney/pancreas, 5 liver, 5 single lung, and 1 heart/lung transplant recipient. At the time of PCP diagnosis, immunosuppression in most cases consisted of prednisone, tacrolimus, and mycophenolate mofetil (79% of patients), and 53% had previously received TMP-SMX for prophylaxis. None were on PCP prophylaxis at the time of illness onset. PCP occurred early in all 5 liver transplant recipients and in 1 kidney transplant recipient, none of whom had ever received prophylaxis (17-204 days post transplant). Of those who had received 6 months of prophylaxis (1 kidney, 1 kidney/pancreas), PCP occurred at 846 and 4778 days, respectively. Late onset PCP occurred in lung recipients who had received 12 months of prophylaxis (lung 645-1414 days, heart/lung 1583 days post transplant). Five patients had experienced acute rejection and 6 patients had cytomegalovirus (CMV) viremia on average 59 and 204 days preceding PCP, respectively. Three deaths (1 liver, 2 lung) were thought to be directly related to complications of PCP. CONCLUSION: Our experience with late PCP cases in lung transplant recipients receiving only 1 year of prophylaxis lends support to prolonged PCP prophylaxis in this group. Given the number of patients who had experienced an acute rejection episode or CMV disease preceding PCP in non-lung SOT recipients, consideration should be given to re-institution of PCP prophylaxis for a period of time after these events in kidney, kidney/pancreas, and liver transplant recipients.


Assuntos
Transplante de Órgãos/efeitos adversos , Pneumocystis carinii , Pneumonia por Pneumocystis/epidemiologia , Adulto , Idoso , Quimioprevenção , Citomegalovirus , Infecções por Citomegalovirus/epidemiologia , Feminino , Humanos , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/prevenção & controle , Fatores de Tempo , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adulto Jovem
12.
Can J Gastroenterol ; 23(3): 180-4, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19319382

RESUMO

BACKGROUND: Pegylated interferon (pegIFN) and ribavirin combination therapy remains the first-line treatment for chronic hepatitis C virus (HCV) infection. In contrast to the wealth of studies in treatment-naive patients, the effectiveness of retreatment in patients who have previously failed pegIFN-based therapy is largely unreported. AIM: To assess the effectiveness of the retreatment of patients who have previously failed an initial course of pegIFN-based therapy with pegIFNalpha-2a and ribavirin. METHODS: A post-hoc analysis of a multicentre open-label study was performed. Patients received pegIFNalpha-2a and ribavirin at a dose of 800 mg/day and later 1000 mg/day to 1200 mg/day for 24 to 48 weeks at the discretion of the investigator. Outcomes at week 12 (early virological response [EVR]) and week 24 (sustained virological response [SVR]) were analyzed. RESULTS: Eighty-seven patients who had relapsed after previous pegIFN-based therapy (n=28; 78% genotype 1) or were nonresponders (n=59; 71% genotype 1) were analyzed. Of the relapsers, 86% achieved an EVR and 68% achieved an SVR. In relapsers to pegIFN monotherapy (n=15) or pegIFN plus ribavirin (n=13), 60% and 77% achieved an SVR, respectively. Fibrosis and genotype did not affect the likelihood of SVR in relapsers although this may be the result of the relatively small number of patients. In previous nonresponders, an EVR was achieved in 53% but an SVR occurred in only 17%. In nonresponders to pegIFN monotherapy (n=9) and pegIFN plus ribavirin (n=50), 33% and 14% achieved an SVR, respectively. Genotype did not affect SVR in nonresponders. Only 10% with a METAVIR score of F3 or F4 on liver biopsy achieved an SVR. CONCLUSIONS: Relapse after previous pegIFN-based therapy is associated with a strong probability of treatment success whereas retreatment of those with previous nonresponse does not.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Antivirais/administração & dosagem , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Cirrose Hepática/fisiopatologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes , Recidiva , Retratamento , Estudos Retrospectivos , Ribavirina/administração & dosagem , Resultado do Tratamento , Adulto Jovem
13.
Can J Gastroenterol ; 23(2): 91-2, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19214282

RESUMO

The role of biological agents in moderate to severe ulcerative colitis has been shown to be effective in the induction of clinical remission. However, the role of infliximab therapy for induction of remission in patients with fulminant colitis is debatable. A case of a hospitalized patient with a new diagnosis of severe ulcerative colitis refractory to intravenous steroids is presented. The patient was treated with infliximab and discharged with clinical remission, but subsequently presented back to hospital with a lower gastrointestinal hemorrhage.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Hemorragia Gastrointestinal/etiologia , Adulto , Povo Asiático , Colite Ulcerativa/diagnóstico , Resistência a Medicamentos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/cirurgia , Glucocorticoides/uso terapêutico , Humanos , Infliximab , Terapia a Laser/métodos , Masculino , Mesalamina/uso terapêutico , Reto/patologia , Reto/cirurgia , Recidiva , Sigmoidoscopia
14.
J Viral Hepat ; 16(3): 178-86, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19175870

RESUMO

SUMMARY: Noninvasive markers that accurately follow changes in fibrosis may provide alternatives to liver biopsy for assessment of histological endpoints of antiviral therapy in chronic hepatitis C (CHC). This study compared two commercially available serum marker panels (HCV FibroSURE and FIBROSpect II) during interferon-based therapy. Ninety-five interferon-naïve patients with genotype 1 CHC were enrolled in a phase 2b, active-controlled study of albinterferon alfa-2b/ribavirin for 48 weeks. Proprietary and simple biochemical marker panels were independently evaluated in serum before and during the study. Baseline liver biopsies were evaluated for METAVIR fibrosis by a single pathologist. Index scores were obtained for HCV FibroSURE (n = 84) and FIBROSpect II (n = 95); mean biopsy length: 17.8 +/- 8.0 mm. For detecting fibrosis stages 2-4 (prevalence 23% [22/95] and 21% [18/84]), HCV FibroSURE and FIBROSpect II indicated high sensitivity (1.00 and 0.95, respectively), lower but comparable specificity (0.61 and 0.66, respectively), and a good area under the receiver operating characteristic curve (0.89 and 0.90, respectively). Simple indices had high indeterminate rates (31-40%) at baseline. Patients with a sustained virological response had lower baseline scores than nonresponders, and reduced median percent changes in index scores for HCV FibroSURE (-20.0%vs 2.9%; P = 0.14) and FIBROS Spect II (-6.8%vs 18.4%; P = 0.05). The panels demonstrated comparable performance characteristics for differentiating mild from moderate-severe stage disease in CHC. Lower index scores at baseline that continue to decline likely reflect reduced fibrogenesis activity in patients with successful antiviral responses to therapy.


Assuntos
Albuminas , Antivirais , Biomarcadores/análise , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/fisiopatologia , Interferon-alfa , Cirrose Hepática/fisiopatologia , Kit de Reagentes para Diagnóstico , Ribavirina , Adulto , Albuminas/administração & dosagem , Albuminas/uso terapêutico , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Biomarcadores/sangue , Biópsia , Quimioterapia Combinada , Feminino , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico , Sensibilidade e Especificidade , Resultado do Tratamento
15.
Ann Hepatol ; 7(1): 63-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18376368

RESUMO

BACKGROUND: The metabolic syndrome and non-alcoholic fatty liver disease are increasing at alarming rates. AIMS: To determine the effect of HMG-CoA reductase inhibitors (statins) on elevated liver enzymes in patients with hyperlipidemia. PATIENTS: Patients with AST above 60 U/L prior to or during treatment with statin therapy at a quaternary care lipid clinic were reviewed. METHODS: A retrospective analysis was conducted. Patients were separated into two groups: Group 1--elevated AST prior to statin therapy; and Group 2--elevated AST during statin therapy. RESULTS: Forty six patients with one or more measurements of AST >60 U/L remained after exclusion criteria were applied. Ten of 13 (77%) group 1 patients had reduced AST levels after initiation of statin therapy. Thirty two of 33 patients (97%) in group 2 had transient AST elevations while on statin therapy; one patient had persistently elevated AST after initiation of treatment. There were no significant adverse events reported. CONCLUSION: Use of HMG-CoA reductase inhibitors in patients with elevated AST resulted in normalization of AST levels. HMG-CoA reductase inhibitors were safe in patients with mildly elevated AST. This may translate to use of HMG-CoA reductase inhibitors in diseases such as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.


Assuntos
Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Adulto , Aspartato Aminotransferases/sangue , Bases de Dados Factuais , Feminino , Humanos , Fígado/metabolismo , Masculino , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Ambulatório Hospitalar , Estudos Retrospectivos
16.
Aliment Pharmacol Ther ; 28(1): 43-50, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18397386

RESUMO

BACKGROUND: The impact of reduced drug exposure on outcomes in patients with chronic hepatitis C has not been determined in routine clinical practice. AIM: To examine the impact of exposure to peginterferon alpha-2a and ribavirin on early virological response (EVR) and sustained virological response (SVR) in treatment-naive patients with HCV genotype 1 infection enrolled in a large expanded access programme. METHODS: Eight hundred and ninety-one patients treated for 48 weeks with an initial ribavirin dose of 800 or 1000/1200 mg/day were evaluated. Ribavirin 1000 mg/day (<75 kg) or 1200 mg/day (>or=75 kg) and peginterferon alpha-2a 180 microg/week were considered optimal. The impact of reduced drug exposure (expressed as a percentage of optimal) on EVR and SVR was evaluated. RESULTS: Mean ribavirin exposure in week 0-12 was 70% and 96% in patients assigned to ribavirin 800 and 1000/1200 mg/day, respectively. EVR and SVR rates were lower in patients assigned to ribavirin 800 than 1000/1200 mg/day (EVR, 75% vs. 84%, respectively, P < 0.001; SVR, 45% vs. 54%, respectively, P = 0.011). Furthermore, there was a strong correlation between achievement of EVR and SVR and ribavirin dose over the first 12 weeks expressed either as absolute dose or proportion of optimal dose received (P < 0.001 for both). CONCLUSIONS: Ribavirin exposure to week 12 is significantly associated with EVR and SVR in genotype 1 patients. Maintenance of an optimal ribavirin dose is the most important modifiable factor during combination therapy for chronic hepatitis C.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Hepacivirus , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Resultado do Tratamento
17.
Can J Gastroenterol ; 22(2): 153-4, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18299733

RESUMO

Allograft failure secondary to recurrence of hepatitis C virus (HCV) infection is the most common cause of death and retransplantation among recipients with HCV infection. It has been suggested that patients transplanted for HCV have had worse outcomes in more recent years than in previous years (the 'era effect'). A Canadian transplantation registry database was analyzed to determine the outcomes of patients transplanted over the years for HCV. The results of the present analysis of 1002 patients show that the 'era effect' was not seen in liver transplantation recipients with HCV in Canada, because no survival difference was noted based on the year of transplantation. All groups had overall two-year and five-year survival rates of 76% to 83% and 69% to 72%, respectively. The present study's national results prove continued benefit to transplantation of HCV patients.


Assuntos
Hepatite C/mortalidade , Hepatite C/cirurgia , Transplante de Fígado/mortalidade , Canadá/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Recidiva , Sistema de Registros , Taxa de Sobrevida/tendências , Resultado do Tratamento
19.
J Viral Hepat ; 15(1): 52-7, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18088245

RESUMO

Chronic hepatitis C virus (HCV) infections with genotype 2 or 3 are associated with favourable sustained virologic response (SVR) rates. However, genotype 3 may respond less well. We reassessed all treatment-naive patients with genotype 2 and 3 participating in a large expanded-access, non-randomized, open-label trial, evaluating 180microg pegylated interferon (peg-IFN) alpha-2a (40kD) once weekly and 800 mg/day ribavirin for 24-48 weeks. Factors measured prior to initiation of antiviral therapy were considered in the multiple logistic regression model for predicting SVR. In total, 180 patients were analysed of which 72 (40%) were infected by genotype 2 and 108 (60%) genotype 3. The baseline characteristics between patients infected by genotype 2 or 3 were no different including the distribution of hepatic fibrosis stages by METAVIR score. Overall SVR was lower in those patients infected with genotype 3. The significant multivariate predictors of lack of SVR were hepatic fibrosis (P = 0.014) and genotype 3 (P = 0.030). The negative impact of cirrhosis (METAVIR score F4) on treatment response was more evident among subjects with genotype 3 than those with genotype 2 (P = 0.027). There is significant interaction between cirrhosis and genotype 3 leading to a poor antiviral response in such patients requiring an alternate management strategy. This finding should be confirmed in a larger population.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/classificação , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Antivirais/administração & dosagem , Canadá , DNA Viral/genética , Esquema de Medicação , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polietilenoglicóis/administração & dosagem , Reação em Cadeia da Polimerase , Proteínas Recombinantes , Ribavirina/administração & dosagem , Resultado do Tratamento
20.
Can J Gastroenterol ; 21(11): 753-5, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18026580

RESUMO

Malakoplakia is a rare inflammatory condition seen in transplant patients. There are two previously reported cases of malakoplakia involving the gastrointestinal tract in liver transplant patients. The present paper reports a case of colonic malakoplakia in a 58-year-old woman, a liver transplant recipient who was receiving immunosuppressive drugs. She presented with chronic diarrhea while on tacrolimus. There was no history of antecedent infection. Colonoscopy showed patchy mucosal edema, but no discrete yellow plaques or nodules. The diagnosis was made by colon biopsies, which showed chronic inflammation with many histiocytes containing Michaelis-Gutmann bodies. Although rare, malakoplakia is one of many potential causes of diarrhea in a transplant patient. The present case indicates that malakoplakia may be associated with chronic diarrhea, even if there are no macroscopic lesions seen during colonoscopy.


Assuntos
Transplante de Fígado/efeitos adversos , Malacoplasia/diagnóstico , Malacoplasia/etiologia , Diarreia/etiologia , Feminino , Humanos , Imunossupressores/efeitos adversos , Pessoa de Meia-Idade , Tacrolimo/efeitos adversos
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