RESUMO
Patients with active hepatitis C virus (HCV) infection at transplantation experience rapid allograft infection, increased risk of graft failure and accelerated fibrosis. MBL-HCV1, a neutralizing human monoclonal antibody (mAb) targeting the HCV envelope, was combined with a licensed oral direct-acting antiviral (DAA) to prevent HCV recurrence post-transplant in an open-label exploratory efficacy trial. Eight subjects received MBL-HCV1 beginning on the day of transplant with telaprevir initiated between days 3 and 7 post-transplantation. Following FDA approval of sofosbuvir, two subjects received MBL-HCV1 starting on the day of transplant with sofosbuvir initiated on day 3. Combination treatment was administered for 8-12 weeks or until the stopping rule for viral rebound was met. The primary endpoint was undetectable HCV RNA at day 56 with exploratory endpoints of sustained virologic response (SVR) at 12 and 24 weeks post-treatment. Both subjects receiving mAb and sofosbuvir achieved SVR24. Four of eight subjects in the mAb and telaprevir group met the primary endpoint; one subject achieved SVR24 and three subjects relapsed 2-12 weeks post-treatment. The other four subjects experienced viral breakthrough. There were no serious adverse events related to study treatment. This proof-of-concept study demonstrates that peri-transplant immunoprophylaxis combined with a single oral direct-acting antiviral in the immediate post-transplant period can prevent HCV recurrence.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Antivirais/administração & dosagem , Anticorpos Anti-Hepatite C/administração & dosagem , Hepatite C/prevenção & controle , Transplante de Fígado , Prevenção Secundária , Aloenxertos , Anticorpos Monoclonais/efeitos adversos , Antivirais/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Anticorpos Anti-Hepatite C/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagem , Oligopeptídeos/efeitos adversos , Estudo de Prova de Conceito , RNA Viral/sangue , Sofosbuvir/administração & dosagem , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Transplantados , Resultado do TratamentoRESUMO
Early data regarding the "real-world" experience with novel therapies for hepatitis C (HCV) are encouraging. Data are still limited, however, regarding real-world rates of sustained virologic response (SVR) for ledipasvir-sofosbuvir (LDV-SOF), particularly for patients with prior treatment failure. We performed a retrospective cohort study of 1597 patients with chronic genotype 1 HCV who were treated using 12 weeks of the following regimens LDV-SOF±ribavirin (RBV) (n=1521 without RBV, n=76 with RBV). The primary outcome was SVR-determined at 12 weeks in an intention-to-treat design. Prescription according to Food and Drug Administration (FDA) approved labelling (adding RBV for patients with cirrhosis and treatment failure) was assessed in multivariate models. The study population was aged 60 years on average (range 19-89), 60% male, 50% Caucasian, 43% cared for at an academic centre and 30% cirrhotic. Overall, LDV-SOF resulted in a 94% SVR rate. Only 44 (2.9%) patients relapsed. LDV-SOF+RBV yielded SVR in 97% with 0 viral relapses. While cirrhosis and thrombocytopenia were associated with lower odds of SVR, in a multivariable regression model, only treatment at an academic centre and prescriptions contrary to FDA labelling were significantly associated with lower SVR-odds ratios, 0.56 95% CI (0.35-0.87) and 0.29 95% CI(0.12-0.68), respectively. The real-world experience with LDV-SOF mirrors the SVR rates observed in clinical trials. Efforts to promote prescription within FDA recommendations are warranted.
Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Uridina Monofosfato/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepacivirus/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ribavirina/uso terapêutico , Sofosbuvir , Resposta Viral Sustentada , Resultado do Tratamento , Uridina Monofosfato/uso terapêutico , Adulto JovemRESUMO
Portal hypertension is a predictor of liver-related clinical events and mortality in patients with hepatitis C and cirrhosis. The effect of interferon-free hepatitis C treatment on portal pressure is unknown. Fifty patients with Child-Pugh-Turcotte (CPT) A and B cirrhosis and portal hypertension (hepatic venous pressure gradient [HVPG] >6 mm Hg) were randomized to receive 48 weeks of open-label sofosbuvir plus ribavirin at Day 1 or after a 24-week observation period. The primary endpoint was sustained virologic response 12 weeks after therapy (SVR12) in patients who received ≥1 dose of treatment. Secondary endpoints included changes in HVPG, laboratory parameters, and MELD and CPT scores. A subset of patients was followed 48 weeks posttreatment to determine late changes in HVPG. SVR12 occurred in 72% of patients (33/46). In the 37 patients with paired HVPG measurements at baseline and the end of treatment, mean HVPG decreased by -1.0 (SD 3.97) mm Hg. Nine patients (24%) had ≥20% decreases in HVPG during treatment. Among 39 patients with pretreatment HVPG ≥12 mm Hg, 27 (69%) achieved SVR12. Four of the 33 (12%) patients with baseline HVPG ≥12 mm Hg had HVPG <12 mm Hg at the end of treatment. Of nine patients with pretreatment HVPG ≥12 mm Hg who achieved SVR12 and completed 48 weeks of follow-up, eight (89%) had a ≥20% reduction in HVPG, and three reduced their pressure to <12 mm Hg. Patients with chronic HCV and compensated or decompensated cirrhosis who achieve SVR can have clinically meaningful reductions in HVPG at long-term follow-up. (EudraCT 2012-002457-29).
Assuntos
Hepacivirus , Veias Hepáticas/fisiopatologia , Hepatite C/complicações , Hepatite C/virologia , Hipertensão Portal/etiologia , Hipertensão Portal/fisiopatologia , Cirrose Hepática/complicações , Cirrose Hepática/etiologia , Pressão na Veia Porta , Adulto , Idoso , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral , Resposta Viral Sustentada , Fatores de Tempo , Carga ViralRESUMO
Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-α and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change in viral load (log10 IU/mL) from baseline was significantly greater (p=0.02) for the antibody-treated group (range -3.07 to -3.34) compared to placebo group (range -0.331 to -1.01) on days 3 through 6 posttransplant. MBL-HCV1 treatment significantly delayed median time to viral rebound compared to placebo treatment (18.7 days vs. 2.4 days, p<0.001). As with other HCV monotherapies, antibody-treated subjects had resistance-associated variants at the time of viral rebound. A combination study of MBL-HCV1 with a direct-acting antiviral is underway.
Assuntos
Anticorpos Monoclonais/farmacologia , Hepacivirus/fisiologia , Hepatite C/tratamento farmacológico , Transplante de Fígado , Idoso , Biópsia , Método Duplo-Cego , Feminino , Genótipo , Hepatite C/virologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , RNA Viral/análise , Fatores de Tempo , Proteínas do Envelope Viral/imunologiaRESUMO
Utilization of livers from expanded criteria donors (ECD) is one strategy to overcome the severe organ shortage. The decision to utilize an ECD liver is complex and fraught with uncertainty for both providers and patients. We assessed patients' willingness to accept ECD liver transplantation (LTx) and acceptable 1-year mortality risk. One hundred eight patients listed for LTx were asked to rate their willingness to accept ECD LTx and the associated 1-year mortality risk they were willing to accept. Also, patients completed the SF-36v2 and sociodemographic and health information was gathered from their medical records. Patients reported significantly higher willingness to accept standard criteria donor (SCD) versus ECD LTx (t = 13.8, p < 0.001), with more than one-third of patients reporting low willingness to accept ECD LTx. Relative to our center's 10% SCD LTx 1-year mortality rate, most patients (71%) were willing to accept moderately or substantially higher 1-year mortality risk for ECD LTx. In multivariable analyses, higher lab MELD score and white race were significant independent predictors of both ECD willingness and ECD increased mortality risk acceptability. Findings highlight the importance of assessing patients' willingness to pursue ECD LTx and the relative mortality risks they are willing to accept.
Assuntos
Hepatopatias/psicologia , Transplante de Fígado , Aceitação pelo Paciente de Cuidados de Saúde , Doadores de Tecidos , Feminino , Humanos , Hepatopatias/mortalidade , Hepatopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Liver transplantation (LT) is the treatment of choice for end-stage liver disease, but is controversial in patients with human immunodeficiency virus (HIV) infection. Using a prospective cohort of HIV-hepatitis B virus (HBV) coinfected patients transplanted between 2001-2007; outcomes including survival and HBV clinical recurrence were determined. Twenty-two coinfected patients underwent LT; 45% had detectable HBV DNA pre-LT and 72% were receiving anti-HBV drugs with efficacy against lamivudine-resistant HBV. Post-LT, all patients received hepatitis B immune globulin (HBIG) plus nucleos(t)ide analogues and remained HBsAg negative without clinical evidence of HBV recurrence, with a median follow-up 3.5 years. Low-level HBV viremia (median 108 IU/mL, range 9-789) was intermittently detected in 7/13 but not associated with HBsAg detection or ALT elevation. Compared with 20 HBV monoinfected patients on similar HBV prophylaxis and median follow-up of 4.0 years, patient and graft survival were similar: 100% versus 85% in HBV mono- versus coinfected patients (p = 0.08, log rank test). LT is effective for HIV-HBV coinfected patients with complications of cirrhosis, including those who are HBV DNA positive at the time of LT. Combination HBIG and antivirals is effective as prophylaxis with no clinical evidence of HBV recurrence but low-level HBV DNA is detectable in approximately 50% of recipients.
Assuntos
Antivirais/uso terapêutico , Lamivudina/uso terapêutico , Transplante de Fígado/efeitos adversos , Transplante de Fígado/imunologia , Adulto , Idoso , Antivirais/imunologia , Antivirais/farmacologia , Sobrevivência de Enxerto/imunologia , HIV/genética , HIV/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Hepatite/tratamento farmacológico , Hepatite/imunologia , Hepatite/virologia , Hepatite B/tratamento farmacológico , Hepatite B/imunologia , Hepatite B/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Imunoglobulinas , Síndromes de Imunodeficiência/tratamento farmacológico , Síndromes de Imunodeficiência/imunologia , Infecções/tratamento farmacológico , Infecções/imunologia , Infecções/virologia , Lamivudina/imunologia , Lamivudina/farmacologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/imunologia , Cirrose Hepática/cirurgia , Falência Hepática/tratamento farmacológico , Falência Hepática/imunologia , Falência Hepática/virologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevenção Secundária , Resultado do Tratamento , Viroses/tratamento farmacológico , Viroses/imunologia , Viroses/virologia , Vírus/genética , Vírus/imunologiaRESUMO
BACKGROUND: Elbasvir-grazoprevir is indicated for chronic hepatitis C virus (HCV) genotypes 1 and 4. AIM: To evaluate the utilization and outcomes of chronic HCV patients treated with elbasvir-grazoprevir in the United States. METHODS: We conducted a retrospective cohort study of adults treated with elbasvir-grazoprevir with or without ribavirin for chronic HCV genotypes 1 or 4 infection. Data were collected from healthcare providers and specialty pharmacies through Innervation Platform, a proprietary, cloud-based disease management program from Trio Health. The primary endpoint was per protocol sustained virological response 12 weeks post-treatment (SVR12). RESULTS: Among 470 patients treated in 2016, 95% had HCV genotype 1 infection, 80% (373/468) were HCV treatment naïve and 70% (327/468) had non-cirrhotic disease. Almost 3 quarters (73%) of patients received care in community practices. The majority (89%) of patients received elbasvir-grazoprevir for 12 weeks. Per protocol SVR12 rates were 99% (396/402) for HCV genotype 1 and 95% (21/22) for HCV genotype 4. Among patients with Stage 4 or 5 chronic kidney diseases, 99% (113/114) achieved SVR12. In univariate analyses, variables significantly associated with per protocol SVR12 for the entire sample were therapy duration (P = 0.001), treatment experience (P = 0.016), and cirrhosis status (P = 0.001). However, among HCV genotype 1 patients, no variables were significant. Intent-to-treat SVR12 rates were 89% (396/447) for HCV genotype 1 and 91% (21/23) for HCV genotype 4. CONCLUSION: Elbasvir-grazoprevir is highly effective, and in this 2016 cohort, its use was predominantly in patients with HCV genotype 1 and as a 12-week therapy without ribavirin.
Assuntos
Antivirais/uso terapêutico , Benzofuranos/uso terapêutico , Genótipo , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Imidazóis/uso terapêutico , Quinoxalinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/farmacologia , Benzofuranos/farmacologia , Estudos de Coortes , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Hepatite C Crônica/diagnóstico , Humanos , Imidazóis/farmacologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , Masculino , Pessoa de Meia-Idade , Quinoxalinas/farmacologia , RNA Viral/efeitos dos fármacos , RNA Viral/genética , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/genética , Estudos Retrospectivos , Resposta Viral SustentadaRESUMO
BACKGROUND: Treatment of genotype 1 hepatitis C virus (HCV) infection with combination direct acting anti-virals is associated with very high rates of sustained virological response (SVR). Daily combination of ledipasvir and sofosbuvir for 12 weeks is approved for the treatment of genotype 1 HCV patients, though noncirrhotic patients who are naïve to treatment with a baseline HCV RNA <6 million IU/mL can be treated for 8 weeks. This guidance stemmed from a post hoc analysis of the ION 3 clinical trial, which demonstrated similar SVR for patients treated with ledipasvir and sofosbuvir with or without ribavirin for 8 or 12 weeks. AIM: To compare the SVR for 8 weeks vs 12 weeks of ledipasvir and sofosbuvir in HCV infected patients in a real-world setting. METHODS: We performed an observational real-world cohort study of treatment success following 8 or 12 weeks of ledipasvir and sofosbuvir for treatment-naïve genotype 1 HCV patients. RESULTS: A total of 826 patients were treated for either 8 (n=252) or 12 weeks (n=574) with ledipasvir and sofosbuvir and achieved SVR rate of 95.3% and there was no statistical difference in SVR rates in the two groups irrespective of any clinical or virological variables. CONCLUSIONS: In treatment-naïve HCV genotype 1 patients, SVR was 95% in those treated for either 8 weeks or 12 weeks with ledipasvir and sofosbuvir. 8 week ledipasvir and sofosbuvir can reduce costs without compromising outcomes for those patients who qualify for such regimen.
Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Sofosbuvir/administração & dosagem , Idoso , Antivirais/uso terapêutico , Estudos de Coortes , Feminino , Genótipo , Hepacivirus/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resultado do TratamentoRESUMO
Murine and human studies have demonstrated that the normal liver contains significant numbers of resident lymphocytes that have functions distinct from those found in blood and other organs. To characterize these cells requires the isolation of viable lymphocytes that can be analysed by flow cytometry and in functional assays. The techniques classically used to isolate single cell suspensions of hepatic lymphocytes for phenotypic and functional studies involve mechanical and/or enzymatic dissociation of liver tissue. The aim of this study was to determine the effect of these procedures on surface molecule expression and lymphocyte function and to optimise an isolation technique that minimises these effects. Mechanical homogenisation of liver tissue alone resulted in low viable lymphocyte yields but these were improved by the combined use of mechanical and enzymatic techniques. A mean yield of 2.3 x 10(6) lymphocytes with a mean viability was 88.8% was obtained from 200 mg wedge biopsy samples of normal adult human liver using a combination of gentle mechanical dissociation followed by digestion with collagenase type IV and DNase I. These cells were suitable for phenotypic characterisation by flow cytometry. They also retained their ability to grow in vitro, to respond to cytokines and activation stimuli, to mediate cytotoxic killing of target cells, and to produce inflammatory and regulatory cytokines.
Assuntos
Separação Celular , Fígado/citologia , Linfócitos/classificação , Linfócitos/imunologia , Soluções para Preservação de Órgãos , Adenosina , Adulto , Alopurinol , Animais , Biomarcadores , Separação Celular/métodos , Separação Celular/normas , Sobrevivência Celular , Células Cultivadas , Testes Imunológicos de Citotoxicidade , Endopeptidases/metabolismo , Glutationa , Humanos , Imunofenotipagem , Insulina , Interferon gama/biossíntese , Interleucina-4/biossíntese , Células K562 , Linfócitos/citologia , Camundongos , RafinoseRESUMO
Total complement 4 (C4) levels, when analysed on the Beckman Array nephelometer, were found to increase number of serum specimens [predominantly from patients with hepatitis C virus (HCV) infection] after overnight storage at 4 degrees C. In order to investigate whether the phenomenon of in vitro cold-dependent activation of complement (CDAC) was the explanation for this increase, paired specimens were collected from 63 patients with HCV infection in tubes with no anticoagulant (serum) and in tubes containing EDTA (which inhibits complement activation). C4 levels increased after overnight storage at 4 degrees C in 33 serum specimens (52%). In contrast, no increase in C4 levels was observed in any of the 63 EDTA specimens. Immunofixation of intact and activated C4 products confirmed that complement activation had taken place in the serum specimens in which C4 levels had increased after storage. There was a higher frequency of hepatitis C viraemia (P<0.0001), HCV antibody positivity (P<0.05) and the presence of rheumatoid factor (P<0.05) in the group of patients in whose serum samples CDAC had occurred (n = 33) than in the other group (n = 30). As a result of our findings on C4 analysis in stored serum specimens, we would recommend potassium EDTA plasma as the specimen of choice for complement analysis on the Beckman Array.
Assuntos
Complemento C4/análise , Via Clássica do Complemento , Hepatite C/imunologia , Análise Química do Sangue/instrumentação , Análise Química do Sangue/métodos , Temperatura Baixa , Ácido Edético , Humanos , Técnicas In Vitro , Nefelometria e Turbidimetria/instrumentação , Nefelometria e Turbidimetria/métodosAssuntos
Carcinoma de Células Escamosas/patologia , Seio Cavernoso , Neoplasias Laríngeas/patologia , Neoplasias Vasculares/secundário , Carcinoma de Células Escamosas/diagnóstico , Evolução Fatal , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neoplasias Vasculares/diagnósticoRESUMO
BACKGROUND: Hepatic osteodystrophy occurs in the majority of patients with advanced chronic liver disease with the abnormalities in bone metabolism accelerating following orthotopic liver transplantation (OLT). AIMS: To examine changes in bone mineral density (BMD) following OLT and to investigate factors that lead to bone loss. METHODS: Twelve patients had BMD (at both the lumbar spine (LS) and femoral neck (FN)) and biochemical markers measured preoperatively and for 24 months following OLT. RESULTS: BMD was low in 75% of patients prior to OLT and decreased significantly from baseline at the LS at three months and the FN at six months. BMD began to increase thereafter at both sites, approaching baseline values at the LS by 12 months. Bone formation markers, osteocalcin and procollagen type I carboxy propeptide, decreased immediately post-OLT, with a concomitant increase seen in the resorption markers pyridinoline and deoxypyridinoline. This resulted in a negative uncoupling index early post-OLT, that rebounded to positive values after six months. There was a significant correlation between the change in the uncoupling index between six and three months which preceded the increase in BMD at 12 months. The decrease in BMD recorded early post-OLT correlated with vitamin D levels at three months. CONCLUSIONS: Results suggest that increased resorption and inadequate formation are the major contributors to additional bone loss following OLT. Non-invasive biochemical markers precede later changes in BMD in this patient group following OLT and may have a role in investigating and planning intervention strategies to prevent bone loss in future studies.
Assuntos
Hepatopatias/complicações , Osteólise/etiologia , Idoso , Biomarcadores , Densidade Óssea , Osso e Ossos/metabolismo , Feminino , Humanos , Hepatopatias/metabolismo , Hepatopatias/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Osteólise/metabolismoRESUMO
BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is associated with the development of chronic liver disease and extra-hepatic manifestations, which include autoantibody production, immune-mediated diseases such as cryoglobulinaemia and B-cell lymphoproliferation. Recent identification of intra-hepatic clonal B cells capable of rheumatoid factor production, selective infection of B cells over T cells and of an HCV receptor on B lymphocytes strongly supports a central role for these cells in the immune response to HCV infection. In particular, CD5+ B cells which are capable of producing natural antibodies with autoreactive specificities are likely to be important in the development of HCV-associated autoimmunity and lymphoproliferation. METHODS: We have investigated the presence of CD5+ B cells in a unique cohort of HCV-infected women who were infected with a single inoculum of HCV genotype 1b following immunisation with contaminated anti-D immunoglobulin in 1977. RESULTS: CD5+ B cells are significantly increased in chronic HCV infection (37.66+/-1.92%) as compared with those with resolved infection (25.33+/-1.90%). High levels of CD5+ B cells were associated with the production of rheumatoid factor. The number of peripheral blood CD5+ B cells correlated negatively with histological activity index. CONCLUSIONS: The expansion of this B cell population in patients with active HCV infection may give rise to immune-mediated sequelae associated with HCV infection. This expanded population of CD5+ B cells may protect against the development of progressive liver disease.
Assuntos
Linfócitos B/imunologia , Antígenos CD5/imunologia , Hepacivirus/imunologia , Hepatite C Crônica/imunologia , Adulto , Antígenos CD19/análise , Feminino , Citometria de Fluxo , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/patologia , Humanos , Fígado/imunologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Viral/análise , Fator Reumatoide/sangueRESUMO
AIMS: To compare the diagnostic performance of hepatic arterial (HA) Doppler ultrasound post-liver transplantation for hepatic artery thrombosis and stenosis in our unit with the literature. To evaluate the role of the technique in clinical practice. MATERIALS AND METHODS: In a two-phase 'audit cycle' study, adult OLT patients had Doppler studies comprising detection of HA flow and measurements of peak systolic velocity, resistive index and systolic acceleration time. In phase I, patients had Doppler examinations 'routinely' and for any hepatic biochemical abnormality. In phase II, Doppler ultrasound was performed early post-OLT and later only if a senior transplant clinician suspected graft ischaemia. In addition to HA measurements the waveform was visually assessed. Clinical outcome was the 'gold standard'. RESULTS: Phase 1: 38 patients, 40 OLT operations, 125 Doppler studies; 14 arteriograms. Phase 2: 35 patients, 42 OLT operations, two HA angioplasties, one HA revision, one non-occlusive thrombus, 140 studies; 17 arteriograms. Results; Phase 1 [Phase 2]: sensitivity 80% [100%]; specificity 71% [81%]; PPV 28% [56%]; NPV 96% [100%]; incidence of HA abnormality 12.5% [19. 5%]; likelihood ratio of negative result 0.28 [0]; of positive result 2.8 [5.3]. CONCLUSION: Previously reported results are reproducible. Normal HA waveform should also be a criterion of normality. The technique is very sensitive but relatively non-specific. Predictive values improve with discriminate use. MacEneaney, P. M. (2000). Clinical Radiology55, 517-524.
Assuntos
Artéria Hepática/diagnóstico por imagem , Transplante de Fígado , Complicações Pós-Operatórias/diagnóstico por imagem , Trombose/diagnóstico por imagem , Adulto , Constrição Patológica/diagnóstico por imagem , Estudos de Avaliação como Assunto , Humanos , Sensibilidade e Especificidade , Ultrassonografia DopplerRESUMO
The presence and phenotype of lineage-committed hematopoietic progenitors in the normal adult human liver (AHL) were investigated and compared with the profiles of differentiating hematopoietic precursor populations detected in liver bearing metastases of colonic origin. Levels of hematopoietic stem cells (HSCs) (CD34(+)CD45(+)) detected in hepatic mononuclear cell (HMNC) populations were increased 6-fold when compared with matched peripheral blood samples. In normal liver, less than 5% of HSCs expressed the myeloid-associated antigen, CD33, whereas considerable proportions expressed lymphoid-associated markers (T cell, 33.39%; B cell, 17.39%; and natural killer [NK] cell, 37.17%). Significant increases were observed in the relative proportions of hepatic HSCs coexpressing CD33 (20.53%; P =.001), and the T-cell marker (CD7, 58. 13%; P =.02) in tumor-bearing liver compared with normal liver. HSCs with B-cell progenitor phenotype (CD19(+)) were significantly decreased in tumor-bearing liver (0.06%; P =.02). Despite these differences, the activation status of hematopoiesis, as measured by the coexpression of the differentiation and activation markers, CD38 and CD45RA, did not differ significantly between normal and tumor-bearing liver. These results indicate that the normal AHL harbors lineage-committed hematopoietic progenitors, and the vast majority of these progenitors express lymphoid-associated antigens with changes occurring in both the myeloid and lymphoid compartments of the hepatic hematopoietic pathway on tumor challenge. While tumor-bearing livers are enriched for intrahepatic myeloid precursors and T-cell progenitor cells, further studies are required to establish the origin and in situ development potential of hepatic HSCs in the adult human and their role in tumor immunity.