RESUMO
Liver cirrhosis accounts for over 2 million deaths annually worldwide. A subset of these patients - those with alcoholic hepatitis and decompensated cirrhosis, have abysmal short-term survival. Liver transplant is the only intervention of proven survival benefit; however organ availability is a major limitation. It is thus imperative to assess potential benefit of experimental therapies as a bridge to transplant. Stem cell therapies have shown some promise in patients with end-stage liver disease. Of these, bone-marrow derived hematopoietic stem cells have generated the most interest. Animal as well as human data suggest biological plausibility of stem cell translocation from bone marrow to liver, giving credence to cytokine therapies based on bone marrow stimulation. Granulocyte colony stimulating factor has been the most frequently used cytokine for this purpose. This intervention has shown encouraging results in terms of safety as well as survival benefits in small clinical trials. The evidence, however, is sparse and heterogeneous. In this review we describe the biological plausibility, mechanisms of action, and clinical evidence of the use of cytokine based stem cell therapy in patients with end-stage liver disease.
Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Hepatite Alcoólica/terapia , Cirrose Hepática/terapia , Transplante de Células-Tronco , HumanosRESUMO
Rapid overcorrection of chronic hyponatremia can lead to osmotic demyelination syndrome or central pontine myelinolysis (CPM), a diagnosis often triggered by observing the characteristics of neurological abnormalities developed as a result of CPM. However, anyone with chronic hyponatremia and overcorrection of serum sodium is at risk of physiological CPM despite the lack of clinical symptoms. We report an adult patient who presented as post-op delirium, had incidental finding of CPM by magnetic resonance imaging (MRI) of the head after a liver transplant. Despite his non-typical presentation, the patient had the typical risk factors of CPM such as chronic hyponatremia, rapid overcorrection of serum sodium and cirrhosis undergoing a transplant. As hyponatremia and neurological disorder such encephalopathy simultaneously affect patients with cirrhosis, CPM may be more common than once thought in the chronic liver disease population and inappropriate hyponatremia management has important medical consequences that can go unnoticed.
Assuntos
Delírio/diagnóstico , Hidratação/métodos , Hiponatremia/terapia , Achados Incidentais , Cirrose Hepática Biliar/cirurgia , Transplante de Fígado , Mielinólise Central da Ponte/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Delírio/complicações , Hidratação/efeitos adversos , Humanos , Hiponatremia/sangue , Cirrose Hepática Biliar/sangue , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mielinólise Central da Ponte/complicações , Mielinólise Central da Ponte/etiologia , Cuidados Pré-OperatóriosRESUMO
INTRODUCTION AND AIM: Sofosbuvir (SOF)-based regimen has been shown to have high efficacy even in patients with decompensated cirrhosis. Treated patients may experience various degrees of hepatic recovery ranging from stabilization of liver function, to removal from liver transplant wait lists. The frequency of these occurrences in larger transplant eligible patient populations is unknown. The aim of this study was to assess the efficacy of SOF-based therapy in HCV infected transplant eligible patients and to evaluate short term changes in liver function and the effect on their liver transplant status. MATERIAL AND METHODS: A retrospective multicenter Canadian study of liver transplant candidates with advanced HCV cirrhosis treated with SOF-based therapy. Outcomes included sustained virologic response (SVR), and liver transplant status. RESULTS: 105 liver transplant candidates with advanced liver disease due to HCV were evaluated. The overall SVR was 83.8%. Hepatocellular carcinoma was diagnosed in 39 (37.1%) prior to transplant evaluation. In short term follow-up, 14 (13.3%) remained active on the list at the time of SVR12, 22 (20.9%) patients underwent liver transplantation, 7 (6.6%) patients were deactivated due to clinical improvement, 3 patients were delisted, and 10 deaths were reported. CONCLUSIONS: SOF-based therapy for patients progressing to liver transplantation leads to high SVR rates, short term stability in liver function, and deactivation from the transplant list .
Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Transplante de Fígado , Sofosbuvir/uso terapêutico , Adulto , Idoso , Antivirais/efeitos adversos , Canadá , Progressão da Doença , Quimioterapia Combinada , Feminino , Hepatite C/diagnóstico , Hepatite C/mortalidade , Hepatite C/virologia , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento , Listas de EsperaRESUMO
In the not so distant past, organs from hepatitis C infected donors were either discarded or rarely transplanted into HCV viremic recipients - but never allocated to non-infected patients. However, the simplicity, ease and unprecedented success rates of HCV direct acting antiviral regimens has raised the possibility of utilizing such organs in an attempt to expand the donor pool. The thinker trial reports the first of such attempts. However, caution must be exercised prior to the widespread adoption of such strategy.
Assuntos
Antivirais , Hepatite C , Transplante de Rim , Aloenxertos , Hepacivirus , Humanos , Doadores de TecidosRESUMO
ABSTRACT Background. Chronic renal failure (CRF) is a significant cause of morbidity and mortality in post-liver transplantation (LT) recipients. The risk factors associated with the development of renal dysfunction are not clearly elucidated. Objectives. To examine the risk factors in the development of CRF in these patients. Material and methods. Retrospective case-cohort of liver transplant patients without baseline kidney dysfunction who developed chronic renal failure during their follow-up. Results. Of 370 patients, 254 met the inclusion criteria. 30% (76) of these patients had CRF of which 57% (43) were male. Age, estimated glomerular filtration rate (eGFR) at discharge, and HCV infection were found to be risk factors for CRF post-LT. The odds ratio of developing CRF was 1.4 (0.6-3.3) in males with HCV, 1.6 (0.7-3.9) in females without HCV and 4.4 (1.5-13.2) among females with HCV when compared to men without HCV. Conclusions. In this cohort of LT receipients of a major Canadian city, age, eGFR, and HCV infection were risk factors for CRF. Female gender and HCV increased this odds by a factor of more than 4.
Assuntos
Humanos , Transplante de Fígado/efeitos adversos , Hepatite C/complicações , Falência Renal Crônica/etiologia , Fatores de Tempo , Colúmbia Britânica , Distribuição de Qui-Quadrado , Modelos Logísticos , Razão de Chances , Fatores Sexuais , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Hepatite C/diagnóstico , Medição de Risco , Taxa de Filtração Glomerular , Rim/fisiopatologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/fisiopatologiaRESUMO
BACKGROUND: Chronic renal failure (CRF) is a significant cause of morbidity and mortality in post-liver transplantation (LT) recipients. The risk factors associated with the development of renal dysfunction are not clearly elucidated. OBJECTIVES: To examine the risk factors in the development of CRF in these patients. MATERIAL AND METHODS: Retrospective case-cohort of liver transplant patients without baseline kidney dysfunction who developed chronic renal failure during their follow-up. RESULTS: Of 370 patients, 254 met the inclusion criteria. 30% (76) of these patients had CRF of which 57% (43) were male. Age, estimated glomerular filtration rate (eGFR) at discharge, and HCV infection were found to be risk factors for CRF post-LT. The odds ratio of developing CRF was 1.4 (0.6-3.3) in males with HCV, 1.6 (0.7-3.9) in females without HCV and 4.4 (1.5-13.2) among females with HCV when compared to men without HCV. CONCLUSIONS: In this cohort of LT receipients of a major Canadian city, age, eGFR, and HCV infection were risk factors for CRF. Female gender and HCV increased this odds by a factor of more than 4.
Assuntos
Hepatite C/complicações , Falência Renal Crônica/etiologia , Transplante de Fígado/efeitos adversos , Adulto , Idoso , Colúmbia Britânica , Distribuição de Qui-Quadrado , Feminino , Taxa de Filtração Glomerular , Hepatite C/diagnóstico , Humanos , Rim/fisiopatologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do TratamentoRESUMO
The goal of treatment for chronic hepatitis C viral (HCV) infection is to cure the infection rather than suppress the virus. Historically, a sustained virological response (SVR) defined as undetectable HCV RNA at 24 weeks following the completion of treatment was considered the gold standard to define successful eradication of the virus as a primary endpoint in clinical trials. SVR measured at 12 weeks post-treatment has been shown to be highly concordant with SVR24 in trials of pegylated interferon and ribavirin. The appropriateness and durability of SVR12 as the efficacy endpoint with new oral direct-acting antivirals is less established. A literatura search was performed using PubMed, EMBASE and CENTRAL databases to identify any studies that examined the concordance between SVR24 and earlier time points. Two studies and 4 abstracts were found that performed concordance analyses using positive and negative predictive values. Overall, SVR4 and SVR12 were highly concordant with SVR24 with high positive (> 97%) and negative (> 94%) predictive values; however there was a higher risk of HCV relapse occurring after post-treatment week 4. The majority of the data focused on SVR12 and demonstrated that SVR12 reliably predicted SVR24 in several populations infected with HCV (treatment-naïve, prior null responders, different genotypes) using various new oral direct-acting antiviral regimens. In conclusion, the available data suggests that SVR12 is a reliable assessment of HCV eradication and could be used instead of SVR24 for drug development clinical trials assessing efficacy of new direct-acting antivirals. Data on the long-term durability of SVR12 is still needed.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , RNA Viral/sangue , Resposta Viral Sustentada , 2-Naftilamina , Ácidos Aminoisobutíricos , Ciclopropanos , Quimioterapia Combinada , Hepacivirus/genética , Humanos , Interferons/uso terapêutico , Lactamas Macrocíclicas , Leucina/análogos & derivados , Compostos Macrocíclicos/uso terapêutico , Oligopeptídeos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Prolina/análogos & derivados , Quinolinas , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Tiazóis/uso terapêutico , Fatores de Tempo , Uracila/análogos & derivados , Uracila/uso terapêutico , Carga ViralRESUMO
Renal dysfunction frequently occurs in liver transplant recipients and is associated with increased morbidity and mortality. BK virus is a human polyoma virus that reactivates during immunocompromised states and is a known cause of renal allograft dysfunction in renal transplant recipients. However, BK nephropathy of native kidneys is rare in non-renal transplant recipients. There is no published data linking BK virus and renal dysfunction in liver transplant recipients. We describe the first confirmed case of native polyomavirus BK nephropathy in a liver transplant recipient. BK nephropathy should be considered in the differential diagnosis of new renal failure in liver transplant recipients.
Assuntos
Rejeição de Enxerto/prevenção & controle , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Nefropatias/induzido quimicamente , Transplante de Fígado , Infecções por Polyomavirus/induzido quimicamente , Infecções Tumorais por Vírus/induzido quimicamente , Vírus BK , Colangite Esclerosante/complicações , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/cirurgia , Humanos , Nefropatias/virologia , Masculino , Pessoa de Meia-IdadeRESUMO
Pegylated interferon alpha (PEG-IFN α), a key component of chronic hepatitis C therapy, has been linked to the development of auto-antibodies and autoimmune disease. We report the first case of antimitochondrial antibody (AMA) seroconversion during PEG-INF α based therapy after liver.1-4 transplantation. A fiftyseven year-old man five months after liver transplantation was initiated on hepatitis C triple therapy with PEG-INF α, ribavirin and telaprevir. He had failed previous PEG-IFN α and ribavirin 12 years pre-transplant and his AMA remained negative pre-transplant. After twelve weeks of antiviral therapy, he developed elevated liver enzyme tests associated with an AMA seroconversion to seropositivity. A liver biopsy failed to show histological evidence of primary biliary cirrhosis or graft rejection. He was initiated on urseodeoxycholic acid with subsequent improvement of his liver enzymes. This case demonstrates that despite adequate immunosuppression, AMA seroconversion may occur post-transplant during interferon-based therapy. As AMA seroconversion did not occur during the pre-transplant PEG-IFN therapy, we speculate that donor allograft antigens in combination with PEG-IFN may have been a factor in the post-transplant seroconversion.